tbuckley/cabot-search huggingface dataset:
10-Year Clinical Experience With 18F-Choline PET/CT
Authors: Fabio Zattoni, Ilaria Ravelli, Marco Rensi, Decio Capobianco, Eugenio Borsatti, Tania Baresic, Agostino Chiaravalloti, Orazio Schillaci, Pierpaolo Alongi, Tommaso Vincenzo Bartolotta, Ilaria Rambaldi, Mirco Bartolomei, Mohsen Farsad, Manuel Tredici, Davide Donner, Franca Chierichetti, Giuseppe Trifirò, Elisabetta Brugola, Marta Burei, Fabrizio Dal Moro, Diego Cecchin, Laura Evangelista
Journal: Clinical Nuclear Medicine (2020)

Purpose The primary aim of this multicenter retrospective analysis is to examine the role of 18 F-choline PET/CT as a diagnostic tool for staging and restaging prostate cancer (PCa) in a large population in the light of 10 years of clinical experience. A secondary aim of the study is to produce data on the predictors of a positive 18 F-choline PET/CT result in the setting of PCa primaries and biochemical recurrences. Materials and Methods This multicenter retrospective cohort study is based on data collected by 9 Italian nuclear medicine departments. Between October 2008 and September 2019, 3343 men underwent 18 F-choline PET/CT scans before receiving definitive treatments for a primary PCa or biochemical recurrence. Inclusion criteria were (1) histologically proven PCa (on surgical specimens or prostate biopsies from patients not treated surgically) and (2) availability of clinical and pathological data, including serum prostate specific antigen (PSA) level at the time of PET/CT scanning. Results 18 F-choline PET/CT was performed in 545 cases (16.4%) for cancer staging and in 2798 (83.6%) for restaging purposes, and the result was positive in 540 (99.1%) for the former and 1993 (71.2%) for the latter. A positive PET/CT result was always associated with a high Gleason score (&gt;7) and high PSA levels ( P &lt; 0.01). The percentage of patients with a PSA threshold less than 1.0 ng/mL for performing PET/CT was higher in the years 2014 to 2019 (n = 341, 25% of cases) than during the previous period (n = 148, 16%; in 2008–2013). When used for staging purposes, receiver operating characteristic analysis showed that PSA levels of 9.2, 16.4, and 16.6 ng/mL were the optimal cutoffs for distinguishing between positive and negative PET/CT findings for local disease, lymph node involvement, and metastasis, respectively. In the restaging setting, a PSA level of 1.27 ng/mL was the optimal cutoff for distinguishing between a positive and negative PET/CT scan. Conclusions 18 F-choline PET/CT can help identify early recurrences, even in the case of low PSA levels (&lt;1 ng/mL). Our data suggest that important improvements have been made in the interpretation of 18 F-choline images and in patient selection in the last 5 years.
Location-specific cell identity rather than exposure to GI microbiota defines many innate immune signalling cascades in the gut epithelium
Authors: Ozge Kayisoglu, Franziska Weiss, Carolin Niklas, Isabella Pierotti, Malvika Pompaiah, Nina Wallaschek, Christoph-Thomas Germer, Armin Wiegering, Sina Bartfeld
Journal: Gut (2020)

Objective The epithelial layer of the GI tract is equipped with innate immune receptors to sense invading pathogens. Dysregulation in innate immune signalling pathways is associated with severe inflammatory diseases, but the responsiveness of GI epithelial cells to bacterial stimulation remains unclear. Design We generated 42 lines of human and murine organoids from gastric and intestinal segments of both adult and fetal tissues. Genome-wide RNA-seq of the organoids provides an expression atlas of the GI epithelium. The innate immune response in epithelial cells was assessed using several functional assays in organoids and two-dimensional monolayers of cells from organoids. Results Results demonstrate extensive spatial organisation of innate immune signalling components along the cephalocaudal axis. A large part of this organisation is determined before birth and independent of exposure to commensal gut microbiota. Spatially restricted expression of Toll-like receptor 4 ( Tlr4 ) in stomach and colon, but not in small intestine, is matched by nuclear factor kappa B (NF-κB) responses to lipopolysaccharide (LPS) exposure. Gastric epithelial organoids can sense LPS from the basal as well as from the apical side. Conclusion We conclude that the epithelial innate immune barrier follows a specific pattern per GI segment. The majority of the expression patterns and the function of TLR4 is encoded in the tissue-resident stem cells and determined primarily during development.
EAACI Guidelines on the effective transition of adolescents and young adults with allergy and asthma
Authors: Graham Roberts, Marta Vazquez‐Ortiz, Rebecca Knibb, Ekaterina Khaleva, Cherry Alviani, Elizabeth Angier, Katharina Blumchen, Pasquale Comberiati, Bettina Duca, Audrey DunnGalvin, Teresa Garriga‐Baraut, Claudia Gore, M. Hazel Gowland, Valérie Hox, Britt Jensen, Charlotte G. Mortz, Oliver Pfaar, Helena Pite, Alexandra F. Santos, Silvia Sanchez‐Garcia, Frans Timmermans
Journal: Allergy (2020)

