tbuckley/cabot-search huggingface dataset:
AB0776 MULTIPLE AUTOIMMUNE SYNDROME
Authors: A. Fraj, S. Arfa, O. Jomaa, F. Boubaker, I. Bannour, O. Berriche, H. Sfar
Journal: Annals of the Rheumatic Diseases (2021)

Background: Multiple autoimmune syndrome (MAS) is a rare entity, defined by the association of three autoimmune diseases in the same patient. MAS can be classified into three groups. Objectives: The objective of this work was to describe the autoimmune diseases profile in MAS in An Internal Medicine Department. Methods: We report a retrospective analysis including 14 cases of MAS seen in The Internal Medicine Department at Taher Sfar Hospital, Mahdia, TUNISIA over a period of 10 years. Results: We followed 14 patients with MAS. They were 14 women. The mean age of patients was 52 years. SAM was type 3 in 12 patients (85%), type 2 in one patient (7.1%) and one patient satisfied both type 2 and type 3 MAS criteria (7.1%). No cases of MAS type 1 had been reported. We found 13 patients with 3 associated autoimmune diseases and one patient with 4 associated autoimmune diseases. The autoimmune diseases were: Sjögren’s syndrome in 14 patients (100%), Hashimoto’s thyroiditis in 11 cases (78%), systemic lupus erythematosus in 7 cases (50%), Addison’s disease in 4 cases (28, 5%), scleroderma, thymoma, vitiligo, Biermer and primary biliary cholangitis each in one case (7.1%). Conclusion: Multiple autoimmune syndrome remains a rare but probably under-diagnosed entity. Thus, in patients with autoimmune disease, initial investigation and follow-up of clinical signs and biological stigmas of other autoimmune diseases should be cautious. Disclosure of Interests: None declared
GM-CSF mediates immune evasion via upregulation of PD-L1 expression in extranodal natural killer/T cell lymphoma
Authors: Qi-xiang Rong, Fang Wang, Zhi-xing Guo, Yi Hu, Sai-nan An, Min Luo, Hong Zhang, Shao-cong Wu, Hui-qiang Huang, Li-wu Fu
Journal: Molecular Cancer (2021)

Abstract Background Granulocyte-macrophage colony stimulating factor (GM-CSF) is a cytokine that is used as an immunopotentiator for anti-tumor therapies in recent years. We found that some of the extranodal natural killer/T cell lymphoma (ENKTL) patients with the treatment of hGM-CSF rapidly experienced disease progression, but the underlying mechanisms remain to be elucidated. Here, we aimed to explore the mechanisms of disease progression triggered by GM-CSF in ENKTL. Methods The mouse models bearing EL4 cell tumors were established to investigate the effects of GM-CSF on tumor growth and T cell infiltration and function. Human ENKTL cell lines including NK-YS, SNK-6, and SNT-8 were used to explore the expression of programmed death-ligand 1 (PD-L1) induced by GM-CSF. To further study the mechanisms of disease progression of ENKTL in detail, the mutations and gene expression profile were examined by next-generation sequence (NGS) in the ENKTL patient’s tumor tissue samples. Results The mouse-bearing EL4 cell tumor exhibited a faster tumor growth rate and poorer survival in the treatment with GM-CSF alone than in treatment with IgG or the combination of GM-CSF and PD-1 antibody. The PD-L1 expression at mRNA and protein levels was significantly increased in ENKTL cells treated with GM-CSF. STAT5A high-frequency mutation including p.R131G, p.D475N, p.F706fs, p.V707E, and p.S710F was found in 12 ENKTL cases with baseline tissue samples. Importantly, STAT5A-V706fs mutation tumor cells exhibited increased activation of STAT5A pathway and PD-L1 overexpression in the presence of GM-CSF. Conclusions These findings demonstrate that GM-CSF potentially triggers the loss of tumor immune surveillance in ENKTL patients and promotes disease progression, which is associated with STAT5 mutations and JAK2 hyperphosphorylation and then upregulates the expression of PD-L1. These may provide new concepts for GM-CSF application and new strategies for the treatment of ENKTL.
Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection
Authors: Louis Bernard, Cédric Arvieux, Benoit Brunschweiler, Sophie Touchais, Séverine Ansart, Jean-Pierre Bru, Eric Oziol, Cyril Boeri, Guillaume Gras, Jérôme Druon, Philippe Rosset, Eric Senneville, Houcine Bentayeb, Damien Bouhour, Gwenaël Le Moal, Jocelyn Michon, Hugues Aumaître, Emmanuel Forestier, Jean-Michel Laffosse, Thierry Begué, Catherine Chirouze, Fréderic-Antoine Dauchy, Edouard Devaud, Benoît Martha, Denis Burgot, David Boutoille, Eric Stindel, Aurélien Dinh, Pascale Bemer, Bruno Giraudeau, Bertrand Issartel, Agnès Caille
Journal: New England Journal of Medicine (2021)

The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear.
POS1115 DESCRIPTIVE STUDY OF THE PERCEPTIONS AND PREVENTIVE PRACTICES OF POSTMENOPAUSAL TUNISIAN WOMEN REGARDING OSTEOPOROSIS
Authors: S. Ben Jemaa, Y. Mejdoub, H. Fourati, J. Damak, S. Baklouti
Journal: Annals of the Rheumatic Diseases (2021)

Background: Due to their serious consequences affecting quality of life, prevention of osteoporosis is considered a priority. Thus, identifying the level of knowledge is useful in developing effective interventions and in guiding public health programs to prevent osteoporosis. Objectives: The aim of this study is to describe beliefs and practices of menopaused Tunisian women related to health and osteoporosis in order to develop effective and targeted interventions for the prevention of this disease. Methods: A descriptive cross-sectional study was conducted among menopaused Tunisian women who consult the basic health center in the area of Sfax region in Tunisia. Data collection include socio-demographic characteristics, the “osteoporosis health belief scale” developed by Kim and his colleagues and the daily calcium intake which was calculated by a questionnaire developed by Patrice Fardellone. Results: We have included 170 women. The mean age was 58.92 ± 9.07 years. Seventy-seven percent of women were housewives, 14.7% were active and 8.3% were retired. Seventy-five percent were married. Forty-two women (24.7%) were illiterate, sixty-three (37.1%) were at primary level and 33.5% were at secondary level. One hundred twelve women (65.3%) live in an urban environment, against 34.7% who belong to a rural environment. The level of perception of osteoporosis was very altered in 22.9%, altered in 32.4% and moderately altered in 31.8% of women. Women’s perceptions of the benefits of physical exercise and calcium intake were moderately altered in 42.4% and 51.2%, respectively. For obstacles to the practice of physical exercise, the level of perception was altered in 43.5% of women. Regarding the obstacles to calcium intake, the perceptions of our population were altered in 32.9% of cases. The daily intakes of calcium vary from 215 to 1444 mg per day with an average of 620.20 ± 204.523 mg / day. Only eight women (4.7%) had sufficient daily intake. Conclusion: Our study showed that all subscale of the “osteoporosis health belief scale” were altered. Promotion programs should aim at creating a supportive physical and social environment for the adoption of safer behaviors and especially education must be targeted. References: [1]Belgacem, A. Nouira, et S. Soussi, « Les perceptions des femmes tunisiennes selon le modèle des croyances liées à la santé et leurs pratiques relativement à l’ostéoporose », Pan Afr Med J, vol. 23, 2016. [2]H. Ahmadieh, A. Basho, A. Chehade, A. Al Mallah, et A. Dakour, « Perception of peri-menopausal and postmenopausal Lebanese women on osteoporosis: A cross-sectional study », Journal of Clinical &amp; Translational Endocrinology, vol. 14, p. 19-24, déc. 2018. Disclosure of Interests: None declared.
