tbuckley/cabot-search huggingface dataset:
AB0176 PATHOLOGICAL PHENOTYPES OF BODY COMPOSITION IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Feklistov, N. Toroptsova, O. Nikitinskaya, A. Efremova, N. Demin
Journal: Annals of the Rheumatic Diseases (2021)

Background: Inflammation, decreased physical activity, hormonal disorders, and the use of glucocorticoids lead to changes in the composition of the body in rheumatoid arthritis (RA). Various combinations of decreased muscle and bone mass and increased adipose tissue have led to the release of various pathological phenotypes of the composition of the body. Objectives: To determine the frequency of pathological phenotypes of body composition in patients with RA. Methods: The study included 79 women with RA, with a median age of 60 y.o. [55; 65]. 92% of the women were postmenopausal. The median duration of the disease was 9 years [3; 11]. Basic anti-inflammatory therapy was received by 81% of patients. Methotrexate was used most often as the basic therapy – in 52% of cases. 49% of patients were treated with glucocorticoid drugs. All patients underwent dual-energy X-ray absorptiometry. The mineral density of the tissues was determined in the standard measurement areas - the spine and the proximal thigh, and the content of muscle and adipose tissue was analyzed. We calculated appendicular muscle mass (AMM), which is the sum of upper and lower limb muscle mass and appendicular muscle index (AMI), the ratio of appendicular muscle mass to the square of height. AMM&lt; 15 kg, AMI &lt; 6 kg / m2 corresponds to sarcopenia. Results: The average AMM was 17.8±3.0 kg. 18% patients had AMM &lt;15 kg / m2. The average AMI was 6.8±1.0 kg / m2. 25% patients had AMI &lt; 6 kg/m2. The average body mass index (BMI) was 27.6±4.8 kg/m2. 37% patients were overweight (25≤ BMI &lt;29.9 kg/m2), 28% of women had a BMI corresponding to obesity. The average fat content was 28.2 kg. 71% of women had an obesity, according to X-ray absorptiometry, which is 2.5 times higher than the number of cases of obesity detected by BMI. A decrease a bone mineral density (BMD) was found in 73% of women, including osteoporosis in 25%. The most frequent phenotype was osteopenic obesity (Table 1), which was detected in almost 40% of patients. Isolated osteoporosis (16.5%) and obesity (17.7%) and osteosarcopenic obesity (16.5%) were found with approximately the same frequency. Osteosarcopenia was found in 9% of patients. In 4%, no changes in the compositional composition of the human body were detected. Table 1. Pathological phenotypes of body composition Pathological phenotypes of body composition n=79 Osteoporosis, n (%) 13 (16,5) Obesity, n (%) 14 (17,7) Osteosarcopenia, n (%) 7 (8,9) Osteopenic obesity, n (%) 29 (36,7) Osteosarcopenic obesity, n (%) 13 (16,5) Conclusion: The overall frequency of pathological phenotypes of body composition was high and amounted to 96.2% in women with RA. The most common pathological phenotype was an osteopenic obesity characterized by a decrease in BMD and an increase in fat mass. Disclosure of Interests: None declared
Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial
