tbuckley/cabot-search huggingface dataset:
Abstract 14047: Extended Follow-Up Results From a Prospective RCT for Transcatheter Bariatric Embolotherapy for Weight Loss in Obese Subjects
Authors: Vivek Y Reddy, Martin Fried, Petr Neuzil, Robert Rosen, Petra Sramkova, Nodar Kipshidze, Nickolas kipshidze
Journal: Circulation (2021)

Introduction: Obesity is an important risk factor associated with poor cardiovascular outcomes. Lifestyle modification, pharmaceutical, and intragastric balloons weight loss therapy are often unsuccessful, unsustainable, or accompanied by risks. Transcatheter bariatric embolotherapy (TBE) is a promising therapy in which the left gastric artery is embolized to reduce the expression of “hunger” hormones from the gastric fundus. Despite several early clinical trials, long-term safety or efficacy has yet to be studied. We originally studied TBE in a double-blind, sham procedure, first in human RCT of 40 obese patients (pts) (NCT03185949). Complete details regarding the initial RCT were previously published, briefly the study demonstrated up to 9.3% TBWL at 1-year post-TBE. Following completion of the initial study at 1 year follow-up, we asked subjects to return for long-term evaluation. Methods: Subjects who previously completed the RCT with no major protocol deviations were asked to return for SOC follow-up visits at 2-, 2.5-, and 3-years post-embolization for further evaluation on weight loss, blood pressure, pre-diabetic clinical status, satiety, and Quality of Life (QoL). Given the evolving situation of the COVID-19 pandemic, the study site was unable to complete all planned study visits. Results: Between 2-3 years post-TBE subjects (n=11) demonstrated a mean 9% TBWL and 25% EBWL. This cohort of patients demonstrated a long-term weight loss maintenance, with previously reported weight loss of 8% TBWL at 1-year post-embolization. Overall QoL at 2 years post-TBE increased by approximately 22%. The volume to achieve satiety was reduced by 33% in long-term follow-up. Oral Disposition Index increased from 1.89 mM -1 at 6 months post-TBE to 4.41 mM -1 2 years post-TBE. 1-hr Oral Glucose Tolerance Test (OGTT) C-Peptide levels decreased from 3.22 nmol/L at 6 months to 2.53 nmol/L at 2 years post-TBE. 2-hr OGTT C-Peptide levels also showed a decrease from 2.95 nmol/L at 6 months to 1.78 nmol/L at 2 years post-TBE, possibly indicating an improvement in pre-diabetic status. Conclusions: Bariatric embolization is safe and when used along with lifestyle therapy, results in clinically significant and sustained weight loss up to 2-3 years post-TBE.
Characteristics and risk factors for thrombosis in <scp>POEMS</scp> syndrome: A retrospective evaluation of 230 patients
Authors: Patrick W. Mellors, Taxiarchis Kourelis, Ronald S. Go, Eli Muchtar, Morie A. Gertz, Shaji K. Kumar, Francis K. Buadi, Prashant Kapoor, Martha Q. Lacy, David Dingli, Yi Hwa, Amie Fonder, Miriam Hobbs, Suzanne Hayman, Rahma Warsame, Nelson R. Leung, Yi Lin, Wilson Gonsalves, Mustaqeem Siddiqui, Robert A. Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: American Journal of Hematology (2021)

Thromboses are prevalent in POEMS syndrome, but few risk factors for POEMS-associated thrombosis have been identified. The objective of this study is to identify novel risk factors for POEMS-associated thrombosis. In this retrospective cohort of 230 POEMS patients, 27% developed thrombosis. Arterial events were slightly more common than venous. Stroke accounted for 26% of all thromboses and 53% of arterial events. There were differences in baseline features between the thrombosis group and the no thrombosis group, and these were driven by patients with arterial thrombosis. Risk factors for arterial thrombosis included thrombocytosis, elevated hemoglobin/hematocrit, extravascular volume overload, and splenomegaly. Hyperprolactinemia appeared to be a risk factor for venous thrombosis. The risk of thrombosis was most striking among men with elevated hemoglobin (32% vs. 5%, p < .001) and hematocrit (42% vs. 5%, p < .001) compared to men without. Most thromboses occurred prior to POEMS directed therapy, and most that occurred during therapy happened within 3 months of diagnosis. Twenty-one percent of patients with thrombosis had recurrence. In recognition of high overall rates of thrombosis in this population, all patients with POEMS syndrome should receive prophylactic antiplatelet therapy, and clinicians should consider anticoagulation in patients with risk factors for POEMS-associated thrombosis.