AB0637 THE STATE OF GOUT MANAGEMENT IN WALES RHEUMATOLOGY UNITS
Authors: M. Saleh
Journal: Annals of the Rheumatic Diseases (2021)

Background: Gout is the most common inflammatory arthritis with both the prevalence and incidence showed significant rise in the UK in recent years 1 . The most frequent reasons for referral from primary care were diagnostic uncertainty 54%, failure to respond to primary care management 28%, and complex comorbidity 25% 2 . From primary care perspective, increased urate level (p=0.0001), young age (p=0.009), fewer comorbidities (p=0.039) constituted the most common risk for gout General Practice consultations and in addition to poor compliance to urate lowering treatment ULT (p=0.004) and lower CVS risk scores (p=0.038) these all factors comprised the independent risk factors for Gout flares 3 . Objectives: To compare the management of gout in the rheumatology services in Wales against the 2017 British Society for Rheumatology (BSR) Guidelines. Methods: •A descriptive study over an 8-week period from January to February 2019, used Simple Analysis in calculating the frequency (%). •Data were collected from notes of 79 patients referred to rheumatology departments across Wales using the British Society for Rheumatology (BSR) 2017 Gout Guidelines Audit Tool. •The audit cohort comprised 62% of chronic gout patients and 38% of acute admissions. Results: Conclusion: •Gout management by rheumatologists across Wales concords well with the recent BSR guidelines for most audit standards and showed an improvement in percentage of patients who achieved a target serum uric acid level &lt;300 and &lt;360 umol/L according to the BSR and EULAR guidelines, respectively. •Areas for improvement include documentation of Patient Education, improvement of audit tool (Age, Alcohol, current ULT). •To spread the message to primary care setting, where gout is predominantly managed, to ensure that ULT is optimized to achieve target serum uric acid level to benefit patients. References: [1]Kuo C, Grainge MJ, Mallen C , et al Rising burden of gout in the UK but continuing suboptimal management: a nationwide population study, Annals of the Rheumatic Diseases 2015; 74: 661-667. [2]*Management of gout by UK rheumatologists: a British Society for Rheumatology national audit. Roddy E, Packham J, Obrenovic K, Rivett A, Ledingham JM.Rheumatology (Oxford). 2018 May 1; 57(5):826-830. [3]Callear J, Blakey G, Callear A , et al Gout in primary care: Can we improve patient outcomes? BMJ Open Quality 2017;6:u210130.w4918. doi: 10.1136/bmjquality.u210130.w4918 Acknowledgements: Dr Martin Bevan for supervising the work and Rheumatology Units across Wales for collecting data and the British Society for Rheumatology in formulating the audit tool. Disclosure of Interests: None declared.
AB0110 DETERMINING THE AMOUNT OF COPPER–CONTAINING PROTEIN, ITS BIOCHEMICAL AND IMMUNOLOGIC ACTIVITY IN RHEUMATOID ARTHRITIS PATIENTS
Authors: O. Rusanova, A. Trofimenko, N. Emelyanov, O. Emelyanova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Production of antibodies to ceruloplasmin (CP) in rheumatoid arthritis is an issue that has not been studied well enough. It was not by chance that this copper–containing alpha 2-glycorpoteid of blood plasma showing multienzymatic properties was chosen as an object of investigation. Data on the content and activity of CP in the blood of rheumatoid arthritis patients are contradictory, which has to do with different approaches to selection of patients and different measuring methods. Objectives: Improving diagnosis of rheumatoid arthritis by determination of antibodies to CP as well as its amount and enzymatic activity. Methods: We studied the serum from 30 apparently healthy individuals, and 108 rheumatoid arthritis patients. Antibodies to CP were determined by enzyme immunoassay using immobilized granulated antigen preparations (modification by Gontar et al, 2002). The amount of CP was determined by enzyme immunoassay according to the method of I.S. Kuzmina et al (1991) using commercial diagnostic agent manufactured by Mechnikov Research Institute for Vaccines and Sera. Results: Enzyme immunoassay showed a mean level of CP antibodies in donor sera of 0,020±0,006 optical density units. The level