tbuckley/cabot-search huggingface dataset:
Abstract 14406: The COVID-19 Pandemic Impact on Daily Activity and AF Burden in TRIM-AF Clinical Trial Patients
Authors: Cheryl Lin, Han Sun, John Barnard, Niraj Varma, David R Van Wagoner, Mina K Chung
Journal: Circulation (2021)

Introduction: The COVID-19 pandemic presented an unexpected intervention to examine the association between activity and AF in patients enrolled in the TRIM-AF (Targeting Risk Interventions and Metformin for AF) clinical trial, which collects daily activity and AF burden through implanted devices. Hypothesis: We tested the hypotheses that: 1) daily activity reduction during the pandemic, compared to pre-pandemic matched periods, can be detected by implanted devices; and 2) activity reduction was associated with increased daily AF burden. Methods: Daily AF burden (%) and active minutes were obtained from manufacturers for 45 subjects (28 male, 17 female, mean age 69.5 years) enrolled in the TRIM-AF 2x2 randomized clinical trial of metformin and lifestyle/risk factor modification in patients with pacemakers/defibrillators (NCT03603912). We defined pre-pandemic and pandemic matched months for each subject, maintaining constancy of pre- vs post-randomization periods and fit a linear mixed model, including age, sex, and pandemic periods, to compare the pre- and during pandemic periods (Figure A). Results: Mean daily active minutes decreased during the pandemic from 148.6 to 144.4 mins (mixed model p =&lt;1E-10). Mean daily AF burden increased during the pandemic from 6.0 to 8.3 (mixed model p= 3.7E-14). Both mean values were compared to matched pre-pandemic time after adjusting for sex, age, and race. AF burden % was associated with age (median AF burden increased by a factor of 1.06/year of age, mixed model p= 1.38E-02) as expected. AF daily duration percent was negatively correlated with the daily active minutes as seen by the Kendall's rank correlation tau is -0.037 (z = -7.6232, p-value = 2.474e-14). Conclusions: The data suggests that activity decreased and device-detected AF burden increased during the pandemic. Further analyses could compare results to historical trends within these patients.
Abstract 10382: Large Lipid-Rich Plaque Predicts Intra-Stent Thrombus Formation After Primary Pci in Patients with Acute Coronary Syndrome: Insights from Near-infrared Spectroscopy and Optical Coherence Tomography Imaging Analysis
Authors: Satoshi Kitahara, Yu Kataoka, Kota Murai, Takamasa Iwai, Kenichiro Sawada, Hideo Matama, Satoshi Honda, Masashi Fujino, Shuichi Yoneda, Kensuke Takagi, Fumiyuki Otsuka, Yasuhide Asaumi, Kenichi Tsujita, Teruo Noguchi
Journal: Circulation (2021)