Abstract Adolescent and young adult (AYA) patients need additional support, while they experience the challenges associated with their age. They need specific training to learn the knowledge and skills required to confidently self‐manage their allergies and/or asthma. Transitional care is a complex process, which should address the psychological, medical, educational and vocational needs of AYA in the developmentally appropriate way. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline to provide evidence‐based recommendations for healthcare professionals to support the transitional care of AYA with allergy and/or asthma. This guideline was developed by a multidisciplinary working panel of experts and patient representatives based on two recent systematic reviews. It sets out a series of general recommendations on operating a clinical service for AYA, which include the following: (a) starting transition early (11‐13 years), (b) using a structured, multidisciplinary approach, (c) ensuring AYA fully understand their condition and have resources they can access, (d) active monitoring of adherence and (e) discussing any implications for further education and work. Specific allergy and asthma transition recommendations include (a) simplifying medication regimes and using reminders; (b) focusing on areas where AYA are not confident and involving peers in training AYA patients; (c) identifying and managing psychological and socio‐economic issues impacting disease control and quality of life; (d) enrolling the family in assisting AYA to undertake self‐management; and (e) encouraging AYA to let their friends know about their allergies and asthma. These recommendations may need to be adapted to fit into national healthcare systems.
Recurrence of Atrial Fibrillation After Catheter Ablation or Antiarrhythmic Drug Therapy in the CABANA Trial
Authors: Jeanne E. Poole, Tristram D. Bahnson, Kristi H. Monahan, George Johnson, Hoss Rostami, Adam P. Silverstein, Hussein R. Al-Khalidi, Yves Rosenberg, Daniel B. Mark, Kerry L. Lee, Douglas L. Packer, Jeanne E. Poole, Nazem Akoum, Pierre Aoukar, Ulrika Birgersdotter-Green, Joseph Blatt, Yong Mei Cha, Mina Chung, Marye Gleva, Taya Glotzer, Charles Henrickson, Jack Kron, Vikas Kuriachan, Siva Mulpuru, Peter Noseworthy, Kris Patton, Jordan Prutkin, Ravi Ranjan, Robert Rho, Andrea Russo, Eric Stecker, Wendy Tzou, Laura Vitali Serdoz, Mauri Wilson
Journal: Journal of the American College of Cardiology (2020)
OP0176 CHRONOLOGICAL ORDER OF DECREASE OF SYNOVITIS, OSTEITIS AND TENOSYNOVITIS IN ARTHRITIS PATIENTS RECEIVING FIRST DMARD-TREATMENT
Authors: X. Matthijssen, E. Niemantsverdriet, S. Le Cessie, A. Van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2020)

