tbuckley/cabot-search huggingface dataset:
THU0224 Celecoxib decreased dyspepsia in osteoarthritis and rheumatoid arthritis patients: severity of dyspepsia assessment (soda) results from the ?celecoxib long-term arthritis safety study? (class 2), a randomised trial comparing celecoxib and diclofenac
Authors: JL Goldstein, BM Pena, D Dedhiya, LS Simon
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Dyspepsia associated with NSAIDs is a cost-driver in the clinical management of arthritis patients and leads to discontinuation of medications. <h3>Objectives</h3> To assess the impact of dyspepsia in arthritis patients randomised to celecoxib (C) or diclofenac (D) using SODA. <h3>Methods</h3> As part of the double-blind, randomised CLASS trial, SODA (previously validated in dyspepsia patients) was administered at baseline and Weeks 4, 13, 26, and 52 (final visit) to 1997 C patients (400 mg BID, 4 x the OA dose) and 1996 D patients (75 mg BID). Patients with &gt; = 1 response missing at baseline were excluded, leaving 1791 C and 1816 D patients in the modified ITT (M-ITT) group. SODA has three subscales: pain intensity (6 items characterising the abdominal pain associated with dyspepsia, ranging from 2 to 47); nonpain symptoms (7 items describing the impact of dyspeptic symptoms on daily living activities, ranging from 7 to 35); and satisfaction (4 items describing satisfaction with dyspepsia Rx). Lower SODA scores are better. <h3>Results</h3> SODA change scores were moderately correlated with number of dyspepsia adverse events and increased with dyspepsia adverse event severity levels (none, mild, moderate, severe) and dyspepsia withdrawal status, irrespective of treatment. An M-ITT analysis with last observation carried forward showed that both groups were equivalent at baseline. Patients receiving C had lower pain intensity at all follow-up time points, ranging from 12.3 vs 14.5 at Week 4 to 12.6 vs 14.2 at Week 52 (p &lt; 0.001 at all time points). Patients receiving C were more satisfied at all follow-up time points, ranging from 6.0 vs 6.7 at Week 4 to 6.3 vs 6.9 at Week 52 (p &lt; 0.001 for all time points). Patients receiving C had fewer nonpain symptoms at Week 4 (12.0 vs 12.4, p &lt; 0.003) and showed a trend toward fewer nonpain symptoms at subsequent time points. Self-reported dyspepsia was lower with C (16.5% vs 19.5%, p &lt; 0.05). Similarly, GI-driven AE withdrawal rates were significantly lower for C than D at Week 52 (12.2% vs 16.6%, p &lt; 0.05). <h3>Conclusion</h3> Celecoxib patients had less pain intensity and were more satisfied than diclofenac patients, as measured by SODA. These results parallel self-reported dyspepsia and GI-driven withdrawal rates in the study. Sponsored by Pharmacia Corporation and Pfizer, Inc.
Abstract A68: Increasing intracellular glucose levels decreased expression of Enolase-I promoting cisplatin resistance in ovarian cancer cells
Authors: Robert J. Rabelo-Fernandez, Yasmarie Santana, Nilmary Grafals, Blanca Quiñones, Ginette Santiago, Eunice Lozada, Jeyshka Reyes, Pablo E. Vivas-Mejía
Journal: Clinical Cancer Research (2020)

Abstract Cytoreductive surgery in combination with platinum-based chemotherapy has been used for more than four decades for treat ovarian cancer. Although initially most ovarian tumors respond well to cisplatin treatment, many of those tumors become resistant to chemotherapy. Although many mechanisms of cisplatin resistance have been proposed, the molecular mechanism leading to the cisplatin resistance in ovarian cancer tumors has not been fully understood. In this study, we sought to identify novel proteins associated with the cisplatin resistance of ovarian cancer cells. A proteomic analysis showed 48 proteins differentially abundant in cisplatin-resistant (A2780CP20) compared to their counterpart cisplatin-sensitive (A2780) ovarian cancer cells. The quantitative analysis revealed low protein levels of Enolase-1 (ENO1) in A2780CP20 cells. Small-interference RNA (siRNA)-targeted ENO1 showed a reduction in the sensitivity of ovarian cancer cells to cisplatin treatment. In contrast, ectopic expression of ENO1 in cisplatin-resistant ovarian cancer cells reduced the sensitivity of these cells to cisplatin treatment. Since ENO1 is an enzyme involved in glucose metabolism, we evaluated ovarian cancer cells’ metabolic state by measuring their glucose consumption. Intracellular glucose uptake was measured in pairs of cisplatin-sensitive and cisplatin-resistant cells. The glucose content levels were higher in all cisplatin-resistant cells compared with their -sensitive counterparts. Overall, these results suggest that low levels of ENO1 are associated with the cisplatin resistance of ovarian cancer cells. Therefore, targeting the glycolytic pathways could be a strategy to overcome the cisplatin resistance of women with advanced and drug-resistant ovarian cancer. Citation Format: Robert J. Rabelo-Fernandez, Yasmarie Santana, Nilmary Grafals, Blanca Quiñones, Ginette Santiago, Eunice Lozada, Jeyshka Reyes, Pablo E. Vivas-Mejía. Increasing intracellular glucose levels decreased expression of Enolase-I promoting cisplatin resistance in ovarian cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research; 2019 Sep 13-16, 2019; Atlanta, GA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(13_Suppl):Abstract nr A68.
