tbuckley/cabot-search huggingface dataset:
AODTU-002 Per oral endoscopic myotomy: updated results from a uk case series
Authors: S Gulati, A Emmanuel, H Inoue, A Haji, B Hayee
Journal: Gut (2017)

Introduction  Per-oral endoscopic myotomy (POEM) has been adopted as a minimally invasive treatment option for achalasia and even spastic oesophageal conditions. The first case of POEM was performed at the King’s Institute of Therapeutic Endoscopy (KITE) in 2013. Here we present our updated UK case series including the first UK case of diffuse oesophageal spasm (DES).  Method  Prospective data was collected for consecutive patients undergoing POEM including demographics, technique, use of Endoluminal Functional Lumen Imaging Probe (EndoFLIP) and adverse events. Clinical success was defined as a reduction of Eckardt score (ES) to ≤2 or by 4 points. Follow up data at 3 and 12–24 months (m) post-POEM was analysed using the Wilcoxon signed ranks test to compare pre- and post-POEM ES, 4sIRP and pre and post-treatment GORD-HRQoL score. Repeated-measures ANOVA was used for multiple time-point comparisons.  Results  POEM was performed in 51 patients (22F, age 48.6+/-13.5 years). Median gastric and oesophageal myotomy was 3 cm (2-4) and 10(3-18) respectively with selective circular myotomy in all cases and posterior approach in 11. POEM was clinically successful in n=41/44 (93%) eligible for review at 3m. Reduction in ES at 3m; 8.5 (5–12) vs 0 (0–6) p  Pre and post-myotomy EndoFLIP showed an increase in oesophago-gastric junction diameter from 5.87 to 11.27.27 mm(p  Median post-POEM GORD-HRQoL score (n=41) was 1 (0–31). 8 patients with scores>12 improved with conservative treatment; 15.5 (13–31) vs 6.5 (1–11, p=0.0078) as did 5 cases of acid reflux identified by 24 hr pH testing in n=19 at time of analysis.  Endoclip displacement was encountered in n=2 and replaced endoscopically including readmission of 1 patient for delayed mucosal incision site healing (Clavien-Dindo Grade IIIb). There were no cases of mortality, perforation, infection/major bleeding.  Conclusion  This is the largest UK case series of POEM for achalasia including the first successful UK POEM procedure for DES. At our institute, POEM was performed successfully in a potentially more challenging cohort where 52.9% had prior treatment. Our results are in line with international consortia and ASGE1 findings that POEM is a safe and efficacious procedure for the treatment of achalasia and oesophageal spastic disorders for both short term and sustained symptomatic benefit.  Reference  . Stavropoulos S, Desilets D, Fuchs KHet al; Per-oral endoscopic myotomy white paper summary; Gastrointestinal Endoscopy; 2014;1:1–15  Disclosure of Interest  None Declared
Palliative Care for Persons Living With Parkinson Disease
Authors: Leonard L. Sokol, Benzi M. Kluger
Journal: JAMA (2020)

Benzi M. Kluger, MD; Janis Miyasaki, MD; Maya Katz, MD; Nicholas Galifianakis, MD; Kirk Hall, MBA; Steven Pantilat, MD; Ryan Khan, MDiv; Cari Friedman, LCSW; Wendy Cernik, BSN; Yuika Goto, MD; Judith Long, MS; Diane Fairclough, DrPH; Stefan Sillau, PhD; Jean S. Kutner, MD
Efficacy, immunogenicity, and safety of a plant-derived, quadrivalent, virus-like particle influenza vaccine in adults (18–64 years) and older adults (≥65 years): two multicentre, randomised phase 3 trials
Authors: Brian J Ward, Alexander Makarkov, Annie Séguin, Stéphane Pillet, Sonia Trépanier, Jiwanjeet Dhaliwall, Michael D Libman, Timo Vesikari, Nathalie Landry
Journal: The Lancet (2020)
The Functional Landscape of Patient-Derived RNF43 Mutations Predicts Sensitivity to Wnt Inhibition
Authors: Jia Yu, Permeen A. Mohamed Yusoff, Daniëlle T.J. Woutersen, Pamela Goh, Nathan Harmston, Ron Smits, David M. Epstein, David M. Virshup, Babita Madan
Journal: Cancer Research (2020)