Abstract 13285: Sensitivity to Beta-Adrenergic Stimulation in Pediatric Failing Single Ventricle Myocardium
Authors: Stephanie J Nakano, Jessica A Schwisow, Bonnie Neltner, Matthew Stone, Brian L Stauffer, Carmen Sucharov, Michael Bristow, Shelley Miyamoto
Journal: Circulation (2021)

Introduction: Children with heart failure (HF) in the context of palliated single ventricle congenital heart disease (SV) are treated with various pharmacotherapies, all with limited efficacy. Specifically, outcomes with β-blockade for HF in SV children are disparate from those in adult HF, even with similar downregulation of β 1 -adrenergic receptors (AR) in both populations. Hypothesis: Downregulation of β 1 -AR in pediatric SV subjects results in a unique contractile phenotype. Methods: Hearts were obtained from SV children who underwent transplant between 2010-2020. Non-failing SV (SV-NF) subjects underwent primary transplantation and had no signs of HF at the time of transplant. Failing SV (SV-F) subjects required transplantation due to end-stage HF (including refractory protein losing enteropathy or plastic bronchitis). At the time of transplant, trabeculae are isolated from the right ventricle of the explanted SV heart and mounted in a multi-chamber muscle bath. Ex vivo contractile response of isolated trabeculae is measured in response to the non-selective β-agonist isoproterenol; only trabeculae with an appropriate isoproterenol response are included in analyses. Results: Although β 1 -AR density is decreased in both SV-NF and SV-F myocardium, trabecular contractility assessment demonstrates increased sensitivity to isoproterenol in SV-F compared to SV-NF. Maximal tension generation with isoproterenol is similar between SV-NF and SV-F. Isoproterenol sensitivity in SV-F is comparable to that of non-failing adult hearts (age &lt;40, n=4). Conclusions: Pediatric SV-F trabeculae demonstrate increased sensitivity to β-adrenergic stimulation when compared to SV-NF, but is similar to that of non-failing adult hearts. The preservation of adrenergic responsiveness may suggest that chronic, adverse β 1 -AR signaling is not part of the pathophysiology of failing SV, which may limit the effectiveness of β-blockade for HF indications in this population.
Abstract 10039: Rise in Incidence of Takotsubo Syndrome, Associated Comorbidities and Major Adverse Cardiac and Cerebrovascular Events Among Cancer Survivors: A Nationwide Analysis of Two Cohorts a Decade Apart (2007 & 2017)
Authors: Malak Modi, Nilay R Bhatt, Jamila Begum Jabar Ali, Mounika Binkam, Mimoza Isufi, Nibras yar khan, Ummul Asfeen, Zainab J Gandhi, Bansari Kalolia, Rupak Desai
Journal: Circulation (2021)

Introduction: Studies in the last decade have shown an increased prevalence of Takotsubo syndrome (TTS); however, there is limited data on the prevalence and impact of TTS on hospitalizations among...