Should the number of acute exacerbations in the previous year be used to guide treatments in COPD?
Authors: Mohsen Sadatsafavi, James McCormack, John Petkau, Larry D. Lynd, Tae Yoon Lee, Don D. Sin
Journal: European Respiratory Journal (2020)

Background In contemporary management of chronic obstructive pulmonary disease (COPD), the frequent exacerbator phenotype, based on a 12-month history of acute exacerbation of COPD (AECOPD), is a major determinant of therapeutic recommendations. However, there is considerable debate as to the stability of this phenotype over time. Methods We used fundamental principles in time-to-event analysis to demonstrate that variation in the frequent exacerbator phenotype has two major sources: variability in the underlying AECOPD rate and randomness in the occurrence of individual AECOPDs. We re-analysed data from two large cohorts, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study and the SubPopulations and InteRmediate OutcoMes In COPD Study (SPIROMICS), using a Bayesian model that separated these sources of variability. We then evaluated the stability of the frequent exacerbator phenotype based on these results. Results In both cohorts, the pattern of AECOPDs strongly supported the presence of an individual-specific underlying AECOPD rate which is stable over time (Bayes Factor less than 0.001). Despite this, the observed AECOPD rate can vary markedly year-to-year within individual patients. For those with an underlying rate of 0.8–3.1 events·year −1 , the frequent exacerbator classification, based on the observed rate, changes more than 30% of the time over two consecutive years due to chance alone. This value increases to more than 45% for those with an underlying rate of 1.2–2.2 events·year −1 . Conclusions While the underlying AECOPD rate is a stable trait, the frequent exacerbator phenotype based on observed AECOPD patterns is unstable, so much so that its suitability for informing treatment decisions should be questioned. Whether evaluating AECOPD history over longer durations or using multivariate prediction models can result in more stable phenotyping needs to be evaluated.
AB0079 EFFECT OF HYALURONIC ACIDLOCAL INJECTIONS ON ACHILLES TENDINOPATHIES: AN OBSERVATIONAL STUDY ON TENDON VISCOELASTIC PROPERTIES AND THEIR RELATIONSHIPS WITH CLINICAL OUTCOMES
Authors: Piero Sestili
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Effect of hyaluronic acid local injections on Achilles tendinopathies: an observational study on tendon viscoelastic properties and their relationships with clinical outcomes. <h3>Objectives:</h3> Achilles tendinopathy (AT) affects athletes, recreational exercisers and also inactive people, where it is sometimes associated with arthritic phenotypes. The aim of this study was to evaluate the efficacy of a three-local injections regimen of hyaluronic acid (HA) in middle aged patients with a diagnosis of AT; the relationships of the functional, biochemical and clinical outcomes with the viscoelastic properties of the tendon were also studied <h3>Methods:</h3> 8 patients previously diagnosed for monolateral AT were enrolled. AT was confirmed before the first local HA injection (T0) by clinical examination, MRI and thermography. At T0 patients were assessed for maximal voluntary isometric contraction (MVI) involving Achilles tendon (both injured and healthy), and pain level with a Likert scale; Achilles tendon viscoelastic state, i.e. tone and stiffness, were then measured at relaxed state and at 10% of MVI with MyotonPro (Myoton Ltd, UK). Finally patients received the first HA injection (RegenFlex T&amp;M, a blend of 2 to 1000 KDa HA, Regenyal, IT). All the measurements were repeated at T1 (15 days after the first injections and immediately prior the second), at T2 (15 days after the second injection and prior the third) and at T3 (15 days after the third injection), i.e. over a total of 45 days in which clinical visits were also performed. Furthermore, before each injection, injured tendon exudates were collected by needle aspiration and the levels of IL-1β and matrix metalloprotease 3 (MMP-3) were determined with an ELISA test. <h3>Results:</h3> At T0, pain score and MVI were significantly higher and lower in injured tendons, respectively. Accordingly, tone and stiffness values were significantly different between injured and contralateral tendons, especially when measured at the relaxed state. Interestingly, the above differences gradually disappeared at T1, 2 and 3. In keeping with these results, tendon exudates volumes also decreased over time, as well as the levels of IL-1β and MMP-3. <h3>Conclusion:</h3> RegenFlex T&amp;M promoted a progressive healing of AT, with recovery of clinical, functional and tendon's viscoelastic state. <h3>References</h3> [1] P. Sestili, M. Gervasi, E. Barbieri, I. Capparucci, G. Annibalini, S. Contarelli, D. Sisti, S. Amatori and Department of Biomolecular Sciences, University Urbino Carlo Bo, via A. Saffi 2, 61029 Urbino, Italy <h3>Disclosure of Interests:</h3> None declared
