tbuckley/cabot-search huggingface dataset:
Abstract 14278: Microglial Calcium Activity During Ischemic Stroke
Authors: Kathryn N Kearns, Lei Liu, Khadijeh A Sharifi, Kenneth A Stauderman, Min S Park, Petr Tvrdik
Journal: Circulation (2020)

Introduction: Ischemic stroke triggers waves of propagating action potentials followed by a loss of homeostatic ion gradients, known as cortical spreading depolarizations (SD). Our data indicate that microglia respond to SD by raising intracellular Ca 2+ , triggering a release of proinflammatory cytokines that may exacerbate post-stroke morbidity. Hypothesis: Inhibiting calcium release-activated calcium (CRAC) channels may block microglial Ca2+ influx and activation to potentially provide therapeutic benefit in ischemic stroke. Methods: We generated a mouse line expressing the Ca2+ indicator GCaMP5 in cortical microglia. Using two-photon microscopy, we imaged microglia in vivo following physical stroke via middle cerebral artery occlusion (MCAo) or chemical stroke via 1M KCl solution application. Controls were compared to mice treated with lipopolysaccharide (LPS) to mimic the inflammation of ischemic stroke. To study CRAC channels as a therapeutic target, we administered CM-EX-137, a CRAC channel blocker, and compared Ca2+ activity to controls. Results: We identified periodical Ca2+ waves in cortical microglia following MCAo (Fig. 1A), or localized KCl application (Fig. 1B-E). Further, when compared to controls, LPS-exposed mice expressed significantly greater microglial Ca2+ activity during KCl-triggered SD (Fig. 1C). Additionally, administration of CM-EX-137 effectively abolished the Ca2+ signals in the microglia and propagation of SD upon application of KCl (Fig. 1E). Conclusions: Blocking the Ca2+ influx into microglia after ischemic stroke may decrease the frequency of SD and reduce microglial activation, potentially leading to smaller stroke volumes and improved clinical outcomes. Figure 1: Microglial Ca 2+ after SD. (A) Ca 2+ transients in microglia after MCAo. (B) KCl-induced Ca 2+ activity in naïve microglia. (C) KCl-induced Ca 2+ activity after LPS. (D, E) KCl-induced Ca 2+ wave after (D) vehicle or (E) CM-EX-137 administration.
A macrophage-targeted platform for extending drug dosing with polymer prodrugs for pulmonary infection prophylaxis
Authors: Thomas E.J. Chavas, Fang-Yi Su, Selvi Srinivasan, Debashish Roy, Brian Lee, Lara Lovelace-Macon, Guilhem F. Rerolle, Elaine Limqueco, Shawn J. Skerrett, Daniel M. Ratner, T. Eoin West, Patrick S. Stayton
Journal: Journal of Controlled Release (2020)
Air Pollution, Cardiovascular Disease, and Dementia
Authors: Kosuke Inoue, Kimberly C. Paul, Beate R. Ritz
Journal: JAMA Neurology (2020)

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Practical tips to manage travel fatigue and jet lag in athletes
Authors: Dina Christina (Christa) Janse van Rensburg, Peter Fowler, Sebastien Racinais
Journal: British Journal of Sports Medicine (2020)

Travel forms an integral part of modern-day athletes lives. The interrelated effects of travel fatigue, jet lag and increased risk of illness, are likely to affect performance unless managed appropriately.1 Travel fatigue follows any long journey and resolve following a good night’s sleep, but can accumulate with frequent travel.2 Jet lag ensues misalignment between the internal circadian rhythms and new destination time after rapid travel across more than three time zones,2–4 resulting in sleep disruption, daytime fatigue and gastrointestinal disturbances.3 5 Sleep loss appears to be central to the detrimental impact of long-haul travel on performance.5 Additionally, circadian rhythms of numerous psychological and physiological variables with a typical early-morning nadir and late afternoon peak will be misaligned to the new destination time, which, depending on time of competition, could affect performance directly.5

Recovery from jet lag requires resynchronisation of the human circadian systems to the new light–dark cycle.2 Various peripheral rhythms resynchronise at different rates but internal desynchronisation progressively disappear as all rhythms synchronise to local time,5 probably explaining why athletes often feel worse …
Abstract 13483: Predictors of Thirty-day Readmission for Patients Undergoing Left Atrial Appendage Occlusion Device Placement: Insights From the National Readmission Database 2016-2017
Authors: Farhad Sami, Moghniuddin Mohammed, Sagar Ranka, Amit Noheria, Seth Sheldon, Madhu Reddy
Journal: Circulation (2020)

