tbuckley/cabot-search huggingface dataset:
SAT0036 ULTRASOUND IN THE ASSESSMENT OF JOINT DAMAGE IN RHEUMATOID ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW BY THE OMERACT ULTRASOUND WORKING GROUP
Authors: I. Gessl, B. Wildner, P. Balint, M. A. D’agostino, P. Mandl
Journal: Annals of the Rheumatic Diseases (2020)

Background: The detection of damage in patients with rheumatoid arthritis (RA) is crucial for monitoring of therapy targets as well as for early diagnosis. Conventional radiography (CR) is commonly used to detect structural damage, in the form of bone erosions or loss of hyaline cartilage. Over the last years, musculoskeletal ultrasound (MSUS) was shown to be a sensitive and reliable method to detect erosion and cartilage loss as well as damage to soft tissue structures. Objectives: To identify and synthesize the evidence for the use and measurement properties of MSUS in assessing structural damage in patients with RA. Methods: A systematic literature search (SLR) of the PubMed, Embase and Cochrane Library was performed. Original articles were included that were published in English until 01/01/2019, reporting MSUS of bone erosion, cartilage loss or damage and tendon damage, and the measurement properties of MSUS according to the OMERACT Filter 2.1. Results: Of the 1.266 identified articles 79 were finally included, most of which reported on cross-sectional studies. The majority of the studies used the OMERACT definitions for ultrasonographic pathology. Among these, erosions were assessed in 72 (91.1%), cartilage damage in 12 (15.2%), tendons in 4 (5.1%) studies and enthesophytes in a single (1.3%) study. Erosions were rated by binary grading in 56 (77.8%) studies and by semiquantitative scoring in 27 (37.5%) studies. Global or sum scores were calculated in only 9 (12.5%) studies. Among 23 studies assessing erosions both by US and CR, only 1/23 (4.3%) study found a higher sensitivity of CR as compared to MSUS. Among studies assessing tendons, 3 (75%) used a semiquantitative score and one scored tendon rupture as being present or absent. Cartilage damage was graded in binary fashion, quantitatively by measuring cartilage thickness or semi-quantitatively. Hand joints were the most frequently evaluated joints (58, 73.4%). The overwhelming majority of studies assessed structural damage bilaterally (68, 86.1%), with 5 (6.3%) studies assessing only the dominant hand, 5 (6.3%) studies evaluating the clinically more affected side and 1 (1.3%) study assessing only the right hand. Validity, reliability and responsiveness were assessed in only 8 (10.1%), 10 (12.7%) and 4 (5.1%) studies respectively. Feasibility was not considered in any of the studies. Conclusion: While the results of this SLR suggest that US is a sensitive and feasible tool to detect damage in RA, they also highlight the need for further research and validation. Findings of this SLR will inform the next steps of the Working Group in developing an ultrasound score for assessing structural damage in patients with RA. Disclosure of Interests: None declared
The “double string” sign: a warning image after cold endoscopic mucosal resection
Authors: Óscar Nogales Rincón, Julia García García, Olga Ortega Lobete, Carlos Carbonell Blanco, Laura Rayón Moreno, Javier Aranda Hernández, Beatriz Merino Rodríguez
Journal: Endoscopy (2020)

A 52-year-old man underwent screening colonoscopy. A sessile serrated lesion (Paris 0-Is, NICE-1; 17 mm diameter) was observed in the right colon. After submucosal injection with gelofusine plus indigo carmine, en bloc cold endoscopic mucosal resection (cold-EMR) was attempted using a 25-mm braided snare (SnareMaster SD-210U-25; Olympus, Tokyo, Japan) ([Fig. 1]). After snare closure, moderate traction of the snare sheath was applied to remove the lesion; however, the lesion remained trapped due to a large amount of tissue caught. The snare was repositioned slightly, and resection was successful. On inspection of the mucosal defect, the submucosal layer was observed with apparent “bubble sign” after waterjet irrigation ([Fig. 2 a], [Video 1]), followed by a “double string” sign, suggesting exposure of damaged muscle fibers ([Fig. 2 b]). After insufflation and water irrigation, these muscle fibers separated showing deep muscular injury with visible serosa ([Fig. 2 c]). The defect was immediately closed with endoscopic clips ([Fig. 2 d]). The patient was monitored for 4 hours and discharged with prophylactic antibiotics and no symptoms. No complications occurred. Histology confirmed a 21 × 12 × 2 mm specimen and suspicion of serrated lesion without dysplasia.
Efficacy and Safety of Ursodeoxycholic Acid for the Prevention of Gallstone Formation After Gastrectomy in Patients With Gastric Cancer
Authors: Sang Hyub Lee, Dong Kee Jang, Moon-Won Yoo, Sun-Hwi Hwang, Seong-Yeob Ryu, Oh Kyoung Kwon, Hoon Hur, Hong Man Yoon, Bang Wool Eom, Hye Seong Ahn, Taeil Son, Kyo Young Song, Han Hong Lee, Min-Gew Choi, Ji Yeong An, Sang-Il Lee, Kyung Ho Lee, Soyeon Ahn, Young Suk Park, Do Joong Park
Journal: JAMA Surgery (2020)