A subset of Wnt-addicted cancers are sensitive to targeted therapies that block Wnt secretion or receptor engagement. RNF43 loss-of-function (LOF) mutations that increase cell surface Wnt receptor abundance cause sensitivity to Wnt inhibitors. However, it is not clear which of the clinically identified RNF43 mutations affect its function in vivo. We assayed 119 missense and 45 truncating RNF43 mutations found in human cancers using a combination of cell-based reporter assays, genome editing, flow cytometry, and immunofluorescence microscopy. Five common germline variants of RNF43 exhibited wild-type activity. Cancer-associated missense mutations in the RING ubiquitin ligase domain and a subset of mutations in the extracellular domain hyperactivate Wnt/β-catenin signaling through formation of inactive dimers with endogenous RNF43 or ZNRF3. RNF43 C-terminal truncation mutants, including the common G659fs mutant are LOF specifically when endogenous mutations are examined, unlike their behavior in transient transfection assays. Patient-derived xenografts and cell lines with C-terminal truncations showed increased cell surface Frizzled and Wnt/β-catenin signaling and were responsive to porcupine (PORCN) inhibition in vivo, providing clear evidence of RNF43 impairment. Our study provides potential guidelines for patient assignment, as virtually all RNF43 nonsense and frameshift mutations, including those in the C-terminal domain and a large number of patient-associated missense mutations in the RING domain and N-terminal region compromise its activity, and therefore predict response to upstream Wnt inhibitors in cancers without microsatellite instability. This study expands the landscape of actionable RNF43 mutations, extending the benefit of these therapies to additional patients. SIGNIFICANCE: Systematic examination of patient-derived RNF43 mutations identifies rules to guide patient selection, including that truncation or point mutations in well-defined functional domains sensitize cancers to PORCN inhibitors.
Frequency-dependent attenuation reconstruction with an acoustic reflector
Authors: Richard Rau, Ozan Unal, Dieter Schweizer, Valery Vishnevskiy, Orcun Goksel
Journal: Medical Image Analysis (2020)

Attenuation of ultrasound waves varies with tissue composition, hence its estimation offers great potential for tissue characterization and diagnosis and staging of pathology. We recently proposed a method that allows to spatially reconstruct the distribution of the overall ultrasound attenuation in tissue based on computed tomography, using reflections from a passive acoustic reflector. This requires a standard ultrasound transducer operating in pulse-echo mode and a calibration protocol using water measurements, thus it can be implemented on conventional ultrasound systems with minor adaptations. Herein, we extend this method by additionally estimating and imaging the frequency-dependent nature of local ultrasound attenuation for the first time. Spatial distributions of attenuation coefficient and exponent are reconstructed, enabling an elaborate and expressive tissue-specific characterization. With simulations, we demonstrate that our proposed method yields a low reconstruction error of 0.04 dB/cm at 1 MHz for attenuation coefficient and 0.08 for the frequency exponent. With tissue-mimicking phantoms and ex-vivo bovine muscle samples, a high reconstruction contrast as well as reproducibility are demonstrated. Attenuation exponents of a gelatin-cellulose mixture and an ex-vivo bovine muscle sample were found to be, respectively, 1.4 and 0.5 on average, consistently from different images of their heterogeneous compositions. Such frequency-dependent parametrization could enable novel imaging and diagnostic techniques, as well as facilitate attenuation compensation of other ultrasound-based imaging techniques.
SP0127 Prioritisation of patients with inflammatory arthritis – a nurse led pre-assessment clinic
Authors: H Groeneveld
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> It is now widely accepted that Rheumatoid Arthritis should be treated with disease modifying anti-rheumatic drugs (DMARDs) early in the disease process,<sup>1–4</sup> in order to reduce the incidence of erosive change, and improve long term outcome.<sup>5</sup> A national Clinical Guideline for Scotland<sup>6</sup> has recently been published, which advocates that all patients with disease duration greater than 6–8 weeks "should be considered for referral for Specialist rheumatology opinion and DMARD therapy, preferably within 12 weeks". This course of action should, if followed, lead to the early diagnosis and treatment of patients with inflammatory arthritis. There are, however, two inherent difficulties for hospital rheumatology services. Firstly, even if the referral is made promptly, many referral letters contain insufficient clinical information for the Consultant Rheumatologist to determine from the letter whether or not the patient has inflammatory arthritis. Secondly, in many services the waiting time for a first appointment with a consultant is several months long, thus negating the benefit of an early referral. In an initiative to identify those patients who would benefit from early diagnosis and treatment, a nurse-led rheumatology Pre-assessment clinic was developed in Wolverhampton. This was run by an experienced Rheumatology Specialist Nurse, supported and supervised by a Consultant Rheumatologist, and complied with professional<sup>7,8</sup> and legal guidelines for nursing practice within the UK. It has been found that the clinic has been effective in identifying patients with inflammatory arthritis and expediting the commencement of DMARD treatment. <h3>References</h3> Emery P. The Roche Rheumatology Prize Lecture. The optimal management of early rheumatoid disease: the key to preventing disability. Br J Rheumatol. 1994;33:765–8 Emery P. Therapeutic approaches for early rheumatoid arthritis. How early? How aggressive? Br J Rheumatol. 1995;34(Suppl 2):87–90 Hochberg MC. Early aggressive DMARD therapy. The key to slowing disease progression in rheumatoid arthritis. Scand J Rheumatol Suppl. 1999;112:3–7 Irvine S, Munro R, Potter D. Early referral, diagnosis and treatment of rheumatoid arthritis: evidence for changing medical practice. Ann Rheum Dis. 1999;58(8):510–13 Symmon DP, Jones MA, Scott DL, Prior P. Long term mortality outcome in patients with rheumatoid arthritis: early presenters tend to do well. J Rheumatol. 1998;25:1072–7 Scottish Intercollegiate Guidelines network<i>. Management of early rheumatoid arthritis</i>. Edinburgh: Royal College of Physicians, 2000 The Scope of Professional Practice. United Kingdom Central Council for Nursing, Midwifery and Health Visiting, London, 1992 Code of Professional Conduct. United Kingdom Central Council for Nursing, Midwifery and Health Visiting, London, 1992
Abstract 17333: Myeloid-Specific Deletion of Epsins 1 and 2 Reduces Atherosclerosis by Preventing LRP-1 Downregulation
Authors: Hong Chen, Megan Brophy
Journal: Circulation (2018)