Introduction: Watchman device is an alternative for anticoagulation in atrial fibrillation (AF) patients for stroke prevention but there is paucity of data on 30-day readmission trends and factors influencing it. Methods: We queried the 2016-2017 National Readmission Database for all adult AF patients, who had procedure done in January to November and discharged alive, using ICD10 code of 02L73DK. We divided the study population into deciles and used the annual procedure volume cut-off of 20 to compare the lowest volume decile with rest of the study population. Hierarchical multivariable logistic regression model was created to identify predictors of 30-day readmission and hospitals were included as random effect. Results: A total of 4565 and 9219 procedures were included for 2016 and 2017; respectively. Overall readmission rate was 1287 (9.3%) and of these 43 (3.3%) died on readmission. The 30-day readmission rate in 2017 was 906 (9.8%) compared to 381 (8.4%) in 2016 (p = 0.053) but the mortality associated with readmission was significantly higher in 2017 at 38 (0.42%) compared to 5 (0.11%) in 2016 (p=0.01). The proportion of patients with Charlson co-morbidity index ≥5 was significantly higher in 2017 at 1177 (12.8%) compared to 384 (8.4%) in 2016 (p &lt;0.001). Annual procedure volume was a significant predictor of readmissions even after controlling for sex, co-morbidities and index-hospital complications (Figure 1). Septicemia (25.2%) and GI bleeding (17.9%) were the most common cause of readmission in patients who died and survived readmission; respectively (Figure 2). Conclusions: Thirty-day readmission rate and mortality has been increasing along with the procedural volume which could be related to patients with higher number of co-morbidities receiving the device. Lower procedural volume of the hospital is an independent predictor of readmission.
Intranasal delivery of interferon-β-loaded nanoparticles induces control of neuroinflammation in a preclinical model of multiple sclerosis: A promising simple, effective, non-invasive, and low-cost therapy
Authors: Luis F. González, Eric Acuña, Gabriel Arellano, Paola Morales, Paula Sotomayor, Felipe Oyarzun-Ampuero, Rodrigo Naves
Journal: Journal of Controlled Release (2020)
Etanercept or Methotrexate Withdrawal in Rheumatoid Arthritis Patients in Sustained Remission
Authors: Jeffrey R. Curtis, Paul Emery, Elaine Karis, Boulos Haraoui, Vivian Bykerk, Priscilla K. Yen, Greg Kricorian, James B. Chung
Journal: Arthritis & Rheumatology (2020)

Objective Patients with rheumatoid arthritis (RA) in whom remission is achieved following combination therapy with methotrexate plus etanercept face an ongoing medication burden. This study was undertaken to investigate whether sustained remission achieved on combination therapy can be maintained with either methotrexate or etanercept monotherapy, as assessed following discontinuation of one or the other medication from the combination. Methods Of the 371 adult patients with RA who received combination therapy with methotrexate plus etanercept, remission (defined as a Simplified Disease Activity Index [SDAI] score of ≤3.3) was sustained in 253 patients through a 24‐week open‐label period. These 253 patients then entered a 48‐week, double‐blind period and were randomized to receive either 1) methotrexate monotherapy (n = 101), 2) etanercept monotherapy (n = 101), or 3) methotrexate plus etanercept combination therapy (n = 51). Patients who subsequently experienced disease‐worsening received rescue therapy with the combination regimen at the same dosages as used in the initial run‐in period. The primary end point was the proportion of patients in whom SDAI‐defined remission was maintained without disease‐worsening at week 48 in the etanercept monotherapy group as compared to the methotrexate monotherapy group. Secondary end points included time to disease‐worsening, and the proportion of patients in whom SDAI‐defined remission was recaptured after initiation of rescue therapy. Results Baseline demographic and clinical characteristics of the RA patients were similar across the treatment groups. At week 48, SDAI‐defined remission was maintained in significantly more patients in the etanercept monotherapy group than in the methotrexate monotherapy group (49.5% versus 28.7%; P = 0.004). Moreover, as a secondary end point, sustained SDAI‐defined remission was achieved in significantly more patients who received combination therapy than in those who received methotrexate monotherapy (52.9% versus 28.7%; P = 0.006). Time to disease‐worsening was shorter in those who received methotrexate monotherapy than in those who received etanercept monotherapy or those who received combination therapy (each P &lt; 0.001 versus methotrexate monotherapy). Among the patients who received rescue therapy, SDAI‐defined remission was recaptured in 70–80% in each treatment group. No new safety signals were reported. Conclusion The efficacy of etanercept monotherapy was superior to that of methotrexate monotherapy and similar to that of combination therapy in maintaining remission in patients with RA. SDAI‐defined remission was recaptured in most of the patients who were given rescue therapy. These data could inform decision‐making when withdrawal of therapy is being considered to reduce treatment burden in patients with well‐controlled RA.
Abstract 14165: In-hospital Outcomes and 30-day Readmissions in Patients Hospitalized With Myocarditis
Authors: Robert Weidling, venkat vuddanda, Ioannis Mastoris, Sean Lacy, Tiana Moala, Andrew J Sauer, Zubair Shah
Journal: Circulation (2020)