The incidence of gallstones has been reported to increase after gastrectomy. However, few studies have been conducted on the prevention of gallstone formation in patients who have undergone gastrectomy.To evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing gallstone formation after gastrectomy in patients with gastric cancer.The PEGASUS-D study (Efficacy and Safety of DWJ1319 in the Prevention of Gallstone Formation after Gastrectomy in Patient with Gastric Cancer: A Multicenter, Randomized, Double-blind, Placebo-controlled Study) was a randomized, double-blind, placebo-controlled clinical trial conducted at 12 institutions in the Republic of Korea. Adults (aged ≥19 years) with a diagnosis of gastric cancer who underwent total, distal, or proximal gastrectomy were enrolled between May 26, 2015, and January 9, 2017; follow-up ended January 8, 2018. Efficacy was evaluated by both the full analysis set, based on the intention-to-treat principle, and the per-protocol set; full analysis set findings were interpreted as the main results.Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. Ursodeoxycholic acid and placebo were administered daily for 52 weeks.Gallstone formation was assessed with abdominal ultrasonography every 3 months for 12 months. Randomization and allocation to trial groups were carried out by an interactive web-response system. The primary end point was the proportion of patients developing gallstones within 12 months after gastrectomy.A total of 521 patients (175 received 300 mg of UDCA, 178 received 600 mg of UDCA, and 168 received placebo) were randomized. The full analysis set included 465 patients (311 men; median age, 56.0 years [interquartile range, 48.0-64.0 years]), with 151 patients in the 300-mg group, 164 patients in the 600-mg group, and 150 patients in the placebo group. The proportion of patients developing gallstones within 12 months after gastrectomy was 8 of 151 (5.3%) in the 300-mg group, 7 of 164 (4.3%) in the 600-mg group, and 25 of 150 (16.7%) in the placebo group. Compared with the placebo group, odds ratios for gallstone formation were 0.27 (95% CI, 0.12-0.62; P = .002) in the 300-mg group and 0.20 (95% CI, 0.08-0.50; P < .001) in the 600-mg group. No significant adverse drug reactions were detected among the enrolled patients.Administration of UDCA for 12 months significantly reduced the incidence of gallstones after gastrectomy for gastric cancer. These findings suggest that UDCA administration prevents gallstone formation after gastrectomy in patients with gastric cancer.ClinicalTrials.gov Identifier: NCT02490111.
Gestational Diabetes Mellitus and Glucose Sample Handling
Authors: Sarah A.L. Price, Robert G. Moses
Journal: Diabetes Care (2020)

Gestational diabetes mellitus (GDM) continues to provide challenges in terms of both diagnosis and management. Recent scientific discussions around the preanalytical processing of glucose samples from the glucose tolerance test (GTT) have generated considerable interest and debate (1,2).

For most women, the diagnosis of GDM is based on the measurement of plasma glucose after the GTT. The observational Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study (3) and the consensus agreement about diagnostic criteria by the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) (4) provided glucose thresholds for the diagnosis of GDM.

The HAPO study was meticulous in the preanalytical and analytical processing of glucose samples (3). Given that our current diagnostic criteria are based on the findings of the HAPO study, if results are to be comparable, the same meticulous processing must also be applied to glucose samples processed in routine clinical care.

