tbuckley/cabot-search huggingface dataset:
FRI0431 Why the findings of published rheumatoid arthritis multiple treatment comparisons are so different – an overview of recurrent methodological shortcomings
Authors: K. Thorlund, E. Mills
Journal: Annals of the Rheumatic Diseases (2013)

Background Several multiple treatment comparison meta-analysis (MTCs) have been conducted over the past years to establish comparative effectiveness between biologic disease modifying anti rheumatic drugs (bDMARDs). Unfortunately, major inconsistencies exist in the findings across these MTCs. Objectives To methodologically review the published literature on rheumatoid arthritis MTCs. To identify methodological issues that can explain the substantial discrepancies in the findings of these MTCs. Methods We searched MEDLINE for rheumatoid arthritis multiple treatment comparisons. Following the PRISMA guidelines, we extracted a large set of methodological items from the identified reviews. These included, but were not limited to, inclusion/exclusion criteria, information sources (e.g., MEDLINE), approaches to dealing with monotherapies versus combination therapies, approaches to dealing with potential covariate effect modifiers (i.e., sources of heterogeneity). Results We identified 12 published MTC, of which 7 were published since 2009. We identified major discrepancies in the inclusion of trials, despite highly similar eligibility criteria and literature searches. The total number of trials covered among all MTCs was 61. However, the number of trials included in the individual MTCs published since 2009 spanned from 15 to 31 – i.e., 25% to 50% of all available trials. We identified inconsistencies in approaches to dealing with monotherapy and combination therapy trials. Most MTCs lumped the two sets of trials without either controlling for the effect of concomitant use of disease modifying anti rheumatic drugs (DMARDs) or separately comparing the effectiveness estimates in the two. Approximately half of the identified MTCs did not explore potential sources of heterogeneity. Among those that did, the explored sources were inconsistent. Conclusions Major methodological shortcomings and inconsistencies exist throughout published rheumatoid arthritis MTCs. There are many lessons to be learned from these previous publications which can potentially strengthen the current evidence base. Disclosure of Interest None Declared
PTU-190 Isolated upright oesophageal acid exposure is associated with less favourable outcomes after laparoscopic anti-reflux surgery
Authors: J A Cornish, E O'Dea, C Thomas, G W Clark
Journal: Gut (2012)

<h3>Introduction</h3> With the increasing use of antireflux surgery since the widespread dissemination of the laparoscopic approach, preoperative indicators to predict success could reduce the number of patients with a poor outcome. The aim of this study was to identify if poorer outcomes could be predicted in patients with upright reflux alone vs mixed upright and supine reflux, in the presence of a positive DeMeester score. <h3>Methods</h3> This was a retrospective cohort study of all patients undergoing antireflux surgery from 2001 to 2009 in a tertiary centre under a single surgeon. Patients undergoing fundoplication and/or repair of paraoesophageal hernias were included. Patients underwent preoperative assessment by means of endoscopy, oesophageal manometry and 24 h oesophageal pH monitoring. Patients were grouped on the basis of their 24 h pH profile into upright refluxers (daytime increased oesophageal acid exposure) and mixed refluxers (night-time increased oesophageal acid exposure +/− daytime reflux). Primary outcomes included if the patient had stopped PPIs following surgery and the incidence of postoperative dysphagia, vomiting and reflux symptoms. Secondary outcomes included if the patients deemed the operation a success. <h3>Results</h3> 120 patients were included, with a median age of 49 years (range 24–81) at time of surgery. 53% (n=63) were male and 93% were laparopscopic procedures. 100 patients (83.3%) had Nissen fundoplication and 13% had a combination of fundoplication and paraoesophageal hernia repair. A DeMeester score &gt;15 was present in 97.8% (n=88) patients, with 21% (n=19) patients having upright reflux and 68.5% (n=63) having mixed reflux symptoms on pH studies. Mixed refluxers were nearly twice as likely to have significant oesophagitis (grade B+) and or Barrett9s oesophagus on preoperative endoscopy (mixed reflux 57.1% vs 31% upright reflux; p=0.051). Those patients with mixed reflux symptoms were significantly more likely to stop PPIs postoperatively (mixed reflux 96%, n=48 vs 75% n=12, upright reflux; p=0.01). Further, the incidence of significant post operative dysphagia was doubled in the upright reflux group (upright reflux 53.3% vs mixed reflux 26.7%; p=0.058). Overall, 83.5% (n=76) deemed the operation to have been a success, 7.7% (n=7) a partial success and 8.8% (n=8) considered that surgery had failed to improve their symptoms. <h3>Conclusion</h3> In addition to the DeMeester score for predicting outcomes in antireflux surgery, the presence of reflux only in the upright position may indicate a poorer outcome. <h3>Competing interests</h3> None declared.
Terlipressin given by continuous intravenous infusion versus intravenous boluses in the treatment of hepatorenal syndrome: A randomized controlled study
Authors: Marta Cavallin, Salvatore Piano, Antonietta Romano, Silvano Fasolato, Anna Chiara Frigo, Gianpiero Benetti, Elisabetta Gola, Filippo Morando, Marialuisa Stanco, Silvia Rosi, Antonietta Sticca, Umberto Cillo, Paolo Angeli
Journal: Hepatology (2015)

