tbuckley/cabot-search huggingface dataset:
AB0512 Anti-tnf-therapy reduces uveitis flares in patients with ankylosing spondylitis
Authors: A. Godzenko, A. Botchkova, O. Rumyantceva, S. Erdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Acute anterior uveitis (AAU) is most common extraskeletal manifestation of ankylosing spondylitis (AS). Course of uveitis not always correlate with spine and joint inflammation. Effect of biologics to uveitis is not studied enough. <h3>Objectives</h3> To assess significance of reducing of uveitis flares in AS pts using anti-TNF-therapy as compared with traditional anti-inflammatory therapy. <h3>Methods</h3> 48 pts with AS and recurrent uveitis, treated by anti-TNF drugs, were assessed at the Institute of Rheumathology RAMS. 25 used infliximab, 15 adalimumab, 9 etanercept. 7 pts used 2 and more drugs sequentially. Mean duration of TNF-therapy was 3,7 (3,5-5), [1;9] years. Mean duration of therapy from first attack of uveitis to start of anti-TNF therapy was 6,5 (5-9,7) [1;30] years: 18 pts used only NSAD and 30 – NSAD and DMARD, including sulfaslazine (23 pts), metotrexate(4 pts), cyclosporine (4 pts). <h3>Results</h3> The mean rate of uveitis attacks during traditional anti-inflammatory therapy was 2,2 per year, during anti-TNF therapy – 0,6 per year, p=0,0007. 19 of 42 pts (45%) had not episodes of uveitis during the course of anti-TNF therapy. For infliximab frequency of uveitis decreased from 1, 9 to 0,4 episodes per year (p=0,002), for adalimumab – from 3,25 to 0,7 (p=0,04), for etanercept – from 1,2 to 0,09 (p=0,001). <h3>Conclusions</h3> Anti-TNF therapy significantly reduces number of uveitis attacks in AS pts. <h3>References</h3> <h3>Disclosure of Interest</h3> None Declared
An international, double-blind, randomized, placebo-controlled phase III trial (EXAM) of cabozantinib (XL184) in medullary thyroid carcinoma (MTC) patients (pts) with documented RECIST progression at baseline.
Authors: Patrick Schoffski, Rossella Elisei, Stefan Müller, Marcia S. Brose, Manisha H. Shah, Lisa F. Licitra, Barbara Jarzab, Viktor Medvedev, Michael Kreissl, Bruno Niederle, Ezra E. W. Cohen, Lori J. Wirth, Haythem Y. Ali, Colin Hessel, Yifah Yaron, Douglas Wilmot Ball, Barry Nelkin, Steven I. Sherman, Martin Schlumberger
Journal: Journal of Clinical Oncology (2012)

5508 Background: MTC arises from parafollicular cells of the thyroid gland, accounts for 5-8% of thyroid cancers and represents an unmet medical need. Cabozantinib (cabo) is an oral inhibitor of MET, VEGFR2, and RET. We conducted a phase III study of cabo vs placebo (P) in pts with progressive, unresectable, locally advanced or metastatic MTC. Methods: Eligible pts were required to have documented RECIST progression within 14 months of screening. The primary efficacy measure was progression-free survival (PFS) as assessed by an independent review facility (IRF) using RECIST. Secondary efficacy measures included objective response rate (ORR) and overall survival (OS). The study has 90% power to detect a 75% increase in PFS and 80% power to detect a 50% increase in OS. Tumor assessments occurred every 12 weeks. Crossover between treatment arms was not allowed. Results: Between Sept 2008 and Feb 2011, 330 pts (median age 55 yrs; 67% male; 96% measureable disease; RET mutation status: pos 48%; neg 12%; unknown 39%; prior TKI exposure: yes 21%, no 78%, unknown 2%) were randomized 2:1 to cabo (140 mg free base [175 mg salt form] qd; n=219) or P (n=111). The planned primary PFS analysis included events through the date of the 138th event. As of 15June2011, 44.7% of pts on cabo and 13.5% on P were still receiving study treatment. Statistically significant PFS prolongation of 7.2 mo was observed; median PFS for cabo was 11.2 mo vs 4.0 mo for P (HR 0.28, 95% CI 0.19-0.40, p&lt;0.0001). PFS results favored the cabo group across subset analyses including RET status and prior TKI use. ORR was 28% for cabo vs 0% for P (p&lt;0.0001). An interim analysis of OS (44% of the 217 required events) did not show a difference between cabo and P. The most frequent grade ≥3 adverse events (cabo vs P) were diarrhea (15.9 vs 1.8%), palmar-plantar erythrodysesthesia (12.6 vs 0%), fatigue (9.3 vs 2.8%), hypocalcemia (9.3 vs 0%), and hypertension (7.9 vs 0%). Conclusions: This phase III study met its primary objective of demonstrating substantial PFS prolongation with cabo vs. P in a patient population with MTC and documented progressive disease in need of therapeutic intervention.
Reuse of a Transplanted Kidney
Authors: Amado Andres, Jose Maria Morales, Joseph Lloveras
Journal: New England Journal of Medicine (1993)