Introduction: Myocarditis, induced by various etiologies, remains a major cause of dilated cardiomyopathy. Data on patient characteristics, hospital outcomes and readmissions of myocarditis remains limited. Our study evaluated outcomes and 30-day readmission rates of patients admitted with myocarditis. Methods: We retrospectively analyzed the US National Readmissions Database years 2016-2017 for all adults (age ≧ 18 years) with an index admission for myocarditis. The primary outcomes sought were inpatient mortality, ventricular fibrillation (VF)/ sudden cardiac death (SCA) and 30 day readmission rates. Secondary outcomes included: patient characteristics and diagnostic or therapeutic interventions. Results: A total of 7100 index admissions with myocarditis were identified whereby males composed the majority of admissions (64.9%). Women were at a significantly greater risk of VF/SCA (5.2% vs 2.1%, p&lt;0.05) and cardiogenic shock (10.2% vs 4.7%, p&lt;0.001). In-hospital mortality was greatest in females (3.8% vs 1.4%, p&lt;0.001). Temporary mechanical circulatory support was utilized more among females as compared to males by way of IABP (2.4% vs 0.9%, p = 0.002) or PVAD (1.9% vs 0.9%, p = 0.009). Mean length of stay was greater in females (3 ± 5 vs 2 ± 3 days, p&lt;0.001). The overall 30-day readmission rate was 6.4% and the top three etiologies for readmission in order of frequency were: myocarditis, acute on chronic systolic heart failure and sepsis. Conclusions: Significant gender outcome disparities were noted among identified index admissions for myocarditis. Females had disproportionately higher rates of VF/SCA, cardiogenic shock and inpatient mortality. Additionally, females had a higher rate of temporary mechanical circulatory support utilization and a longer length of stay. The overall 30 day readmission rate was significant at 6.4% with the most frequency causes of readmission being recurrent myocarditis, acute on chronic systolic heart failure and sepsis.
AB0934 DUAL-ENERGY COMPUTED TOMOGRAPHY IN GOUT PATIENTS: IS IT USEFUL IN GENERAL PRACTICE?
Authors: Y. Sherman, P. Lipsky, M. Bramwit, N. Schlesinger
Journal: Annals of the Rheumatic Diseases (2020)

Background: Dual-Energy CT (DECT) has high sensitivity and specificity for detecting monosodium urate (MSU) crystal deposition. Although widely used in research, few studies have evaluated the usefulness of DECT in clinical practice. Objectives: To evaluate the use of DECT in a clinical setting and determine its utility Methods: We retrospectively evaluated the records of all patients referred for DECT scans over a 6.5-year period. Patient charts were reviewed for clinical features. Results: 113 patients (17.5/yr) received DECT evaluation at a university hospital over the study period (234 scans). All were referred by rheumatologists. Medical records were available for 69 patients (134 scans), including 44 males and 25 females (mean age 62 (SD, 12.9, range: 34-85 yrs). Mean duration of gout was 6.7 (SD, 8.1) yrs. DECT was ordered to evaluate known gout (36/69, 52.1%), suspected gout (32/69, 46.4%), and suspected calcium pyrophosphate (CPP) disease (1/69, 1.4%). 32/69 (46.4%) of patients were on urate-lowering therapy. 61% (42/69) had MSU crystal and none had CPP deposition. Mean MSU volume was 1.6cc (SD, 5.2cc; range: 0.01-35 cc.) The joints imaged were feet/ankles (80/134, 60%) and hands/wrists (53/134, 40%). 23/33 (69.7%) patients with DECT positivity had elevated serum urate (SU) levels &gt;6mg/dL; however, elevated SU was not significantly associated with DECT positivity (odds ratio (OR) 1.9, 95% CI:0.59-5.95, p=0.28). For patients with positive scans, mean gout duration from first known flare was 9.5 (SD, 8.8) yrs. Among patients who had scans completed within 1 yr of the first known gout flare, 1/10 were positive (10%); 4/16 within 2 yrs (25%); and 8/21 within 3 yrs (29.6%). Of patients with positive DECT scans, 24/42 (57%) had symmetric distribution of MSU crystal deposition: 10/24 (42%) hands and 14/24 (58%) feet; with gout duration of 7.9 (SD, 8.0) yrs. Conclusion: DECT was infrequently utilized and only by rheumatologists. Only 60 % of patients referred for DECT scanning because of known or suspected gout had MSU deposition. DECT was uncommonly positive in patients with a 1-3 yr history of gout. When positive, the MSU crystal deposition was symmetrical in most gout patients. DECT scans, while important in furthering our understanding of gout biology, are not routinely used in general practice and often do not provide important decision support information. Establishment of practice guidelines might be important in developing more appropriate utilization of DECT. Disclosure of Interests: Yekaterina Sherman: None declared, Peter Lipsky Consultant of: Horizon Therapeutics, Mark Bramwit: None declared, Naomi Schlesinger Grant/research support from: Pfizer, AMGEN, Consultant of: Novartis, Horizon Pharma, Selecta Biosciences, Olatec, IFM Therapeutics, Mallinckrodt Pharmaceuticals, Speakers bureau: Takeda, Horizon
In older adults with CKD and mild acidosis, oral sodium bicarbonate did not improve physical function
Authors: Orly F. Kohn
Journal: Annals of Internal Medicine (2020)