A major source of preanalytical error in measuring glucose is loss of glucose from blood samples …
Effect of delaying treatment of first-episode psychosis on symptoms and social outcomes: a longitudinal analysis and modelling study
Authors: Richard J Drake, Nusrat Husain, Max Marshall, Shôn W Lewis, Barbara Tomenson, Imran B Chaudhry, Linda Everard, Swaran Singh, Nick Freemantle, David Fowler, Peter B Jones, Tim Amos, Vimal Sharma, Chloe D Green, Helen Fisher, Robin M Murray, Til Wykes, Iain Buchan, Max Birchwood
Journal: The Lancet Psychiatry (2020)

Delayed treatment for first episodes of psychosis predicts worse outcomes. We hypothesised that delaying treatment makes all symptoms more refractory, with harm worsening first quickly, then more slowly. We also hypothesised that although delay impairs treatment response, worse symptoms hasten treatment, which at presentation mitigates the detrimental effect of treatment delay on symptoms.
From combinations to multitarget‐directed ligands: A continuum in Alzheimer's disease polypharmacology
Authors: Claudia Albertini, Alessandra Salerno, Pedro de Sena Murteira Pinheiro, Maria L. Bolognesi
Journal: Medicinal Research Reviews (2020)

The continued drug discovery failures in complex neurodegenerative diseases, including Alzheimer's disease (AD), has raised questions about the classical paradigm "one-drug, one-target, one-disease." In parallel, the ever-increasing awareness of the multiplicity of the underlying pathways has led to the affirmation of polypharmacological approaches. Polypharmacology, which broadly embodies the use of pharmaceutical agents acting on multiple targets, seems to be the best way to restore the complex diseased network and to provide disease-modifying effects in AD. In this review, our aim is to provide a roadmap into a world that is still only partly explored and that should be seen as a continuum of pharmacological opportunities, from drug combinations to multitarget-directed ligands (both codrugs and hybrids). Each modality has unique features that can be effectively exploited by medicinal chemists. We argue that understanding their advantages and drawbacks is very helpful in choosing a proper approach and developing successful AD multitarget drug-discovery endeavors. We also briefly dwell on (co)target validation, an aspect that is quite often neglected, but critical for an efficient clinical translation. We substantiate our discussion with instructive examples taken from the recent literature. Our wish is that, in spite of the specter of the high attrition rates, best researchers preferring to enter, stay, and progress in the field would help grow the sector and develop AD polypharmacology to full potential.
Deletion of the <i>lon</i> gene augments expression of <i>Salmonella</i> Pathogenicity Island (SPI)-1 and metal ion uptake genes leading to the accumulation of bactericidal hydroxyl radicals and host pro-inflammatory cytokine-mediated rapid intracellular clearance
Authors: Perumalraja Kirthika, Amal Senevirathne, Vijayakumar Jawalagatti, SungWoo Park, John Hwa Lee
Journal: Gut Microbes (2020)

In the present study, we characterized the involvement of Lon protease in bacterial virulence and intracellular survival in Salmonella under abiotic stress conditions resembling the conditions of a natural infection. Wild type (JOL401) and the lon mutant (JOL909) Salmonella Typhimurium were exposed to low temperature, pH, osmotic, and oxidative stress conditions and changes in gene expression profiles related to virulence and metal ion uptake were investigated. Expression of candidate genes invF and hilC of Salmonella Pathogenicity Island (SPI)-1 and sifA and sseJ of SPI-2 revealed that Lon protease controls SPI-1 genes and not SPI-2 genes under all stress conditions tested. The lon mutant exhibited increased accumulation of hydroxyl (OH·) ions that lead to cell damage due to oxidative stress. This oxidative damage can also be linked to an unregulated influx of iron due to the upregulation of ion channel genes such as fepA in the lon mutant. The deletion of lon from the Salmonella genome causes oxidative damage and increased expression of virulence genes. It also prompts the secretion of host pro-inflammatory cytokines leading to early clearance of the bacteria from host cells. We conclude that poor bacterial recovery from mice infected with the lon mutant is a result of disrupted bacterial intracellular equilibrium and rapid activation of cytokine expression leading to bacterial lysis.
18F-FDG Uptake in a Mesonephric Carcinoma
Authors: Thien Vinh Luong, Jacob Christian Lindegaard, Frede Donskov, Else Mejlgaard, Kirsten Bouchelouche
Journal: Clinical Nuclear Medicine (2020)