Backgrounds: The formation of intrastent thrombus is a PCI-related complication in subjects with ACS, which infrequently causes acute stent thrombosis. Given that lipid-rich plaque, a substrate for ACS, activates inflammation inducing prothrombotic state, the degree of lipidic plaque materials may associate with intrastent thrombus formation. Methods: Culprit lesions in 70 ACS subjects (=STEMI/NSTEMI/uAP=28/27/15) receiving newer-generation DES implantation were evaluated by both near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) imaging. NIRS-derived 4-mm maximum lipid-core-burden index (maxLCBI 4mm ) at culprit lesion was measured prior to PCI. OCT-derived intrastent thrombus-burden index (ITBI) after stent implantation were calculated as follows: [Σ(every 1-mm cross sectional thrombus-arc score: 1=1-90°,2=91-180°,3=181-270°,4=271-360°)/analyzed length]x(averaged longitudinal length). ITBI was compared between subjects with maxLCBI 4mm &lt;400 and ≥400. Result: The averaged maxLCBI 4mm was 525±236, and dual-antiplatelet therapy with aspirin and clopidogrel, and aspirin and prasugrel was used in 43 and 56%, respectively. On OCT imaging analysis, maxLCBI 4mm was significantly associated with ITBI (r=0.55, p &lt;0.001, Figure), whereas there were no significant relationships of minimum stent area (MSA) (r=0.18, p=0.13) and stent malapposition diameter with ITBI (r=0.00. p=0.97). Multivariate analysis demonstrated maxLCBI 4mm as an independent predictor of higher ITBI even after adjusting MSA, stent malapposition and other clinical characteristics (Table). Conclusions: The presence of lipid-rich plaque was associated with intrastent thrombus formation in the setting of ACS. Our findings suggest the potential importance to modulate activated prothrombotic cascade by using more potent antiplatelet agent in ACS patients exhibiting lipid-rich plaques.
TMOD-21. A NOVEL IN-VITRO METHOD TO MODEL MACROPHAGES IN GLIOBLASTOMA
Authors: Hasan Alrefai, Andee Beierle, Lauren Nassour, Nicholas Eustace, Zeel Patel, Joshua Anderson, Patricia Hicks, Peter King, Christopher Willey
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The GBM tumor microenvironment (TME) is comprised of a plethora of cancerous and non-cancerous cells that contribute to GBM growth, invasion, and chemoresistance. In-vitro models of GBM typically fail to incorporate multiple cell types. Others have addressed this problem by employing 3D bioprinting to incorporate astrocytes and macrophages in an extracellular matrix; however, they used serum-containing media and classically polarized anti-inflammatory macrophages. Serum has been shown to cause GBM brain-tumor initiating cells to lose their stem-like properties, highlighting the importance of excluding it from these models. Additionally, tumor-associated macrophages (TAMs) do not adhere to the traditional M2 phenotype. METHODS THP-1 monocytes and normal human astrocytes (NHAs) were transitioned into serum-free HL-1 and neurobasal-based media, respectively. Monocytes were stimulated towards a macrophage-like state with PMA and polarized by co-culturing them with GBM patient-derived xenograft(PDX) lines, using a transwell insert. CD206 expression was used to validate polarization and a cytokine array was used to characterize the cells. RESULTS There was no difference in proliferation rates at 72 hours for THP-1 monocytes grown in serum-free HL-1 media compared to serum-containing RPMI 1640 (p &amp;gt; 0.95). Macrophages polarized via transwell inserts expressed the lymphocyte chemoattractant protein, CCL2, whereas resting(M0), pro-inflammatory(M1), and anti-inflammatory(M2) macrophages did not. Additionally, these macrophages expressed more CXCL1 and IL-1ß relative to M1 macrophages. We have also demonstrated a method to maintain a tri-culture model of GBM PDX cells, NHAs, and TAMs in a serum-free media that supports the growth/maintenance of all cell types. CONCLUSIONS We have demonstrated a novel method by which we can polarize macrophages towards a tumor-supportive phenotype that differs in cytokine expression from traditionally polarized macrophages. This higher-fidelity method of modeling TAMs in GBM can aid in the development of targeted therapeutics that may one day enter the clinic in hopes of improving outcomes in GBM.
Abstract 12800: Echocardiographic Findings in Hospitalized Patients With COVID-19
Authors: Qasim Jehangir, Yi Lee, Laila Poisson, Katie Latack, Anupam Sule, Shiyi Song, Dinesh Reddy Apala, Abdul R Halabi, Kirit Patel, Geetha Krishnamoorthy, Dee Dee Wang
Journal: Circulation (2021)