Authors: Lore Vanderbeke, Nico A. F. Janssen, Dennis C. J. J. Bergmans, Marc Bourgeois, Jochem B. Buil, Yves Debaveye, Pieter Depuydt, Simon Feys, Greet Hermans, Oscar Hoiting, Ben van der Hoven, Cato Jacobs, Katrien Lagrou, Virginie Lemiale, Piet Lormans, Johan Maertens, Philippe Meersseman, Bruno Mégarbane, Saad Nseir, Jos A. H. van Oers, Marijke Reynders, Bart J. A. Rijnders, Jeroen A. Schouten, Isabel Spriet, Karin Thevissen, Arnaud W. Thille, Ruth Van Daele, Frank L. van de Veerdonk, Paul E. Verweij, Alexander Wilmer, Roger J. M. Brüggemann, Joost Wauters, Bart Rijnders, Paul Verweij, Frank van de Veerdonk, Alexander Schauwvlieghe, Tom Wolfs, Joost Wauters, Katrien Lagrou
Journal: Intensive Care Medicine (2021)
Effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery: multicentre, double blind, randomised controlled trial
Authors: Karim Asehnoune, Charlene Le Moal, Gilles Lebuffe, Marguerite Le Penndu, Nolwen Chatel Josse, Matthieu Boisson, Thomas Lescot, Marion Faucher, Samir Jaber, Thomas Godet, Marc Leone, Cyrus Motamed, Jean Stephane David, Raphael Cinotti, Younes El Amine, Darius Liutkus, Matthias Garot, Antoine Marc, Anne Le Corre, Alexandre Thomasseau, Alexandra Jobert, Laurent Flet, Fanny Feuillet, Morgane Pere, Emmanuel Futier, Antoine Roquilly
Journal: BMJ (2021)

Abstract Objective To assess the effect of dexamethasone on complications or all cause mortality after major non-cardiac surgery. Design Phase III, randomised, double blind, placebo controlled trial. Setting 34 centres in France, December 2017 to March 2019. Participants 1222 adults (&gt;50 years) requiring major non-cardiac surgery with an expected duration of more than 90 minutes. The anticipated time frame for recruitment was 24 months. Interventions Participants were randomised to receive either dexamethasone (0.2 mg/kg immediately after the surgical procedure, and on day 1) or placebo. Randomisation was stratified on the two prespecified criteria of cancer and thoracic procedure. Main outcomes measures The primary outcome was a composite of postoperative complications or all cause mortality within 14 days after surgery, assessed in the modified intention-to-treat population (at least one treatment administered). Results Of the 1222 participants who underwent randomisation, 1184 (96.9%) were included in the modified intention-to-treat population. 14 days after surgery, 101 of 595 participants (17.0%) in the dexamethasone group and 117 of 589 (19.9%) in the placebo group had complications or died (adjusted odds ratio 0.81, 95% confidence interval 0.60 to 1.08; P=0.15). In the stratum of participants who underwent non-thoracic surgery (n=1038), the primary outcome occurred in 69 of 520 participants (13.3%) in the dexamethasone group and 93 of 518 (18%) in the placebo group (adjusted odds ratio 0.70, 0.50 to 0.99). Adverse events were reported in 288 of 613 participants (47.0%) in the dexamethasone group and 296 of 609 (48.6%) in the placebo group (P=0.46). Conclusions Dexamethasone was not found to significantly reduce the incidence of complications and death in patients 14 days after major non-cardiac surgery. The 95% confidence interval for the main result was, however, wide and suggests the possibility of important clinical effectiveness. Trial registration ClinicalTrials.gov NCT03218553 .
AB0645 CLINCAL CHARACTERISTICS OF GOUT PATIENTS WITH RENAL CYSTS
Authors: F. Feng, Y. Huang, Y. Liu, Z. Zhong, W. Deng, T. W. Li
Journal: Annals of the Rheumatic Diseases (2021)