Introduction: Atherosclerosis is in part caused by immune and inflammatory cell infiltration into the vascular wall, leading to enhanced inflammation and lipid accumulation in the aortic endothelium. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity. Given the fundamental contribution lesion macrophages make to fuel atherosclerosis, whether and how myeloid specific epsins promote atherogenesis is an open and significant question. Hypothesis: We hypothesize that myeloid specific epsins regulate lesion macrophage function during atherosclerosis. Methods and Results: We engineered myeloid cell-specific epsins double knockout mice (LysM-DKO)on an ApoE -/- background. On Western diet, these mice exhibited marked decrease in atherosclerotic lesion formation, diminished immune and inflammatory cell content in aortas, and reduced necrotic core content but increased smooth muscle cell content in aortic root sections.Epsins deficiency hindered foam cell formation and suppressed the pro-inflammatory macrophage phenotype but increased efferocytosis and the anti-inflammatory macrophage phenotype in primary macrophages.Mechanistically, we show that epsins loss specifically increased total and surface levels of LRP-1, an efferocytosis receptor with anti-atherosclerotic properties. We further show thatepsin and LRP-1 interact via epsin’s Ubiquitin Interacting Motif (UIM) domain. Oxidized LDL treatment increased LRP-1 ubiquitination and subsequent binding to epsin while mutation of cytoplasmic lysine residues attenuated LRP-1 ubiquitination, suggesting that epsins promote the ubiquitin-dependent internalization and downregulation of LRP-1. Crossing ApoE -/- /LysM-DKO mice onto a LRP-1 heterozygous background restored, in part, atherosclerosis, suggesting that epsin-mediated LRP-1 downregulation in macrophages plays a pivotal role in propelling atherogenesis. Conclusions: Myeloid epsins promote atherogenesis by facilitating pro-inflammatory macrophage recruitment and inhibiting efferocytosis in part by downregulating LRP-1, implicating that targeting epsins in macrophages may serve as a novel therapeutic strategy to treat atherosclerosis. Key words: epsin, macrophage, atherosclerosis, LRP-1, inflammation, efferocytosis
73P Anti-angiokinases in patient-specific combination regimens can improve outcomes in advanced metastatic cancers
Authors: D. Patil, D. Akolkar, N. Srivastava, V. Datta, S. Schuster, C. Bose, J. Bhatia, A. Ghaisas, C. Sims, R. Patil, S. Patil, S. Apurwa, V. Mhase, S. Pawar, P. Devhare, J. John, R. Gosavi, A. Srinivasan, R. Datar
Journal: Annals of Oncology (2020)
A novel small molecular inhibitor targets the MDM2-p53 interaction significantly reducing cell viability in both embryonal and alveolar rhabdomyosarcoma cells with wild-type p53.
Authors: Jason Canner, Ke Ding, Shaomeng Weng, Dajun Yang, Jiayuh Lin
Journal: Cancer Research (2007)

