tbuckley/cabot-search huggingface dataset:
Reply to Camporota <i>et al.</i>: The 4DPRR Index and Mechanical Power: A Step Ahead or 4 Steps Backward?
Authors: Eduardo L. V. Costa, Arthur S. Slutsky, Marcelo B. P. Amato
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

recruitment, increases lung homogeneity, or alters dead space).The mechanical effects of PEEP on mortality hazard may be more complex.Indeed, although PEEP's effect on total lung stress and strain will depend on multiple factors (e.g., baseline compliance, recruitability, and lung homogeneity), its amount is not indifferent to the outcome because PEEP can influence driving pressure (for a given VT) and dead space (and can indirectly influence the respiratory rate) as well as acting independently as a key component of the total mechanical energy delivered.The relevance of PEEP in determining total stress and strain of the respiratory system is, in one sense, intuitive: omitting PEEP from a calculation of energy would imply that applying 30 cm H 2 O of PEEP to an individual patient adds no risk of VILI or other adverse outcomes.On the contrary, it is clear from the univariate, population-based models presented by Costa and colleagues (1) that PEEP, the static elastic component of mechanical power and of total power, impacts mortality with an effect size of similar magnitude as respiratory rate and driving pressure.There are not sufficient data available to fully elucidate the effect of PEEP on outcome, but there is already evidence-some from the same authors-that mechanical power is associated to outcome in the same populations (4).Second, the simplicity of the bedside calculation of 4DPRR is not superior to the simplicity of the bedside calculation of mechanical power through simplified formulas (5).In addition, the 4DPRR formulation obscures the conceptual understanding of the delivered mechanical energy.Therefore, we argue that moving from the physical and physiological model of mechanical power to a contrived expression based on statistical models devoid of direct physical meaning may be a retrograde step.
Abstract 13280: Inhibition of miR-33a and b in Non-Human Primates Raises Plasma HDL Cholesterol and Reduces VLDL Triglycerides
Authors: Ryan E Temel, Katey J Rayner, Christine C Esau, Allison L McDaniel, Stephanie M Marshall, Cynthia J Lees, Janine M van Gils, Carlos Fernandez-Hernando, Edward A Fisher, Kathryn J Moore
Journal: Circulation (2011)

MicroRNAs have emerged as important post-transcriptional regulators of lipid metabolism, and are thus a new class of targets for therapeutic intervention. MicroRNA-33a and b (miR-33a/b) are recentl...
AB0458 SURVIVAL OF SCLERODERMA PATIENTS WITH INTERSTITIAL LUNG DISEASE: OBSERVATION DATA FROM A MALAYSIAN TERTIARY CENTRE
Authors: J. Raja, S. Muthusamy, C. M. Ng
Journal: Annals of the Rheumatic Diseases (2021)