Background: Gout is a crystal-related arthropathy caused by monosodium urate deposition, which is a common and treatable form of inflammatory arthritis and becoming more prevalent[1]. A few studies have found that gout patients have an increased prevalence of simple renal cysts[2, 3]. The relationship between gout and renal cysts is still insufficient. Objectives: Compare the difference between gout with renal cyst and without renal cyst. Methods: We retrospectively collected data on 200 gout patients. The data includes age, gender, uric acid, creatinine, glomerular filtration rate, 24-hour urine collection, and whether they have kidney stones, renal cysts, coronary heart disease, hypertension, and diabetes. Chi-square and exact Fisher’s tests were utilized, while continuous variables were assessed by Student’s t-test. A P value of less than 0.05 was considered statistically significant. Results: Of the 200 gout patients, 56 have kidney cysts(28%). In gout patients who had a renal cyst, were significantly older than patients without renal cysts (59.14 vs. 46.87, P = 0.000), more number of people suffering from coronary heart disease (7 vs. 5, P = 0.016). The glomerular filtration rate was lower (58.5 vs. 71.6, P = 0.000), with lower urinary creatinine, uric acid, and urinary potassium. Conclusion: Gout patients with and without simple renal cysts have significant differences in age, hypertension, cardiovascular disease, GFR, serum creatinine, urine creatinine, and urine potassium. References: [1]N. Dalbeth, T.R. Merriman, L.K. Stamp, Gout, Lancet 388(10055) (2016) 2039-2052. [2]E.M. Hasegawa, R. Fuller, M.C. Chammas, F.M. de Mello, C. Goldenstein-Schainberg, Increased prevalence of simple renal cysts in patients with gout, Rheumatol Int 33(2) (2013) 413-6. [3]Y. Han, M. Zhang, J. Lu, L. Zhang, J. Han, F. Zhao, H. Chen, Y. Bao, W. Jia, Hyperuricemia and overexcretion of uric acid increase the risk of simple renal cysts in type 2 diabetes, Sci Rep 7(1) (2017) 3802. Table 1. Clinical characteristics of gout patients Renal cyst(n=56) Without Renal cyst(n=144) P Disease duration, (month) 98.7(±64.1) 91.2(±67.0) 0.468 Age, (year) 59.14(±14.3) 46.78(±15.9) 0.000 Gender, n(F/M) 7/49 11/133 0.281 Smoking history, n(%) 18(32.1%) 47(32.6%) 0.946 Drinking history, n(%) 10(17.9%) 32(22.2%) 0.496 Hypertension, n(%) 31(55.3%) 49(34.0%) 0.006 Diabetes, n(%) 9(16.1%) 15(10.4%) 0.269 CVDs, n(%) 7(12.5%) 5(3.4%) 0.016 Nephrolithiasis, n(%) 14(25%) 43(29.9%) 0.494 UA, (μmol/L) 494.8(±158.0) 544.3(±121.0) 0.037 Serum creatinine, (μmol/L) 139.4(±57.2) 116.5(±35.45) 0.007 GFR, (ml/L) 58.5(±22.5) 71.6(±22.3) 0.000 FEUA, (%) 7.0(±3.2) 6.0(±3.2) 0.052 Urine creatinine, (μmol/L) 4687.09(±1832.9) 5565.2(±2599.8) 0.008 Urine Uric acid, (μmol/L) 1204.9(±772.0) 1542.1(±1048.5) 0.030 Urine sodium, (mmol) 132.1(±68.7) 131.2(±76.6) 0.939 Urine potassium, (mmol) 25.6(±12.5) 31.8(±14.2) 0.005 Disclosure of Interests: None declared.
Abstract 14225: Proton Pump Inhibitor Decrease the Risk of Upper Gastrointestinal Bleeding in Anticoagulation Treatment: A Systematic Review and Meta-Analysis
Authors: Wasawat Vutthikraivit, Sakolwan Suchartlikitwong, Pattara Rattanawong, Mohamed Elmassry, Pablo Paz, Barbara Mantilla, M Rubayat Rahman, Saif El Nawaa, Genanew Bedanie, Mohammad M Ansari
Journal: Circulation (2019)

Introduction: Direct oral anticoagulation (DOAC) has gained more universal acceptance for use in patients with venous thrombosis or atrial fibrillation because of its safety profile and the elimina...