Introduction: Data on echocardiographic findings in COVID-19 patients is limited. Atrial arrhythmias (AA) are common in COVID-19 but their impact on echocardiographic phenotypes is not well studied. We aimed to assess transthoracic echocardiographic (TTE) findings in adult hospitalized patients with COVID-19 undergoing TTE, and compare patients with new-onset or history of AA to patients with normal sinus rhythm (NSR). Methods: We studied TTE findings in adult patients who were admitted to one tertiary care and five community hospitals in Michigan with PCR-proven SARS-CoV-2 infection from 3/1/2021 to 12/1/2020, and stratified them into three groups: Group 1 (NSR), group 2 (new-onset AA including atrial fibrillation and atrial flutter), and group 3 (history of AA). Results: Among 6927 (5522 in group 1, 626 in group 2, 779 in group 3) hospitalized patients (mean age 65.4 ± 17.1 years, 50.7 % females) 115 patients underwent TTE (Table). Group 2 and 3 patients were significantly older, more commonly males, Whites, smokers, and more frequently had diabetes mellitus, hypertension, heart failure, history of coronary artery disease, and cerebrovascular accident compared to group 1 (p≤0.05 for all). The most common TTE abnormalities were valvular abnormalities (40.9%), RV dilation (29.6% of patients), elevated PASP (16.5%), reduced LV ejection fraction (13.9%), pericardial effusion (9.6%), and LV dilation (6.1%) with no significant difference in the prevalence of these echocardiographic abnormalities between the 3 groups. Conclusions: TTE abnormalities are common in hospitalized COVID-19 patients with valvular abnormalities, RV dilation, and PASP elevation being the most common. Current or prior history of atrial arrhythmias did not increase the prevalence of echocardiographic abnormalities. Clinicians should have a low threshold to obtain echocardiogram in hospitalized COVID-19 patients if clinically indicated even in the absence of AA.
Voluntary erasure of Northern Ireland neurologist being investigated for poor diagnosis to be challenged
Authors: Clare Dyer
Journal: BMJ (2021)

A decision to allow the neurologist at the centre of the biggest patient recall in Northern Ireland to remove himself from the medical register voluntarily is to be challenged in the High Court.

The General Medical Council criticised the decision by a medical practitioners tribunal to let Michael Watt take himself off the register without a hearing, but the regulator has no power to appeal against voluntary erasure.

Now the Professional Standards Authority (PSA), which does …
Abstract 12435: Impact of Non-Cyanotic Congenital Heart Disease in the Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide In-Patient Sample Analysis
Authors: Neel Patel, Birendra Amgai, Adrija Hajra, Chakraborty Sandipan, Zeel Patel, Binit Aryal, mazin Khalid, Prodip Kumar Paul, Sukhvir Singh, Wilbert S Aronow
Journal: Circulation (2021)

Introduction: Reported total congenital heart disease (CHD) birth prevalence has increased substantially over time. It varies from 1.9 to 9.3 per 1000 live births based on geographic location. Aortic stenosis(AS) is a common pathology associated with advanced age. It is found to be in the 11.7-15.0% population over 75-year-old cohort. TAVR is the preferred intervention for severe AS patients. It is now being performed in extreme- to low-risk patients. We sought to determine the impact of non-cyanotic CHD in the patients undergoing TAVR. Method: We reviewed National Inpatient Sample (NIS) database from 2016-2018 using Stata 16.0. The NIS is the ICD-10-CM code-based healthcare database. Patients who underwent TAVR were identified and divided into with and without CHD. Multivariate logistic regression, linear regression, and student t-tests were used for analysis. Results: Among 134,195 patients who underwent TAVR, 1,135(0.9%) were having NCHD. Patients with NCHD were younger (77.9±11.2 vs. 79.6±8.4 with P=0.02) with equal gender distribution. NCHD patients had longer lengths of stay than others (5.9±6.3 vs. 4.3±5.4 with P=&lt;0.001) and were associated with higher co-morbidities such as anemia, atrial fibrillation, and pulmonary hypertension. 55 (4.9%) patients died in the NCHD group, whereas 1956 (1.5%) patients died in the other. The difference was found to be statistically significant on multivariant logistic regression analysis. (OR:2.9, 95%-Confidence Interval: 1.6-5.3, P=&lt;0.001). Complications such as post-operative shock, AMI, AKI, bleeding requiring transfusion, acute respiratory failure, cardiogenic shock, and pacemaker implantation were comparable between both groups. The mean total charge for the NCHD group was $68688, whereas others were $ 54794. Conclusion: NCHD was associated with higher in-patient mortality and LOS in the patients undergoing TAVR for severe AS. However, Complications were comparable in patients with and without NCHD.
Abstract 12076: Whole Genome Sequencing Association Study for Coronary Heart Disease in a Middle Eastern Cohort Validates Polygenic Risk Scores and Replicates Known Loci
Authors: Mohamad Saad, Khalid Kunji, Ehsan Ullah, Ayman El-Menyar, Iftikhar J Kullo, Jassim Al Suwaidi
Journal: Circulation (2021)

