tbuckley/cabot-search huggingface dataset:
POS0141 ACTIVE SCREENING FOR GOUT IDENTIFIES A LARGER CARDIOVASCULAR POPULATION AT HIGH MORTALITY RISK
Authors: S. Ruiz-Simón, I. Calabuig, M. Gomez-Garberi, M. Andrés
Journal: Annals of the Rheumatic Diseases (2021)

Background: We have recently revealed by active screening that about a third of gout cases in the cardiovascular population is not registered in records [1], highlighting the value of field studies. Objectives: To assess whether gout screening in patients hospitalized for cardiovascular events may also help identify patients at higher risk of mortality after discharge. Methods: A retrospective cohort field study, carried out in 266 patients admitted for cardiovascular events in the Cardiology, Neurology and Vascular Surgery units of a tertiary centre in Spain. The presence of gout was established by records review and face-to-face interview, according to the 2015 ACR/EULAR criteria. The occurrence of mortality during follow-up and its causes were obtained from electronic medical records. The association between gout and subsequent mortality was tested using Cox regression models. Whether covariates affect the gout-associated mortality was also studied. Results: Of 266 patients recruited at baseline, 17 were excluded due to loss to follow-up (&gt;6mo), leaving a final sample of 249 patients (93.6%). Thirty-six cases (14.5% of the sample) were classified as having gout: twenty-three (63.9%) had a previously registered diagnosis, while 13 (36.1%) had not and was established by the interview. After discharge, the mean follow-up was 19.9 months (SD ±8.6), with a mortality incidence of 21.6 deaths per 100 patient-years, 34.2% by cardiovascular causes. Gout significantly increased the risk of subsequent all-cause mortality, with a hazard ratio (HR) of 2.01 (95%CI 1.13 to 3.58). When the analysis was restricted to gout patients with registered diagnosis, the association remained significant (HR 2.89; 95%CI 1.54 to 5.41). The adjusted HR for all-cause mortality associated with gout was 1.86 (95% CI 1.01-3.40). Regarding the causes of death, both cardiovascular and non-cardiovascular were numerically increased. Secondary variables rising the mortality risk in those with gout were age (HR 1.07; 1.01 to 1.13) and coexistent renal disease (HR 4.70; 1.31 to 16.84), while gender, gout characteristics and traditional risk factors showed no impact. Conclusion: Gout was confirmed an independent predictor of subsequent all-cause mortality in patients admitted for cardiovascular events. Active screening for gout allowed identifying a larger population at high mortality risk, which may help tailor optimal management to minimize the cardiovascular impact. References: [1]Calabuig I, et al. Front Med (Lausanne). 2020 Sep 29;7:560. Disclosure of Interests: Silvia Ruiz-Simón: None declared, Irene Calabuig: None declared, Miguel Gomez-Garberi: None declared, Mariano Andrés Speakers bureau: Grunenthal, Menarini, Consultant of: Grunenthal, Grant/research support from: Grunenthal
Equity and the JAMA Network
Authors: Phil B. Fontanarosa, Annette Flanagin, John Z. Ayanian, Robert O. Bonow, Neil M. Bressler, Dimitri Christakis, Mary L. Disis, S. Andrew Josephson, Melina R. Kibbe, Dost Öngür, Jay F. Piccirillo, Rita F. Redberg, Frederick P. Rivara, Kanade Shinkai, Clyde W. Yancy
Journal: JAMA Internal Medicine (2021)

The key objective of JAMA is "To promote the science and art of medicine and the betterment of the public health"; similar objectives and mission statements are supported by all 12 JAMA Network Journals.Together this family of journals is committed to publishing the best research, reviews, and opinion articles to advance medical science, promote public health, and improve patient care.The ultimate goal is to promulgate truth in science and medicine.On February 23, 2021, a podcast titled "Structural Racism for Doctors-What Is It?" was posted by the JAMA Network and on the following day, a tweet was posted to promote the podcast.Assertions in both that disavowed the presence of structural racism in medicine and among physicians were wrong, misguided, and uninformed.An extensive evidence base strongly supports the presence of structural racism in medicine and its adverse influence on health. 