NCOG-40. AWAKE CRANIOTOMY FOR EXCISION OF BRAIN TUMORS; INITIAL 200 CONSECUTIVE CASES FROM AN LMIC
Authors: Saqib Kamran Bakhshi, Erum Baig, Altaf Ali Laghari, Daniyal Aziz Khan, Mazin Junaid, Faraz Shafiq, Muhammad Shahzad Shamim, Saad Akhtar Khan, Syed Ather Enam
Journal: Neuro-Oncology (2021)

Abstract In recent years, reports from developed countries have shown that awake craniotomy has been shown to improve outcomes of surgical resection of brain tumors. However, no such data is available from low- and middle-income countries. We retrospectively reviewed 200 cases of awake craniotomy performed at our center for excision of brain tumors during last 5 years, and assessed clinical outcomes. Data was collected from patients’ medical records, and included demographics, tumor location/histology, clinical complains, and functional status. We used Karnofsky performance scale (KPS) to assess function. Extent of resection was determined on post-operative MRI. Statistical analysis was done using SPSS version 22. Seven attending surgeons performed these cases; however, 168 (84%) surgeries were performed by a single surgeon who is the senior author (SA Enam). Mean age was 39.3 ± 11.9 years and 79% (158) were male. Left frontal lobe was the most common location for tumors (50; 25%). Although 52% (104) patients had malignant neoplasms, seizures were the most common presenting symptom in 63% (126) cases followed by motor deficits in 29% (58). The most common tumors were low grade oligodendroglioma (58; 29%%) followed by glioblastoma (42; 21%). Mean length of hospital stay was 3.15 days ± 1.7 days. Gross total resection was achieved in 82 (41%) patients. New intraoperative neurological complains were seen in 31 (15.5%) patients, however, 22 (11%) of these had recovered by median follow-up of 1.4 months. KPS at last follow-up improved in 92 (46%), remained stable in 94 (47%) and deteriorated in 14 (7%) patients. Although absence of a control group decreases the strength of this, with our large sample size we can safely conclude that AC allows maximum safe excision of brain tumors, and offers a good chance of preserving patients’ functional status, along with adequate extent of resection.
NCOG-16. RELEVANCE OF GERIATRIC ASSESSMENT FOR PRIMARY BRAIN TUMOR PATIENTS: IMPLICATIONS FOR RESEARCH AND CARE
Authors: Heather Leeper, Anna Choi, Elizabeth Vera, Alvina Acquaye, Nicole Briceno, Alexa Christ, Ewa Grajkowska, Varna Jammula, Jason Levine, Matthew Lindsley, Jennifer Reyes, Kayla Roche, James Rogers, Michael Timmer, Lisa Boris, Eric Burton, Nicole Lollo, Marissa Panzer, Marta Penas-Prado, Valentina Pillai, Lily Polskin, Brett Theeler, Jing Wu, Mark Gilbert, Terri Armstrong
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The utility of geriatric assessment (GA) has been evaluated in older adults diagnosed with solid tumors other than primary brain tumors (PBT). We assessed several key GA domains in adults with PBT receiving tumor-directed treatment. METHODS Patient and disease characteristics and key GA domains within patient-reported outcomes (PROs) including symptom burden (MDASI-BT), Anxiety/ Depression (PROMIS-short forms) and general health status (EQ-5D-3L) were systematically and prospectively collected between 9/2016–8/2019 from adults diagnosed with PBT. Descriptive statistics and regression analyses were used to assess PROs. RESULTS Of 581 participants, 92 were 65 – 85 years old (median age = 70 years; “older”) and 489 were ≤ 64 years (median age = 46 years; “younger”). Tumor grade distribution in the older group was 74% WHO grade III/IV, 26% WHO grade I/II; tumor types included gliomas and meningiomas with no tissue diagnosis in 3 patients. Older patients were 49% less likely to receive chemotherapy and twice as likely to have KPS ≤ 80 (p=0.003, OR=0.51, OR=1.98). More older patients reported problems with mobility (57% vs 44%), self-care (38% vs 26%), and usual activities (64% vs 51%) than younger patients. Charlson Comorbidity Index mean scores were significantly higher in older patients (3.5 vs 0.6, p&amp;lt; 0.001). The top 3 most frequently reported moderate-to-severe symptoms were similar in older vs younger groups: fatigue (44% vs 41%), feeling drowsy (29% vs 30%) and difficulty remembering (28% vs 29%). Feeling distressed was the only symptom whose frequency differed between the age groups (11% older vs 27% younger, p=0.001). CONCLUSION Older PBT patients had lower performance status, more co-morbidities and increased functional impairments, affirming that GA is relevant. Symptom burden was similarly high in both age groups. These findings support conducting GA concurrently in future symptom intervention and therapeutic clinical trials for adults with PBT receiving tumor-directed treatment.