To the Editor: Pasic et al. (Feb. 4 issue)1 report the successful reuse of a transplanted heart. In our hospital, Moreno et al.2 reused a liver graft with a favorable result. Recently, we reused a ...
Successful salvage treatment of peptic duodenal stenosis with repeat insertion of self-expanding stent after failed balloon dilation
Authors: S. Park, H. Chun, B. Keum, B. Lee, Y. Seo, Y. Kim, J. Park, Y. Jeen, H. Lee, S. Um, C. Kim, H. Ryu
Journal: Endoscopy (2011)

A 63-year-old man attended the hospital due to early satiety and indigestion. He had had peptic ulcer disease for several years and had received proton pump inhibitor (PPI) therapy for a prolonged period at another center without satisfactory outcome. Endoscopic examination revealed a narrowed pyloric channel that precluded passage of a scope ([Fig. 1 a]). Urea breath test result was negative, proving that previous Helicobacter pylori eradication treatment had been successful. To alleviate the patient's symptoms, we carried out repeated endoscopic balloon dilation at 7 – 10-day intervals, using through-the-scope (TTS) balloon dilation catheters up to 12 mm diameter. However, after five sessions of this intervention there was no improvement in the symptoms. As the patient did not want to undergo surgery, endoscopic self-expanding metallic stent (SEMS) installation was attempted. A 7-cm, partial covered stent (Hanarostent, M. I. Tech Co., Ltd., Seoul, Korea) was deployed using an endoscope and the TTS method ([Fig. 1 b]). There were no immediate complications and the patient was put on a liquid diet that night. After 2 weeks, follow-up endoscopy revealed a patent stent in a fairly good position. Considering the possibility of in-stent growth of granulation tissue, the stent was removed after the fourth week of insertion via endoscopy with forceps ([Fig. 1 c]). Use of argon plasma coagulation (APC) to ablate the in-growing granulation tissue ([Fig. 1 d]) allowed reinsertion of the SEMS at 4 – 8 weeks intervals at the endoscopist's discretion. The removal/insertion process was repeated six times. The final endoscopic examination revealed a significantly wider pyloric channel, which allowed easy passage of an endoscope ([Fig. 2]). The patient is currently on double doses of PPI, and has had no signs or symptoms of obstruction over 1 year of follow-up.
An experience that changed my practice: Breaking news
Authors: R. N Siddiqui
Journal: BMJ (2001)