Background: During the last decennium advanced imaging modalities have refined our understanding of the tissues involved in RA and have shown that not only joints but also bones and tendons can be inflamed at diagnosis. However, the time-order of decrease of these inflammatory features after initiation of DMARDs is unknown. Whether this differs for ACPA-positive and ACPA-negative patients is also unknown. Objectives: To achieve better understanding of the time order in which the different inflamed tissues (joint, tendon, bone) respond to DMARD-treatment and whether this differs between ACPA-subgroups. Methods: 216 consecutive patients with early undifferentiated or rheumatoid arthritis, who received DMARD-treatment, were studied. Unilateral 1.5 Tesla contrast-enhanced MRIs of MCPs, wrists and MTPs were performed at baseline (before treatment) and after 4, 12 and 24 months. MRIs were scored for synovitis, osteitis and tenosynovitis in line with the RAMRIS, in known time-order but blinded for clinical data. Data of 4 serial time-points (three time intervals) were studied with autoregressive cross-lagged models. These models evaluated the influence of two time patterns in one model: 1) a simultaneous pattern (“extra change in one inflammatory feature was associated with extra change in another feature”) and 2) a subsequent pattern (“change in one inflammatory feature preceded change in another feature”). All analyses were repeated stratified for ACPA-status (anti-CCP2). Results: In all patients, all combinations of inflammatory features showed significant simultaneous decrease in all time intervals (0 – 4 /4 – 12/12 – 24 months; all p&lt;0.05). In addition to simultaneous changes there were also time orders identified: synovitis change between 0 – 4 months preceded tenosynovitis change between 4 – 12 months (p=0.03) and synovitis change between 4 - 12 months preceded tenosynovitis change between months 12 - 24 months (p=0.02). When considering ACPA-negative and ACPA-positive patients separately, similar results were obtained. In addition, in ACPA-positive patients, synovitis change between 4 - 12 months preceded osteitis change at 12 – 24 months (p = 0.002); this was significantly different from ACPA-negative patients (p&lt;0.001). Conclusion: This study increased the understanding of the response to treatment on tissue level. In addition to simultaneous decrease of synovitis, osteitis and tenosynovitis, also time orders of inflammation decrease were identified. These differed between ACPA-subgroups, implying a different interaction of synovium and bone in these patients. Disclosure of Interests: None declared
High nitrogen stainless steel drug-eluting stent - Assessment of pharmacokinetics and preclinical safety in vivo
Authors: Shanshan Chen, Zhifeng Yao, Yongbiao Guan, Hui Yang, M. Babar Shahzad, Yizhe Wu, Bingchun Zhang, Li Shen, Ke Yang
Journal: Bioactive Materials (2020)

Pharmacokinetic analyses were performed using 20 pigs for 120-days implantation, while one sirolimus-eluting stent was implanted into one of their coronary artery. At different time points, the residual sirolimus on the stent, delivered locally (to artery wall), regionally (to adjacent and downstream muscle) and systemically (to plasma and visceral organs), was detected throughout 120 days. Preclinical safety evaluation was performed using 32 pigs for 180-days implantation to study the safety of metal platform material and the effectiveness of sirolimus eluting coating on the HNS stent. The neointima area, restenosis rate and inflammatory grade for HNS and control group stents were detected and analyzed. Approximately 80% sirolimus was eluted from the sirolimus-eluting stents after 30-days implantation in vivo. Additionally, there was sustained sirolimus in the artery wall, cardiac muscle and heart throughout 120-days implantation, and sirolimus accumulated to the peak at 90-days implantation. It was inferred that the sirolimus eluting stent in this study was covered by neointima before 90-days implantation, indicating that the sirolimus eluting coating on the HNS stent was safe and effective. Very little sirolimus was distributed in visceral organs after 14-days implantation. HNS sirolimus-eluting stent exhibited lower restenosis rate and lower inflammatory grade than control group, which verified that the sirolimus-eluting coating design in this study was reasonable and practical. In addition, there were no significant difference in restenosis rate and inflammatory score between HNS bare-metal stent and drug-eluting stents, illustrating that HNS has good bio-compatibility and is suitable to use as coronary artery stent material.
Health-Related Quality of Life in Patients With Hodgkin Lymphoma: A Longitudinal Analysis of the German Hodgkin Study Group
Authors: Stefanie Kreissl, Horst Müller, Helen Goergen, Julia Meissner, Max Topp, Martin Sökler, Jana Markova, Jürg Bernhard, Richard Greil, Bastian von Tresckow, Karolin Behringer, Jens-Ulrich Rüffer, Hans-Henning Flechtner, Michaela Möstl, Michael Fuchs, Andreas Engert, Volker Diehl, Peter Borchmann
Journal: Journal of Clinical Oncology (2020)