In patients with cirrhosis and hepatorenal syndrome (HRS), terlipressin has been used either as continuous intravenous infusion or as intravenous boluses. To date, these two approaches have never been compared. The goal of this study was to compare the administration of terlipressin as continuous intravenous infusion versus intravenous boluses in the treatment of type 1 HRS. Seventy‐eight patients were randomly assigned to receive either continuous intravenous infusion (TERLI‐INF group) at the initial dose of 2 mg/day or intravenous boluses of terlipressin (TERLI‐BOL group) at the initial dose of 0.5 mg every 4 hours. In case of no response, the dose was progressively increased to a final dose of 12 mg/day in both groups. Albumin was given at the same dose in both groups (1 g/kg of body weight at the first day followed by 20‐40 g/day). Complete response was defined by decrease of serum creatinine (sCr) from baseline to a final value ≤133 μmol/L, partial response by a decrease ≥50% of sCr from baseline to a final value &gt;133 μmol/L. The rate of adverse events was lower in the TERLI‐INF group (35.29%) than in the TERLI‐BOL group (62.16%, P &lt; 0.025). The rate of response to treatment, including both complete and partial response, was not significantly different between the two groups (76.47% versus 64.85%; P value not significant). The mean daily effective dose of terlipressin was lower in the TERLI‐INF group than in the TERLI‐BOL group (2.23 ± 0.65 versus 3.51 ± 1.77 mg/day; P &lt; 0.05). Conclusion : Terlipressin given by continuous intravenous infusion is better tolerated than intravenous boluses in the treatment of type 1 HRS. Moreover, it is effective at doses lower than those required for intravenous bolus administration. (H epatology 2016;63:983–992)
Abstract P5-13-02: Impact of Adjuvant Trastuzumab on Local Regional Recurrence: Data from the NCCTG N9831 Study
Authors: MY Halyard, AC Dueck, TM Pisansky, SA McLaughlin, LJ Pierce, LB Marks, LJ Solin, BA Pockaj, EA. Perez
Journal: Cancer Research (2010)

Abstract Background: Trastuzumab (H) improves disease-free survival (DFS) in patients (pts) with HER2 positive breast cancer (BR Ca) when used with adjuvant chemotherapy. We herein compare the rates of local regional recurrence (LRR) in pts randomized to adjuvant chemotherapy with or without adjuvant H. Methods: The phase 3 randomized trial NCCTG N9831 enrolled 3505 pts with high risk HER2 positive Br Ca to evaluate the effect of adjuvant H on DFS. Pts were randomized to either doxorubicin (A) and cyclophosphamide (C) followed by paclitaxel (T); or AC→TH→H. RT was given concurrently with H after ACT chemotherapy. Pts analyzed underwent lumpectomy (L) + radiotherapy (RT), mastectomy (M) alone, or M+RT. All pts underwent sentinel lymph node biopsy alone and/or axillary dissection. 2816 pts were eligible for competing risk analysis of LRR as a first event (competing risks were distant recurrence, contralateral Br Ca, second primary cancer, or death). Median follow-up is 5.3 years. Results: Primary breast therapy included L+RT 1062 (38%), M 711 (25%), and M+RT 1043 (37%). Axillary dissection was performed in 90% of pts but less frequently with L+RT (83%) compared to M (88%) or M+RT (98%), chi-sq P&amp;lt;0.001. Stage at presentation was I 41%, II 51%, and III 8% with a significant greater proportion of higher stage pts undergoing M+RT, chi-sq P&amp;lt;0.001. Overall the 5-year LRR rate was 4.1% (95% CI 3.5-4.9%) and similar among the treatment groups: L+RT 4.7% (95% CI 3.6-6.1%), M 3.5% (95% CI 2.4-5.1%), and M+RT 2.3% (95% CI 1.6-3.4%). Among pts with a LRR, 66% were local recurrence only, 11% were local-regional, and 23% were regional only. In the L+RT patients with a LRR, the corresponding rates were 74%, 7%, and 19%, respectively. In the M patients with a LRR, the corresponding rates were 40%, 23%, and 37%, respectively. In the M+RT patients with LRR, the rates were 79%, 4%, and 17%, respectively. H is associated with a non-statistically significant reduction in the risk of LRR for pts who receive L+RT or M+RT (Table 1). No such trend was seen in the M alone group but the number of events was low. Table 1. LRR According to Local and Adjuvant Treatment Groups Conclusion: The LRR as the first reported site of failure was low with a median 5. 3 year follow-up. Adjuvant H was associated with a trend of lower LRR in the pts treated with L + RT or M+RT. This observation suggests an additive effect of RT and H on LRR that warrants further investigation. The small number of local-regional events in this one randomized trial supports further investigation of LRR across other adjuvant trastuzumab trials. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-13-02.
A Study of Illness in a Group of Cleveland Families
Authors: William E. S. James, George F. Badger, John H. Dingle
Journal: New England Journal of Medicine (1960)