Jaundice is the commonest presentation of patients with liver and biliary disease.The cause can be established in most cases by simple non-invasive tests, but many patients will require referral to a specialist for management.Patients with high concentrations of bilirubin ( > 100 mol/l) or with evidence of sepsis or cholangitis are at high risk of developing complications and should be referred as an emergency because delays in treatment adversely affect prognosis. JaundiceHyperbilirubinaemia is defined as a bilirubin concentration above the normal laboratory upper limit of 19 mol/l.Jaundice occurs when bilirubin becomes visible within the sclera, skin, and mucous membranes, at a blood concentration of around 40 mol/l.Jaundice can be categorised as prehepatic, hepatic, or posthepatic, and this provides a useful framework for identifying the underlying cause.Around 3% of the UK population have hyperbilirubinaemia (up to 100 mol/l) caused by excess unconjugated bilirubin, a condition known as Gilbert's syndrome.These patients have mild impairment of conjugation within the hepatocytes.The condition usually becomes apparent only during a transient rise in bilirubin concentration (precipitated by fasting or illness) that results in frank jaundice.Investigations show an isolated unconjugated hyperbilirubinaemia with normal liver enzyme activities and reticulocyte concentrations.The syndrome is often familial and does not require treatment.
Basophil Histamine-Release Test with a Modification Is Useful for Diagnosis of Allergy to Formaldehyde
Authors: Yusuke Tanaka, Yuko Nakase, Naoya Sugimoto, Hidenori Arai, Hiroyuki Nagase, Masao Yamaguchi, Ken Ohta
Journal: Journal of Allergy and Clinical Immunology (2015)
Fungal colonization of intragastric balloons
Authors: Zahide Şimşek, Oğuz Gürbüz, Şahin Çoban
Journal: Endoscopy (2014)

Intragastric balloon therapy is used for weight reduction as a short-term intervention in obese patients. The procedure is usually well tolerated, however, some complications including intolerance, vomiting, gastroesophageal reflux, gastric erosions and esophagitis, gastric ulcers, and spontaneous deflation of the balloon have been observed. In addition, gastric perforation, dilatation, and small-intestinal obstructions are occasionally reported [1] [2]. Different types of intragastric balloon may be used for weight reduction [3]. Herein, we present three asymptomatic patients with intragastric balloons infected by Candida albicans yeast colonies.
Folliculitis Induced by Actinomycin D
Authors: Ervin H. Epstein, Marvin A. Lutzner
Journal: New England Journal of Medicine (1969)

In nine of 11 adult patients treated with actinomycin D a characteristic skin eruption developed, with predictable progression from erythema to papules and pustules and from face to trunk. The dominant histologic feature of these lesions was initial replacement of the hair follicles and sebaceous glands with neutrophils. After resolution of the inflammation, plugged, dilated follicles persisted for several months. Although often dramatic and unsightly, this eruption was benign and required no modification of treatment.
Abstract 430: Serpin-A1 and A3 as potential pharmacodynamic biomarkers for NOV-002, a redox-modulating anti-cancer agent
Authors: Christina L. Grek, Danyelle M. Townsend, Joachim D. Uys, Christopher J. Pazoles, Kenneth D. Tew
Journal: Cancer Research (2010)

Abstract NOV-002 is a formulation of disodium glutathione disulfide (GSSG) that is in Phase III clinical trials for the treatment of advanced non-small cell lung cancer and other oncology indications in combination with standard chemotherapeutic regimens. In addition to increased efficacy compared to chemotherapy alone (survival, tumor growth), NOV-002 has been shown to mitigate chemotherapy-induced hematological suppression. In animal studies it was found that, when administered after chemotherapy, NOV-002 stimulated proliferation of bone marrow progenitor cells and normalized peripheral blood levels of leukocytes and platelets. NOV-002's pharmacokinetic properties demonstrate first order absorption / elimination with a plasma half-life of ∼13 mins. The redox regulation of protein thiols persist in plasma for ∼4 hours. Using mass spectrometry, we identified that Serpin-A1 and -A3 were S-glutathionylated following NOV-002 administration to mice. Serpin-A1 and -A3 were also glutathionylated in a dose- and time- dependent S-glutathionylation following NOV-002 treatment of mouse or human plasma in vitro. There is evidence that members of the Serpin protein family can influence myeloproliferation and hematopoetic progenitor cell mobilization (Winkler et al., 2005; van Pel et al., 2006). Specifically, down regulation of serpins has been demonstrated in bone marrow during progenitor cell mobilization (van Pel et al., 2006), and this influences the marrow microenvironment and migratory behavior of hematopoetic precursor cells. Furthermore, glutathionylation of Serpins has been shown to inhibit their activity (Taygi et al., 1991 and 1992). Since our data shows that Serpins A1 and A3 are S-glutathionylated in plasma following NOV-002 treatment, there may be a mechanistic link between this effect and its in vivo myeloproliferative actions. Moreover, liberation of serpins into the peripheral circulation may also provide an indication that proteolytic pathways have been activated. Since the plasma half-life of S-glutathionylated proteins is ∼4 hours (Townsend et al., 2006), it may be possible to identify and develop these post-translationally modified blood proteins as pharmacodynamic biomarkers. 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 430.
Safety notes: how to avoid infections in natural orifice transluminal endoscopic surgery
Authors: A. Fritscher-Ravens, A. Arlt
Journal: Endoscopy (2011)

