tbuckley/cabot-search huggingface dataset:
Abstract 9678: The Association of Statins Use With Survival of Covid-19 Patients
Authors: Matsuo So, Mai Takahashi, Natalia Egorova, Toshiki Kuno
Journal: Circulation (2021)

Introduction: Statins are frequently prescribed for patients with hypertension, dyslipidemia and diabetes mellitus. These comorbidities are highly prevalent in COVID-19 patients. Statin’s beneficial effect on mortalities in COVID-19 infection has been reported in several studies, but still inconclusive. Hypothesis: The inconclusive study results in association of satin use and COVID-19 can be resulted from variable timing of statins used among the studies. Our aim was to investigate whether consistent use of statins before and during hospitalization was effective to decrease the mortality due to COVID-19. Methods: We conducted a retrospective study among 6,095 patients with COVID-19 hospitalized in New York City between March 1st 2020 and May 7th 2021. Patients were stratified into two groups: statins use prior or during hospitalization (N=2,423) versus no statins (N=3,672). We evaluated in-hospital mortality as a primary outcome using propensity score matching and inverse probability treatment weighted (IPTW) analysis. In addition, we compared continuous use of statins (N=1,108) versus no statins. Results: Statins use prior or during hospitalization group were older (70.8±12.7 versus 59.2±18.2, P&lt;0.001) and had more comorbidities compared to no statins group. After matching by propensity score (1,790 pairs), there were no significant differences in in-hospital mortality between patients with statins versus those without (28.9% versus 31.0%, P=0.19, odds ratio (OR) [95% confidence interval (CI)]: 0.91 [0.79-1.05]). This result was confirmed using IPTW analysis (OR [95% CI]: 0.96 [0.81-1.12], P=0.53). As the additional analysis comparing continuous use of statins versus no statins group, in-hospital mortality was significantly lower in continuous use of statins compared to no statins group (26.3% versus 34.5%, P&lt;0.001, OR [95% CI]: 0.68 [0.55-0.82]) after matching by propensity score (944 pairs). IPTW analysis showed the similar result (OR [95% CI]: 0.77 [0.64-0.94], P=0.009). Conclusions: Use of statins prior or during hospitalization was not associated with a decreased risk of in-hospital mortality, however, continuous use of statins might have potential benefit of a decreased risk of in-hospital mortality due to COVID-19.
CNTM-04. Alterations in structural connectomic properties associated with neurocognitive changes following glioma resection
Authors: Kyle Noll, Drew Mitchell, Henry Chen, Jeffrey Wefel, Vinodh Kumar, Ping Hou, Sherise Ferguson, Ganesh Rao, Jason Johnson, Donald Schomer, Sujit Prabhu, Ho-Ling Liu
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Patients with brain tumors often experience decline in neurocognitive functioning (NCF) following surgical tumor resection. Connectomic studies have begun to uncover how abnormalities to underlying cerebral networks contribute to NCF deficits; however, few studies have investigated relationships between pre- to postoperative changes in structural connectomics and NCF. METHODS Fifteen right-handed adults with left perisylvian tumors underwent MRI of the brain with diffusion tensor imaging (DTI) and neuropsychological assessment before and after awake tumor resection. Graph theoretical analysis was applied to DTI-derived connectivity matrices to calculate structural network properties. Structural network properties and NCF measures were compared across the pre- to postoperative periods with matched pairs Wilcoxon signed-rank tests. Associations between pre- to postoperative change in network properties and change in NCF were determined with Spearman rank-order correlations (ρ). RESULTS Nearly 90% of the sample showed postoperative decline on 1 or more NCF measures. Significant postoperative NCF decline was found across measures of verbal memory, processing speed, executive functioning, receptive language, and the Clinical Trial Battery Composite (CTB COMP) index. Regarding connectomic properties, significant postoperative changes were observed in global and local efficiency, characteristic path length, clustering coefficient, betweenness centrality, and assortativity, with medium effect sizes. Significant associations (ρ = .59 to .62, all p &amp;lt; .05) were observed between changes in aspects of NCF and connectomic properties. CONCLUSIONS Decline in NCF was common following resection and some postoperative outcomes were associated with changes in structural connectomic properties following surgery.
CTIM-06. CLINICAL EFFICACY AND BIOMARKER ASSESSMENT OF VT1021, A CD36/CD47 DUAL-TARGETING AGENT, IN RECURRENT GLIOBLASTOMA
Authors: Manmeet Ahluwalia, James Battiste, Bruno Bockorny, Andrea Bullock, Manish Patel, Patrick Wen, Dale Shepard, Lou Vaickus, Melanie Vincent, Jian jenny Chen, Suming Wang, Randolph Watnick, Marsha Crochiere, Michael Cieslewicz, Jing Watnick
Journal: Neuro-Oncology (2021)