Abstract We present the case of a 39-year-old woman with vaginal bleeding and abdominal pain. An 18 F-FDG PET/CT showed high 18 F-FDG uptake in a tumor in the pouch of Douglas, in 3 lymph nodes in the pelvis, and in the left tuber ischiadicum. Biopsies revealed a mesonephric carcinoma with metastases. Six series of empiric chemotherapy with carboplatin, paclitaxel, and bevacizumab were not sufficient to treat the cancer, and checkpoint immunotherapy with nivolumab and ipilimumab was initialized.
Clare Gerada: What to do with appraisal
Authors: Clare Gerada
Journal: BMJ (2020)

As we wait for the next phase of the pandemic, many of us are beginning to take stock of our experiences (good and bad) over the past tumultuous months. Despite the problems, there have been positive aspects to the changes in our working lives. For example, doctors have enjoyed the freedom of being able to determine their own learning needs—as adults should—for team working, clinical supervision, and a focus on psychological wellbeing.

They have welcomed new flexibilities in revalidation and appraisal. When appraisal became compulsory in 2004 it was …
Prostate Cancer Drug Degarelix Rapidly Treats Pedophilic Disorder
Authors: Anita Slomski
Journal: JAMA (2020)

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Cost-effectiveness of Diabetes Prevention Interventions Targeting High-risk Individuals and Whole Populations: A Systematic Review
Authors: Xilin Zhou, Karen R. Siegel, Boon Peng Ng, Shawn Jawanda, Krista K. Proia, Xuanping Zhang, Ann L. Albright, Ping Zhang
Journal: Diabetes Care (2020)

OBJECTIVE We conducted a systematic review of studies evaluating the cost-effectiveness (CE) of interventions to prevent type 2 diabetes (T2D) among high-risk individuals and whole populations. RESEARCH DESIGN AND METHODS Interventions targeting high-risk individuals are those that identify people at high risk of developing T2D and then treat them with either lifestyle or metformin interventions. Population-based prevention strategies are those that focus on the whole population regardless of the level of risk, creating public health impact through policy implementation, campaigns, and other environmental strategies. We systematically searched seven electronic databases for studies published in English between 2008 and 2017. We grouped lifestyle interventions targeting high-risk individuals by delivery method and personnel type. We used the median incremental cost-effectiveness ratio (ICER), measured in cost per quality-adjusted life year (QALY) or cost saved to measure the CE of interventions. We used the $50,000/QALY threshold to determine whether an intervention was cost-effective or not. ICERs are reported in 2017 U.S. dollars. RESULTS Our review included 39 studies: 28 on interventions targeting high-risk individuals and 11 targeting whole populations. Both lifestyle and metformin interventions in high-risk individuals were cost-effective from a health care system or a societal perspective, with median ICERs of $12,510/QALY and $17,089/QALY, respectively, compared with no intervention. Among lifestyle interventions, those that followed a Diabetes Prevention Program (DPP) curriculum had a median ICER of $6,212/QALY, while those that did not follow a DPP curriculum had a median ICER of $13,228/QALY. Compared with lifestyle interventions delivered one-on-one or by a health professional, those offered in a group setting or provided by a combination of health professionals and lay health workers had lower ICERs. Among population-based interventions, taxing sugar-sweetened beverages was cost-saving from both the health care system and governmental perspectives. Evaluations of other population-based interventions—including fruit and vegetable subsidies, community-based education programs, and modifications to the built environment—showed inconsistent results. CONCLUSIONS Most of the T2D prevention interventions included in our review were found to be either cost-effective or cost-saving. Our findings may help decision makers set priorities and allocate resources for T2D prevention in real-world settings.
Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement
Authors: Grace Lai-Hung Wong, Vincent Wai-Sun Wong, Alex Thompson, Jidong Jia, Jinlin Hou, Cosmas Rinaldi Adithya Lesmana, Adityo Susilo, Yasuhito Tanaka, Wah-Kheong Chan, Ed Gane, Arlinking K Ong-Go, Seng-Gee Lim, Sang Hoon Ahn, Ming-Lung Yu, Teerha Piratvisuth, Henry Lik-Yuen Chan
Journal: The Lancet. Gastroenterology & hepatology (2020)
Excessive Polyamine Generation in Keratinocytes Promotes Self-RNA Sensing by Dendritic Cells in Psoriasis
Authors: Fangzhou Lou, Yang Sun, Zhenyao Xu, Liman Niu, Zhikai Wang, Siyu Deng, Zhaoyuan Liu, Hong Zhou, Jing Bai, Qianqian Yin, Xiaojie Cai, Libo Sun, Hong Wang, Qun Li, Zhouwei Wu, Xiang Chen, Jun Gu, Yu-Ling Shi, Wufan Tao, Florent Ginhoux, Honglin Wang
Journal: Immunity (2020)
Diagnostic accuracy of VIDISCA-NGS in patients with suspected central nervous system infections
Authors: I.E. van Zeggeren, A.W.D. Edridge, D. van de Beek, M. Deijs, S.M. Koekkoek, K.C. Wolthers, L. van der Hoek, M.C. Brouwer
Journal: Clinical Microbiology and Infection (2020)