Witham MD, Band M, Chong H, et al. Sodium bicarbonate to improve physical function in patients over 60 years with advanced chronic kidney disease: the BiCARB RCT. Health Technol Assess. 2020;24:1-90. 32568065.
Abstract 13712: Association Between Soluble Vascular Endothelial Growth Factor Receptor-2 and Prognosis in Patients With Chronic Heart Failure: The PREHOSP-CHF Study
Authors: Moritake Iguchi, Hiromichi Wada, Tsuyoshi Shinozaki, masahiro suzuki, Yoichi Ajiro, Morihiro Matsuda, Akihiro Koike, Tomomi Koizumi, masatoshi shimizu, Yujiro Ono, Takashi Takenaka, Satoru Sakagami, Yukiko Morita, Kazuteru Fujimoto, Kazuya Yonezawa, Kazuro Yoshida, Akiyo Ninomiya, Toshihiro Nakamura, JUNICHI FUNADA, Yutaka Kajikawa, Yoshifumi Oishi, Toru Kato, Kazuhiko Kotani, Mitsuru Abe, Masaharu Akao, Koji Hasegawa
Journal: Circulation (2020)

Introduction: Soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) acts as an endogenous inhibitor of VEGF, a key regulator of angiogenesis and lymphoangiogenesis. However, little is known about the critical role of sVEGFR-2 in heart failure (HF). Methods: We performed a multicenter prospective cohort study (PREHOSP-CHF Study) to determine the predictive value of sVEGFR-2 for major adverse cardiovascular (CV) events (MACE) among patients with chronic HF (CHF). A total of 1,021 patients were included in the analyses. The mean age (SD) was 75.5 (12.6) years. 59.6% were male. The primary outcome was MACE defined as a composite of CV death or HF hospitalization. The secondary outcomes were all-cause death and CV death. Serum levels of sVEGFR-2 were determined employing specific enzyme-linked immunosorbent assays. Results: The patients with lower sVEGFR-2 concentrations were older, and had higher rates of female sex, atrial fibrillation and anemia. The baseline sVEGFR-2 level was inversely correlated with left ventricular ejection fraction, and was positively correlated with the body mass index. During the median follow-up of 730 days, a total of 210 (20.6%) all-cause deaths, 99 (9.7%) CV deaths and 308 (30.2%) HF hospitalizations occurred. Unadjusted Cox proportional hazard analyses revealed that the patients with the lowest quartile (Q1) of sVEGFR-2 did not show a significantly higher risk of MACE (p=0.7), but showed the greatest risks of CV death (p=0.003) and all-cause death (p=0.007). Even after adjusting for established risk factors and CV biomarkers (N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin-I, and high-sensitivity C-reactive protein), those with the Q1 of sVEGFR-2 exhibited the greatest risk of CV death (p=0.02; hazard ratio [HR], 2.05; 95% confidence interval [CI], 1.17-3.66 [vs. Q2]; HR, 2.42; 95%CI, 1.30-4.68 [vs. Q3]; HR, 1.52; 95%CI, 0.80-2.99 [vs. Q4]), but not that of all-cause death. The sex-stratified analyses revealed that the association between sVEGFR-2 and CV death was still significant in men, but not in women (p for interaction, 0.07). Conclusions: A low sVEGFR-2 value was not associated with MACE, but was independently associated with CV mortality among patients with CHF.
Abstract 12902: Aerobic Exercise Adherence Among Older People Living With HIV
Authors: Crista L Irwin, Drenna Waldrop, Raphiel Murden, Rebecca Gary
Journal: Circulation (2020)