Decoy bypass for appetite suppression in obese adults: role of synergistic nutrient sensing receptors GPR84 and FFAR4 on colonic endocrine cells
Authors: Madusha Peiris, Rubina Aktar, David Reed, Vincent Cibert-Goton, Ausra Zdanaviciene, Writaja Halder, Adam Robinow, Simon Corke, Harween Dogra, Charles H Knowles, Ashley Blackshaw
Journal: Gut (2021)

Objective Colonic enteroendocrine cells (EECs) store and release potent anorectic hormones that are key regulators of satiety. EECs express multiple nutrient sensing receptors, particularly for medium-chain fatty acids (MCFAs): GPR84 and FFAR4. Here we show a non-surgical approach with targeted colonic delivery of MCFA, which induces EEC and neuronal activation leading to anorectic effects. Design A randomised, double-blind, placebo-controlled, cross-over study was performed in obese adults given combined GPR84 and FFAR4 agonists in colonic release capsules before meals. We measured serum hormones, energy intake and appetite perception. Cell type, activation by agonists and hormone/serotonin release were determined in human colonic explants. Mouse colonic afferent nerve responses to nutrients/mediators were recorded electrophysiologically. Results Subjects receiving GPR84 and FFAR4 agonists had reduced overall calorific intake and increased postprandial levels of PYY versus placebo. Receptors including GPR84 and FFAR4 were coexpressed on human colonic EEC. Activation of GPR84 exclusively induced intracellular pERK, whereas FFAR4 selectively activated pCaMKII. Coactivation of GPR84 and FFAR4 induced both phosphoproteins, and superadditive release of GLP-1 and PYY. Nutrients and hormones convergently activated murine colonic afterent nerves via GLP-1, Y2 and 5-HT3 receptors. Conclusions Colonic GPR84 and FFAR4 agonists reduce energy intake and increase postprandial PYY in obese adults. Human colonic EECs coexpress these receptors, which activate cells via parallel intracellular pathways and synergistically evoke hormone release. Further synergism occurs in sensory nerve responses to MCFA and EEC mediators. Thus, synergistic activation of colonic endocrine cells via nutrient receptors is an important target for metabolic regulation. Trail registration number NCT04292236 .
OP0215 MENTAL HEALTH, SLEEP AND COGNITION CHARACTERISTICS IN RHEUMATOID ARTHRITIS AND ASSOCIATIONS WITH RHEUMATOID FACTOR STATUS IN THE UK BIOBANK
Authors: I. Stanciu, S. Siebert, D. Mackay, D. Lyall
Journal: Annals of the Rheumatic Diseases (2021)

Background: There are significant gaps in the literature regarding sleep, mental health, and cognition for people with rheumatoid arthritis (RA) despite being important aspects of patients’ overall quality of life. Similarly, there is a lack of understanding about the role of rheumatoid factor (RF) on these domains. Objectives: The aim of the current study was to characterize mental health, cognition, and sleep variables in people with RA and to compare these associations in people with positive RF (RF+) and negative RF (RF-) in a large population cohort. Methods: This cross-sectional study used baseline data from the UK Biobank cohort (n= 502,506) to compare people with and without RA and people that are RF+ versus RF- on a variety of sociodemographic, lifestyle, illness-related factors and depression, neuroticism, performance on cognitive tests and sleep-related factors. Logistic regression analyses were also performed to determine whether RF seropositivity was associated with mental health, cognition, and sleep variables. We adjusted for the covariates of age, sex, ethnicity, deprivation index, smoking status, BMI and alcohol intake. Results: In this sample 5,907 people self-reported having RA (1.17%), of which 74% were RF- and 26% were RF+. There were