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain malignancy in adults and recurs after treatment in &amp;gt;90% of all patients. Prognosis of patients with recurrent GBM (rGBM) is poor with a median progression free survival of ~1.8 months and median overall survival of 8-10 months. VT1021, a cyclic peptide derived from prosaposin, induces the expression of thrombospondin-1 (TSP-1) in myeloid derived suppressor cells (MDSCs), which are heavily recruited to the tumor microenvironment. Following completion of the Phase 1 Dose Escalation study and determination of the RP2D, an expansion study was conducted in a heavily pretreated rGBM population. The results of the expansion study reveal that VT1021 is safe and well tolerated in rGBM. Pharmacodynamic response to VT1021 was observed by induction of TSP-1 in circulating MDSCs and in the tumor microenvironment. VT1021 demonstrated significant single agent activity. Among 22 evaluable GBM subjects, 3 had complete response (CR), 1 had partial response (PR), and 7 had stable disease (SD) with an average study duration of over 120 days. The overall disease control rate (DCR) was 50%. Among the 3 CR, 2 showed complete radiological regression of the target lesion, the third was found to have no evidence of disease upon pathological examination following surgery. Nine of the 19 (47%) evaluable subjects with available biopsy samples showed high expression levels of both CD36 AND CD47. Among these 9 subjects, 3 achieved CR, representing an overall response rate of 33.3%, with another 3 patients achieving SD for a DCR of 67%. In conclusion, VT1021 demonstrates promising single-agent clinical activity in rGBM, particularly in subjects with high expression levels of CD36 and CD47. Additional clinical studies have been planned to further investigate the efficacy of VT1021 in rGBM and other solid tumor indications.
RNA binding protein DDX5 directs tuft cell specification and function to regulate microbial repertoire and disease susceptibility in the intestine
Authors: Tianyun Long, Nazia Abbasi, Juan E Hernandez, Yuxin Li, Ibrahim M Sayed, Shengyun Ma, Attilio Iemolo, Brian A Yee, Gene W Yeo, Francesca Telese, Pradipta Ghosh, Soumita Das, Wendy Jia Men Huang
Journal: Gut (2021)

Tuft cells residing in the intestinal epithelium have diverse functions. In the small intestine, they provide protection against inflammation, combat against helminth and protist infections, and serve as entry portals for enteroviruses. In the colon, they had been implicated in tumourigenesis. Commitment of intestinal progenitor cells to the tuft cell lineage requires Rho GTPase Cell Division Cycle 42 (CDC42), a Rho GTPase that acts downstream of the epidermal growth factor receptor and wingless-related integration site signalling cascades, and the master transcription factor POU class 2 homeobox 3 (POU2F3). This study investigates how this pathway is regulated by the DEAD box containing RNA binding protein DDX5 in vivo.
Surgery versus radiofrequency ablation in patients with Child- Pugh class-A/single small (≤3 cm) hepatocellular carcinoma
Authors: Jungnam Lee, Young-Joo Jin, Seung Kak Shin, Jung Hyun Kwon, Sang Gyune Kim, Young Ju Suh, Yujin Jeong, Jung Hwan Yu, Jin-Woo Lee, Oh Sang Kwon, Soon Woo Nahm, Young Seok Kim
Journal: Clinical and Molecular Hepatology (2021)