1 The process for reviewing and publishing the podcast and tweet was also flawed.On March 4, 2021, Howard Bauchner, MD, editor in chief of JAMA and the 12 JAMA Network Journals, took responsibility and issued an apology for the podcast and tweet.This editorial team also expresses a profound apology for the misinformation in the podcast and tweet and recognizes the hurt, anger, and outrage that resulted.These events and developments make it clear that JAMA and the JAMA Network Journals can and must do better and advance toward inclusion and antiracism in all journalrelated activities.Even though these journals have made progress, additional commitment and work are needed to build on and intensify these efforts to achieve meaningful, sustainable change.For instance, previous efforts include the more than 650 research, review, and opinion articles on race, racism, and racial and ethnic disparities and inequities that have been published in JAMA and the JAMA Network Journals since 2015, 1 including editorials in JAMA on topics such as race and medical research, 2 race and poverty and medicine, 3 enhancing diversity in medical schools, 4 and equity related to COVID-19 vaccines. 5n addition, within the past year, JAMA Network Open and JAMA Health Forum issued calls for manuscripts on prevention and effects of systemic racism in health 6,7 ; JAMA Psychiatry initiated an editorial fellowship prioritized to early-career academic psychiatrists from underrepresented backgrounds; and JAMA Surgery issued a "Call to Action" to all surgery journal editors for diversity in the editorial and peer review process. 8The JAMA editors and editorial staff also began a thorough revision of guidance for authors and
Duration of amoxicillin-clavulanate for protracted bacterial bronchitis in children (DACS): a multi-centre, double blind, randomised controlled trial
Authors: Tom J C Ruffles, Vikas Goyal, Julie M Marchant, I Brent Masters, Stephanie Yerkovich, Helen Buntain, Anne Cook, Andre Schultz, John W Upham, Anita Champion, Lesley Versteegh, Anne B Chang
Journal: The Lancet Respiratory Medicine (2021)
POS0133 MONOSODIUM URATE CRYSTALS REDUCE HUMAN LIGAMENT CELLS VIABILITY THROUGH INCREASE OF ROS PRODUCTION
Authors: Y. Huang, Y. Liu, Q. Huang, W. Deng, T. W. Li
Journal: Annals of the Rheumatic Diseases (2021)

Background: Ligament destruction is a frequent complication of gout and is strongly associated with tophi. Ligament fibroblasts are important cellular mediators of ligament remodeling. None of study has paid attention to the effects of monosodium urate (MSU) crystals on ligament fibroblasts. Objectives: The study aims to investigate the effects and mechanism of MSU crystals on ligament fibroblasts. Methods: MSU crystals were added to human ligament fibroblasts(HLFs) cultures or primary ligament cells cultures. Cell counting kit-8 (CCK-8) assay, cell migration assay, Annexin V-FITC/PI assay were conducted. Reactive Oxygen Species(ROS) was tested by ROS Assay Kit. Results: The higher concentrations of MSU crystals (0.5-1mg/mL) reduced the viability of HLFs or primary ligament cells after 24 h as assessed by CCK8 assays, with a further reduction in viability observed at the 48 h time point. When observed under light microscopy, HLFs cultured with MSU crystals (0.5mg/mL) appeared unhealthy with fewer cells present. The cell migration ability of HLFs was decreased significantly on MSU crystals (0.5mg/mL). According to the result of Annexin V-FITC/PI assay, the survival rate of HLFs on MSU crystals (0.5mg/mL) was lower than that of 0.25mg/ml and 0 mg/ml at 72h. ROS assay results showed that the production of ROS increased as the concentrations of MSU crystals increased. Conclusion: MSU crystals inhibit human ligament cells viability through the increase of ROS production. It may contribute to disordered ligament remodeling in gout patients with ligament destruction. References: [1]Ashika Chhana, et al. Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state. Arthritis Res Ther. 2018, 20(1): 208. Figure 1. MSU crystals reduce human ligament fibroblasts and primary human ligament cells viability over time. A: CCK-8 assay; B: Observation of HLFs morphology; C: Annexin V-FITC/PI assay. Disclosure of Interests: None declared