ObjectivesConfirming the diagnosis in viral central nervous system (CNS) infections can be difficult with the currently available diagnostic tools. Virus discovery cDNA-amplified fragment length polymorphism next-generation sequencing (VIDISCA-NGS) is a promising viral metagenomic technique that enables the detection of all viruses in a single assay. We performed a retrospective study on the diagnostic accuracy of VIDISCA-NGS in cerebrospinal fluid (CSF) of individuals with suspected CNS infections.MethodsConsecutive adult patients presenting to the Emergency Department or inpatients, who underwent a lumbar puncture for the suspicion of a CNS infection, were included if they were diagnosed with a viral CNS infection, or if a viral CNS infection was initially suspected but eventually a different diagnosis was made. A quantitative PCR panel of the most common causative viruses was performed on CSF of these patients as reference standard and compared with the results of VIDISCA-NGS, the index test.ResultsWe included 38 individuals with viral CNS infections and 35 presenting with suspected CNS infection for whom an alternative aetiology was finally established. Overall sensitivity and specificity were 52% (95% CI 31%–73%) and 100% (95% CI 91%–100%), respectively. One enterovirus, detected by VIDISCA-NGS, was only identified by quantitative PCR upon retesting. Additional viruses identified by VIDISCA-NGS consisted of GB virus C, human papillomavirus, human mastadenovirus C, Merkel cell polyoma virus and anelloviruses.ConclusionIn patients for whom routine diagnostics do not yield a causative pathogen, VIDISCA-NGS can be of additional value as it can detect a broader range of viruses, but it does not perform well enough to replace quantitativePCR.
Non-mutated self protein murine TPD52 (mD52) induces anti-tumor immunity following active vaccination
Authors: Robert K. Bright, Laura A. Payton, Jennifer D. Lewis
Journal: Cancer Research (2006)

2248  Tumor protein D52 (TPD52) is involved in tumor cell proliferation, trafficking and metastasis. Multiple investigators have demonstrated TPD52 over expression in various human tumors to include prostate, breast, lung and colon carcinomas. Murine TPD52 (mD52) naturally mirrors human TPD52 with respect to known function and over expression in tumor cells compared to normal cells and tissues, and thus represents a “self,” non-mutated tumor associated antigen (TAA) with direct relevance to several human cancers. Two murine cancer models, a spontaneously metastatic sarcoma and Transgenic Adeno-carcinoma of the Mouse Prostate (TRAMP) were employed to study mD52 as a target for active vaccination. To assess immunogenicity of the TAA mD52, naA−ve mice were immunized with bacterial, recombinant mD52 protein in combination with CpG/ODN as a TLR9 ligand or plasmid DNA encoding mD52 as a nucleic acid-based vaccine. Following the final immunization, mice were challenged s.c. with a lethal dose of mD52 positive, syngeneic tumor cells. Greater than 50% of mice immunized with mD52 rejected sarcoma tumor cell challenge and metastasis completely and >60% of the TRAMP-C1 challenged mice were tumor free ∼85 days post s.c. challenge with 5e6 cells. Only those mice that rejected challenge with mD52 positive tumor cells generated detectable anti-mD52-specific antibody titers and specific cytotoxic T lymphocytes. Though mD52 is expressed at low levels in the kidneys of mice, no auto-immune pathology was detected. Strikingly, mD52-based vaccination was able to break tolerance without inducing harmful autoimmunity and induced anti-tumor immunity in vivo. Together, these data demonstrate that mD52 is capable of inducing an immune response that results in the rejection of tumors that over express mD52 and that the vaccine induced mD52-immunity does not appear to result in potentially harmful autoimmunity. Our findings support the notion that mD52 is a promising target for anti-cancer vaccination and a relevant model for in vivo, preclinical evaluation.