significant differences (p &lt; 0.05) between people with and without RA for depression, neuroticism, nap during the day, getting up in the morning, insomnia, reaction time, fluid intelligence and prospective memory. There were significant differences (p &lt; 0.05) between RF+ and RF- people for depression, neuroticism, sleep duration, nap during the day, getting up in the morning, insomnia, and reaction time. In the unadjusted regression analyses neuroticism ( B =-0.06, SE = 0.01, p &lt; 0.001), sleep duration ( B =0.02, SE = 0.005, p &lt; 0.001), nap during the day (OR=1.28, 95% CI: 1.02-1.65, p &lt; 0.05) and reaction time ( B =4.55, SE =0.53, p&lt; 0.001) were significantly associated with RF status. After adjusting for covariates, only sleep duration ( B =0.01, SE =0.005, p&lt; 0.01) remained significant. Conclusion: The current study suggests that RA diagnosis and RF status are associated with differences in mental health, sleep, and cognition, highlighting the importance of addressing these aspects in clinical settings and future research. Disclosure of Interests: None declared
Hemodialysis-Related Glycemic Disarray Proven by Continuous Glucose Monitoring; Glycemic Markers and Hypoglycemia
Authors: Akinori Hayashi, Naoya Shimizu, Agena Suzuki, Kenta Matoba, Akari Momozono, Tsuguto Masaki, Akifumi Ogawa, Ibuki Moriguchi, Koji Takano, Naoyuki Kobayashi, Masayoshi Shichiri
Journal: Diabetes Care (2021)

OBJECTIVE There is a high risk of asymptomatic hypoglycemia associated with hemodialysis (HD) using glucose-free dialysate; therefore, the inclusion of glucose in the dialysate is believed to prevent intradialytic hypoglycemia. However, the exact glycemic fluctuation profiles and frequency of asymptomatic hypoglycemia using dialysates containing &amp;gt;100 mg/dL glucose have not been determined. RESEARCH DESIGN AND METHODS We evaluated the glycemic profiles of 98 patients, 68 of whom were men, with type 2 diabetes undergoing HD (HbA1c 6.4 ± 1.2%; glycated albumin 20.8 ± 6.8%) with a dialysate containing 100, 125, or 150 mg/dL glucose using continuous glucose monitoring. RESULTS Sensor glucose level (SGL) showed a sustained decrease during HD, irrespective of the dialysate glucose concentration, and reached a nadir that was lower than the dialysate glucose concentration in 49 participants (50%). Twenty-one participants (21%) presented with HD-related hypoglycemia, defined by an SGL &amp;lt;70 mg/dL during HD and/or between the end of HD and their next meal. All these hypoglycemic episodes were asymptomatic. Measures of glycemic variability calculated using the SGL data (SD, coefficient of variation, and range of SGL) were higher and time below range (&amp;lt;70 mg/dL) was lower in participants who experienced HD-related hypoglycemia than in those who did not, whereas time in range between 70 and 180 mg/dL, time above range (&amp;gt;180 mg/dL), HbA1c, and glycated albumin of the two groups were similar. CONCLUSIONS Despite the use of dialysate containing 100–150 mg/dL glucose, patients with diabetes undergoing HD experienced HD-related hypoglycemia unawareness frequently. SGL may fall well below the dialysate glucose concentration toward the end of HD.
Abstract 14265: Altered Reticulum-Mitochondria Interactions Contribute to Mitochondrial Ca2+ Signaling Impairment and Diabetic Cardiomyopathy
Authors: Maya Dia, Ludovic Gomez, Helene Thibault, Bruno Pillot, Christelle Leon, Yves Gouriou, Nolwenn Tessier, Emily Tubbs, Nadia Bendridi, Michel Ovize, Jennifer Rieusset, Melanie Paillard
Journal: Circulation (2019)

Introduction: Type 2 diabetic cardiomyopathy has been linked to Ca2+ signaling alterations, notably a decreased mitochondrial Ca2+ uptake. Uncovering of Ca2+ microdomains between cardiac mitochondr...