Introduction: The potential use of polygenic risk scores (PRSs) in clinical practice is tempered by concern about their portability among diverse populations. To prevent disparities in genomic medicine, there is an urgent need to conduct genome-wide association studies in non-European ancestry cohorts. Methods: We conducted whole genome sequencing (WGS) with 30x coverage on coronary heart disease patients (n=1,067, mean age ± SD = 59.96 years ± 10.99; 70.32% males) and controls (n=6,170, mean age ± SD = 40.02 years ± 12.56; 43.45% males) in a Middle Eastern cohort to compare the performance of available PRSs for CHD (LDpred, metaGRS, lassosum, and P+T) and identify common variants associated with CHD (via generalized linear mixed models). Results: Excepting lassosum, all PRSs performed well. LDpred and metaGRS performed similarly (AUC= ~0.685) and outperformed P+T (AUC=0.667). Based on the OR per 1 SD increase (OR 1sd ), P+T (OR 1sd =1.85 [1.69-2.02], P =3.69x10 -41 ) outperformed other PRSs (OR 1sd =1.61 [1.48-1.74], P =3.02x10 -31 for LDpred and OR 1sd =1.61 [1.49-1.75], P =9.47x10 -31 for metaGRS). After binning PRSs into 10 deciles, the odds of CHD in the top decile compared to all others was highest for metaGRS (3.87 [3.07-4.88]) and LDpred (3.45 [2.74-4.341]). Thirty-two known GWAS loci (e.g., ABCG8 , CELSR2 , and SLC22A4 ) were replicated in our analysis with P &lt;0.05. Seven suggestive new loci/genes ( P &lt;10 -6 ) with relevant biological function were identified (e.g., CORO7 , RBM47 , and PDE4D ). The well-established 9p21 locus was not replicated. Conclusions: Genome-wide PRSs derived from European ancestry cohorts performed well in a Middle Eastern cohort. Further studies are needed to develop and validate an ancestry specific PRS and to confirm the suggestive loci/genes.
Top 100 Cited Articles on Hematopoietic Stem Cell Transplantation: A Bibliometric Analysis
Authors: Moazzam Shahzad, Muhammad Arslan, Zehra Naseem, Sakina Abbas, Naira Fatima, Ali Hussain, Tayyaba Ali, Iqra Anwar, Raheel S Siddiqui, Sibgha Gull Chaudhary, Nausheen Ahmed, Sunil Abhyankar, Peiman Hematti, Joseph P. McGuirk, Muhammad Umair Mushtaq
Journal: Blood (2021)
Predictors and microbiology of respiratory and bloodstream bacterial infection in patients with COVID-19: living rapid review update and meta-regression
Authors: Bradley J. Langford, Miranda So, Valerie Leung, Sumit Raybardhan, Jennifer Lo, Tiffany Kan, Felicia Leung, Duncan Westwood, Nick Daneman, Derek R. MacFadden, Jean-Paul R. Soucy
Journal: Clinical Microbiology and Infection (2021)
Abstract 12407: A Comparison of Hemodynamic and Cardiopulmonary Exercise Stress Variables for Advanced Heart Failure Prognosis
Authors: Matthew K Cochran, Mark N Belkin, Umar Siddiqi, Ann Nguyen, Bow Chung, Bryan Smith, Nitasha Sarswat, Gene H Kim, Sean P Pinney, Jonathan Grinstein, Sara Kalantari
Journal: Circulation (2021)

