tbuckley/cabot-search huggingface dataset:
Abstract 12907: Endovascular Mechanical Thrombectomy And Intravenous Alteplase In Patients Acute Stroke: A Network Meta-analysis Of Randomized Controlled Trials
Authors: Shingo Matsumoto, Takahisa Mikami, Takanori Ikeda, Hisato Takagi, Toshiki Kuno
Journal: Circulation (2021)

Background: The benefit and risk of administration of intravenous alteplase (IA) before endovascular mechanical thrombectomy (EMT) in acute stroke is actively debated. Objectives: We aimed to investigate the efficacy and safety of direct EMT compared to EMT with pre-administration of IA and IA alone with a network meta-analysis. Methods: PUBMED and EMBASE were searched through April 2021 for randomized control trials (RCTs) investigating the efficacy and safety of the treatment with direct EMT or EMT with IA or IA in patients with acute stroke caused by anterior large vessel occlusion. The primary outcome was functional independence evaluated by the modified Rankin Scale (mRS) score of 0 to 2 at 90 days from the onset of symptoms. The secondary outcomes were successful recanalization within 72 hours all-cause mortality at 90 days and symptomatic intracranial hemorrhage within 7 days. Results: We identified 11 RCTs with a total of 3,640 patients with acute stroke. Compared to EMT with IA, direct EMT had similar effects on achieving the primary outcome (relative risk (RR): 1.02; 95% confidence interval (CI): 0.88-1.19, P=0.12, I 2 =36.6%) (Figure 1A) and successful recanalization within 72 hours (RR: 0.95; 95% CI: 0.85-1.07, P=0.04, I 2 =61.2%) and had similar risk of all-cause mortality (RR: 1.05; 95% CI: 0.85-1.31, P=0.69, I 2 =0%) and symptomatic intracranial hemorrhage within 7 days (RR: 0.83; 95% CI: 0.57-1.20, P=0.96, I 2 =0%). In addition, direct MT had higher proportions in the primary outcome (RR: 1.41; 95% CI: 1.15-1.74) (Figure 1B) and successful revascularization (RR: 1.63; 95% CI: 1.32-2.01) than IA alone therapy. Conclusions: The current study suggested that direct EMT therapy provided acceptable outcomes even in comparison to EMT with IA. Further RCTs are warranted to identify the specific population requiring the administration of IA before EMT compared to direct EMT.
The Coiled‐Coil Forming Peptide (KVSALKE)<sub>5</sub> Is a Cell Penetrating Peptide that Enhances the Intracellular Delivery of Proteins
Authors: Jie Li, Jan Tuma, Hesong Han, Hansol Kim, Ross C. Wilson, Hye Young Lee, Niren Murthy
Journal: Advanced Healthcare Materials (2021)

Protein-based therapeutics have the potential to treat a variety of diseases, however, safe and effective methods for delivering them into cells need to be developed before their clinical potential can be realized. Peptide fusions have great potential for improving intracellular delivery of proteins. However, very few peptides have been identified that can increase the intracellular delivery of proteins, and new peptides that can enhance intracellular protein delivery are greatly needed. In this report, the authors demonstrate that the coiled-coil forming peptide (KVSALKE)
Abstract 11006: Prevalence and Hemodynamic Profiles of Pulmonary Hypertension in Cardiac Amyloidosis
Authors: Jeremy Slivnick, Karolina Zareba, Juliet Varghese, Vien Truong, Alexander Wallner, Matthew S Tong, Christopher Hummel, Wojciech Mazur, Saurabh Rajpal
Journal: Circulation (2021)