509  The interruption of p53’s role in apoptosis and DNA repair is known to be one of the major mechanisms by which cancer cells evade current therapy and continue to proliferate. When the normal balance between the MDM2 protein and p53 is disrupted, MDM2 upregulation specifically inhibits p53’s ability to activate appropriate signaling pathways and necessary cell death and/or repair. Targeting MDM2 specifically has shown promise for improvement in cancer therapy. By blocking the interaction between the abnormal MDM2 and wild-type p53 in cancer cells, reactivation of the p53 tumor suppressor protein function has led to successful cell death. MI-63 is a novel non-peptide small molecule that has shown strong binding affinity (Ki=3nM) for the MDM2 protein initiating an increase in p53 protein concentration and cell death in prostate cancer cell lines with wild-type p53. The effect of MI-63 on pediatric cancer cells and the specific mechanism of the tumor suppressor reactivation has not been evaluated. Rhabdomyosarcoma is the most common childhood soft tissue sarcoma. Both subtypes, embryonal and alveolar rhabdomyosarcoma cells with wild-type p53, RH36 and RH18 respectively, were cultured in RPMI. Multiple concentrations of MI-63 dissolved in DMSO, were added to cell cultures and cell viability was evaluated by MTT analysis at 24, 48 and 72 hours. Treatment with MI-63 at both 5 and 10µM concentrations was successful in reducing cell viability in both RH36 and RH18 cell lines in vitro. RH36 cells treated with 5µM MI-63 showed cell viability of 13.4% at 72 hours and RH18 cells treated similarly displayed a cell viability of
Impact of Oral Voriconazole As Prophylaxis during Intensive Chemotherapy for Adult Patients with Acute Myeloid Leukemia: A Retrospective Cohort Study Using Japanese Administrative Database
Authors: Ikuyo Ota Tsutsumi, Chikashi Yoshida, Masanori Seki, Takuya Komeno, Susumu Kunisawa, Kiyohide Fushimi, Yuichi Imanaka
Journal: Blood (2017)
68Ga-PSMA PET/CT With Incidental Finding of COVID-19 in an Asymptomatic Patient
Authors: Sarai Morón, Eliana González, Julián Rojas
Journal: Clinical Nuclear Medicine (2020)

Abstract A 70-year-old man with prostate adenocarcinoma was diagnosed by transrectal biopsy, with Gleason of 4 + 5 and initial PSA of 225 ng/mL since March 2020. 68 Ga-PSMA PET/CT was performed as part of initial staging. The images showed an enlarged prostate with focal PSMA uptake in both lobes. Retroperitoneal and pelvic lymph nodes with moderate uptake of PSMA were shown. Another finding was a moderate PSMA uptake in the both lung parenchymas associated with opacities in CT. The patient denied any symptoms of coronavirus disease and was referred to the emergency department for RT-PCR COVID-19, and the result was positive.
18F-FDG PET/CT of Double Expressor High-Grade B-Cell Lymphoma in an Isolated Chest Wall Mass
Authors: Punit Sharma
Journal: Clinical Nuclear Medicine (2020)

F-FDG PET/CT is now an integral part of management of high-grade B-cell lymphoma. It is used for staging, response evaluation, restaging, and surveillance. Although high-grade B-cell lymphoma most commonly presents with involvement of the lymph nodes, spleen, liver, and bone marrow, chest wall involvement is very rare. We present the staging F-FDG PET/CT findings in a case of an 82-year-old woman with double expressor high-grade B-cell lymphoma of isolated presternal anterior chest wall mass.
Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells
Authors: Jake R. Thomas, Anna Appios, Xiaohui Zhao, Roksana Dutkiewicz, Maria Donde, Colin Y.C. Lee, Praveena Naidu, Christopher Lee, Joana Cerveira, Bing Liu, Florent Ginhoux, Graham Burton, Russell S. Hamilton, Ashley Moffett, Andrew Sharkey, Naomi McGovern
Journal: The Journal of Experimental Medicine (2020)

Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.
Australian GP registrars forced to re-sit exam after IT malfunction
Authors: Paul Smith
Journal: BMJ (2020)

Over 1400 general practice registrars in Australia are being forced to re-sit their fellowship exams after the online test they were taking at home was aborted following an IT malfunction.