Intravenous Delivery of Lung‐Targeted Nanofibers for Pulmonary Hypertension in Mice
Authors: Kathleen Marulanda, Alexandra Mercel, David C. Gillis, Kui Sun, Maria Gambarian, Joshua Roark, Jenna Weiss, Nick D. Tsihlis, Mark R. Karver, S. Ruben Centeno, Erica B. Peters, Tristan D. Clemons, Samuel I. Stupp, Sean E. McLean, Melina R. Kibbe
Journal: Advanced Healthcare Materials (2021)

Pulmonary hypertension is a highly morbid disease with no cure. Available treatments are limited by systemic adverse effects due to non-specific biodistribution. Self-assembled peptide amphiphile (PA) nanofibers are biocompatible nanomaterials that can be modified to recognize specific biological markers to provide targeted drug delivery and reduce off-target toxicity. Here, PA nanofibers that target the angiotensin I-converting enzyme and the receptor for advanced glycation end-products (RAGE) are developed, as both proteins are overexpressed in the lung with pulmonary hypertension. It is demonstrated that intravenous delivery of RAGE-targeted nanofibers containing the targeting epitope LVFFAED (LVFF) significantly accumulated within the lung in a chronic hypoxia-induced pulmonary hypertension mouse model. Using 3D light sheet fluorescence microscopy, it is shown that LVFF nanofiber localization is specific to the diseased pulmonary tissue with immunofluorescence analysis demonstrating colocalization of the targeted nanofiber to RAGE in the hypoxic lung. Furthermore, biodistribution studies show that significantly more LVFF nanofibers localized to the lung compared to major off-target organs. Targeted nanofibers are retained within the pulmonary tissue for 24 h after injection. Collectively, these data demonstrate the potential of a RAGE-targeted nanomaterial as a drug delivery platform to treat pulmonary hypertension.
Deconstructing Current Postpartum Recovery Research—The Need to Contextualize Patient-Reported Outcome Measures
Authors: Ruth Landau
Journal: JAMA Network Open (2021)

Pervez Sultan, MBChB, MD(Res); Nadir Sharawi, MBBS, MSc; Lindsay Blake, MLIS; Kazuo Ando, MD, PhD; Ellile Sultan, BMBS, MMedSci, MSc, CRA; Nima Aghaeepour, PhD; Brendan Carvalho, MBBCh; Nishant Sadana, MBBS, DipMedEd
POS1284 FASCIAL ULTRASOUND: THE CONTEXT FOR DRY NEEDLING TRIGGER POINTS IN TREATMENT OF MYOFASCIAL PAIN, POSTURAL IMBALANCE
Authors: R. Bubnov, L. Kalika
Journal: Annals of the Rheumatic Diseases (2021)

Background: Muscles and fascia are the major source of pain in rheumatic diseases. Dry needling under ultrasound guidance (DN-US) is a crucial therapeutic approach to treat muscle pain [1,2], the definition `myo-fascial` calls for searching trigger points (TrPs) in fascia to improve the treatment effectiveness. Objectives: Aim was to evaluate the relevance of fascial ultrasound for DN-US in myo-fascial pain. Methods: We included 36 patients (21 females, 20-69 years old) with myofascial pain different localisations (low back, limbs, shoulder, neck pain), postural imbalance; did DN-US protocol according to R. Bubnov [1]: trigger points were identified according, fine (28G) steel needle DN-US was applied. Additionally considered fascial structures for detecting areas of abnormalities (hypervascularity, heterogeinity, hypomotility, adhesions) aka `trigger points` and potental nerve compression/irritation and did precise DN-US where appropriate. Results: In all patients movement restored and pain decreaed after muscles DN; in 30 patients additionally we detected and did successful DN-US the major fascial points as follows: thoracolumbar fascia, sacroiliac joint, pelvis ligaments, rotator cuff; potential nerve compressions (e.g., arcade of Frochse, soleus arcade); nerve sheath surrounding nerves (sciatic nerve, brachial plexus) and vessels (thoracic outlet syndrome), smaller fascia, joint capsule thickening. We detected higher rates of motility, improvement postural balance and pain