of normal values of specific antibodies determined as M±2σ included an extinction value in the range 0 – 0,086. The mean value of oxidase activity and the amount of CP in healthy people was 716±26,3 and 921±32 ng/ml, correspondingly. In the process of study we revealed a reliable increase in CP antibody count, the activity and amount of CP in patients with rheumatoid arthritis while in all cases the parameters under study correlated with the degree of disease activity (p&lt;0,05): at activity degree I CP antibodies were 0,098±0,011; CP activity was 954±48,1; CP amount was 1292±73,4. At activity degree II CP antibodies were 0,138±0,007; CP activity was 1163±39,6; CP amount was 1763±69,3. At activity degree III, CP antibodies were 0,182±0,015; CP activity was 1368±89,5; CP amount was 1794±102,8. After a course of hospital treatment was completed, we noted a reliable decrease in the activity and amount of CP (at degree I of rheumatoid arthritis activity p&lt;0,001, at degree II of rheumatoid arthritis activity p&lt;0,01for both parameters; at degree III, p&lt;0,05) compared with baseline findings. A decrease in CP antibodies shows decelerated dynamics, especially in patients with pronounced disease activity, which indicates severe disorders in the immunity that cannot be cured completely within 30 – 40 days of hospital treatment course. Conclusion: Determination of CP antibodies, as well as quantitative content of CP and its oxidase activity can serve as indicators of the activity of rheumatoid arthritis, as well as an accessory criterion of the effectiveness of administered therapy. Disclosure of Interests: None declared
Target-switchable Gd(III)-DOTA/protein cage nanoparticle conjugates with multiple targeting affibody molecules as target selective T1 contrast agents for high-field MRI
Authors: Hansol Kim, Seokha Jin, Hyukjun Choi, MungSoo Kang, Seong Guk Park, Heejin Jun, HyungJoon Cho, Sebyung Kang
Journal: Journal of Controlled Release (2021)
Hotspot DNMT3A mutations in clonal hematopoiesis and acute myeloid leukemia sensitize cells to azacytidine via viral mimicry response
Authors: Marina Scheller, Anne Kathrin Ludwig, Stefanie Göllner, Christian Rohde, Stephen Krämer, Sina Stäble, Maike Janssen, James-Arne Müller, Lixiazi He, Nicole Bäumer, Christian Arnold, Joachim Gerß, Maximilian Schönung, Christian Thiede, Christian Niederwieser, Dietger Niederwieser, Hubert Serve, Wolfgang E. Berdel, Ulrich Thiem, Inga Hemmerling, Florian Leuschner, Christoph Plass, Matthias Schlesner, Judith Zaugg, Michael D. Milsom, Andreas Trumpp, Caroline Pabst, Daniel B. Lipka, Carsten Müller-Tidow
Journal: Nature Cancer (2021)
In vitro models replicating the human intestinal epithelium for absorption and metabolism studies: A systematic review
Authors: Arianna Fedi, Chiara Vitale, Giulia Ponschin, Seyoum Ayehunie, Marco Fato, Silvia Scaglione
Journal: Journal of Controlled Release (2021)

Absorption, distribution, metabolism and excretion (ADME) studies represent a fundamental step in the early stages of drug discovery. In particular, the absorption of orally administered drugs, which occurs at the intestinal level, has gained attention since poor oral bioavailability often led to failures for new drug approval. In this context, several in vitro preclinical models have been recently developed and optimized to better resemble human physiology in the lab and serve as an animal alternative to accomplish the 3Rs principles. However, numerous models are ineffective in recapitulating the key features of the human small intestine epithelium and lack of prediction potential for drug absorption and metabolism during the preclinical stage. In this review, we provide an overview of in vitro models aimed at mimicking the intestinal barrier for pharmaceutical screening. After briefly describing how the human small intestine works, we present i) conventional 2D synthetic and cell-based systems, ii) 3D models replicating the main features of the intestinal architecture, iii) micro-physiological systems (MPSs) reproducing the dynamic stimuli to which cells are exposed in the native microenvironment. In this review, we will highlight the benefits and drawbacks of the leading intestinal models used for drug absorption and metabolism studies.