Safety, Pharmacokinetics and Pharmacodynamics of Oral TLR8 Agonist GS-9688 in Patients with Chronic Hepatitis B: A Randomized, Placebo-Controlled, Double-Blind Phase 1b Study
Authors: Edward J Gane, Hyung Joon Kim, Kumar Visvanathan, Yoon Jun Kim, Anh-Hoa Nguyen, Adarsh Joshi, Maribel Reyes, Audrey H Lau, Anuj Gaggar, Mani Subramanian, Stuart Keith Roberts, Young-Suk Lim
Journal: Hepatology (2018)
Abstract 13609: Functional Iron Deficiency is Independently Associated With Increased Risk of Morbidity and Mortality in Older Adults With Heart Failure and Incident Anemia
Authors: Andrew P Ambrosy, Grace Tabada, Jerry Gurwitz, Andrew Artz, Stanley Schrier, Sunil V Rao, Kristi Reynolds, David H Smith, Pamela N Peterson, Sue Hee Sung, Harvey Cohen, Alan S Go
Journal: Circulation (2019)

Introduction: Iron deficiency is common but infrequently tested for among older adults with heart failure (HF) and anemia. A low transferrin saturation (TSAT) and/or a reduced ferritin are suggesti...
Diuretic effect of sodium artesunate in patients with Malaria
Authors: Antonio C. Seguro, Silvia B. Campos
Journal: Journal of the American Society of Nephrology (2002)

Previously, we described a direct inhibitory effect of sodium artesunate on sodium chloride transport in the thick ascending limb of Henle's loop, indicating that artesunate acts as a diuretic agent. Here we present 2 cases of falciparum malaria treated with 4 intravenous 60-mg doses of sodium artesunate. Neither diuretics nor vasoactive drugs were administered. A rise in diuresis (6 L/24 hours) was accompanied by an increase in natriuresis, and both declined at the end of the treatment. This diuretic effect has not been reported previously in patients and may modify the course of renal failure and respiratory distress syndrome, both of which complicate severe malaria.
Type of Androgen Deprivation Therapy and Risk of Dementia Among Patients With Prostate Cancer in Taiwan
Authors: Wen-Kuan Huang, Chi-Hung Liu, See-Tong Pang, Jia-Rou Liu, John Wen-Cheng Chang, Chuang-Chi Liaw, Cheng-Lung Hsu, Yung-Chang Lin, Lai-Chu See
Journal: JAMA Network Open (2020)

<h3>Importance</h3> It remains unclear whether androgen deprivation therapy (ADT) is associated with subsequent dementia risk in patients with prostate cancer. There are limited data regarding dementia risk across ADT types. <h3>Objective</h3> To examine the association between all-cause dementia, including Alzheimer disease (AD), and different ADT types in patients with prostate cancer. <h3>Design, Setting, and Participants</h3> This cohort study used linked data from the Taiwan National Cancer Registry, the National Health Insurance Research Database, and the Taiwan National Death Registry. A cohort of 23 651 patients with newly diagnosed prostate cancer between January 1, 2008, and December 31, 2015, was identified and followed up from 1 year after diagnosis until December 31, 2017. Data analysis was performed between January 2019 and May 2020. <h3>Exposures</h3> Patients who received and did not receive ADT, including gonadotropin-releasing hormone (GnRH) agonists, orchiectomy, or antiandrogen monotherapy. <h3>Main Outcomes and Measures</h3> The primary outcomes were all-cause dementia or AD. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. The association between dementia and various ADT types was examined using the Cox proportional hazards model. Furthermore, a multivariate Cox proportional model with age as the time scale was conducted for complementary comparison. <h3>Results</h3> In the cohort of 23 651 male patients (median [interquartile range] age, 73 [66-79] years), 6904 (29.2%) did not receive ADT, 11 817 (50.0%) received GnRH agonists, 876 (3.7%) received orchiectomy, and 4054 (17.1%) received antiandrogen monotherapy. Overall, 1525 patients were diagnosed with incident dementia (1.72 per 100 person-years) during a median (interquartile range) follow-up of 3.46 (1.92-5.51) years. Compared with those who did not receive ADT, those using antiandrogen monotherapy showed an increased risk of dementia (weighted hazard ratio [HR], 1.34; 95% CI, 1.16-1.55) and AD (weighted HR, 1.52; 95% CI, 1.13-2.04). The risk of dementia was similar between GnRH agonist use or orchiectomy and no ADT use (GnRH agonist: weighted HR, 1.13; 95% CI, 1.00-1.28; orchiectomy: 1.00; 95% CI, 0.74-1.37). Several sensitivity analyses revealed consistent findings for both outcomes. <h3>Conclusions and Relevance</h3> In this study, the use of antiandrogen monotherapy was associated with increased risk of dementia or AD, while GnRH agonist use and orchiectomy had no significant difference compared with patients who did not receive ADT. Further prospective studies are warranted to confirm these findings.