decrease, fewer sessions needed in patients after extensive protocol. Conclusion: Fascia dry needling is accessible and effective method for myo-fascial pain treatment, may provide additional mechanical benefit and help to maintain treatment effect. Affected fascia can be considered as relevant trigger points, specific ultrasound symptoms should be validated. References: [1]Bubnov R Trigger Points Dry Needling Under Ultrasound Guidance for Low Back Pain Therapy. Comparative Study. Annals of the Rheumatic Diseases2015;74:624. http://dx.doi.org/10.1136/annrheumdis-2015-eular.2323 [2]Bubnov R, Kalika L, Babenko L. Dynamic ultrasound for multilevel evaluation of motion and posture in lower extremity and spine. Annals of the Rheumatic Diseases 2018;77:1699. http://dx.doi.org/10.1136/annrheumdis-2018-eular.3949 Disclosure of Interests: None declared
POS1248 SAFETY PROFILE OF PFIZER-BIONTECH COVID-19 VACCINE IN PATIENTS WITH RHEUMATIC DISEASES: PRELIMINARY ASSESSMENT
Authors: G. Cuomo, M. Atteno, C. Naclerio, L. E. Adinolfi, C. Romano
Journal: Annals of the Rheumatic Diseases (2021)

Background: Efficacious vaccines are urgently needed to contain the ongoing coronavirus disease 2019 (Covid-19) pandemic of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). On December 11, 2020, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 vaccine to prevent COVID-19, administered as 2 doses separated by 21 days (1) On December 27, 2020, Italy started use of Pfizer-BioNTech COVID-19 vaccine and initial doses were reserved for health care personnel Objectives: The primary end points were the safety of each administered dose in patients with Rheumatic diseases (RD’s) Methods: In this multicenter, observational study, we interviewed by phone 27 patients with rheumatic diseases (RDs) and 30 healthy subjects receiving the Pfizer-BioNTech vaccine (0.3 ml i.m. in two doses 21 days apart, time 0 and 3 weeks). Results: As of 30 January 2021, 57 subjects (27 patients and 30 healthy subjects) were interviewed. The epidemiological and clinical features of the 27 patients are reported in Table 1. Among the whole population, 35 subjects (16 patients and 19 healthy subjects) complained of an adverse event after the first vaccine dose, with symptom onset occurring within 1 day of vaccination. All adverse events (100%) were classified as nonserious and included: injection site pain (17), fatigue (5), headache (16), fever (3), tachycardia (2), and paresthesia (2). After 21 days, 6 patients and 11 healthy subjects received the second vaccine dose. Fifteen (5 patients and 10 healthy subjects) of them (88%) reported adverse events, again categorized as nonserious. Specifically, injection site pain (7), fatigue (10), headache (10), fever (10), paresthesia (1), cutaneous vasculitis (1), itchy and scratchy throat (1), diarrhea (4), lymph node enlargement (1) were recorded. No differences were noted between patients with RDs and healthy subjects in terms of adverse events. Conclusion: This preliminary study shows that the Pfizer-BioNTech COVID-19 vaccine is as safe in patients with RDs as in healthy subjects. Whether patients with RDs will develop protective titers of anti-SARS-CoV-2 antibodies as compared to healthy subjects will be evaluated in further, ongoing studies. References: [1]Dooling K et al. MMWR Morb Mortal Wkly Rep 2020; 69:1857 Table 1. Acknowledgements: I thank the Italian League of Systemic Sclerosis for launching a survey for ssc patients. Disclosure of Interests: None declared
Evolution of Castration-Resistant Prostate Cancer in ctDNA during Sequential Androgen Receptor Pathway Inhibition
Authors: Matti Annala, Sinja Taavitsainen, Daniel J. Khalaf, Gillian Vandekerkhove, Kevin Beja, Joonatan Sipola, Evan W. Warner, Cameron Herberts, Amanda Wong, Simon Fu, Daygen L. Finch, Conrad D. Oja, Joanna Vergidis, Muhammad Zulfiqar, Bernhard J. Eigl, Christian K. Kollmansberger, Matti Nykter, Martin E. Gleave, Kim N. Chi, Alexander W. Wyatt