A Smart Nanoplatform with Photothermal Antibacterial Capability and Antioxidant Activity for Chronic Wound Healing
Authors: Tengfei Ma, Xinyun Zhai, Yongkang Huang, Mengzhen Zhang, Xiaoli Zhao, Yaping Du, Chunhua Yan
Journal: Advanced Healthcare Materials (2021)

Abstract Chronic wounds, such as the diabetic ulcer wounds have serious effect on people's lives, and can even lead to death. Diabetic ulcer wounds are different from normal wounds and much easier to be infected and induce oxidative stress due to the special surrounding microenvironment, which makes it necessary to prepare materials with antibacterial property and antioxidant activity simultaneously. The molybdenum disulfide‐ceria (MoS 2 ‐CeO 2 ) nanocomposite possesses both the photo‐thermal therapy (PTT) antibacterial capability of polyethylene glycol modified molybdenum disulfide nanosheets and the antioxidant activity of cerium dioxide nanoparticles (CeO 2 NPs). By combining the inherent antibacterial activity of CeO 2 NPs, the MoS 2 ‐CeO 2 nanocomposite exhibits excellent PTT antibacterial capability against both gram‐positive and gram‐negative bacteria through 808 nm laser treatment, thereby reducing the risk of wound infection. Owing to the abundant oxygen vacancies in CeO 2 NPs, Ce 3+ and Ce 4+ can transform reversibly which endows MoS 2 ‐CeO 2 nanocomposite with remarkable antioxidant ability to clear away the excessive reactive oxygen species around the diabetic ulcer wounds and promote wound healing. The results demonstrate that MoS 2 ‐CeO 2 nanocomposite is a promising class for the clinical treatment of chronic wounds especially the diabetic ulcer wounds, and 808 nm laser can be used as a PTT antibacterial switch.
PTU-075 Making dysphagia easier to swallow
Authors: H Glover, D Marshall, J Sutton
Journal: Gut (2017)

Introduction  Around 9000 new cases of oesophageal cancer are diagnosed each year,a 43% increase over the last 40 years .1 Currently 80% of these are stage III or IV at diagnosis.A dedicated nurse led dysphagia clinic was established to reduce the referral to diagnosis time and to improve patients’ experience.Gwynedd is a district general hospital in north wales serving a population of 2 25 000 spread across 1260 square miles.  Method  Over 13 months,referrals were vetted and those with dysphagia selected.200 patients attended a nurse endoscopist led clinic in the morning and underwent diagnostic endoscopy the same afternoon.The CSN (cancer specialist nurse) was available to see those diagnosed with malignancy,give contact details and appointments for further investigations were made the same day.Comparative data was retrospectively collected from the cancer services database for all oesophageal cancers diagnosed during the same time period via other pathways.  Results  Data collected included referral to diagnosis time,endoscopic diagnosis and histology,performance status,staging and treatment.Questionnaires were given to those attending the one stop clinic assessing their patient experience.33 patients were diagnosed with oesophageal cancer,with equal numbers in each group.The average time from referral to diagnosis was 5.75 days for group A (dysphagia clinic) and 15.5 days for group B (other routes).50% of patients in group A were TNM stage I or II and 50% III or IV compared to 29% of patients in group B and 71% respectively.All patients in group A had a performance status recorded compared to 59% in group B.Curative treatment was the outcome of MDT for 56% of patients in group A and 38% group B.This is likely to reflect the non specific symptoms patients in group B present with leading to a delay in referral.  Conclusion  Patients rated the dysphagia clinic 0–5, 72% scored 5/5% and 27% 4/5.Patients were complimentary of the service with comments “excellent, friendly staff, needing to take fewer days off work, less anxiety waiting for a diagnosis”. The reduction in number of visits to the hospital was a benefit mentioned by many, reflecting the large distance travelled.Our pilot demonstrates that streamlining those with dysphagia into a one stop clinic is advantageous. Fewer journeys and days off work are needed and patient satisfaction is high.A history is taken including performance status informing discussions at MDT and taking into account patients’ wishes. A rapport is built with staff making breaking bad news a better experience for the patient.The referral to diagnosis time is significantly reduced.The proportion of patients diagnosed with TNM stage I or II (50%) is significantly higher than the average of 21%–30%.1Further studies into other red flag symptoms yielding a high number of oesophageal cancer diagnoses will be done to included in future referral screening hopefully leading to earlier diagnoses.  Reference  . Cancerresearchuk.org  Disclosure of Interest  None Declared
Rapid single-molecule detection of COVID-19 and MERS antigens via nanobody-functionalized organic electrochemical transistors
Authors: Keying Guo, Shofarul Wustoni, Anil Koklu, Escarlet Díaz-Galicia, Maximilian Moser, Adel Hama, Ahmed A. Alqahtani, Adeel Nazir Ahmad, Fatimah Saeed Alhamlan, Muhammad Shuaib, Arnab Pain, Iain McCulloch, Stefan T. Arold, Raik Grünberg, Sahika Inal
Journal: Nature Biomedical Engineering (2021)