tbuckley/cabot-search huggingface dataset:
PTU-237 Complications and outcomes following percutaneous endoscopic gastrostomy (PEG) tube insertion: a single centre experience
Authors: N Maqboul, A Murugananthan, I Kronborg
Journal: Gut (2012)

<h3>Introduction</h3> PEG insertion has a reported 30-day mortality of 19%–24%<sup>1 2</sup> suggesting a significant number of inappropriate insertions that were unnecessary for good care. Despite this there are no consistent Australian guidelines regarding patient selection for this procedure. To try and identify patients who would not benefit from PEG insertion we conducted an audit of all PEG insertions undertaken at our hospital, with particular reference to indications, complications and outcome. <h3>Methods</h3> PEG insertions from 15 January 2009 to 22 July 2011 were identified from an endoscopy database and then medical notes were reviewed. We assessed indication for PEG insertion, the use of prophylactic antibiotics, complications during the procedure, 30 day complications and longer term complication rates. <h3>Results</h3> 28 patients were identified (13 male and 15 female). The mean age was 71.8 years. The most common indication for PEG insertion was dysphagia following a cerebrovascular accident (CVA) (65%). Other indications included head and neck tumours (14%), other neurological disorders and poor oral intake due to severe depression (21%). 64% of patients received prophylactic antibiotics during the procedure with cephazolin compared to the recommended 100%. Despite this low rate, no patients were re-admitted with PEG site infections. 30-day mortality was 23%. In patients with CVAs 30-day mortality was 45% vs 0% in patients with other indications (p=0.038; Fishers exact test). Eleven patients had episodes of aspiration within 30 days of PEG insertion—the majority of these were from the CVA group (72%). The median time between CVA and PEG insertion was 25.5 days (range 10–53 days). Overall survival at 1 year was 38%. There were three cases in which the PEG fell out: two of the three were due to the patient removing it. <h3>Conclusion</h3> Our data shows a significantly higher 30-day mortality in CVA patients as well as a higher frequency of aspiration in this group. This is in keeping with other studies<sup>3</sup> and re-iterates the fact that insertion of a PEG does not prevent the development of aspiration pneumonia, which is a common misconception. It would therefore be reasonable to suggest a minimum period of 30 days of observation plus NG feeding in such patients to allow for any change in clinical condition. <h3>Competing interests</h3> None declared. <h3>References</h3> 1. <b>Janes SE</b>, Price SG, Khan S. Percutaneous endoscopic gastrostomy: 30-day mortality trends and risk factors. <i>J Postgrad Med</i> 2005;<b>51</b>:23–8. 2. <b>Mitchell SL</b>, Tetroe JM. Survival after percutaneous endoscopic gastrostomy placement in older persons. <i>J Gerontol A Biol Sci Med Sci</i> 2000;<b>55</b>:735–9. 3. <b>Marik PE</b>. Primary care: aspiration pneumonitis and aspiration pneumonia. <i>N Engl J Med</i> 2001;<b>344</b>:665–71.
RENDIMIENTO DIAGNÓSTICO DEL TEST DE UREASA EN EL TRATAMIENTO CRÓNICO CON INHIBIDORES DE BOMBA DE PROTONES
Authors: CL Rosales, C Huertas, M Figa, X Aldeguer
Journal: Endoscopy (2014)

Introducción: La determinación de Helicobacter Pylori (HP) mediante el test de ureasa (TU) puede verse influenciada por diversos factores, algunos no modificables (distribución parcheada del microorganismo, densidad bacteriana), y otros modificables (ingesta previa de antibióticos o inhibidores de la bomba de protones, IBP).