POS0579 LOCAL ADAPTATION OF RECOMMENDATION-BASED MATERIALS FOR SHARED DECISION-MAKING AND MANAGEMENT OF COMORBIDITY IN RHEUMATOID ARTHRITIS
Authors: J. M. Alvaro-Gracia, C. Barbazan, J. F. Garcia Llorente, S. Muñoz-Fernández, A. Gomez-Centeno, A. Urruticoechea-Arana, M. A. Caracuel-Ruiz, E. Loza, J. Calvo
Journal: Annals of the Rheumatic Diseases (2021)

Background: Evolving the management of rheumatoid arthritis (eRA) is a European-wide educational initiative aiming to support improved patient care through practical and educational tools addressing specific unmet needs. The aims of the eRA program were: (1) To identify priority unmet needs with the greatest impact on disease outcomes; (2) To develop practical, educational and guidance tools in line with EULAR recommendations to address identified unmet needs; and (3) To improve RA management and patient care. Objectives: To describe the process by which local adaptations were made of materials derived from evidence-based recommendations in a training programme in rheumatoid arthritis (RA). Methods: A multidisciplinary Steering Committee (17 members, 12 countries) identified unmet needs within the management of RA and prioritised those with the greatest impact on patient outcomes. Practical educational tools addressing priority needs were then developed for dissemination and implementation by the rheumatology community across Europe, including shared decision making practises and a checklist for managing comorbidity in RA, among others. These materials were evaluated in detailed and discussed in small regional groups by practicing rheumatologists. Voting, open discussions and recommendations were extracted from the meetings. Results: Thirty-five Spanish rheumatologists from diverse geographic regions discussed a comorbidity checklist and a shared decision making tool. The results of the local meetings were synthesised as (1) a judicious commitment to check agreed comorbidities, and (2) a list of barriers and facilitators for the implementation of shared decision making at the local settings. With regards to ways to implement the agreed list and periodicity, two issues standed-out: (1) patient education and (2) the need of easy access to information and the use of local organisational systems in place. With respect to shared decision-making, issues raised included messages for self-awareness, challenges, and practical facilitators. Conclusion: Discussion, adaptation, and planning are needed before implementing any evidence-based recommendation and materials if we want to achieve a successful implementation. Further studies should demonstrate whether this initiative was successful in achieving the goals of improved patient care. Our experience could be used as a guidance or example for implementation elsewhere. Disclosure of Interests: None declared
First-in-Human Study of PF-06647020 (Cofetuzumab Pelidotin), an Antibody–Drug Conjugate Targeting Protein Tyrosine Kinase 7, in Advanced Solid Tumors
Authors: Michael L. Maitland, Jasgit C. Sachdev, Manish R. Sharma, Victor Moreno, Valentina Boni, Shivaani Kummar, Erica Stringer-Reasor, Nehal Lakhani, Allison R. Moreau, Dawei Xuan, Ray Li, Eric L. Powell, Amy Jackson-Fisher, Michelle Bowers, Shilpa Alekar, Xiaohua Xin, Anthony W. Tolcher, Emiliano Calvo
Journal: Clinical Cancer Research (2021)

Abstract Purpose: We investigated safety, tolerability, pharmacokinetics, and antitumor activity of the protein tyrosine kinase 7 (PTK7)-targeted, auristatin-based antibody–drug conjugate (ADC) PF-06647020/cofetuzumab pelidotin (NCT02222922). Patients and Methods: Patients received PF-06647020 intravenously every 3 weeks at 0.2–3.7 mg/kg or every 2 weeks at 2.1–3.2 mg/kg, in sequential dose escalation, following a modified toxicity probability interval method. In dose expansion, pretreated patients with advanced, platinum-resistant ovarian cancer, non–small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC) received PF-06647020 2.8 mg/kg every 3 weeks. Results: The most common, treatment-related adverse events for PF-06647020 administered every 3 weeks were nausea, alopecia, fatigue, headache, neutropenia, and vomiting (45%–25%); 25% of patients had grade ≥ 3 neutropenia. Two patients experienced dose-limiting toxicities (grade 3 headache and fatigue) at the highest every 3 weeks dose evaluated. The recommended phase II dose was 2.8 mg/kg every 3 weeks. The overall safety profile observed with PF-06647020 administered every 2 weeks was similar to that of the every 3 weeks regimen. Systemic exposure for the ADC and total antibody generally increased in a dose-proportional manner. Antitumor activity was observed in treated patients with overall objective response rates of 27% in ovarian cancer (n = 63), 19% in NSCLC (n = 31), and 21% in TNBC (n = 29). Responders tended to have moderate or high PTK7 tumor expression by IHC. Conclusions: This PTK7-targeted ADC demonstrated therapeutic activity in previously treated patients with ovarian cancer, NSCLC, and TNBC at a dose range of 2.1–3.2 mg/kg, supporting further clinical evaluation to refine dose, schedule, and predictive tissue biomarker testing in patients with advanced malignancies.