Background: Interstitial lung disease (ILD) is the leading cause of death in scleroderma (SSc) with decline in FVC as a predictor of mortality in patients with SSc-ILD, especially in the early course of the disease. Objectives: The aim of this study is to determine the survival rate of SSc-ILD in a Malaysian cohort of patients from University Malaya Medical Centre (UMMC). Methods: 61 patients clinically diagnosed with SSc-ILD were identified and prospectively recruited. Baseline demographic data were collected. Kaplan-Meier analysis was used to estimate the survival. Results: Females were predominant (56, 91.8%). 39 (64%) had limited cutaneous SSc. Majority were ethnicity Chinese 30 (49.2%), followed by Malays 20 (32.8%), Indians 7 (11.4%) and others 4 (6.6%). Mean age was 56.25 (SD ± 12.5) years while mean duration of disease (non-Raynaud’s disease onset) was 10.5 years (SD ± 9.2) (range of 1 year to 44 years) years. 29 (47.5%) patients were positive for anti-ScL-70, whereas 6 (9.8%) patients were anti-centromere positive. There were 16 (26.2%) deaths. Median survival was 24 years. Patients had a sharper drop in survival probability for the first 10 years compared to the next 20 years (Figure 1). Median survival in limited subset was 24 years whereas in diffuse subset was 11 years. Patients from the limited subset appeared to have higher chance of surviving for 10 years and above, compared to those in the diffuse subset (Figure 2). Conclusion: The results demonstrate the poor survival in SSc-ILD patients. The survival rate tends to be worse in the first 10 years of SSc disease duration. Survival rate was poorer in patients with diffuse cutaneous subset. References: [1]Parelas A et al. Lancet Resp Med 2020 [2]Goh NS et al. Am J Respir Crit Care Med 2008 Disclosure of Interests: JASMIN RAJA Speakers bureau: For Boehringer Ingelheim for topic on Scleroderma-ILD, Grant/research support from: From Boehringer Ingelheim for scleroderma research, Shantini Muthusamy: None declared., CHOUNG MIN NG: None declared.
Abstract 16165: Type 2 Cell Low Density Lipoprotein Receptor-Related Protein 1 Regulates Surfactant Lipid, Pulmonary Function, and Extrapulmonary Metabolism
Authors: Christina Agudelo, Saioa Mendizuri, Estela Area-Gomez, Yimeng Xu, Patrick Geraghty, Abdoulaye Dabo, Ira Goldberg, Robert Foronjy, Itsaso Garcia-Arcos
Journal: Circulation (2019)

The low-density lipoprotein receptor-related protein 1 (LRP1) is a ubiquitously expressed multi-ligand receptor that participates in a wide range of tissue- and cell-type-specific events, including...
Immune Cells and Immunotherapy for Cardiac Injury and Repair
Authors: Joel G. Rurik, Haig Aghajanian, Jonathan A. Epstein
Journal: Circulation Research (2021)

Cardiac injury remains a major cause of morbidity and mortality worldwide. Despite significant advances, a full understanding of why the heart fails to fully recover function after acute injury, and why progressive heart failure frequently ensues, remains elusive. No therapeutics, short of heart transplantation, have emerged to reliably halt or reverse the inexorable progression of heart failure in the majority of patients once it has become clinically evident. To date, most pharmacological interventions have focused on modifying hemodynamics (reducing afterload, controlling blood pressure and blood volume) or on modifying cardiac myocyte function. However, important contributions of the immune system to normal cardiac function and the response to injury have recently emerged as exciting areas of investigation. Therapeutic interventions aimed at harnessing the power of immune cells hold promise for new treatment avenues for cardiac disease. Here, we review the immune response to heart injury, its contribution to cardiac fibrosis, and the potential of immune modifying therapies to affect cardiac repair.
Radiofrequency ablation of pancreatic serous cystic neoplasms: feasibility, but for the wrong indication
Authors: Diane Lorenzo, Benedicte Jais, Philippe Levy
Journal: Endoscopy (2021)

See also: Reply to Lorenzo et al.Endoscopy 2021; 53(06): 667-667DOI: 10.1055/a-1345-8614 See also: Endoscopic ultrasound-guided radiofrequency ablation of pancreatic microcystic serous cystic neoplasms: a retrospective study Endoscopy 2021; 53(07): 739-743DOI: 10.1055/a-1250-7786
Parkinson disease risks: correctly identifying environmental factors for a chronic disease
Authors: Karl Kieburtz, E. Ray Dorsey
Journal: Journal of Clinical Investigation (2021)