THE behavior of infections due to Group A strcptococci that occurred in a group of Cleveland families is described in this paper. Many other studies have emphasized various aspects of the epidemiology of streptococcal infections as they occurred in military populations,1 , 2 hospital patients,3 outpatient groups,4 children,5 , 6 communities7 and patients seen in private practice.8 The present paper includes data regarding the frequency of acquisition of beta-hemolytic streptococci, the illnesses that occurred coincident with acquisitions and the factors influencing spread within families.MethodsThese observations were made as part of a long-term study of illness, the essential features of which have previously . . .
Bilateral Adrenal Metastases Revealed by F-18 FDG Coincidence Detection Positron Emission Tomography in a Patient with Lung Cancer
Authors: Myoung-Hoon Lee, Chan H Park, Yoon-Jung Oh
Journal: Clinical Nuclear Medicine (2002)

From the Departments of Nuclear Medicine* and Pulmonology,† School of Medicine, Ajou University, Suwon, Korea Received for publication September 20, 2001. Accepted October 26, 2001. Correspondence: Chan H. Park, Department of Nuclear Medicine, School of Medicine, Ajou University, San 5, Wonchon-dong, Paldal-gu, Suwon 442-749, Korea. E-mail: [email protected]
PWE-199 Diagnostic Radiation Exposure in Patients with Crohn’S Disease Treated with Infliximab
Authors: H-L Ching, R Pandey, F Chariah, G Lipman, M Train, S Mann
Journal: Gut (2013)

<h3>Introduction</h3> Exposure to radiation from diagnostic imaging is thought to be associated with an increase in cancer risk. Patients with Crohn’s Disease (CD) frequently require x-ray exposure throughout the course of their illness. Studies have quantified cumulative radiation exposure in patients with CD<sup>1</sup>. However, as far as we know, there has only been one study that has identified infliximab as an independent risk factor for increased radiation exposure<sup>2</sup>. We aimed to quantify all imaging and associated radiation exposure for this subset of patients in our institution. <h3>Methods</h3> Our unit is in a district hospital serving a population of 500,000 across 2 sites. All patients with CD who have received infliximab from January 1997 to January 2013 were identified from our hospital databases. Diagnostic imaging records were also retrieved from the databases. Using local protocols, a mean effective dose for each imaging modality was calculated. The cumulative effective dose (CED) per patient was calculated as the sum of the mean effective dose for all imaging modalities. The mean diagnostic radiation exposure per year = CED/years of follow-up. <h3>Results</h3> 131 patients (52% female, mean age 46 years) were included in the study. Total number of imaging procedures was 624 (plain abdominal film = 351, CT abdomen/pelvis = 168, barium study = 105). Other imaging modalities included MRI abdomen/pelvis = 72 and abdominal ultrasound = 65. Average total number of imaging per patient was 5 (plain abdominal film = 3, CT abdomen/pelvis = 1, barium study = 1). The total CED for all imaging was 1828.1 mSv (85% attributed to CT imaging). The mean CED per patient was 14.0mSv (range 0–171.9mSv) with the mean diagnostic radiation exposure per year being 2.4mSv/year (range 0–28.7mSv/year). <h3>Conclusion</h3> Imaging requests in patients with CD is high, particularly when they have received infliximab. In spite of concerns about radiation risk, 93% of our patients have CED less than 50mSv exposure, a level considered to be associated with a low cancer risk. However, most patients are young and are likely to accumulate more radiation exposure over time. The move towards more specialised care should lead to reduction in use of CT scans and increased use of MRI and ultrasound studies. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Peloquin JM,<i> et al.</i> Diagnostic ionising radiation exposure in a population-based cohort of patients with inflammatory bowel disease. Am J Gastro 2008; 103:2015–22 2. Desmond AN,<i> et al.</i> Crohn’s disease: factors associated with exposure to high levels of diagnostic radiation. Gut 2008; 57:1524–1529
ARE POTENTIALLY RESECTABLE COLORECTAL LIVER METASTASES SLIPPING THROUGH THE NET?
Authors: N Keville, C Jones, A McAfee, J Ahmad, B Dasari, L McKie, M A Taylor, T Diamond
Journal: Gut (2013)