Background: While cardiac amyloidosis (CA) classically involves the left ventricle (LV), less is known about its impact on the right ventricle (RV) and pulmonary vasculature. Objectives: We aimed to determine the prevalence and types of PH profiles in CA, and to determine hemodynamic and cardiovascular magnetic resonance (CMR) predictors of major adverse cardiovascular events (MACE). Methods: CA patients who underwent CMR and right heart catheterization (RHC) from 2010-2019 were included. Patients were assigned the following hemodynamic profiles: no PH, pre-capillary PH, isolated post-capillary PH (IPCPH), or combined pre- and post-capillary PH (CPCPH). Transpulmonary gradient (TPG)—the difference between mean pulmonary artery and wedge pressures, was calculated. The relationship between PH profile and MACE (death, heart failure hospitalization) was assessed using survival analysis. CMR and RV parameters were correlated with MACE using Cox-Regression analysis. To evaluate the importance of parameters for predicting MACE, Random Forest algorithm for survival analysis were applied. Results: A total of 52 patients were included (age 69±9 years, 85% male, 60% transthyretin, and 40% light chain CA). PH was present in 50 (96%) patients. RHC was performed during biopsy in 44(85%) and for clinical indications in 8(15%) patients. Rates of no PH, pre-capillary PH, IPC-PH, and CPCPH were 5(10%), 3(6%), 29(55%) and 15(29%) respectively (Panel A). Hemodynamic PH profile did not correlate with death (p=0.98) or MACE (p=0.67) (Panel B). TPG (HR 0.88, CI 0.80-0.97), RV, (HR 0.95, CI 0.92-0.98), and LV ejection fraction (HR 0.95, CI 0.92-0.98) were significantly associated with MACE. In Random Forest analysis, LVEF, RVEF, and TPG were the most important predictors of MACE (Panel C). Conclusions: PH is highly prevalent in CA, even at the time of diagnosis. While IPC-PH was most common, CPCPH is not infrequent. TPG and RVEF are prognostic markers in this population.
Abstract 13882: Increase in Reporting of Coronary Calcium: Is This a Sign of Improved Provider Awareness
Authors: Blake Campbell, Prabhakaran Gopalakrishnan
Journal: Circulation (2021)

Background: Coronary calcium (CC) is often demonstrated in Low dose chest CT scans (LDCT) performed for attenuation correction during SPECT myocardial perfusion studies (MPS). Reporting of presence or absence of CC (CC status) during MPS is variable. Absence of coronary calcium signifies lower risk for cardiovascular events. Methods: MPS performed in study period 1 (SP1) - first 2 months of 2018 (n=629) and study period 2 (SP2) - first 2 months of 2021 (n=611) were analyzed. Procedures without LDCT and patients with previous surgical or percutaneous revascularization were excluded. Final analysis included 487 studies from SP1 and 475 studies from SP2. LDCT images were analyzed for presence or absence of CC. MPS reports were analyzed for reporting of CC status. Provider level analysis was performed. Findings: During SP1, 10 cardiologists and 4 radiologists interpreted the studies. During SP2, 14 cardiologists and 6 radiologists interpreted the studies. In SP1, CC status was reported in 9.4% [cardiology 2.9% (Range: 0% - 13.8%), radiology 12.3% (0% - 26.2%)] of all studies and 16% [cardiology 5.3% (0% - 23.5%), radiology 19% (0% -40%)] of studies with CC. In SP2, CC status was reported in 70.1% [cardiology 71.7% (9.5%-100%), radiology 67.9% (0% - 100%)] of all studies and 74.4% (cardiology 78.9% (25% - 100%), radiology 66.3% (0%-100%)] of studies with CC. CC status reporting increased 7-fold (9.4% → 70.1%, p &lt;0.001). The increase was more significant among cardiologists (2.9% → 71.7%, p &lt; 0.001), than radiologists (12.3% → 67.9%, p = 0.16). Conclusion: Reporting of CC status during MPS was low in 2018 but improved significantly in 2021. The 25-fold increase in reporting of CC status among cardiology readers is likely related to increased awareness of significance of coronary calcium in Preventive cardiology. Routine reporting of CC noted during MPS may assist in cardiovascular risk stratification and disease prevention, especially when no perfusion defect is seen in the MPS study.