Introduction: Both invasive hemodynamics as measured by right heart catheterization (RHC) and cardiopulmonary exercise testing (CPET) are used for prognostication in advanced heart failure patients. We aimed to compare the prognostic performance of these variables in patients with advanced heart failure with a particular focus on defining the incremental prognostication of advanced hemodynamic metrics compared to CPET variables. Methods: We retrospectively analyzed patients who underwent both a RHC and CPET within one year of each other from January 2013 to January 2019 at our institution. The CPET variables of peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2), oxygen pulse (VO2/HR), and the RHC variables of left ventricular stroke work index (LVSWI), cardiac power output (CPO), and aortic pulsatility index (API) were used. The primary outcome was death, left ventricular assist device, or heart transplant at one year following the RHC. Results: A total of 55 patients were included in the analysis: 35% women, 51% Black, and 27% ischemic cardiomyopathy. Overall, using Spearman’s analysis, there were no significant correlations between the RHC and CPET variables. On Kaplan-Meier analysis, lower LVSWI was significantly associated with the primary outcome when compared to lower VO2/HR, HR 5.3 (95% CI 1.2-23, p = 0.02.), lower VE/VCO2, HR 3.7 (95% CI 1.3-10.4, p = 0.014), and lower peak VO2, HR 7.0 (95% CI 0.9-56, p = 0.06). Conclusion: LVSWI is more associated with one-year outcomes in patients with advanced heart failure than other prognostic hemodynamic or CPET variables. Furthermore, advanced hemodynamic metrics are more prognostic than CPET measurements when these values are discordant.
CTNI-12. PHASE II MULTICENTRIC ITALIAN TRIAL ON REPOSITIONING OF THE ANTIPSYCHOTIC DRUG CHLORPROMAZINE AND ITS SYNERGISM WITH TEMOZOLOMIDE IN MGMT UNMETHYLATED GLIOBLASTOMA PATIENTS: THE RACTAC TRIAL
Authors: Andrea Pace, Giuseppe Lombardi, Silvia Matteoni, Veronica Villani, Caludia Abruzzese, Giulia Cerretti, Marta Padovan, Mario Caccese, Dario Benincasa, Antonio Silvani, Marco Paggi
Journal: Neuro-Oncology (2021)

Abstract The poor prognosis of patients affected by glioblastoma (GBM) prompts the search for new and more effective therapies, particularly for GBMs with unmethylated MGMT. In this regard, drug repurposing, can represent a safe and inexpensive way to bring novel pharmacological approaches from bench to bedside. Chlorpromazine, a medication in use since six decades for the therapy of psychiatric disorders, shows in vitro features that make it eligible for repositioning in GBM therapy. In our experimentation on six GBM cell lines, chlorpromazine inhibited cell viability in an apoptosis-independent way, induced polyploidy, reduced cloning efficiency as well as neurosphere formation and downregulated the expression of stemness genes. Notably, we found that chlorpromazine synergized with temozolomide, in reducing cell viability and strongly cooperated in reducing cloning efficiency and inducing cell death in vitro for all the GBM cell lines assayed. With these assumptions, we started a multicentric Phase II clinical trial on newly diagnosed GBM patients with unmethylated MGMT by adding chlorpromazine to temozolomide in the adjuvant phase of the standard first-line therapeutic protocol. The experimental procedure involves the combination of CPZ with standard treatment with TMZ in the adjuvant phase of the Stupp protocol. CPZ is administered orally at a dose of 50 mg/day – GG 1-28 – of every cycle of the adjuvant treatment with TMZ. At present, 28 patients out of 41 patients planned have been enrolled, without relevant toxicity.
Abstract 11116: Relationship Between Skeletal Muscle Decline During Acute Care and Recovery of Physical Function in Patients with Aortic Disease
Authors: Masashi Yamashita, Kentaro Kamiya, Tadashi Kitamura, Nobuaki Hamazaki, Takafumi Ichikawa, Shota Uchida, Takumi Noda, Emi Maekawa, Atsuhiko Matsunaga, Minako Yamaoka-tojo, Junya Ako, Kagami Miyaji
Journal: Circulation (2021)