PURPOSE Many important details of health-related quality of life (HRQoL) after diagnosis and treatment of Hodgkin lymphoma (HL) are still unknown because large longitudinal studies of HRQoL are rare. Therefore, we analyzed a systematically assessed, comprehensive range of HRQoL domains in patients with HL of all stages from diagnosis up to 5 years of survivorship. PATIENTS AND METHODS We included patients with HL age 18-60 years at diagnosis from the German Hodgkin Study Group trials HD13, HD14, and HD15. We analyzed HRQoL using all functional and symptom scales of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 including deviations from reference values. We estimated the effect of different disease, patient, and treatment characteristics using multiple regression and repeated measures analysis and computed correlations of HRQoL scores. RESULTS We analyzed 4,215 patients with any HRQoL assessment within 5 years after treatment. Higher tumor burden at diagnosis was associated with impaired baseline scores in many HRQoL domains. During survivorship, cognitive, emotional, role, and social functioning and fatigue, dyspnea, sleep, and financial problems were severely and persistently affected. From year 2 on, mean deviations from reference values ranged between 12 and 29 points, with 10 points being a commonly used margin of clinical relevance. In all 3 trials, HRQoL domains 2 and 5 years after therapy were significantly influenced by baseline scores and age but not by randomized treatments. Fatigue was most closely correlated with other symptoms and scales. CONCLUSION Our results show a high and persistent amount of different HRQoL deficits in survivors of HL that are largely independent of the applied chemotherapies. Our analysis underscores the high, unmet medical need of these rather young survivors of HL regarding the psychosocial adverse effects of the cancer experience.
Covid-19: Call for a rapid forward looking review of the UK’s preparedness for a second wave—an open letter to the leaders of all UK political parties
Authors: Victor Adebowale, Derek Alderson, Wendy Burn, Jeanette Dickson, Fiona Godlee, Andrew Goddard, Michael Griffin, Katherine Henderson, Richard Horton, Martin Marshall, Jo Martin, Edward Morris, Chaand Nagpaul, Maggie Rae, Anne Marie Rafferty, Jackie Taylor
Journal: BMJ (2020)

<b><i>Objective:</i></b> To perform a health maintenance organization–based case-control study to evaluate the association of total and high density lipoprotein (HDL) cholesterol with the risk of stroke subtypes and in patient subgroups. <b><i>Methods:</i></b> Cases had a confirmed incident ischemic stroke (n = 1,242) or hemorrhagic stroke (n = 313). Controls (n = 6,455) were identified in a companion myocardial infarction study. Risk of stroke was modeled using logistic regression. <b><i>Results:</i></b> The highest total cholesterol quintile was associated with an increased risk of ischemic stroke compared to the lowest quintile (OR = 1.6, 95% CI 1.3 to 2.0) with the strongest subtype associations for atherosclerotic stroke (OR = 3.2) and lacunar stroke (OR = 2.4). The highest HDL cholesterol quintile was associated with a decreased risk of ischemic stroke compared to the lowest quintile (OR = 0.8, CI 0.6 to 1.0). Subgroup analyses suggested that the total cholesterol association was more important for patients &lt; 66 years of age and those with HDL &lt; 50 mg/dL; the HDL association was more important for patients without diabetes or atrial fibrillation. The second through fourth total cholesterol quintiles were associated with a decreased risk of hemorrhagic stroke compared to the lowest quintile (OR = 0.7, CI 0.5 to 1.0). <b><i>Conclusions:</i></b> Higher total and lower HDL cholesterol levels were associated with increased risk of ischemic stroke, especially certain stroke subtypes and patient subgroups. The lowest levels of total cholesterol were associated with an increased risk of all hemorrhagic strokes.
Regulatory roles for SOX11 in development, stem cells and cancer
Authors: Siu Man Tsang, Erik Oliemuller, Beatrice A. Howard
Journal: Seminars in Cancer Biology (2020)