RTID-07. AN INVESTIGATOR-LEAD PHASE II CLINICAL TRIAL OF ACCELERATOR-BASED BNCT FOR REFRACTORY AND RECURRENT HIGH-GRADE MENINGIOMA
Authors: Shin-Ichi Miyatake, Shinji Kawabata, Satoshi Takai, Masahiko Wanibuchi
Journal: Neuro-Oncology (2021)

Abstract BACKGROUD Boron neutron capture therapy (BNCT) is tumor-selective particle radiation. We applied this unique technique and achieved excellent clinical results for recurrent and refractory high-grade meningiomas (HGM) using reactor neutron sources (Neuro-Oncology, in press, doi:10.1093/neuonc/noab108). Recently accelerator-based neutron sources (ABNS) was approved for medical device in Japan for refractory H&amp;N cancers. PURPOSES Based on these situations, we proposed “A phase II clinical trial using accelerator-based BNCT system for refractory recurrent HGM” for AMED in Japan which is similar to NIH in USA. This proposal was successfully accepted. DESIGN We prepared 2 study groups, BNCT test treatment group and control best supportive care group, for RCT. PFS and OS were set-up as primary and secondary endpoints, respectively. Rescue BNCT is allowed for control group patients, if they showed PD during observation. The trial started in August 2019. METHODS Twelve BNCT and 6 control subjects will be included. Patients’ eligibility criteria is recurrent HGM after some radiotherapy. Cyclotron-based ABNS system is used for neutron source. Neutron-irradiation time is determined not to exceed to 7.5 Gy-Eq for scalp dose which was referencing preceding phase I trial for malignant gliomas. PROGRESS As of March 2021, 13 subjects were included, 9 for BNCT treatment group, 4 for control best supportive care group. All 4 control subjects showed PD during 2 months while 8 out of 9 subjects showed SD or PR during observation period and there is a statistical significance in both groups, by Log-rank and Wilcoxon analyses with p=0.0012 and 0.0020, respectively. CONCLUSION We started this RCT and will introduce the interim report of this clinical trial in the meeting. At the SNO meeting we will present further detail of this trial.
Outcomes of Anti-PD1 Treatment for Relapsed/Refractory Hodgkin Lymphoma: A German Hodgkin Study Group (GHSG) Multi-Center Real-World Analysis
Authors: Jesko Momotow, Ina Bühnen, Karolin Trautmann-Grill, Guido Kobbe, Martin Wilhelm, Bernhard Heinrich, Tobias Gaska, Helmut Forstbauer, Burkhard Schmidt, Andreas Hüttmann, Gerhard Heil, Doris M. Kraemer, William Hermann Krüger, Vanja Zeremski, Norbert Grobe, Kathleen Jentsch-Ulrich, Michael Fuchs, Bastian von Tresckow, Peter Borchmann, Andreas Engert, Paul J Bröckelmann
Journal: Blood (2021)
Abstract 13839: Knowledge, Attitude & Practice of Health Care Workers Regarding Pediatric Early Warning System - A Cross Sectional Study in Karachi, Pakistan
Authors: Azwa Aziz, Qalab Abbas, Mehtab Jaffer, Noureen Sultan, Laila Ladak
Journal: Circulation (2021)

Introduction: The Pediatrics Early Warning Scoring (PEWS) system is a quantitative instrument that measures the severity of the clinical situation of children aged 1 month to 18 years. Hypothesis: ...