Abstract 11032: Compound A, a Ginger Extract, Significantly Suppresses Pressure Overload-Induced Systolic Dysfunction in Mice
Authors: Yuto Kawase, Kana Shimizu, Masafumi Funamoto, Yoichi Sunagawa, Yasufumi Katanasaka, Satoshi Shimizu, Yusuke Miyazaki, Koji Hasegawa, Tatsuya Morimoto
Journal: Circulation (2021)

Introduction: Cardiac remodeling induced by hypertrophic stresses such as hypertension is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. As cardiac remodeling eventually leads to chronic heart failure (HF), there is an urgent need for compounds that can effectively suppress both cardiomyocyte hypertrophy and cardiac fibrosis. In this study, we used a natural compound library to screen for compounds that suppress these two mechanisms with cultured cardiomyocyte and cardiac fibroblasts, and identified compound A, a ginger extract, as a candidate for HF therapy. The purpose of this study is to investigate the effect of compound A on cardiomyocyte hypertrophy and cardiac fibrosis in vitro and on the development of HF in vivo . Methods &amp; Results: First, primary cultured cardiomyocytes were treated with 1 μM of compound A and stimulated with phenylephrine (PE). The results of immunofluorestaining showed that the compound significantly suppressed a PE-induced increase in the surface area of the cells. Quantitative PCR analysis demonstrated that the compound significantly suppressed PE-induced increases in the mRNA levels of hypertrophic response genes such as ANF and BNP. Next, primary cultured cardiac fibroblasts were treated with 1 μM of compound A and then stimulated with transforming growth factor-beta (TGF-β). The results of measurement of L-proline incorporation showed that the compound significantly suppressed TGF-β-induced incorporation. Quantitative PCR and western blotting demonstrated that the compound significantly suppressed TGF-β-induced mRNA and protein levels of α-smooth muscle actin (α-SMA). Finally, C57BL/6J mice were subjected to transverse aortic constriction (TAC) surgery, and were then given a daily oral administration of 1 mg/kg of compound A for 8 weeks. Echocardiographic analysis showed that the compound prevented TAC-induced increases in posterior wall thickness and systolic dysfunction. The compound also suppressed a TAC-induced increase in HW/BW ratio. Conclusions: Compound A suppressed TAC-induced development of HF via the suppression of cardiomyocyte hypertrophy and cardiac fibrosis. These findings suggest that compound A may be an effective agent for HF therapy.
Post-Transplant MRD Negativity on Day +100 Predicts Outcomes for Pre-Transplant Relapsed/Refractory AML Patients
Authors: Evgeny Klyuchnikov, Anita Badbaran, Radwan Massoud, Ulrike Fritsche-Friedland, Maximilian Christopeit, Dietlinde Janson, Francis A. Ayuk, Christine Wolschke, Nicolaus Kröger
Journal: Blood (2021)
Abstract 10943: Deep Vein Thrombosis Frequency at Acute Stroke Admission
Authors: Takahisa Mori, Kazuhiro Yoshioka, Yuichi Miyazaki
Journal: Circulation (2021)

Introduction: Intermittent pneumatic compression (IPC) is used to prevent deep vein thrombosis (DVT) during hospitalization in patients with acute stroke. However, if existing DVT is not examined during admission, IPC massage of the legs with DVT may cause migration of the thrombi. Hypothesis: The frequency of DVT at acute stroke admission is high and significant factors indicate the presence of DVT at acute stroke admission. Methods: We included patients admitted within 24 hours of stroke onset, between 2017 and 2019. We collected patient data on age, sex, anthropometric variables, DVT presence by whole-leg ultrasonography, and biomarkers such as D-dimer and lipids. Results: Of 1129 stroke patients, 907 met our inclusion criteria. DVT was detected in 159 patients (17.5%). Compared to patients without DVT (n=748), patients with DVT were older, females, with lower body weight, higher D-dimer and C-reactive protein levels, lower albumin or triglyceride (TG) levels, and higher National Institutes of Health Stroke Scale score. Multiple logistic regression analysis showed that sex, D-dimer, and TG were independent DVT-presence variables. Conclusions: DVT occurred in 17.5% of acute stroke patients at admission, and significant DVT-presence factors were female sex, high D-dimer level, and low TG level. Patients with the three significant factors at admission must immediately undergo whole-leg ultrasonography to detect DVT.