<h3>Introduction</h3> Liver is the most common site of metastatic spread in colorectal cancer, and its management has significantly evolved in recent decades with liver resection now being the optimal treatment. <h3>Aims/Background</h3> This study aimed to assess referral patterns from colorectal multidisciplinary meetings (MDMs) throughout Northern Ireland to the Regional HPB Unit. <h3>Method</h3> Over a 6 week period all colorectal MDMs throughout the five health and social care trusts were reviewed. Patients with colorectal liver metastases (CRLMs) were included in the study. The following data were included: patient demographics, details of the health and social care trust, date of MDM discussion, primary tumour pathology, and the MDM outcome. These findings were subsequently compared with regional guidelines for the referral of CRLMs to assess if the decision was deemed appropriate. <h3>Results</h3> 21 discussions were recorded, which involved 20 patients, with a mean age of 69 years and 13 were male. 40% of patients were from the Belfast trust, while the remainder was evenly distributed between the 4 remaining trusts. All CRLMs discussed were confirmed by computerised tomography scanning, and the MDM decision was deemed to be appropriate in 85% of patients. Only 15% of patients had KRAS testing performed and 20% were subsequently referred for PET-CT scanning. <h3>Conclusion</h3> The majority of potentially resectable colorectal liver metastases had an appropriate outcome in terms of management and referral to the Regional HPB unit. However, this could still be further streamlined through both education, and highlighting the role of PET-CT and KRAS testing.
Clinical Epidemiology of Sporadic Measles in a Highly Immunized Population
Authors: William Schaffner, Ann E. S. Schluederberg, Earl B. Byrne
Journal: New England Journal of Medicine (1968)

An epidemiologic study of measles occurring in Rhode Island since the institution of an eradication program revealed that statewide elimination of the disease had been very nearly accomplished within only two years. During a 15-month period of intensive surveillance, 106 suspected cases were investigated, but only 49 were ultimately classified as measles. Cases occurred sporadically as solitary events or in self-limited family outbreaks, usually secondary to infections imported from out of state. Military dependents accounted for more than half the cases. Clinical features, including the presence of Koplik's spots, were less reliable than the epidemiologic history in diagnosis. Of 32 "clinically compatible" illnesses studied in detail serologically, only 10 could be confirmed as recent measles infections. One of these was considered a second natural infection with wild measles virus. Other agents, presumably viral, appeared to mimic the measles syndrome.
Abstract 5219: The LIM protein LIMD2 functions as an effector and biomarker for metastasis in multiple tumor types
Authors: Hongzhuang Peng, Zhaoyuan Hou, Mei He, Electron Kebebew, Torben F. Orntoft, Meenhard Herlyn, Andrew J. Caton, William J. Fredericks, Bruce Malkowicz, Frank J. Rauscher
Journal: Cancer Research (2011)