Parkinson disease (PD) is now the world's fastest growing brain disease; however, the factors underlying this rise are unclear. The past 25 years has witnessed a vast expansion in our understanding of the genetics of PD, but few individuals with PD carry one of the major known genetic risk factors. Environmental factors, including individual (e.g., medications) and ambient (e.g., pollutants), may contribute to this rise. In this issue of the JCI, Sasane et al. examined the risk of PD associated with medications commonly used to treat benign prostatic hypertrophy. In contrast with previous studies, certain α1 receptor antagonists failed to lower PD risk. Rather, the commonly used comparator drug, tamsulosin, increased PD risk. This finding highlights the importance of selecting comparator groups to correctly identify risk factors. Future studies to address the rise of PD with emphasis on both individual as well as the understudied ambient environmental factors are warranted.
AB0216 LONG-TERM RESULTS OF T2T THERAPY INITIATED AT THE ONSET OF RHEUMATOID ARTHRITIS (DATA FROM OREL REGISTRY)
Authors: V. Rybakova, A. Avdeeva, Y. Olyunin, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Current guidelines for the treatment of rheumatoid arthritis (RA) recommend early administration of methotrexate (MTX) and addition of a biologic if MTX monotherapy does not provide remission or low activity of the disease. Efficacy of this strategy in real clinical practice was assessed using data from the Russian RA registry OREL. Objectives: To analyze long-term results of intensive treatment initiated at RA onset in real clinical practice. Methods: 141 RA patients with disease duration less than 3 years (29 men, 112 women) were included. 112 were positive for rheumatoid factor and 119 – for anti-cyclic citrullinated peptide antibody. Subcutaneous MTX was initiated at 10-15 mg per week with further dose escalation up to 20-30 mg per week. Therapy was adjusted every 3 months. If MTX monotherapy did not allow to achieve treatment target of remission or low disease activity, biologics were added. Results: Median DAS 28 at baseline was 5,31 [4,79; 6,14]. Initiation of treatment resulted in steady decrease of disease activity ( p &lt;0.05, table1). After 1 year of follow-up 33.8% of patients received MTX monotherapy, 33.8% – MTX in combination with tumor necrosis factor alpha inhibitors, 22.0% – MTX +abatacept, 0.55% – MTX+ tocilizumab, 0.47% – MTX + rituximab. Low disease activity was achieved in 16.3% patients, and remission - in 45.8%. After 6 years median age of patients was 58 [49; 66] years, disease duration – 84 [79; 89] months, low disease activity was documented in 21.3%, and remission – in 7.8% of cases (fig. 1). 7% of patients were able to maintain remission without any treatment. Biologics were discontinued in 15 patients after achieving remission or low disease activity, and synthetic DMARDs – in 5 patients having remission. Conclusion: Intensive therapy initiated at RA onset demonstrates high effectiveness, allowing 61.5% of patients to achieve low disease activity or remission within 12 months, and to maintain these results after 6 years of treatment in 29.2%. Adherence to this strategy allowed to discontinue biologics in 15 patients and synthetic DMARDs in 5 patients after achieving treatment target. Figure 1. Changes of the disease activity during follow-up Table 1. Changes of the main inflammatory activity measures, Me [25 th ; 75 th percentile] Parametres 0 12 months 6 years DAS28 5,31 [4,79; 6,14] 2,85 [2; 3,90] * 4,008 [3,4; 4,59] * SDAI 28,27 [18,79; 40,73] 5,67 [2; 11,98] * 15,06 [9,32; 21] * CDAI 25 [17; 36] 5 [1,7; 11] * 15 [9; 21] * ESR (mm/hr ) 32 [19; 50] 16 [8; 30] * 16 [10; 25] * CRP (mg/l ) 26,55 [6,4; 45,30] 3,85 [1,5; 11,3]* 2,2 [0,9; 4,9] * * p&lt;0.05 in all cases. Disclosure of Interests: None declared
AB0421 MANAGEMENT OF ULCERATION IN SYSTEMIC SCLEROSIS BY A SPECIALIST PODIATRY SERVICE; A CASE SERIES
Authors: L. Parker, R. Field, J. Marks
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic sclerosis is a chronic disorder characterised by diffuse fibrosis and vascular abnormalities in the skin and major organs. Digital ulceration is a common complication, often resulting in patient disability. These ulcers can form through a variety of processes and management should be tailored according to aetiology. In Dorset, the specialist podiatry service has created a unique facility for optimal wound care in the setting of digital ulceration. Objectives: In this case series, we outline podiatric management of 4 common causes of digital ulceration in systemic sclerosis. Methods: Tissue ischaemia, infection, micro-trauma and calcinosis were identified as four major contributory factors resulting in ulceration or delayed wound healing. Four cases exemplifying management of each different contributory factor were identified and their case notes reviewed in order to extract clinically relevant data and images. Results: Case 1 illustrates treatment of ischaemic tissue injury to promote earlier healing, using careful wound care, debridement under local anaesthetic and low-level laser therapy. Case 2 illustrates the importance of identifying repeated micro-trauma as a contributing factor to non-healing ulceration. Case 3 demonstrates how surgical debridement or removal of the subcutaneous calcinosis in an outpatient setting can be a useful adjunct in encouraging ulcer healing. Case 4 illustrates the complexity of correctly identifying infection in the setting of ulceration, with prompt management promoting wound healing. Conclusion: The pathophysiology of ischaemic tissue damage in scleroderma is complex and can reflect a broad range of vascular pathologies, often occurring concurrently 1 including vasospasm, macrovascular disease and microvascular vasculopathy, leading to digital ulceration. Rapid identification of which processes are driving the ischaemia is critical in targeting therapy to the affected individual. A local podiatry service with expertise in management of tissue -related complications of systemic sclerosis is invaluable in promoting wound healing and preventing further complications. References: [1]Hughes M, Herrick A L. Digital ulcers in systemic sclerosis. Rheumatology 2017; 56(1):14-25. Disclosure of Interests: None declared
Women’s Health — Traversing Medicine and Public Policy
Authors: Cynthia A. Stuenkel, JoAnn E. Manson
Journal: New England Journal of Medicine (2021)