When the first natural orifice transluminal endoscopic surgery (NOTES) approach of an anastomosis was presented during the new technology session of Digestive Disease Week 2002 [1], the audience raised questions about infection of the peritoneal cavity. Prevention of infection was defined as a fundamental challenge in the later White Paper of the Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) in 2005 [2], and remained an all important topic at their meeting in 2010.
Abstract 1337: Soluble IL-6Rα regulates endothelial survival and vascular integrity and promotes ovarian cancer progression
Authors: Lin-Hung Wei
Journal: Cancer Research (2010)

Abstract The immunoregulatory cytokine interleukin 6 (IL-6) has been recognized as an important modulator of ovarian cancer progression. However, whether IL-6 plays a direct role in the process remains controversial. On target cells, IL-6 binds to the IL-6 receptor (IL-6Rα) and signals via complex formation with the ubiquitously expressed gp130 receptor. Soluble IL-6 receptor protein (sIL-6Rα) binds IL-6 and can activate target cells that are deficient in or lack IL-6Rα, such as endothelial cells. This process is named trans signaling and serves as the major proinflammatory paradigm of IL-6 signaling under various pathologic conditions, including cancers. In the present report, we showed that sIL-6Rα is significantly elevated in malignant ascites from ovarian cancer patients and is associated with poor prognosis in advanced ovarian cancer patients. We identified that IL-6 trans signaling on endothelial cells prevents chemotherapy-induced apoptosis, induces endothelial hyperpermeability, and increases transendothelial migration of ovarian cancer cells. Selectively blocking the MAPK pathway with the ERK inhibitor PD98059 substantially reduced the IL-6/sIL-6Rα complex-mediated endothelial hyperpermeability. The activation of ERK by the IL-6/sIL-6Rα complex modulated endothelial integrity by initiating the activation of Src kinase activities and Y685 phosphorylation of VE-cadherin. Collectively, these data indicate that sIL-6Rα in malignant ascites of ovarian cancer may drive IL-6 signaling on endothelial cells, which, importantly, is involved in ovarian cancer progression. Specifically, blockage of sIL-6α-mediated signaling may present a promising therapeutic strategy for the management of ovarian cancer. 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 1337.
Abstract P6-12-02: Use of cytochrome P450 interacting medications in the setting of adjuvant therapy for breast cancer.
Authors: UO Njiaju, JM Kolesar, SA Johnston, JC Eickhoff, KR Osterby, LE Poggi, AJ Tevaarwerk, RJ Millholland, KA Oliver, JL Heideman, KB Wisinski
Journal: Cancer Research (2012)