Introduction: Low skeletal muscle area or density identified on computed tomography (CT) is associated with poor prognosis in patients with cardiovascular disease. However, there is a lack of evidence regarding the clinical process of skeletal muscle decline as a longitudinal change in the acute care setting. Hypothesis: Skeletal muscle loss occurs after acute care, and a high degree of skeletal muscle loss is associated with an insufficient recovery of physical function. Methods: This study used routinely acquired CT images for aortic disease management and prospectively reviewed the data of 123 patients who underwent abdominal CT before and after acute care. The area and density of all abdominal muscles and each muscle (such as the rectus abdominis, psoas, and erector spinae) divided into eight parts were measured at the third lumbar vertebra level after patient blinding. The short physical performance battery (SPPB) was used as a physical function parameter at the start and end of in-hospital cardiac rehabilitation. A generalized linear model with patients as random effects was used to investigate skeletal muscle loss during acute care. Multivariate linear regression analysis was performed to assess the relationship between skeletal muscle decline during acute care and the change in SPPB results during inpatient cardiac rehabilitation. Results: The median patient age was 70 years, and 70% of patients were men. All and each abdominal muscle density declined consistently after acute care (interaction: P = 0.998). In contrast, the whole muscle area was found to have no significant change, and the changes were different for each skeletal muscle (interaction: P = 0.037). After adjusting for confounding factors, greater declines in muscle density were associated with lower recovery on the SPPB (β = 0.30, P = 0.007). Conclusions: Muscle density declines consistently after acute care, and a greater decline in muscle density is associated with a lower recovery of physical function during in-hospital cardiac rehabilitation in patients with aortic disease.
Overlapping network meta‐analyses on psoriasis systemic treatments, an overview: quantity does not make quality
Authors: Robin Guelimi, Sivem Afach, Jean Philippe Régnaux, Thomas Bettuzzi, Guillaume Chaby, Emilie Sbidian, Florian Naudet, Laurence Le Cleach
Journal: British Journal of Dermatology (2021)

Network meta-analyses (NMAs) have become successful in addressing gaps in the comparative effectiveness of systemic treatments in moderate-to-severe psoriasis. However, their increasing number carries both a risk of overlap and reproducibility issues that can hamper clinical decision-making.In this overview, we aimed to assess redundancy across these NMAs and to describe their characteristics.We considered all systematic reviews with NMAs of randomized controlled trials that included adult patients with moderate-to-severe psoriasis and that evaluated the efficacy and/or safety of systemic treatments compared with placebo or with an active comparator. PubMed/MEDLINE, Epistemonikos, PROSPERO and the Evidence update of the Centre of Evidence-Based Dermatology of the University of Nottingham were searched up to 25 February 2021. Our main outcome was the number per year of redundant NMAs and the extent of their overlap. We also described their features, especially, the confidence in the results of the reviews, the funding of the studies and the presence of spin (a description that overstates efficacy and/or understates harm), reporting issues and methodological characteristics.In total, 47 redundant NMAs were included. Only two of 47 (4%) included all available treatments. Both efficacy and safety were evaluated in 14 of 47 (30%) NMAs and both short- and long-term evaluations were assessed in five of 47 (11%). Confidence in the results was critically low for 39 of 47 (83%) NMAs and only 10 of 47 (21·3%) registered a protocol. Twenty-six of 47 NMAs (55%) received pharmaceutical funding. Contract research organizations were involved in 19 of 47 (40%) NMAs. Reporting was poor across most of the NMA abstracts and spin was present in all of the abstracts. Almost half of the NMAs failed to consider important limitations such as heterogeneity (considered in 32%) or consistency (considered in 66%).In addition to a duplication of efforts, our overview showed heterogeneous methods and poor confidence in the results in a majority of the included NMAs, further distorted by reporting issues and spin. Clinicians need to interpret NMAs with caution when looking for the most reliable and comprehensive evidence.