Interview with Dr. Cynthia Stuenkel on medical and policy progress and continued challenges in the field of women's health. (11:17)Download The United States has seen advances in reproductive health and improvements in women's well-being throughout the life course, including reductions in cardiovascular and cancer mortality. Championing the role of science as the route to better health remains essential.
Rebalancing expression of HMGB1 redox isoforms to counteract muscular dystrophy
Authors: Giorgia Careccia, Marielle Saclier, Mario Tirone, Elena Ruggieri, Elisa Principi, Lizzia Raffaghello, Silvia Torchio, Deborah Recchia, Monica Canepari, Andrea Gorzanelli, Michele Ferrara, Patrizia Castellani, Anna Rubartelli, Patrizia Rovere-Querini, Maura Casalgrandi, Alessandro Preti, Isabella Lorenzetti, Claudio Bruno, Roberto Bottinelli, Silvia Brunelli, Stefano Carlo Previtali, Marco Emilio Bianchi, Graziella Messina, Emilie Vénéreau
Journal: Science Translational Medicine (2021)

The redox-sensitive HMGB1 protein is a functional link between oxidative stress and persistent inflammation in muscular dystrophies.
Immune responses to SARS-CoV-2 in the lung
Authors: Prabhu S Arunachalam
Journal: Thorax (2021)

