tbuckley/cabot-search huggingface dataset:
Abstract 13280: Obesity is Associated With 1-year Atrial Fibrillation Recurrence After Catheter Ablation in Caucasians but Not in African Americans
Authors: Nathan Kong, Dalise Shatz, Stephanie Besser, Zaid Aziz, Cevher OZCAN, Michael Broman, Andrew Beaser, Gaurav A Upadhyay, Hemal Nayak, Roderick Tung
Journal: Circulation (2020)

Introduction: Observational studies have noted an association between body mass index (BMI) and recurrence of atrial fibrillation (AF) after catheter ablation. However, there is limited data on this association in a multi-racial cohort. We seek to describe AF recurrence after pulmonary vein isolation (PVI) of obese and non-obese patients stratified by race. Hypothesis: The association between BMI and recurrence of AF after PVI differs between Caucasians and African Americans. Methods: Caucasian and African American patients undergoing PVI at the University of Chicago from March 2016 to November 2018 were included. Patients were followed for up to 12 months. Not obese was characterized by BMI &lt; 30kg/m 2 and obese as BMI ≥ 30kg/m 2 . Results: Among 217 consecutive patients, 69 (31.8%) were female with an average age of 64.2 years (range 24 - 89). Forty-four (20.3%) of patients were African American. There were 105 (48.4%) obese patients. No differences were observed in rates of valvular disease between non-obese and obese patients. Obesity was significant in determining time to AF recurrence after PVI (adjusted hazard ratio [aHR] 3.17, 95% CI 1.71 to 5.87, p &lt; 0.001). When adjusted for age, gender, smoking status, hypertension, diabetes, heart failure, estimated glomerular filtration rate, and type of atrial fibrillation, Caucasians had a significant association between obesity and time to recurrence (aHR 3.34, 95% CI 1.91 to 5.85), whereas African Americans had no association between obesity and time to recurrence (aHR 0.87, 95% CI 0.31 - 2.42). This association remained when stratified by AF type. Conclusions: In this multi-racial registry of patients undergoing catheter based PVI, a BMI ≥ 30 kg/m 2 was associated with a higher likelihood of atrial fibrillation recurrence within 12 months for the Caucasian group but not amongst African Americans. These results suggest that in African Americans, obesity is less associated with recurrence of atrial fibrillation after PVI.
Abstract 15904: Echogenic Immunoliposome-targeted Mesenchymal Stem Cells for Imaging and Treatment of Atheroma
Authors: Yong-jian Geng, Melvin E Klegerman, David D McPherson, Song Gao, Saurendro Ghosh, Harnath S Shelat, Mohammad Gareeb
Journal: Circulation (2020)

Background: Vascular stem cell dead impairs the regenerating capacity of the arterial wall with atherosclerosis. A patented technology has been developed to employ biofunctional echogenic immunoliposomes (BF-ELIP) for enhancing entry of stem cells to atherosclerotic lesions. Objective: Determine whethere ultrasound-enhanced delivery of BF-ELIP-targeted stem cells visualize and treat atheroma simultaneously. Methods and Results: BF-ELIP were prepared by conjugating thiolated antibodies specific for the mesenchymal marker CD146 and murine ICAM-1 to phosphatidyl-ethanolamine liposomes through a thioether linkage. CD146 + bone marrow-derived mesenchymal cells (BM-MSC) were prepared from green fluorescence protein (GFP)-transgenic mice. By fluorescence microscopy, BF-ELIP targeted CD146 + cells were clearly visualized being adherent on cultured human endothelial cells that expressed ICAM-1 induced by tumor necrosis factor alpha (TNF-α) (Fig. 1a). BM-MSC/BF-ELIP mixtures were intravenously injected into ApoE-/- mice (n=9). Ultrasound illustrated intense echo signals of BF-ELIP in the aortic arch 15 min after injection of the BM-MSC/BF-ELIP preparation into ApoE-knockout mice (Fig. 1b). Histopathology of the aorta analyzed by H&amp;E and Oil-Red O staining of aortic sections showed that the BF-ELIP targeted MSC delivery reduced plaque sizes, inflammation and lipid loading. Neither normal wild type C57BL/6J nor ApoE-knockout mice without injection showed the intensified echo signals and histological changes in their aortic arch regions. Conclusions: BF-ELIP enhancement of vascular stem cell adherence to inflammatory endothelium facilitates vulnerable plaque detection and targeted stem cell therapy for atheroma. This proof of concept study illustrates on the development of ultrasound-enhanced, BF-ELIP-mediated stem cell delivery and therapeutic approach to stabilize atheroma.
Physician–Public Defender Collaboration — A New Medical–Legal Partnership
Authors: Rahul Vanjani, Sarah Martino, Sheridan F. Reiger, James Lawless, Chelsea Kelly, Vincent J. Mariano, M. Catherine Trimbur
Journal: New England Journal of Medicine (2020)