QOLP-17. YOGA THERAPY AS A SUPPORTIVE CARE STRATEGY FOR FAMILY CAREGIVERS OF HIGH GRADE GLIOMA PATIENTS: RESULTS OF 3-ARM PILOT RANDOMIZED CONTROLLED TRIAL
Authors: Kathrin Milbury, Jing Li, Shiao-Pei Weathers, Rosangela Silva, Stella Snyder, Yisheng Li, Cohen Lorenzo
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND This pilot RCT compared the feasibility and preliminary efficacy of a dyadic versus individual yoga intervention as a supportive care strategy for family caregivers of high grade glioma patients. METHODS Caregivers completed self-reported assessments of QOL (SF-36) and caregiver burden (CRA) and were then randomized to a patient-caregiver dyadic yoga (DY), caregiver yoga (CY) or usual are (UC) arm while patients were undergoing standard radiotherapy. Both yoga programs were delivered over 15 sessions either in-person or via videoconference (Zoom). All groups were re-assessed at the end of treatment and then again 3-months later. RESULTS We consented 76 dyads (59%) and randomized 23 to the DY, 22 to the CY, and 22 to the UC arm. Attendance in the DY was higher than in the CY group (means, DY=12.23, CY=9.00, P=.06, d=.57). Caregivers reported significantly more overall subjective benefit in the CY compared to the DY arm (means, CY=1.39, DY=1.81, P&amp;lt; .05, d=1.45). Caregivers slightly favored the in-person delivery (means, in person: 1.48; zoom: 1.82, P=.10; d=.77). A clinically significant, medium effect size was found for improved QOL in favor of the CY over the DY group (means, CY=49.45, DY=44.45; F=3.58, P=.07; d=.67). Caregivers in the CY group reported less caregiving-related health declines compared to the DY group (means, CY=2.18; DY=2.48; F=4.23, P&amp;lt; .05; d=.42). Caregivers in the CY group reported less caregiving-related financial burden than the UC group (means: CY=2.79; UC=3.21; F=3.32, P=.08; d=.35). CONCLUSION Despite lower attendance, caregivers in the CY arm reported greater subjective overall benefit, experienced better mental QOL and less caregiver burden compared with those in the DY and UC comparison arms. It appears that individual rather than dyadic delivery may be a superior supportive care approach for this vulnerable caregiver population. An adequately powered, larger trial of this intervention strategy is warranted.
Abstract 11859: Elevated Troponins and Ischemic Cardiomyopathy Are Predictive of Percutaneous Coronary Intervention in Patients With Pulmonary Embolism
Authors: Omar K Shahin, Samantha Z Gelman, Scott Kubomoto, Javad Savoj, George Hanna, Patankar Kaustubh
Journal: Circulation (2021)

Introduction: Pulmonary embolism is a common cause of myocardial strain. As such, patients with pulmonary embolism will have evidence of myocardial injury on laboratory assessment. This can be measured using a troponin assay. Of the patients who present with elevated troponins and pulmonary embolism, there is minimal evidence to guide the decision on whether a patient will benefit from left heart catheterization and coronary angiography. We sought to analyze troponin levels and risk factors for percutaneous coronary intervention (PCI) in a large dataset of patients hospitalized with pulmonary embolism. Methods: This was a retrospective study of 3929 patients who were admitted with pulmonary embolism in 2018 and 2019 at HCA Healthcare hospitals across the United States. Patients with other factors that could cause troponin elevation, such as a ST elevation myocardial infarction, chronic kidney disease, and sepsis, were excluded. Binary logistic regression model was utilized to examine risk factors for PCI. Results: Troponin I level was elevated in 68.9% (2707) of patients, 7.68% (208) of those patients with an elevated troponin had a left heart catheterization, and, of the patients that underwent a left heart catheterization, 26.92% (56) had PCI. The mean age of all subjects was 65.1 years and 52.4% of subjects were female. A total of 73.07% (2871) of subjects had coronary artery disease. Multivariable logistic regression showed maximum troponin value was associated with increased chance of PCI. For every ng/mL increase in troponin level, the odds of PCI increased by 2.5% (p=0.017). Patients with ischemic cardiomyopathy were 4.4-times more likely to have PCI than those without (p=0.010). Race, gender, and age were not significantly associated with risk of PCI. Conclusions: Elevated troponin is common in patients admitted with pulmonary embolism. In our dataset 7.7% of patients with elevated troponin received left heart catheterization and 26.9% of left heart catheterizations resulted in PCI. Higher troponin and known ischemic cardiomyopathy were independently associated with increased likelihood of PCI. Further analysis may help find additional factors to suggest which patients with elevated troponin should have left heart catheterization.