O8 SUCCESSFUL RETREATMENT WITH SOFOSBUVIR-CONTAINING REGIMENS FOR HCV GENOTYPE 2 OR 3 INFECTED PATIENTS WHO FAILED PRIOR SOFOSBUVIR PLUS RIBAVIRIN THERAPY
Authors: R. Esteban, L. Nyberg, J. Lalezari, L. Ni, B. Doehle, B. Kanwar, D. Brainard, M. Subramanian, W.T. Symonds, J.G. McHutchison, M. Rodriquez-Torres, S. Zeuzem
Journal: Journal of Hepatology (2014)
Advances in Coronary Angioplasty
Authors: John A. Bittl
Journal: New England Journal of Medicine (1996)

The goal of therapy in patients with coronary artery disease is to alleviate symptoms of angina and reduce the risk of death or nonfatal myocardial infarction. Although coronary angioplasty immediately reduces anginal symptoms in almost all patients who undergo it, its use is associated with death or nonfatal myocardial infarction in about 5 percent of patients18 and with restenosis requiring repeated angioplasty or bypass surgery in about 30 percent.36,9 Recently, several clinical trials have shown that the implantation of coronary stents5,6 or treatment with blockers of platelet glycoprotein IIb/IIIa receptors1012 reduces the occurrence of acute . . .
Abstract 3861: A genome-wide association study of upper aerodigestive tract cancers identifies 4q21, 4q23, and 12q24 as susceptibility loci
Authors: James D. McKay, Therese Truong, Mark Lathrop, Paul Brennan
Journal: Cancer Research (2010)

Abstract To identify risk variants for upper aero-digestive tract (UADT) cancers, we performed a genome-wide association study of 2,091 UADT cancer cases and 8,334 controls followed by replication of 20 variants in an additional 6,545 UADT cancer cases and 7,892 controls. Five common variants presented evidence for significant association in the replication series (one sided p ≤ 0.005 - preplication) and combined analysis (p ≤ 5×10−7 - pcombined). Three variants were in the alcohol dehydrogenase (ADH) gene cluster on 4q23 (rs1573496-ADH7, preplication=7×10−10 /pcombined=5×10−17 rs1229984-ADH1B, preplication=3×10−10 pcombined=5×10−21 and rs698-ADH1C, preplication=0.003 pcombined=3×10−7). The fourth variant (rs4767364, preplication=4×10−4/pcombined=7×10−8) was located in an extended linkage disequilibrium region at 12q24 that contains the aldehyde dehydrogenase 2 (ALDH2) gene and appears to have effects similar, albeit more modest, to that observed with heterozygote ALDH2 null allele (rs671) common in Asian populations. The fifth variant (rs1494961, preplication=9×10−6 pcombined=2×10−8) was located near DNA repair related genes HEL308 and FAM175A (or Abraxas) at 4q21. This 4q21 variant was also associated with lung cancer risk in a series of 5,652 lung cancer cases and 9,338 controls (rs1494961, p=3×10−4). These results further highlight the importance of the genes involved in the metabolism of alcohol in UADT cancer susceptibility, and also implicate 4q21 in susceptibility to both UADT and lung cancers. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3861.
Preliminary experience in external quality control of RT-PCR PML-RARα detection in promyelocytic leukemia
Authors: P Bolufer, E Barragán, MA Sánz, G Martín, R Bornstein, D Colomer, MD Delgado, M González, I Marugan, J Román, MT Gómez, E Anguita, D Diverio, Ch Chomienne, M Briz
Journal: Leukemia (1998)
Aluminum Accumulation during Treatment with Aluminum Hydroxide and Dialysis in Children and Young Adults with Chronic Renal Disease
Authors: I B Salusky, J Foley, P Nelson, W G Goodman
Journal: New England Journal of Medicine (1991)

The control of hyperphosphatemia is a major clinical problem in patients with chronic renal failure receiving regular dialysis treatment. Despite continuing concern about aluminum toxicity, aluminum-containing antacids are still used in many of these patients as phosphate-binding agents. Although maximal acceptable doses of aluminum hydroxide have been recommended, the safety and efficacy of these guidelines have not been evaluated.