Abstract The LIM domain is found in proteins from a wide variety of eukaryotic organisms. The LIM domain is organized as a tandem zinc-finger structure that functions as a modular protein-binding interface. LIM domain containing proteins have diverse cellular roles such as regulators of gene expression, cytoarchitecture, cell adhesion, cell motility, signal transduction, and biosensors. LIMD2 belongs to the LIM only family of LIM proteins and was identified as a biomarker for papillary thyroid carcinoma lymph node metastasis from molecular profiling of matched samples. However, the biological function of LIMD2 remains unknown. To identify whether LIMD2 is a biomarker for other cancers, highly specific LIMD2 polyclonal and monoclonal antibodies were developed and several cancer cell lines were tested for LIMD2 expression. These cancer cell lines were derived from breast cancer, melanoma, bladder cancer, and thyroid cancer. We found that the cancer cell lines derived from more aggressive tumors exhibited higher levels of LIMD2 protein expression. Furthermore, cells expressing higher levels of LIMD2 had increased migratory capabilities. Over-expression of LIMD2 protein in the less aggressive bladder cancer cell line (RT4) showed an increase in migration and colony formation ability. Conversely, knockdown of LIMD2 using siRNA decreased the migratory ability of the malignant melanoma cancer cell line and caused morphological changes in these cells. These data not only underscore the importance of LIMD2 as a key metastatic biomarker, but also suggest that LIMD2 may play a functional role in tumorgenicity. LIMD2 may also serve as a novel anti-metastatic target to improve the efficacy of conventional cancer therapeutics. 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 5219. doi:10.1158/1538-7445.AM2011-5219
Abstract 2901: An integrated matrix factorization algorithm for DNA methylation and gene expression identi es HNSCC clinical subtypes and GLI1 signaling speci c to HPV-negative HNSCC.
Authors: Elana J. Fertig, Ana Markovic, Ludmila V. Danilova, Daria A. Gaykalova, Leslie Cope, Christine H. Chung, Joseph A. Califano, Michael F. Ochs
Journal: Cancer Research (2013)

Abstract Global methylation changes occur heterogeneously in primary head and neck squamous cell carcinoma (HNSCC). To infer methylation-driven changes in expression in subtypes of HNSCC, we integrated global gene expression and DNA methylation measurements in 44 HNSCC and 25 normal samples using a matrix factorization algorithm. This algorithm incorporated novel models to transform methylation and expression measurements to a common scale. Although unsupervised, this integrated matrix factorization inferred patterns common to gene expression and methylation data that differentiate clinical subtypes within the 44 HNSCC samples, including notably HPV status and tumor site. Informatic analysis of the genes associated with these patterns identified specific pathway activity related to HPV status. This algorithm uniquely linked DNA methylation changes and reactivation of genes in the Hedgehog pathway predominantly in HPV-negative samples. We further examined the pathway by determining expression levels of GLI1, one of the downstream target genes of the Hedgehog pathway, in two independent cohorts. We confirmed that GLI1 expression was higher in tumors compared to normal samples and HPV-negative tumors had higher GLI1 expression compared to HPV-positive tumors, suggesting that increased expression of GLI1 plays a role in HPV-negative HNSCC. Citation Format: Elana J. Fertig, Ana Markovic, Ludmila V. Danilova, Daria A. Gaykalova, Leslie Cope, Christine H. Chung, Joseph A. Califano, Michael F. Ochs. An integrated matrix factorization algorithm for DNA methylation and gene expression identi es HNSCC clinical subtypes and GLI1 signaling speci c to HPV-negative HNSCC. [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 2901. doi:10.1158/1538-7445.AM2013-2901
Abstract IA-22: Cellular responses to telomerase perturbations
Authors: S. Li, T. Matsuguchi, B.A. Stohr, L. Xu, K. Perry, B. Ren, Elizabeth H. Blackburn
Journal: Cancer Research (2009)

Abstract Telomerase is a ribonucleoprotein that replenishes the DNA at telomeres, thereby counteracting telomere shortening. Telomerase is highly active in many human malignancies. Telomerase functions in cancer maintenance include replenishing telomeric DNA and maintaining cell immortality. The telomerase RNA component provides a short template that is copied to make telomeric DNA. We found that mutating the template to cause various aberrant telomeric sequences to be added in human cancer cells rapidly caused massive ATM-dependent and ATM-independent chromosome fusions and cell death. We also showed previously that human cancer cells responded rapidly to abrupt depletion of telomerase RNA by rapid and distinctive cellular/transcriptional responses, despite no obvious bulk telomere shortening or loss of telomere integrity. This and evidence from others indicates that, in addition to its telomere-elongating role, telomerase may play other roles in cells: cells lacking or overexpressing telomerase show a variety of responses even in the absence of detectable effects on telomere integrity or functionality. We are performing ChIP—SEQ experiments to identify genomic sites of telomerase interaction. New results of experiments exploring these roles of telomerase in cancer will be presented. Together, these and other findings indicate that telomerase, both via its roles in telomere maintenance and other roles, provides potential new inroads into cancer therapies. Citation Information: Cancer Res 2009;69(23 Suppl):IA-22.