Abstract 11057: Measures of Heart Rate Variability as Predictors of Clinical Outcome in Patients with Chronic Heart Failure - Results from the Myovasc Study
Authors: Alexander Schuch, Silav Zeid, Gregor Buch, David Velmeden, Marc Heidorn, Felix Mueller, Sven-Oliver Troebs, Karl J Lackner, Tomaso Gori, Thomas Muenzel, Juergen Prochaska, Philipp Wild
Journal: Circulation (2021)

Introduction: Evidence supports a potential prognostic value of heart rate variability (HRV) in patients with chronic heart failure (HF). Comprehensive data comparing different domains of HRV in relation to clinical outcome in HF are scarce. Methods: Subjects with chronic HF (i.e. AHA stage C or D) from the MyoVasc study (NCT04064450; N=3,289), a prospective cohort study, were analyzed. Individuals with pacemaker or atrial fibrillation were excluded. All participants received a highly standardized medical-technical examination during a five-hour visit in a dedicated study center. Data from 24-hour Holter ECG recordings were analyzed resulting in HRV markers from the time and frequency domain, and non-linear HRV measures. Information on clinical outcome, i.e. worsening of HF (WoHF), was derived from structured follow-up with subsequent validation and independent adjudication of endpoints. Random forest models were used to identify the most predictive marker of each HRV domain, which were further analyzed with multivariable Cox regression. Results: The analysis sample comprised 554 HF subjects (mean age: 66.4±9.9 years, 34.3% female sex) with HRV data. During a median observational period of 4.08 years (interquartile range 2.22; 5.22), 153 participants experienced WoHF. In random forest analyses, the rMSSD (time domain), high frequency power in normalized units (HF nu ; frequency domain), and SD1/SD2 (non-linear measure) were ranked as most predictive HRV markers for WoHF in each HRV domain. Subsequent Cox regression analysis demonstrated that log(SD1/SD2) (hazard ratio (HR) per standard deviation 1.50, 95%CI 1.29;1.75; P&lt;0.0001), HF nu (HR SD 1.47, 95%CI 1.23;1.77; P&lt;0.0001) and log(rMSSD) (HR SD 1.36, 95%CI 1.17;1.57; P&lt;0.0001) were strong predictors of HF outcome independent of age, sex, clinical profile, and medication. In Cox regression analysis with adjustment for NT-proBNP and the established HF risk score MAGGIC, HF nu (HR SD 1.25, 95%CI 1.05;1.48; P=0.012) and log(SD1/SD2) (HR SD 1.24, 95%CI 1.07;1.43; P=0.005) remained independent predictors of WoHF. Conclusions: Markers of HRV were identified as strong predictors for HF outcome independent of established risk markers, suggesting a potential to advance risk stratification.