<h3>ABSTRACT</h3> The medial prefrontal cortex (mPFC) and the dorsomedial striatum (dmStr) are linked to working memory (WM) but how striatum-projecting mPFC neurons contribute to WM encoding, maintenance, or retrieval remains unclear. Here, we probed mPFC→dmStr pathway function in freely-moving mice during a T-maze alternation test of spatial WM. Fiber photometry of GCaMP6m-labeled mPFC→dmStr projection neurons revealed strongest activity during the delay period that requires WM maintenance. Demonstrating causality, optogenetic inhibition of mPFC→dmStr neurons only during the delay period impaired performance. Conversely, enhancing mPFC→dmStr pathway activity—via pharmacological suppression of HCN1 or by optogenetic activation during the delay— alleviated WM impairment induced by NMDA receptor blockade. Consistently, cellular-resolution miniscope imaging resolved preferred activation of &gt;50% mPFC→dmStr neurons during WM maintenance. This subpopulation was distinct from neurons showing preference for encoding and retrieval. In all periods, including the delay, neuronal sequences were evident. Striatum-projecting mPFC neurons thus critically contribute to spatial WM maintenance.
AB0693 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS DURING CORONAVIRUS 19 PANDEMIC: WHAT DO TUNISIAN RHEUMATOLOGISTS THINK?
Authors: H. Ferjani, H. Boussaa, K. Maatallah, H. Khalfalli, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Concerns over the safety of non-steroidal anti-inflammatory drugs (NSAIDs) use during severe acute respiratory syndrome associated with coronavirus 19 disease (covid-19) have raised. NSAIDs are one of the most commonly prescribed and used pain medications for acute and chronic rheumatic diseases such as spondyloarthritis (SpA) and osteoarthritis. Objectives: This study aimed to assess the impact of covid-19 pandemic on NSAIDs prescription. Methods: A cross-sectional web survey was disseminated to all Tunisian rheumatologists through a mailing system and social media. The French version was accessible on Google form. It included close-ended questions about the prescription of NSAIDs during covid-19 pandemic. Participation was anonymous. Data collection and analysis was performed between January the first and January 30, 2021. Results: Among one hundred and thirty Tunisian rheumatologists, thirty responded to the online questionnaire. Ninety percent of participants were women. The mean age of rheumatologists was 34 years [25-57]. The duration of practice was inferior to 5 years in 59.3%, between 5 and 10 years in 18.5%, and superior to 10 years in 22.2% of cases. Sixty-three percent of rheumatologists reported that their activity decreased during covid-19 pandemic. NSAIDs prescription was avoided as much as possible in 40.7% of cases. The participants indicated NSAIDs less frequently in 33.3% of cases, and as much as before the pandemic in one-quarter of cases. Rheumatologists believed that NSAIDs worsen the respiratory symptoms (67%), delay recovery (55%), and increase mortality (48%), hospitalization in intensive care (44%), and infectious complications (33%). The participants suggested that the most incriminated NSAIDs were: Ibuprofen (7.4%), indomethacin (7.4%), celecoxib (7.4%), and diclofenac (3.4%). The majority of rheumatologists (74%) believed that all NSAIDs had a similar risk. For patients with osteoarthritis, rheumatologists replaced NSAIDs with paracetamol and corticoids in 78% and 11% of cases, respectively. If mandatory, reducing NSAIDs doses or duration was an option in 22% and 74% of cases. For patients with SpA, half of rheumatologists did not change the treatment. However, the participants limited the use of NSAIDs or discontinued the treatment in patients with comorbidities. More than 60% of rheumatologists didn’t know the effect of NSAIDs in the post-covid-19 syndrome. Conclusion: Covid-19 pandemic has affected rheumatologists’ practice. Rheumatic disease management during this pandemic may be challenging. More evidence is mandatory to standardize treatment prescription, especially with NSAIDs. Disclosure of Interests: None declared
AB0897-HPR EVALUATION OF ANXIETY AND DEPRESSION IN PATIENTS WITH KNEE OSTEOARTHRITIS USING THE HAD “HOSPITAL ANXIETY AND DEPRESSION SCALE”
Authors: M. Brahem, S. Abdellatif, H. Hachfi, A. Ben Salem, R. Sarraj, R. Ben Tekaya, Y. Mohamed
Journal: Annals of the Rheumatic Diseases (2021)