We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA).We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2-3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment.The median follow-up period was 64.8 months (interquartile range, 0.1-162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P<0.001), but not in those with HCC of ≤2 cm (P=0.234). The weighted Cox proportional hazards model with IPW provided adjusted hazard ratios (95% confidence interval) for OS, and the RFS after RFA versus SR were 0.698 (0.396-1.232) (P=0.215) and 1.698 (1.777-2.448) (P=0.005), respectively.SR was similar for OS compared to RFA, but was better for RFS in patients with CTP class-A and single small (≤3 cm) HCC. The RFS was determined by the presence or absence of cirrhosis. Hence, SR rather than RFA should be considered in patients without cirrhosis to prolong the RFS, although there is no OS difference.
Abstract 11963: A Digital Heart Failure Coach Intervention for Improving Education, Self-Management and Outcomes in Patients Admitted for Acute Decompensated Heart Failure: Barriers to Effective Implementation
Authors: Georgios Zisis, Melinda J Carrington, Brian Oldenburg, Kristyn Whitmore, Maria Lay, Quan Huynh, Christopher Neil, Jocasta Ball, Thomas Marwick
Journal: Circulation (2021)

Introduction: Heart Failure (HF) education is fundamental for improving outcomes. The use of mobile health (m-health) devices and Artificial Intelligence (AI) are becoming more broadly available. We designed an avatar style digital HF coach (HF-app) to improve HF knowledge and self-care management. Hypothesis: We hypothesized that an avatar style HF-app could improve outcomes by enhancing HF knowledge and improving quality of life and self-care behaviors in patients admitted for Acute Decompensated HF (ADHF). Methods: The Risk-HF trial recruited patients admitted for ADHF who were at high risk for hospital readmission and/or death (defined by a previously developed risk score, ETHELRED trial). Patients were randomized to usual care or intervention, in which the HF-app was a component of a multifactorial intervention aimed at reducing HF readmissions. Our HF-app was designed to engage daily with the patient by monitoring HF symptoms and delivering education over 52-days. Results: Over a period of 16 months (August 2019 up until December 2020), 36 of 74 high risk patients were randomized to the intervention arm and were offered education with our HF-app. Of these, 26/36 (72%) had restricted access to the HF-app ( unable to use a tablet device and/or unwilling to be taught how to use it, n=20; no internet access, n=4; died in hospital n= 2 ) and 10/36 (28%) were enrolled to use the HF-app [ gender male n=7; median age 71.5 years, p&lt;0.01 (IQR: 57.50 - 78.50); mean years of education 11.6(±2.5), p&lt;0.01 ]. Younger patients [ Odds Ratio (OR) 0.89 [95% Confidence Interval (CI): 0.82-0.97], p&lt;0.01 ] and those with a higher education level [ OR 1.58 (1.09-2.28), p=0.03 ] were more likely to enroll. Of those enrolled, only two patients engaged and completed ≥70% of the program. Six of the remaining 8 patients who did not engage were readmitted. Conclusions: Our study provides a note of caution in studies using m-health devices and apps in critically ill and elderly patients with unstable HF. Future research should consider how to use such technology-based interventions with elderly patients as well as to target younger ADHF patients, which may provide stronger evidence of benefits in patient self-care and outcomes.
Selexipag for the treatment of chronic thromboembolic pulmonary hypertension
Authors: Takeshi Ogo, Hiroto Shimokawahara, Hideyuki Kinoshita, Seiichiro Sakao, Kohtaro Abe, Satoaki Matoba, Hirohiko Motoki, Noriaki Takama, Junya Ako, Yasuhiro Ikeda, Shuji Joho, Hisataka Maki, Takahiro Saeki, Teruyasu Sugano, Ichizo Tsujino, Koichiro Yoshioka, Naoki Shiota, Shinichi Tanaka, Chieko Yamamoto, Nobuhiro Tanabe, Koichiro Tatsumi
Journal: European Respiratory Journal (2021)