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Cross-resistance renders multiple lines of androgen receptor (AR) signaling inhibitors increasingly futile in metastatic castration-resistant prostate cancer (mCRPC). We sought to determine acquired genomic contributors to cross-resistance. Experimental Design: We collected 458 serial plasma cell-free DNA samples at baseline and progression timepoints from 202 patients with mCRPC receiving sequential AR signaling inhibitors (abiraterone and enzalutamide) in a randomized phase II clinical trial (NCT02125357). We utilized deep targeted and whole-exome sequencing to compare baseline and posttreatment somatic genomic profiles in circulating tumor DNA (ctDNA). Results: Patient ctDNA abundance was correlated across plasma collections and independently prognostic for sequential therapy response and overall survival. Most driver alterations in established prostate cancer genes were consistently detected in ctDNA over time. However, shifts in somatic populations after treatment were identified in 53% of patients, particularly after strong treatment responses. Treatment-associated changes converged upon the AR gene, with an average 50% increase in AR copy number, changes in AR mutation frequencies, and a 2.5-fold increase in the proportion of patients carrying AR ligand binding domain truncating rearrangements. Conclusions: Our data show that the dominant AR genotype continues to evolve during sequential lines of AR inhibition and drives acquired resistance in patients with mCRPC.
POS1110 RELIABILITY OF VERTEBRAL FRACTURE ASSESSMENT ON DUAL-ENERGY X-RAY ABSORPTIOMETRY
Authors: M. Yasmine, S. Mariem, S. Miladi, A. Fazaa, E. Fguiri, L. Souebni, K. Ouenniche, S. Kassab, S. Chekili, K. Ben Abdelghani, A. Laatar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Vertebral Fracture Assessment (VFA) is a new feature available on modern densitometers. Yet, the assessment of vertebral fracture (VF) status has not become standard practice. Objectives: Our study aimed to evaluate the reliability of VFA as assessed by a rheumatologist and a radiology technician. Methods: We conducted a cross-sectional study assessing the performance of low-radiation single energy x-ray absorptiometry VFA for the detection of VF. We selected patients who were assessed for osteoporosis according to screening protocols. Bone mineral densitometry was measured using standard methods over the lumbar spine L1-L4, the total proximal femur, and results were expressed as T-scores. All VFA were independently evaluated by 2 experienced readers: a rheumatologist and a radiology technician for the identification of VF (T4-L4). VF was classified according to the Genant grading system: grade 1 for an anterior, mid or posterior reduction of 20–25% in vertebral height; grade 2 for a reduction of 25– 40% and grade 3 for a reduction of more than 40% in vertebral height. A score for the inter-rater reliability between the readers was expressed using the kappa statistic. Results: One hundred patients were included with a mean age of 66.9 ± 9.5 years [46.7-83] years. There was a female predominance (91%). Nearly half of patients had osteopenia (48.9%), 27.7% had osteoporosis and 23.4% had a normal bone mineral density. On VFA scans, the non-visible vertebra was mostly located in the upper thoracic spine (60%). The mean number of VF was 1.2 [0-3] for both readers. According to the doctor’s evaluation, 25% of patients had at least one VF, of which 75.9% had a Genant grade 1, 17.2% had a Genant 2, and 6.9% had a VF grade 3. According to the technician evaluation, at least one VF was found in 36% of patients. A grade 1 was assessed in 91.7% of cases, a grade 2 in 8.3% of patients but no VF grade 3 was assessed. A kappa score for the inter-rater reliability between the readers for VFA was 0.545 (p=0.000). The overall agreement by grade between the readers was 0.785 (p=0,000). The exclusion of non-visible vertebra resulted in a better agreement (k=0.853). Further analysis excluding vertebra T4 to D10, revealed a very good agreement (k=0.9). Conclusion: Our study showed a low agreement between the readers on VFA and a better agreement when non-visible vertebrae were excluded. Thus, caution should be advocated when relying exclusively on this device. Disclosure of Interests: None declared.