Mitigating the severity of child homelessness in the UK: a global mixed-methods systematic review
Authors: Kaushik Sarkar, Diana Margot Rosenthal, Daniela Cossio Martinez, Arunima Shrestha, Sushma Acquilla, Nadzeya Svirydzenka, Michelle Heys, Marcella Ucci, Paula Lorgelly, Raghu Raghavan, Rob Aldridge, Monica Lakhanpaul
Journal: The Lancet (2021)
Abstract MP226: Netosis Is Required For S100a8/a9-induced Granulopoiesis After Myocardial Infarction
Authors: Gopalkrishna Sreejit, Robert M Jaggers, Albert Dahdah, Jillian Johnson, Ahmed Abdel Latif, Andrew Murphy, Prabhakara R Nagareddy
Journal: Circulation Research (2021)

Myocardial infarction (MI) provokes a massive systemic inflammatory response characterized by enhanced infiltration of neutrophils to the ischemic heart via granulopoiesis in the bone marrow. We recently discovered that S100A8/A9 is released by infiltrating neutrophils in the infarct to induce granulopoiesis by interacting with TLR4 on naïve neutrophils, priming the NLPR3-inflammasome for release of IL-1β which then leads to increased granulopoiesis. However, the mechanism of S100A8/A9 release from the infiltrating-neutrophils remain unclear. We hypothesized that neutrophils release S100A8/A9 via NETosis, a form of cell-death that involves extrusion of decondensed chromatin along with its entire granular content including S100A8/A9. To validate this hypothesis we found that neutrophils sorted from mouse heart 24 hours post-MI were enriched for genetic signature for an Nox-independent NETosis, dominated by Padi4. Furthermore, we found a robust increase in citrullination of histone moieties, colocalization of S100A8/A9 with H3Cit, and increased S100A8/A9 levels in the heart as early as 6 hours after MI. Depletion of Padi4 in the mouse myeloid cells by bone marrow transplantation studies was also associated with suppressed granulopoiesis, fewer neutrophils in the blood and heart, and reduced cardiac and serum S100A8/A9 after MI. To validate these findings in humans, we measured various markers of NETosis and found a marked increase in serum double-stranded DNA, MPO (myeloperoxidase) elastase, which paralleled S100A8/A9 levels in STEMI patients from the time of admission through post-revascularization by percutaneous coronary intervention. Taken together we propose that interventions to reduce NETosis and/or S100A8/A9 release particularly during the acute inflammatory phase could represent a departure from the status quo in managing post-MI inflammation and the subsequent heart failure.
Abstract 14091: Systemic Hypoxemia Induces Cardiomyocyte Cell Cycle Re-Entry but Few Myocytes Appear to Truly Divide
Authors: Jaslyn Johnson, Yijun Yang, Polina Gross, Deborah Eaton, Giana Schena, Remus M Berretta, Hajime KUBO, Sadia Mohsin, Ying Tian, Steven R Houser
Journal: Circulation (2021)

Rationale: The adult mammalian heart has a very limited capacity to regenerate cardiomyocytes that die from pathological damage. Several studies suggest that those few new myocytes found after injury are derived from pre-existing cardiomyocytes. A recent study suggests that systemic hypoxemia in adult mice can induce their cardiac myocytes to reenter the cell cycle and form two daughter cells. The goal of the present experiments was to determine if hypoxemia can induce adult murine cardiomyocytes to reenter the cell cycle and divide. Hypothesis: Hypoxia induces adult cardiomyocytes to complete the cell cycle and form new cardiac myocytes. Methods and Results: EdU mini pumps were implanted in 2-month-old C57BL/6 mice. Mice were then placed in a hypoxia chamber and the oxygen was lowered by 1% every day for 14 days to reach a final concentration of 7% oxygen. The animals remained in hypoxia (7% Oxygen) for 2 weeks and then were euthanized. Hypoxic mice had an increase in heart weight and echocardiography documented an increase in cardiac pump function and LV wall thickness when compared to control mice. Analysis of isolated cardiac myocytes in C57BL/6 animals showed an increase in EdU+ cardiomyocytes in hypoxemia and DAPI fluorescence intensity was also increased in these EdU+ myocytes which may indicate DNA synthesis. In fixed heart tissue sections, hypoxic mice contained more EdU+ myocytes and had an increase in the total amount of EdU+ cells in the heart. To further evaluate cardiomyocyte proliferation, we employed a mosaic mouse model with double markers (MADM) in which myocytes entering the cell cycle express both red fluorescent protein (RFP) and green fluorescent protein (GFP) and therefore are yellow in color. When cells complete the cell cycle and divide they express only RFP or GFP. MADM mice were exposed to hypoxia at 7% Oxygen as described above. MADM mice subjected to hypoxemia had increased numbers of yellow myocytes versus controls. There was a much smaller number of hypoxic myocytes with just RFP or GFP. Conclusion: Systemic hypoxia induces cardiac myocyte cell cycle re-entry and DNA synthesis, but it seems that very few of these myocytes complete the cell cycle and divide into two daughter cells.