Background Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide. Results The change in PVR was −98.2±111.3 dyn·s·cm −5 and −4.6±163.6 dyn·s·cm −5 in the selexipag and placebo groups, respectively (mean difference −93.5 dyn·s·cm −5 ; 95% CI −156.8 to −30.3; p=0.006). The changes in cardiac index (p&lt;0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue. Conclusion Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.
Abstract 12193: Efficacy and Safety of Rivaroxaban versus Vitamin K Antagonists in the Treatment of Left Ventricular Thrombi: A Meta-Analysis
Authors: Abdullah Al-abcha, Yehia Saleh, Ola Abdelkarim, Harith Ghnaima, Manel Boumegouas, Khader Herzallah, george Abela
Journal: Circulation (2021)

Introduction: Left ventricular (LV) thrombus is a well-recognized complication of LV systolic dysfunction, especially in the setting of acute myocardial infarction. Multiple recent studies looked into the efficacy and safety of direct oral anticoagulants but limited number of studies reported outcomes in patients on rivaroxaban specifically. Hypothesis: Rivaroxaban is as effective as vitamin K antagonists (VKAs) in the treatment of LV thrombus. Methods: We conducted a meta-analysis of all studies that evaluated clinical outcomes of rivaroxaban versus warfarin in the treatment of LV thrombus. The primary outcome was thrombus resolution. Secondary outcomes included bleeding events, and systemic embolism. Results: One randomized clinical trial (RCT), and 3 retrospective observational studies with a total of 988 patients were included. Heterogeneity was low-moderate across the trials (19-54%). Thrombus resolution was numerically higher in the rivaroxaban arm but did not reach statistical significance (Rivaroxaban 80% vs VKAs 70%, p=0.57). Bleeding events (Rivaroxaban 9% vs VKAs 11%, p=0.77) and systemic embolism (Rivaroxaban 21.5% vs VKAs 30.9%, p=0.57) were both similar between the two arms (Figure). Conclusions: Rivaroxaban has similar efficacy and safety when compared to VKAs in the treatment of LV thrombus. Large RCTs are needed to confirm these results.
Abstract 10316: De-escalation of Guideline-Directed Medical Therapy in Ambulatory Heart Failure: Insights from the EPIC-HF Trial
Authors: Jonathan E Lipsey, Larry A Allen, Laura Helmkamp, Geoffrey Harger, Stanley Swat, Tristan Dow, Dan D Matlock, Colleen K McIlvennan
Journal: Circulation (2021)

Background: Despite proven benefits of guideline directed medical therapy (GDMT) for patients with heart failure with reduced ejection fraction (HFrEF), multiple studies have shown that rates of GDMT prescribing are suboptimal worldwide. The recently completed EPIC-HF trial demonstrated that a pre-clinic patient activation tool significantly increased GDMT intensification following a visit with a cardiology provider. However, whether GDMT intensification was sustained or associated with subsequent de-escalation was unknown. Methods: The EPIC-HF trial reported GDMT intensification at 1 month follow-up after the initial clinic visit. We analyzed GDMT prescription data from 1 to 6 month follow-up to examine the effect of an initial GDMT intensification by 1 month on subsequent rates of GDMT de-escalation from 1 to 6 months. Results: A total of 282 patients completed 6 month follow-up. From the study visit to 1 month follow-up, 39.7% (n=112) had an initial GDMT intensification. An initial intensification was not significantly associated with subsequent de-escalation of any GDMT medication from 1 to 6 month follow-up (24.1% de-escalated after no initial change vs 28.6% after initial intensification, p=0.40), nor was it significantly associated with de-escalation of any individual class of medication (BB 8.8% vs 11.6%, p=0.44; ACE-I 5.9% vs 8.9%, p=0.33; ARB 5.3% vs 6.3% p=0.73; MRA 6.5% vs 8.0%, p=0.62). Initial GDMT intensification was associated with dose reduction or discontinuation of loop diuretic (4.1% vs. 11.6%, p=0.02). Conclusions: Patients who had GDMT intensified at an initial visit were not significantly more likely to have a subsequent de-escalation by 6 month follow-up; however, they were more likely to have their loop diuretic down-titrated or discontinued.
Abstract 13188: Invasive versus Conservative Strategy for Stable Coronary Artery Disease in Patients With Low Ejection Fraction
Authors: Qiying Dai, Abhishek Bose, Nitish Sharma, neeta shah, Eddison Ramsaran
Journal: Circulation (2021)