The transcription factor SOX11 (SRY-related high-mobility-group (HMG) box 11), a member of the SOXC group, is expressed during embryogenesis but largely absent in most adult differentiated tissues. SOX11 regulates progenitor and stem cell behavior, and often acts together with the other two SOXC group members, SOX4 and SOX12, in regulating developmental processes, including neurogenesis and skeletogenesis. Dysregulation of SOX11 has been implicated in a number of diseases including, neurodevelopmental disorders and osteoarthritis, and a wide variety of cancers. Functions of SOX11 during both development and disease could be attributed to its context-dependent post-transcriptional modifications or interaction with other co-factors. We review the molecular and functional roles of SOX11 during development where similar processes appear to be deregulated in cancers.
Risk factors in patients with COVID-19 developing severe liver injury during hospitalisation
Authors: Ke Zhan, Shengtao Liao, Jinfang Li, Yang Bai, Lin Lv, Keqi Yu, Liewang Qiu, Chuanfei Li, Guodan Yuan, An Zhang, Zhechuan Mei
Journal: Gut (2020)

Tamoxifen has been the standard adjuvant therapy for patients with breast cancer for several decades. Various recently completed adjuvant trials using aromatase inhibitors have shown the superiority of these agents over Tamoxifen or placebo, when used in post-menopausal women. The results from these trials present a challenging situation for practicing oncologists with regards to the choice, duration, sequence of therapy, follow-up and side-effects of aromatase inhibitors. Various management issues from a practical angle for oncologists are discussed for the effective use of these agents, with an evidence-based approach.
Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor: A Pre-Specified Analysis of the RE-DUAL PCI Trial
Authors: José C. Nicolau, Deepak L. Bhatt, Stefan H. Hohnloser, Takeshi Kimura, Gregory Y. H. Lip, Corinna Miede, Matias Nordaby, Jonas Oldgren, Philippe Gabriel Steg, Jurriën M. ten Berg, Lucas C. Godoy, Christopher P. Cannon
Journal: Drugs (2020)

In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy?The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1-3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor.Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interaction p values > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interaction p values 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy).Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor. CLINICALTRIALS.NCT02164864.
Nevirapine, Zidovudine, and Didanosine Compared with Zidovudine and Didanosine in Patients with HIV-1 Infection
Authors: Richard T. D'Aquila, Michael D. Hughes, Victoria A. Johnson, Margaret A. Fischl, Jean-Pierre Sommadossi, Song-heng Liou, Joseph Timpone, Maureen Myers, Nesli Basgoz, Manette Niu, Martin S. Hirsch
Journal: Annals of Internal Medicine (1996)

Objective: To study the addition of a third human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor, nevirapine, to the combination of zidovudine and didanosine. Design: A 48-we...
Effect of Concomitant Therapy With Steroids and Tumor Necrosis Factor Antagonists for Induction of Remission in Patients With Crohn’s Disease: A Systematic Review and Pooled Meta-analysis
Authors: David M. Faleck, Eugenia Shmidt, Ruiqi Huang, Leah G. Katta, Neeraj Narula, Rachel Pinotti, Mayte Suarez-Farinas, Jean-Frederic Colombel
Journal: Clinical Gastroenterology and Hepatology (2020)
Structural Basis of SARS-CoV-2– and SARS-CoV–Receptor Binding and Small-Molecule Blockers as Potential Therapeutics
Authors: Hariharan Sivaraman, Shi Yin Er, Yeu Khai Choong, Edem Gavor, J. Sivaraman
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other hosts is mediated by host–pathogen interactions, specifically virus–receptor binding. An in-depth understanding of the virus–receptor binding mechanism is a prerequisite for the discovery of vaccines, antibodies, and small-molecule inhibitors that can interrupt this interaction and prevent or cure infection. In this review, we discuss the viral entry mechanism, the known structural aspects of virus–receptor interactions (SARS-CoV-2 S/humanACE2, SARS-CoV S/humanACE2, and MERS-CoV S/humanDPP4), the key protein domains and amino acid residues involved in binding, and the small-molecule inhibitors and other drugs that have (as of June 2020) exhibited therapeutic potential. Specifically, we review the potential clinical utility of two transmembrane serine protease 2 (TMPRSS2)-targeting protease inhibitors, nafamostat mesylate and camostat mesylate, as well as two novel potent fusion inhibitors and the repurposed Ebola drug, remdesivir, which is specific to RNA-dependent RNA polymerase, against human coronaviruses, including SARS-CoV-2.