Bromodomain protein BRD4 directs and sustains CD8 T cell differentiation during infection
Authors: J. Justin Milner, Clara Toma, Sara Quon, Kyla Omilusik, Nicole E. Scharping, Anup Dey, Miguel Reina-Campos, Hongtuyet Nguyen, Adam J. Getzler, Huitian Diao, Bingfei Yu, Arnaud Delpoux, Tomomi M. Yoshida, Deyao Li, Jun Qi, Adam Vincek, Stephen M. Hedrick, Takeshi Egawa, Ming-Ming Zhou, Shane Crotty, Keiko Ozato, Matthew E. Pipkin, Ananda W. Goldrath
Journal: The Journal of Experimental Medicine (2021)

In response to infection, pathogen-specific CD8 T cells differentiate into functionally diverse effector and memory T cell populations critical for resolving disease and providing durable immunity. Through small-molecule inhibition, RNAi studies, and induced genetic deletion, we reveal an essential role for the chromatin modifier and BET family member BRD4 in supporting the differentiation and maintenance of terminally fated effector CD8 T cells during infection. BRD4 bound diverse regulatory regions critical to effector T cell differentiation and controlled transcriptional activity of terminal effector–specific super-enhancers in vivo. Consequentially, induced deletion of Brd4 or small molecule–mediated BET inhibition impaired maintenance of a terminal effector T cell phenotype. BRD4 was also required for terminal differentiation of CD8 T cells in the tumor microenvironment in murine models, which we show has implications for immunotherapies. Taken together, these data reveal an unappreciated requirement for BRD4 in coordinating activity of cis regulatory elements to control CD8 T cell fate and lineage stability.
Impact of COVID-19 on cancer care in India: a cohort study
Authors: Priya Ranganathan, Manju Sengar, Girish Chinnaswamy, Gaurav Agrawal, Rajkumar Arumugham, Rajiv Bhatt, Ramesh Bilimagga, Jayanta Chakrabarti, Arun Chandrasekharan, Harit Kumar Chaturvedi, Rajiv Choudhrie, Mitali Dandekar, Ashok Das, Vineeta Goel, Caleb Harris, Sujai Kolnadguthu Hegde, Narendra Hulikal, Deepa Joseph, Rajesh Kantharia, Azizullah Khan, Rohan Kharde, Navin Khattry, Maqbool M Lone, Umesh Mahantshetty, Hemant Malhotra, Hari Menon, Deepti Mishra, Rekha A Nair, Shashank J Pandya, Nidhi Patni, Jeremy Pautu, Simon Pavamani, Satyajit Pradhan, Subramanyeshwar Rao Thammineedi, G Selvaluxmy, Krishna Sharan, B K Sharma, Jayesh Sharma, Suresh Singh, Gowtham Chandra Srungavarapu, R Subramaniam, Rajendra Toprani, Ramanan Venkat Raman, Rajendra Achyut Badwe, C S Pramesh
Journal: The Lancet Oncology (2021)