Most specialist trainees in Australia are in limbo, having been unable to sit college exams since March because of the covid-19 pandemic. The Royal Australian College of General Practitioners (RACGP) believed it could, however, overcome the social restrictions on mass gatherings by running its written fellowship exams online. On 9 October, registrars at home logged on to their key feature problem exam, scrutinised on webcams by a team of proctors employed by the college’s exam provider Genix Ventures.1

Technical problems reportedly began within 40 minutes when the video conferencing system crashed. Registrars reported being alone in their rooms with little information …
Abstract 11863: Provider Perspectives on Smartwatch Monitoring for Atrial Fibrillation
Authors: Eric Y Ding, Emily Dickson, Daniella Albuquerque, Jane S Saczynski, Ki Chon, David D McManus
Journal: Circulation (2019)

Introduction: Adoption of mobile technologies among older adults is rising. Several commercially available smartwatches are FDA cleared for atrial fibrillation (AF) detection and marketed towards o...
Allogeneic Stem Cell Transplantation for the Treatment of Lymphoproliferative Disorders in Patients Affected By Primary Immunodeficiencies: The UK Experience
Authors: Giulia Prunotto, Giovanna Lucchini, Sujith Samarasinghe, Robert Wynn, Ajay Vora, Ben Carpenter, Claire Gowdy, Kieran Mchugh, Andrew Gennery, Paul Veys, Christopher Bacon, Simon Bomken
Journal: Blood (2017)
Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy
Authors: Florian Moik, Wei-Shin Evelyn Chan, Sarah Wiedemann, Christoph Hoeller, Felix Tuchmann, Marie-Bernadette Aretin, Thorsten Fuereder, Sabine Zöchbauer-Müller, Matthias Preusser, Ingrid Pabinger, Cihan Ay
Journal: Blood (2020)
AB0894 OBSERVANCE OF ZOLEDRONIC ACID INFUSION. A RETROSPECTIVE 3 YEARS STUDY
Authors: J. Zalc, G. Camille, B. Lisa, J. Chloé, B. Frédéric
Journal: Annals of the Rheumatic Diseases (2020)

Background: Osteoporosis is a public health issue. Lack of therapeutic compliance is often a problem in the treatment of osteoroposis, with potentially dramatic consequences. No studies have evaluated the observance of zoledronic acid infusion after 3 years, the time of the therapeutic reassessment. Objectives: The main objective of assessing the level of compliance was to evaluate the level of zoledronic acid infusion adherence at 1, 2 and 3 year periods, in a cohort of osteoporotic patients on discharge from Begin hospital, following treatment for fracture caused by low-energy trauma. The first infusion was prescribed by rheumatologists, with the following infusions to be prescribed by general practitioners. Methods: We performed a retrospective observational study initially conducted by written and telephone questionnaires on a population of patients hospitalized in the rheumatology department of HIA Bégin for an osteoporotic fracture. Data was collected between July 2015 and December 2018. A first letter, containing a stamped addressed envelope to the Bégin hospital for ease of reply, was sent to the patients selected for the study. The protocol had to be modified following a very low response rate, unaided by bad quality addresses. We then tried to contact the patients by phone 3 times and, if unable to reach them, we called their general practitioners on 3 occasions. Results: 94 patients were initially selected. Every year, we retained within the study patients who had followed their annual zoledronic acid infusion protocol. Taking into account all 94 patients, adherence level for the first infusion was 41.4%, down to 29.7% for the second infusion and down to 12.8% for the third infusion. For those who had the first infusion performed, adherence level for the second infusion was 71.8%, down to 30.8% for the third infusion. Conclusion: The observance and follow-up of zoledronic acid infusion in France by general practitioners is not adequate. Follow-up measures on an annual basis by the rheumatologist could significantly improve adherence. References: [1]Curtis JR et al. Adherence with intravenous zoledronate and intravenous ibandronate in the United States Medicare population. Arthritis care &amp; research. 2012;64:1054-60. [2]Jaleel A et al. Improving drug adherence in osteoporosis: an update on more recent studies. Therapeutic advances in musculoskeletal disease. 2018;10:141-9. Acknowledgments: None Disclosure of Interests: None declared