Background: Knee osteoarthritis is considered to be one of the most common causes of functional impairment, which affects the quality of life of patients leading to severe mood disorders. Our goal is to evaluate the frequency of depression and anxiety in patients with knee osteoarthritis. Objectives: Evaluate the frequency of depression and anxiety in patients with knee osteoarthritis. Methods: This is a cross-sectional study over a period of 7 months from February to August 2016, including consecutively patients who consulted in the Rheumatology department at Mahdia university hospital for knee osteoarthritis. We evaluated for each patient a validated version of HAD “Hospital Anxiety and Depression scale”. This score includes 14 items each one rated from 0 to 3 and two components including depression and anxiety. Results: We included in our study 66 patients (56 women and 10 men) with an average age of 60.3 years [40-90 years]. Knee osteoarthritis was bilateral in 56.1% of cases. The examination found limited mobility of the knee in 45.5% and flessum in 13.8% of cases. Standard radiography showed stage 1 knee osteoarthritis in 4.5%, stage 2 in 31.8%, stage 3 in 56.1% and stage 4 in 7.6% of cases. All our patients were treated with analgesics, NSAIDs in 95.5%, local corticosteroid infiltrations in 43.9% and hyaluronic acid in 7.6% of cases.The mean visual analog scale(VAS)was 5.84 ±1.7 out of 10 [2-9]. The mean overall WOMAC index was 47.15±15.6 [12-82]. The average Lequesne index was 16.8±13.1, moderate disability was found in 3% of cases, significant disability in 6.1% of cases, very significant disability in 18.2% of cases and extreme disability in 72.7% of cases. The mean depression score was 9.3±2.6 [4-16], with 24.6% of the patients had no depressive symptomatology (score ≤7), 40% had doubtful depressive symptomatology (score between 8 and 10) and 35.4% of them had certain depressive symptomatology (score ≥11).The mean anxiety score was 8.88 ± 4 [0-19], 33.3% of patients had no anxiety symptoms (score ≤ 7), 34.8% had doubtful anxiety (score between 8 and 10) and 31.8% had certain anxiety (score ≥11). The statistical study found a significant correlation between the depression score and WOMAC score, but we did not find an association with age, sex, radiological stage, mobility limitation and VAS. Regarding anxiety, there was a correlation with age, WOMAC score and female gender. On the other hand, there was no correlation with VAS, Lequesne score, radiological stage and limitation of mobility. Conclusion: Although knee osteoarthritis appears to be a benign pathology, its impact can be severe, including depression and anxiety, which are mainly influenced by the degree of functional disability. Hence psychological care is sometimes necessary in these chronic degenerative diseases. Disclosure of Interests: None declared
Lung-resident memory B cells protect against bacterial pneumonia
Authors: Kimberly A. Barker, Neelou S. Etesami, Anukul T. Shenoy, Emad I. Arafa, Carolina Lyon de Ana, Nicole M.S. Smith, Ian M.C. Martin, Wesley N. Goltry, Alexander M.S. Barron, Jeffrey L. Browning, Hasmeena Kathuria, Anna C. Belkina, Antoine Guillon, Xuemei Zhong, Nicholas A. Crossland, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd
Journal: Journal of Clinical Investigation (2021)

Lung-resident memory B cells (BRM cells) are elicited after influenza infections of mice, but connections to other pathogens and hosts — as well as their functional significance — have yet to be determined. We postulate that BRM cells are core components of lung immunity. To test this, we examined whether lung BRM cells are elicited by the respiratory pathogen pneumococcus, are present in humans, and are important in pneumonia defense. Lungs of mice that had recovered from pneumococcal infections did not contain organized tertiary lymphoid organs, but did have plasma cells and noncirculating memory B cells. The latter expressed distinctive surface markers (including CD69, PD-L2, CD80, and CD73) and were poised to secrete antibodies upon stimulation. Human lungs also contained B cells with a resident memory phenotype. In mice recovered from pneumococcal pneumonia, depletion of PD-L2+ B cells, including lung BRM cells, diminished bacterial clearance and the level of pneumococcus-reactive antibodies in the lung. These data define lung BRM cells as a common feature of pathogen-experienced lungs and provide direct evidence of a role for these cells in pulmonary antibacterial immunity.