A2.42 Clinical utility of measuring naÏve CD4<sup>+</sup>T-cell in early ra patient to predict remission on mtx: A replication study
Authors: F Ponchel, L Hunt, AN Burska, R Parmar, MH Buch, P Emery
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> The current optimal therapeutic approach in early rheumatoid arthritis (RA) is to start Methotrexate (MTX) to target inflammation and induce remission. Prediction of MTX therapy response remains a key clinical need to enable the identification of patients who would benefit from an alternative, more aggressive treatment strategy. T-cell subset analysis has been shown to have biomarker value in predicting MTX remission in early RA.<sup>1</sup> Given the clinical importance of these findings, our aim was to validate the original data<sup>1</sup> using T-cell subset quantification this time performed solemnly by routine hospital services, in order to replicate these original findings and validate naïve T-cell frequencies as biomarker of the the achievement of clinical remission with MTX treatment in early RA. <h3>Methods</h3> T-cell subsets were quantified in 70 drug-naïve early RA patients, commencing MTX. The primary outcome was remission (DAS28 &lt; 2.6) after 6 months. We used previously established reference range (using 120 healthy controls) for inflammation related cells (IRC) and corrected for age variation in naïve and regulatory (Treg) T-cells. Logistic regressions were used to model the remission outcome. <h3>Results</h3> Remission was achieved in 37/70 patients. In univariate analysis, the achievement of remission was strongly associated with age-corrected naïve CD4<sup>+</sup>T-cell frequency and current not-smoking (p &lt; 0.0001), as well as weakly with high frequency of IRC, CRP or DAS28 (p ≤ 0.101). A model using age-corrected naive frequency, currently not-smoking and DAS28 correctly predicted remission in 88.4% of patients. Dichotomising naïve T-cell frequency using the age-related reference line (at 1% above 95% CI), confirmed a sensitivity/specificity 78%/81%, PPV/NPV 78%/81% and OR 15.4 (95% CI 5.02–53.55), p &lt; 0.0001. <h3>Conclusion</h3> This study confirms the ability of baseline naïve T-cell subset analysis in predicting early RA remission with first-line MTX therapy, suggesting clinical utility for the selection of the most appropriate therapy at disease presentation. All data being acquired by hospital routine services, they should be transferable widely towards personalised medicine. <h3>Reference</h3> Ponchel F, Goëb V, Parmar R, <i>et al</i>. An immunological biomarker to predict MTX response in early RA. Ann Rheum Dis 2014;73(11):2047–53
Abstract 2789: Discovery of a novel specific MEK and Raf inhibitor, CH5126766 (RO5126766), hit to lead study of a unique scaffold for kinase inhibitor to a clinical compound
Authors: Hitoshi Iikura, Toshihiro Aoki, Ikumi Hyoudoh, Noriyuki Furuichi, Fumio Watanabe, Sawako Ozawa, Masahiro Sakaidani, Masayuki Matsushita, Nobuo Shimma, Naoki Harada, Yasushi Tomii, Yuko Aoki, Kenji Takanashi
Journal: Cancer Research (2011)

Abstract Background: Among tumor signaling pathways, the most frequently dysregulated in human cancer is Ras-Raf-MEK axis, and therefore allosteric MEK inhibitors and ATP competitive Raf inhibitors are being tested in clinical trials. However, these inhibitors result in marked activation of upstream signal of MEK in tumor cells, especially with mutant K-ras. This feedback activation or activation of Raf would attenuate the anticancer effects of these inhibitors. One of the strategies to prevent this attenuation will be blocking upstream signal concurrent with MEK inhibition. To validate the hypothesis, we executed a hit to lead study of our HTS hit showing MEK/Raf dual inhibition. Methods and Results: To increase direct MEK inhibitory activity (by binding to MEK) of the HTS hit coumarin compound and indirect Raf inhibitory activity (by enhancement of the binding between B-Raf /C-Raf and MEK1), introduction of a sulfamide group afforded the best result, compared with similar functional groups such as urea, amide and sulfonamide. Fluorine-scan (C-H/C-F substitutions) and nitrogen-scan (CH/N substitutions) worked efficient to increase both MEK and Raf inhibitory activities and optimize physicochemical properties (water solubility, hERG inhibition, CYP inhibitions etc). These three key transformations afforded CH5126766, which has MEK1 (IC50 = 160 nM) and B-Raf (IC50 = 19 nM) inhibitions and excellent PK profiles (mouse BA 93%, CL 1.1 mL/min/kg, rat BA 66%, CL 0.7 mL/min/kg, monkey BA 82%, CL 0.1 mL/min/kg). The compound showed potent antitumor activity in human cancer xenograft model (HCT116) by once daily oral administration (128% of tumor growth inhibition at a 1 mg/kg dose). Conclusion: SAR study of our novel type molecule (MEK and Raf dual inhibitor) affords identification of CH5126766. It showed strong antitumor efficacy in vivo, good PK in three animal species and good safety profiles. Thus, CH5126766 is now under clinical investigation with solid tumor patients. 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 2789. doi:10.1158/1538-7445.AM2011-2789