Causes of fever in Tanzanian adults attending outpatient clinics: a prospective cohort study
Authors: N. Boillat-Blanco, Z. Mbarack, J. Samaka, T. Mlaganile, T. Kazimoto, A. Mamin, B. Genton, L. Kaiser, V. D'Acremont
Journal: Clinical Microbiology and Infection (2020)

Exploring fever aetiologies improves patient management. Most febrile adults are outpatients, but all previous studies were conducted in inpatients. This study describes the spectrum of diseases in adults attending outpatient clinics in urban Tanzania.We recruited consecutive adults with temperature ≥38°C in a prospective cohort study. We collected medical history and performed a clinical examination. We performed 27 364 microbiological diagnostic tests (rapid tests, serologies, cultures and molecular analyses) for a large range of pathogens on blood and nasopharyngeal samples. We based our diagnosis on predefined clinical and microbiological criteria.Of 519 individuals, 469 (89%) had a clinically or microbiologically documented infection and 128 (25%) were human immunodeficiency virus (HIV) -infected. We identified 643 diagnoses: 264 (41%) acute respiratory infections (36 (5.6%) pneumonia, 39 (6.1%) tuberculosis), 71 (11%) infections with another focus (31 (4.8%) gastrointestinal, 26 (4.0%) urogenital, 8 (1.2%) central nervous system) and 252 (39%) infections without focus (134 (21%) dengue, 30 (4.7%) malaria, 28 (4.4%) typhoid). Of the 519 individuals, 318 (61%), 179 (34%), 30 (6%) and 15 (3%), respectively, had a viral, bacterial, parasitic and fungal acute infection. HIV-infected individuals had more bacterial infections than HIV-negative (80/122 (66%) versus 100/391 (26%); p < 0.001). Patients with advanced HIV disease had a higher proportion of bacterial infections (55/76 (72%) if CD4 ≤200 cells/mm3 and 25/52 (48%) if CD4 >200 cells/mm3, p 0.02).Viral diseases caused most febrile episodes in adults attending outpatient clinics except in HIV-infected patients. HIV status and a low CD4 level strongly determined the need for antibiotics. Systematic HIV screening is essential to appropriately manage febrile patients.