Abstract 10576: Long-Acting Fc-elabela Improves Heart Functional Performance and Markedly Reduces the Infarction Area in a Non-Human Primate Model of Myocardial Infarction
Authors: Da-Wei Gong, Jian Huang, Stephen S Gottlieb
Journal: Circulation (2021)

Introduction: Agonists for the apelin receptor APJ have exhibited cardioprotective and anti-heart failure effects in numerous basic and clinical studies. Besides apelin, elabela is a new endogenous peptide ligand for APJ. In a previous study, we have shown that Fc-Elabela (Fc-ELA) has an in vivo half-life of 44 hours in mice and mitigates heart dysfunctions in the rat model of myocardial infarction. Hypothesis: We hypothesized that we could reproduce Fc-ELA’s cardioprotective effects in non-human primates. Methods: Sixteen 3-6 kg male cynomolgus monkeys were divided into 2 groups of vehicle (Veh, n=9) and Fc-ELA (n=7), each with a mean LVEF of 73%. The animals were subjected to ligation of the LAD for 60 min of ischemia and reperfusion to induce myocardial infarction (MI) and heart failure, and received administration of Fc-ELA at 1 mg/kg, s.c., daily for 4 weeks or vehicle, starting at reperfusion. Ultrasound was performed before operation, after reperfusion, and 1, 2, 3 and 4 weeks after operation. Hemodynamics were measured before and 4 weeks after the procedure. At the end of the experiment, TTC staining for the infarction area and CD31staing for microvessels were performed. Results: LVEF decreased from baseline 73% to 64% after MI, gradually decreasing to 50% by the end of week 4 in the Veh group, whereas LVEF remained between 63% and 66% in the entire 4 weeks of Fc-ELA treatment (p &lt;0.001 vs. Veh at Week 2, 3 and 4). dP/dt increased from 2,235 to 3,975 mmHg/s with Veh, but from 2,249 to 5,893 mmHg/s with Fc-ELA (p &lt; 0.05 between groups). LVEDP decreased by 63% with Fc-ELA, but did not change with Veh (p &lt; 0.05 between groups). Systolic BP increased with Fc-ELA as compared to Veh . Fc-ELA reduced the infarct area by 48.2% (MI area ratio: Veh vs. Fc-ELA; 5.0% vs 2.6%, p &lt; 0.01. In addition, the Fc-ELA treatment increased the expression of CD31, a vascular endothelial marker, by 26.3% (p &lt; 0.01), compared to the Veh group. Conclusions: In non-human primates, Fc-ELA showed significant cardioprotective effects. Fc-ELA markedly reduced MI infarction area and significantly increased the microvessel density in the model, supporting Fc-ELA as a potential therapeutic for heart failure and MI.