OP0172 The Presence and Intensity of Power Doppler Signal are not Modified by Time of Assessment: Data form Patients with Rheumatoid Arthritis
Authors: A. M. Bertoli, M. J. Audisio, G. E. Py, I. Strusberg
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Power Doppler (PD) ultrasound is a sensitive and reliable method for the assessment of inflammatory activity in rheumatoid arthritis (RA). Many variables, however, were described to modulate the intensity of the PD signal including, but not limited to, the equipment, the operator and room temperature. It is also well recognized that patients suffer more pain and stiffness early in the morning and that these symptoms usually improve during the afternoon. <h3>Objectives</h3> To compare the number of joints with PD signal and the intensity of PD signal in patients with diagnosis of RA (as per the 1987 ACR criteria) assessed both, in the morning and in the afternoon. <h3>Methods</h3> We evaluated 20 patients. The intensity of the PD signal was assessed in 28 joints and graded 0 to 3, where 0 is the absence of synovial flow, 1 represents ≤ 3 isolated signals, 2 represents &gt; 3 isolated signals or confluent signal in less than half of the synovial area and 3 marked signal in more than half of the synovial area. A 28 index for PD signal was obtained by the sum of the PD signal scores of the individual joints. Total number of joints with PD signal and the 28 joints index obtained during the morning and the afternoon were compared using the Mann-Whitney U test <h3>Results</h3> Patients were predominantly females (81%) and they had a mean (SD) age of 46.2 (11.1) years and a mean (SD) disease duration of 125.4 (119.0) months. The Table below depicts total number of joints with PD signal and the 28 joints PD index obtained during the morning and during the afternoon. <h3>Conclusions</h3> In this study, we were not able to find differences neither in the number of joints with PD signal, nor in the 28 joints PD index regarding the time of assessment. This finding should be considered as a practical consideration when performing ultrasound PD examination in patients with RA. <h3>Disclosure of Interest</h3> None Declared
SAT0185 Assessment of Fifth Metatarsophalangeal Joint Erosion in Rheumatoid Arthritis by Ultrasonography
Authors: N. Inanc, G. Ozen, S.Z. Aydin, E. Kasapoglu, H. Direskeneli
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Joint erosions in RA correlate with structural damage progression and functional capacity. Therefore, detection and the follow-up of erosions are of paramount importance for RA diagnosis, monitoring and determining of prognosis. The 5th MTP is usually the first and most commonly destructed joint in RA. Ultrasound (US) is a useful and as good tool as MRI to detect 5th MTP erosions especially in early RA patients. Although a few MRI studies revelaed that most of the MTP erosions were located at the plantar aspect of the joint, it is unknown whether plantar or dorsal or lateral plane US better detects 5th MTP erosions. <h3>Objectives</h3> To determine the best ultrasonographic plane for detection of 5th MTP joint erosion in RA patients and to assess clinical characteristics of patients with 5th MTP erosions. <h3>Methods</h3> The 5th MTP of 92 feet of 48 RA patients were evaluated by B-mode and Power- Doppler US for signs of erosion. US images were obtained from 3 different aspects, the dorsal, lateral and the plantar surface of the foot, in longitudinal and tranverse planes. The presence of erosion was determined according to OMERACT definition. Patients were also assessed clinically (tender/swollen joint count, DAS28, HAQ scores) along with disease characteristics. Each erosion in each aspect were recorded seperately. <h3>Results</h3> The study cohort consisted of 48 RA patients (F/M=35/13, mean age 50.7±12.3 years, mean DAS28 score 4.04±1.47, HAQ score 0.93±0.88) with mean disease duration of 8.2±7.3 years. RF and anti- CCP positivity were 66.7% and 60.4%, respectively. The 5th MTP erosions were detected in 35 of 48 patients (72.9%) and 62 of 92 feet (67.4%). Of the erosions 15 (16.3%) were observed at dorsal plane whereas plantar and lateral planes revelaed majority of the erosions, 53 (57.6%) and 52 (56.5%), respectively. In 26 feet (28.3%), erosions were observed on both plantar and lateral planes, in 15 feet (16.3%) erosions were observed in all three planes. None of the patients had erosion just in dorsal plane examination of the 5th MTP. The presence of 5th MTP erosion in plantar aspect of foot was significantly higher than both lateral and dorsal aspect (<i>P</i>&lt;0.0001, <i>P</i>=0.002, respectively). Patients with dorsal erosion had significantly higher disease duration (13.8 years vs 6.5 years, <i>P</i>=0.005). Patients with erosion in any aspect have similar disease characteristics including, RF, anti-CCP positivity, disease duration, HAQ scores and current biologic requirement, when compared to patients without erosion. <h3>Conclusions</h3> The 5th MTP erosions in RA patients can be better detected with plantar plane US than dorsal and lateral aspect evaluations. These data also indicate that dorsal aspect US of foot may miss erosions in early disease and insufficient when performed solely. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3817
Hypertension Treated with<i>Rauwolfia canescens</i>
Authors: Richard W. P. Achor, Norbert O. Hanson
Journal: New England Journal of Medicine (1956)

THE widespread acceptance of the preparations of Rauwolfia serpentina for the treatment of patients with arterial hypertension and mental disorders has stimulated further investigation regarding other forms of Rauwolfia. One of these species, R. canescens, has been reported by Chakravarti1 to show greater adrenolytic activity with less hypnotic effect than R. serpentina. This effect was attributed by Mukherjee2 to a crystalline alkaloid, rauwolscine, which was isolated in 19413 and was thought to be the active principle of R. canescens. Since then the well known alkaloid, reserpine, has been isolated from R. canescens by Klohs and his co-workers.4 In addition, other . . .
A6.7 The junctional adhesion molecule JAM-3 regulates the motility of fibroblast-like synoviocytes
Authors: U König, M Heitzmann, D Beckmann, J Hillen, U Hansen, U Saunders, C Hartmann, A Korb-Pap, T Pap
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) is a disease of a continuous activation and expansion of the synovium involving migration and dissemination of fibroblast-like synoviocytes (FLS). Several lines of evidence indicate that adhesion molecules play a crucial role in this process. We have focused on the junctional adhesion molecule 3 (JAM-3), known to be involved in adhesion, polarity and migration of other cells. So far it has been demonstrated that blocking of JAM-3 in a serum transfer model of RA ameliorates the disease. However, the question of whether JAM-3 is involved in fibroblast motility or primarily regulates the influx of inflammatory cells remains unknown. Therefore, our objective was to clarify the involvement of JAM-3 in the establishment of cell-cell and cell-matrix contacts as well as in the migration of FLS. <h3>Materials and methods</h3> As an arthritis model we use human TNFalpha transgenic (hTNFtg) mice that due to high levels of human TNFalpha develop a RA-like disease. FLS form these animals as well as form JAM-3 floxed mice CreERT2 (tamoxifen inducible cre line) and control mice were isolated by collagenase digestion of the hind paws. Cells were subjected to electrical cell-substrate impedance sensing (ECIS) surface staining (FACS), immunofluorescence, <i>in vitro</i> cell migration assays and standard molecular biology methods. <h3>Results</h3> JAM-3 was found on both wild type and hTNFtg synoviocytes. Blocking or silencing of JAM-3 significantly increased cell spreading in an modified scratch assay but decreased migration in an <i>in vitro</i> transmigration assay, indicating that JAM-3 is involved in the establishment of cell-cell contacts between FLS. In line with this notion ECIS experiments revealed altered adhesion properties of these cells. Explaining these findings, we found that JAM-3 co-localises with the tight junction molecule zo-1 at cell contact sites, which are connected to actin cell filaments. The ultrastructure of these structures and an influence of Jam-3 on the cytoskeleton dynamics is under investigation. <h3>Conclusions</h3> JAM-3 modulates migration of FLS <i>in vitro</i>, which may contribute to the beneficial effects of JAM-3 inhibition as seen in the serum transfer model of RA <i>in vivo</i>. We suggest that Jam-3 is an adhesion molecule, responsible for controlling motility by organising the cytoskeleton in FLS.