Abstract 4611: A multicenter clinical study of stool DNA test of methylated <i>syndecan-2</i> for colorectal cancer detection
Authors: Jianping Wang, Side Liu, Hui Wang, Lei Zheng, Changchun Zhou, Guoxin Li, Rongkang Huang, Huaiming Wang, Chujun Li, Xinjuan Fan, Xinhui Fu, Xinying Wang, Hongliang Guo, Jie Guan, Yanlai Sun, Xilin Song, Zengjun Li, Dianbin Mu, Jujie Sun, Xianglin Liu, Yan Qi, Feng Niu, Chunhua Chen, Xiaolin Wu, Xianshu Wang, Xianrang Song, Hongzhi Zou
Journal: Cancer Research (2020)

Abstract Study purpose: Previously, we had a pilot study to evaluate the feasibility of a stool DNA test of methylated Syndycan-2 (SDC2) for colorectal cancer (CRC) detection. The purpose of this continuing investigation was to assess the performance of this test in a multicenter hospital-based setting. Methods: Each participant was required to undergo both a stool DNA test and a reference colonoscopy. The stool DNA test assesses the methylation status of a single target of SDC2 gene. Results of real-time methylation-specific PCR were dichotomized as positive and negative by a prespecified cut-off value. The main evaluation indexes were sensitivity, specificity, and kappa value, which was used to assess the diagnostic consistency between stool DNA test and colonoscopy. Tests were performed in blinded fashion and processed independently of the colonoscopic results. Results: Among the 1110 participants from three hospitals included for analysis, 359 and 38 had CRC and advanced adenomas, respectively, according to colonoscopy findings. The sensitivity of the stool DNA test was 83.8% for CRC and 42.1% for advanced adenomas. For CRC at early stage confined to bowel wall (I to II), the sensitivity was 87.0%. Detection rate for CRC did not vary significantly according to age, tumor location, differentiation, and TNM stage, except for gender (P=0.041). The specificity of the stool DNA test was 98.0% among participants with nonadvanced colorectal neoplasia, non-neoplastic disorders, or negative results on colonoscopy. Diagnostic consistency for CRC assessed by kappa value was 0.84, indicating that the agreement in outcome between the stool DNA test and colonoscopy was excellent. Conclusion: Noninvasive stool DNA test using methylated SDC2 as a molecular marker was a sensitive and accurate method for CRC detection. Citation Format: Jianping Wang, Side Liu, Hui Wang, Lei Zheng, Changchun Zhou, Guoxin Li, Rongkang Huang, Huaiming Wang, Chujun Li, Xinjuan Fan, Xinhui Fu, Xinying Wang, Hongliang Guo, Jie Guan, Yanlai Sun, Xilin Song, Zengjun Li, Dianbin Mu, Jujie Sun, Xianglin Liu, Yan Qi, Feng Niu, Chunhua Chen, Xiaolin Wu, Xianshu Wang, Xianrang Song, Hongzhi Zou. A multicenter clinical study of stool DNA test of methylated syndecan-2 for colorectal cancer detection [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4611.
Early‐Onset Hydroxychloroquine Retinopathy and a Possible Relationship to Blood Levels: Comment on the Article by Petri et al
Authors: Naoto Yokogawa, Akiko Ohno‐Tanaka, Masayuki Hashiguchi, Mikiko Shimizu, Hiroko Ozawa, Shinji Ueno, Kei Shinoda, David J. Browning
Journal: Arthritis & Rheumatology (2020)
Abstract 43: Fully integrated single instrument imaging-based digital PCR platform
Authors: Robert Lin, Andrew Zayac, Steve Gallagher, Lingxia Jiang, Felicia Linn, Paul Hung
Journal: Cancer Research (2020)

Abstract Digital PCR (dPCR) has gained popularity in recent years for cancer research such as rare mutation detection, minimal residual disease, treatment selection, and recurrence monitoring. However, currently available technologies suffer from several limitations such as tedious workflow, long time-to-result, poor multiplexity, and inconsistent reagent digitization that severely hindered its broad adoption. We have designed and manufactured a dPCR platform that is capable of consistent sample digitization, thermal cycling and simultaneous interrogation of 20,000 partitions with walk-away workflow. The instrument integrates a loading and digitization manifold, a thermal cycler and an imaging engine with 5 optical channels into a single benchtop box. The Microfluidic Array Partitioning (MAP) consumable is a micro-injection molded, automation-ready plate that contains 16 individual units that can be loaded simultaneously. Each unit partitions an individual sample into 20,000 fluidically isolated partitions while utilizing &amp;gt;90% of inputted sample. We utilized an oncology standard assay, confocal microscopy, and real-time imaging to validate the dynamic range, sample utilization, and digitization consistency of the platform, respectively. Using the European Breast Cancer Standards ERM-AD623 we quantified replicates that were serially diluted from 1 × 105cp/μL down to 10cp/μL. We demonstrated that the dPCR platform can consistently quantify targets over 5-orders-of-magnitude of concentration with high consistency in both quantification and partition numbers. With confocal microscopy, the reagent inside the partitions are visualized to characterize sample utilization. Using conventional qPCR calibration dye ROX and real-time imaging, we show that over 99% of the partitions can be consistently analyzed for high quantification confidence. With the combination of ease-of-use, fast time-to-result and consistent performance, we believe this novel dPCR platform provides unparalleled usability and capability and will allow dPCR to fulfill its promise to impact cancer patient care. Citation Format: Robert Lin, Andrew Zayac, Steve Gallagher, Lingxia Jiang, Felicia Linn, Paul Hung. Fully integrated single instrument imaging-based digital PCR platform [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 43.