Introduction: Patient with stable coronary artery disease (CAD) are asymptomatic or symptom-controlled despite the presence of an underlying supply-demand mismatch. Studies have revealed no significant differences in all-cause mortality between medical therapy and invasive strategy. However, a recent study with subgroup analysis showed high risk patients with an ejection fraction (EF) of 35%-45% faring better with an invasive approach. Since the initial treatment strategy for stable CAD patients with reduced EF remains unclear, we performed a retrospective analysis. Methods: A total of 302 patients were enrolled between 2014-2019 and followed for a period of at least 16 months. All patients were classified as intermediate risk or high risk based on their nuclear stress test with an EF less than 40%. Patients were divided based on whether they underwent an initial invasive strategy versus medical management. A multivariable Cox regression analysis was performed to compare the primary outcome of all-cause mortality between the two groups. Results: Patients undergoing an initial invasive strategy were younger (68.3 ± 11.4 vs 71.1 ± 12.1 years, P = 0.04) compared to the medical therapy group. During follow up, 26 (18.3%) versus 48 (30.0%) patients died in the invasive versus medical therapy group, respectively. After adjusting for baseline demographics and comorbidities, we found no significant difference in mortality between the two groups (P=0.24) ( Figure ). Older age (HR = 1.08, P &lt;0.001) and the presence of chronic lung disease (HR = 1.87, P = 0.014) were factors associated with higher mortality among stable CAD patients with low EF. Conclusions: In patients with stable CAD and low EF, an initial invasive approach has no significant mortality benefit when compared to medical therapy. An older age and a history of chronic lung disease predicted higher mortality in this patient population.
Abstract 11578: Genome-Wide Pleiotropy Analysis of Coronary Artery Disease and Pneumonia
Authors: Zhi Yu, Seyedeh Zekavat, Sara Haidermota, Rachel Bernardo, Peter Libby, Hilary Finucane, Pradeep Natarajan
Journal: Circulation (2021)

Introduction: Pneumonia correlates strongly with coronary artery disease (CAD) risk, and influenza vaccination reduces CAD risk in trials. Elucidating shared pathways may elucidate novel insights regarding residual CAD risk. Hypothesis: Genetic alleles exhibit pleiotropy for pneumonia and CAD, and may be leveraged for causal inference. Methods: We performed genome-wide pleiotropy analyses CAD and pneumonia with the PLACO method using summary statistics from CARDIoGRAMplusC4D (CAD) and FinnGen v4 (pneumonia). For genes near independently replicated SNPs (in UK and Mass General Brigham Biobanks) and expressed in GTEx v8 tissues, we examined the causal effects of index and interacting (by STRING) gene expression with CAD and pneumonia through Mendelian randomization (MR). Lastly, we examined for interactions between prioritized SNPs and smoking status on incident CAD and pneumonia risks. Results: Among 115 SNPs with significant genetic pleiotropy between CAD and pneumonia, 90 of them were replicated, and nearby genes ( ADAMTS7 , IL6R ) showed heritable gene expression. Across tissues, increased ADAMTS7 expression consistently showed decreased risk for CAD and increased risk for pneumonia, and increased IL6R expression showed increased risk for CAD and decreased risk for pneumonia. Among genes that interacted closely with ADAMTS7 and IL6R , NLRP3 similarly demonstrated significant causal effects on CAD and pneumonia in the same directions as that of ADAMTS7 . Sensitivity analysis using multiple MR methods yielded consistent results. The presence of ADAMTS7 p.Ser214Pro conferred a significantly reduced risk of CAD among non-smokers but not those who ever smoked ( P interaction 0.01) and a significantly increased risk of pneumonia only among those who ever smoked ( P interaction 0.0003). Conclusions: Genetic immune-inflammatory axes of CAD linked to respiratory infections implicate ADAMTS7 and IL6R , and related genes.