Abstract Background: In the current era of personalized medicine, oral targeted therapies are increasingly used in cancer treatment. In breast cancer, oral anti-estrogen agents have historically been part of standard treatment for hormone receptor positive disease. More recently, other targeted agents have been introduced in the metastatic setting, and are being evaluated as adjuvant therapies. Many oral medications, including anticancer therapies, are metabolized by cytochrome P450 (CYP450) enzymes raising possibility of drug-drug interactions that may affect toxicities or breast cancer outcomes. We sought to evaluate concomitant CYP450 medication use among women seeing a medical oncologist to discuss adjuvant systemic therapy for breast cancer. Methods: We performed an electronic medical record database extraction. Adult women diagnosed with breast cancer from 1/2008-7/2011 were identified from the University of Wisconsin Hospital and Clinics Cancer Registry. Medication lists were extracted from the first encounter with a medical oncologist after the initial breast cancer diagnosis. Non-systemic medications were excluded. Cytochrome P450 (CYP450) enzyme-interacting medications were categorized as inhibitors, inducers, and/or substrates of specific enzymes including CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2C8, CYP2C9, CYP2D6, CYP2E1, and CYP3A4. CYP450 inhibitors and inducers were further characterized as strong, moderate or weak acting. Results: A total of 455 women with non-metastatic breast cancer were identified. Mean age was 56.6 years (range of 23–90) and 413 (91%) were Caucasian. Polypharmacy, defined as use of 3–5 medications, was seen in 123 (27.0%) women. A total of 236 (51.9%) women were on 0–4; 109 (24.0%) on 5–10; and 13 (2.9%) on &amp;gt; 10 medications at the time of first encounter with a medical oncologist after a breast cancer diagnosis. 23 (5.05%) women were on strong CYP450 enzyme inhibitors while 72 (15.8%) were on strong inducers. CYP450 enzymes most commonly affected were CYP3A4, CYP2C9, and CYP2D6. Among medications taken on a fixed schedule, levothyroxine and simvastatin were the most commonly used, while simvastatin and ranitidine were the most common CYP450 interacting medications. Further classification of potential CYP450 interactions is ongoing. Conclusions: A significant proportion of patients were on one or more CYP450 interacting medications in the setting of adjuvant therapy for breast cancer. Given the number of new oral cancer agents that are also CYP450 interacting, the potential for drug interactions should be recognized and appropriate management strategies implemented. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-12-02.
AB0686 Association between the immunological profile of the patients with primary sjÖgren syndrome and occurrence of the extraglandular manifestations
Authors: M. Mazurek, E. Wielosz, M. Majdan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Primary Sjogren’s syndrome (pSS) is a chronic inflammatory disease characterized by lymphocytes and plazmocytes infiltration of exocrine glands. Typical clinical manifestations of pSS are symptoms of dry mouth and dry eyes, but other organs can be also involved (extraglandular manifestations). Immunological profile of patients with pSS is very heterogeneous. <h3>Objectives</h3> The aim of our study was to assess the association between the immunological profile of patients with primary Sjögren Syndrome and the occurrence of extraglandular manifestations at the time of diagnosis setting. <h3>Methods</h3> The studied group comprised of 58 patients (pts) (1 male and 57 female) aged 48±14.8 years with the diagnosis of pSS according to 2002 year classification criteria. The patients were divided into two groups with or without extraglandular manifestations of pSS, respectively: group I - 40 patients (mean age 47 years), and group II -18 patients (mean age 49). The presence of anti-nuclear antibodies (ANA), anti-Sjögren’s syndrome A antibodies (SSA), anti-Sjögren’s syndrome B antibodies (SSB), anti-cyclic citrullinated peptide (aCCP), α-fodrin IgG and IgA, anti-cardiolipin (aCl) IgM, IgG, anti-β2-glycoprotein I IgG and IgM, lupus anticoagulant (LAC) and rheumatoid factors IgM (RF IgM) was determined in sera of the pts. <h3>Results</h3> In the group I the following extraglandular manifestations were revealed - oligoarthritis in 31 pts (53%); Raynaud phenomenon in 16 pts (28%); leucocytoclastic vasculitis in 12 pts (21%); nervous system involvement in 8 pts (14%); interstitial lung disease in 3 pts (5%); pericarditis in 2 (3%).The following organ non-specific autoantibodies were detected: ANA (83% of pts); anti-SSA (70% of pts); anti-SSB (37% of pts); aCCP (22% of pts); anti α-fodrin IgG (33% of pts) and IgA (25% of pts); aCl IgM (22% of pts); aCl IgG (9% of pts); anti-β2-glycoprotein I IgG (3% of pts) and IgM (5% of pts); LAC (7% of pts) and RF IgM (88% of pts). Statistically significant correlations between the immunological profile of the patients with primary Sjögren Syndrome and occurrence of the extraglandular manifestations were not established. <h3>Conclusions</h3> The extraglandular manifestations are present in 70% of primary Sjögren Syndrome patients, the most common manifestations are: oligoarthritis; Raynaud phenomenon and leucocytoclastic vasculitis. ANA, RF IgM, anti-SSA antibodies are the most commonly detected autoantibodies.There are no differences in immunological profile between primary Sjögren Syndrome patients with or without extraglandular manifestations <h3>Disclosure of Interest</h3> None Declared