Introduction: HIV+ persons are twice as likely to develop cardiovascular disease (CVD) than non-HIV infected persons. CVD is now a major cause of morbidity and mortality in OPLWH. AHA guidelines recommend moderate to vigorous physical activity (MVPA) of at least 150 minutes per week, but less than 50% of the general population meets this standard. Little is known about exercise adherence among OPLWH over longer study periods. Hypothesis: The purpose of this study was to examine preliminary results of adherence to a moderate-intensity exercise regimen among OPLWH randomized to a Let’s Move aerobic exercise intervention (n=76). Methods: Participants (mean age 55, +/-5 (65% male, 82.4%AA) were HIV+ persons with at least 2 CVD risk factors. All participants underwent baseline maximal exercise testing (V0 2max ). Based on maximal heart rate obtained, an individualized, moderate-intensity aerobic exercise prescription was calculated at 60-70% of HR reserve. MVPA was measured in both number of steps/week and number of days/week participants met 60-70% max HR for at least 60 minutes/day. Participants wore activity trackers that were remotely monitored by a secure API data collection platform weekly from BL to 3-months. Based on data collected, real-time feedback was provided on exercise performance including follow-up calls using motivational interviewing (MI) counseling methods. Results: Mean steps/week over 3 months was 43,993 (SD 33376). 75% (n=57/76) walked at least an average of 30K steps/week over 3 months, 13% (10/76) walked more than 70K steps/week. 77.6% (n=59/76) met the AHA guideline, &gt;150 minutes of MVPA/week. 59% (n=45/76) maintained an average of at least 60% max HR for a minimum of 240 min/week. 57.9% (44/76) participants attained 70% max HR at least 240 min/week. Conclusions: OPLWH engaged in a MI supported aerobic exercise program for 3 months exceeded the recommended 150 minutes/week of moderate-intensity exercise by 27.6% more than the general population. HIV+ participants are willing to engage in aerobic exercise which may be a cost-effective approach to reduce CVD risk in this population.
Increased incidence of germline <i>PIEZO1</i> mutations in individuals with idiopathic erythrocytosis
Authors: Mathilde Filser, Muriel Giansily-Blaizot, Mélanie Grenier, David Monedero Alonso, Guillaume Bouyer, Laurent Pérès, Stéphane Egée, Bernard Aral, Fabrice Airaud, Lydie Da Costa, Véronique Picard, Pierre Cougoul, Marlène Palach, Stéphane Béziau, Céline Garrec, Patricia Aguilar-Martinez, Betty Gardie, François Girodon
Journal: Blood (2020)
Abrogation of USP7 is an alternative strategy to downregulate PD-L1 and sensitize gastric cancer cells to T cells killing
Authors: Zhiru Wang, Wenting Kang, Ouwen Li, Fengyu Qi, Junwei Wang, Yinghua You, Pengxing He, Zhenhe Suo, Yichao Zheng, Hong-Min Liu
Journal: Acta Pharmaceutica Sinica B (2020)

Targeting immune checkpoints such as programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for treating melanoma, gastric cancer (GC) and bladder cancer with clinical benefit. Nevertheless, many patients failed to respond to anti-PD-1/PD-L1 treatment, so it is necessary to seek an alternative strategy for traditional PD-1/PD-L1 targeting immunotherapy. Here with the data from The Cancer Genome Atlas (TCGA) and our in-house tissue library, PD-L1 expression was found to be positively correlated with the expression of ubiquitin-specific processing protease 7 (USP7) in GC. Furthermore, USP7 directly interacted with PD-L1 in order to stabilize it, while abrogation of USP7 attenuated PD-L1/PD-1 interaction and sensitized cancer cells to T cell killing in vitro and in vivo. Besides, USP7 inhibitor suppressed GC cells proliferation by stabilizing P53 in vitro and in vivo. Collectively, our findings indicate that in addition to inhibiting cancer cells proliferation, USP7 inhibitor can also downregulate PD-L1 expression to enhance anti-tumor immune response simultaneously. Hence, these data posit USP7 inhibitor as an anti-proliferation agent as well as a novel therapeutic agent in PD-L1/PD-1 blockade strategy that can promote the immune response of the tumor.