Abstract 10692: Combined Methylomics and Transcriptomics Identifies a Race-Specific Signature of Ischemic Heart Failure in Atrial Natriuretic Peptide Gene Regulation
Authors: Sayan Bakshi, Mark E Pepin, Chae-Myeong Ha, Luke Potter, Adam R Wende
Journal: Circulation (2021)

African Americans (AA) face a greater burden of cardiovascular diseases, including ischemic cardiomyopathy (ICM), compared to Caucasian Americans (CA). Our recent work supports that epigenetics is likely a unifying mechanism between health disparities of socioeconomic inequalities and heart failure severity; whereby environmental factors are incorporated as stable DNA modifications to confer susceptibility to heart failure. We hypothesized that ICM possesses racially distinct methylome signatures. Cardiac biopsies from male age- and disease-matched AA (n = 14) and CA (n = 15) heart failure patients with ICM and non-ICM (NICM) were subjected to expression analysis using RNA-seq ( P &lt; 0.05, ±1.5-fold) and differential methylation analysis using Illumina EPIC array ( P &lt; 0.05, ±5%) using generalized linear models with a focus on changes corresponding to ICM and racial differences. Comparing ICM vs NICM, both AA and CA patients showed racially distinct differentially expressed genes (594/366 within AA; 439/487 within CA; up/down respectively). Similarly, pathway analysis using the NIH’s BioPlanet database found a significant change ( Q &lt; 0.1) in AA for adipogenesis (25/133 overlap) and in CA for complement cascade (18/77 overlap). In contrast, racially distinct DNA methylation changes were more prominent for CA (29703/22703; up/down) compared to AA (2904/2897; up/down). Upon combining both datasets, known heart failure marker NPPA , which encodes Atrial Natriuretic Peptide, was found to be downregulated in ICM compared to NICM only for AA ( Q = 0, 18.9-fold change), corresponding to hypermethylation of 6 CpG sites ( P &lt; 0.05, 6.4 - 11.3%). NPPA inhibits cardiac hypertrophy, fibrosis, and decreases inflammation. It is also used as a diagnostic biomarker in ICM. But recent trials found that AA have lower levels of NPPA in blood compared to CA, even in healthy condition. This patient cohort also indicated a racially diverse pattern of NPPA expression and methylation. Given its role in adipogenesis, NPPA may also explain the pathway enrichment specific to AA-ICM patients. Our data indicate that NPPA may connect the socioeconomic effects through DNA methylation with clinical diversity of ICM. It also underscores the need for a better prognostic biomarker for ICM.
Preliminary Functional Outcome Following Robotic Intracorporeal Orthotopic Ileal Neobladder Suspension with Round Ligaments in Women with Bladder Cancer
Authors: Zhiwen Chen, Peng He, Xiaozhou Zhou, Peng Li, Qianwei Li, Ji Zheng, Xuemei Li, Zhansong Zhou
Journal: European Urology (2021)

Chronic urinary retention (CUR) is a frequent complication after orthotopic neobladder (ONB) reconstruction in women. To decrease CUR, several open surgical modifications to provide back support to the ONB have been established on the basis of pelvic anatomical differences between females and males.To illustrate our technique for robotic intracorporeal reconfiguration of ONB as integrated into our open surgical approach to provide back support to the ONB with round ligaments in women.From November 2017 to April 2021, 28 patients underwent robotic intracorporeal ONB with a minimum of 6 mo of follow-up at a single centre.We performed robotic radical cystectomy, pelvic lymphadenectomy, and a complete intracorporeal ONB suspended with round ligaments (rONB). Our surgical procedure is demonstrated in the accompanying video.Demographics and clinical and pathological data were collected. Perioperative and 90-d complications and 6-mo functional outcomes were compared for the rONB group (n = 12) and the patients receiving a traditional ONB (tONB; n = 16).The median total operative time was 305 min (interquartile range [IQR] 270-370) for tONB and 303 min (IQR 287-330) for rONB. The median estimated blood loss was 325 ml (IQR 200-700) for tONB and 350 ml (IQR 262-600) for rONB. Some 50% of the tONB group and 41.7% of the rONB group experienced low-grade complications. A total of 12.5% tONB and 8.3% rONB patients experienced high-grade complications with neobladder-vaginal fistula. The cumulative risk of CUR was 37.5% in the tONB group and 16.7% in the rONB group. This study is limited by the small sample size and the short follow-up period.We established a feasible surgical technique for a robotic intracorporeal ONB configuration suspended with round ligaments. This may prevent the occurrence of emptying dysfunction in women.We describe our stepwise technique for creating a new bladder within the body that is suspended with round ligaments. Patients undergoing removal of the bladder for bladder cancer may benefit from this technique in terms of better urinary function and the advantages of a robotic surgical approach.