Involvement in the criminal justice system is one of the most fundamental upstream determinants of health. Fortunately, a model for helping patients navigate legal issues that negatively affect their health does exist in medicine: the medical–legal partnership.
Abstract 12824: Higher Prevalence of Qt Interval Prolongation in Infants With Intrauterine Tobacco Smoke Exposure
Authors: Kenji Harada, Yukiko Harada
Journal: Circulation (2020)

Background: The association between QT interval prolongation and sudden infant death syndrome (SIDS) has been clearly established. Environmental tobacco smoke (ETS) exposure is also associated with increased risk for SIDS. However, there has been little focus on the relationship between the QT interval and ETS exposure during early infancy. To clarify this, we examined the QT interval with ETS exposure during early infancy. Methods: A total of 2168 infants (age:1-4 months), 743 infants who have been exposed to tobacco smoking since intrauterine life and 1425 age-matched children without ETS exposure, underwent electrocardiographic study. QT data were extracted from the electrocardiogram monitor built-in echocardiogram. The QT interval was measured on the first, second, third, and fourth month. The corrected QT interval (QTc) was calculated by dividing the QT interval by the square root of the RR interval (Bazett’s formula). QT interval prolongation was defined as QTc≧440 msec. The data of the number of cigarettes per day were collected by a questionnaire. Results: In the total study population, the mean QTc in ETS infants was significantly greater than in infants without ETS (402±21 and 395±20 msec, p&lt;0.01). The absolute risk of QT prolongation was 1.11 % (16/1425) in infants without ETS; by contrast, that of ETS infants with QTc≧440 msec was 3.23% (24/743) (odds ratio, 2.94; 95% confidence interval, 2.30 to 3.58). The mean QTc in ETS infants at the first, second and third month was significantly greater than that in infants without ETS (404±20 vs. 397±21 msec, 407±19 vs. 399 ±17 msec and 404±17 vs. 390±18 msec, p &lt; 0.01, respectively), but the mean QTc at the fourth month was similar in the 2 groups. The odds ratios for QTc≧440msec in ETS infants at the second and third month were 7.15 (95% confidence interval, 6.00 to 8.29) and 4.97 (95% confidence interval, 2.74 to 7.18), respectively. Compared with infants without ETS, ETS infants with the number of cigarettes ≧10 cigarettes per day had a significantly higher risk of QTc≧440 msec(odds ratio: 3.32, 95% confidence interval: 2.67-3.99). Conclusions: The present study indicates that environmental tobacco exposure is a risk for QT interval prolongation ≧440msec during early infancy.
Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9–50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study
Authors: Diana Leticia Coronel-MartÍnez, Juliana Park, Eduardo López-Medina, María Rosario Capeding, Andrés Angelo Cadena Bonfanti, María Cecilia Montalbán, Isabel Ramírez, María Liza Antoinette Gonzales, Carlos A DiazGranados, Betzana Zambrano, Gustavo Dayan, Stephen Savarino, Zhenghong Chen, Hao Wang, Sunny Sun, Matthew Bonaparte, Andrey Rojas, Jenny Carolina Ramírez, Mae Ann Verdan, Fernando Noriega
Journal: The Lancet Infectious Diseases (2020)
Abstract 15833: Immune Checkpoint Inhibitor Myocarditis Subtypes are Determined by a Cd8-dependent Transcriptional Program
Authors: Daniel Finke, Markus B Heckmann, Janek Salatzki, Johannes Riffel, Esther Herpel, Benjamin Meder, Oliver J Mueller, Norbert Frey, Hugo A Katus, Florian Leuschner, Ziya Kaya, Lorenz H Lehmann
Journal: Circulation (2020)

Introduction: Immune checkpoint inhibitors (ICIs) are revolutionizing cancer treatment. Nevertheless, their increasing clinical use leads to higher rates of adverse immune related events (irAEs). One of those irAEs is the ICI-induced myocarditis (ICIM) - a rare phenomenon with an estimated mortality rate of up to 50%. We aimed to characterize the molecular changes of ICIM which are not yet understood completely. Methods: Patients suspected for ICIM were assessed in the cardio-oncology units of University Hospitals Heidelberg and Kiel. Via RNA sequencing of myocardial biopsies, we compared transcriptional changes of ICIM (n=9) with samples from dilatative cardiomyopathy (DCM, n=11) and virus-induced myocarditis (VIM, n=5). Results: Clinical analysis of 19 patients with ICIM showed an inconsistent presentation, e.g. an elevation of cardiac biomarkers (hsTnT, NT-proBNP, CK), a drop in leftventricular ejection fraction or late gadolinium enhancement in cMRI. We found 3784 (FDR &lt;0.05) upregulated genes in ICIM. Among the genes that were related to antigen presentation and processing, we mainly found an upregulation of CD8. CD8-dependent clustering of ICI-patients, on the other hand, was associated with a number of immune cell-specific genes (compared to VIM: CXCL11 (log2 fc 3.24), CXCL9 (log2 fc 4.37), GBP6 (log2 fc 5.37), GBP5 (log2 fc 3.21). Analysis of high- and low-expressing CD8 positive biopsies identified two expression patterns, suggesting different pathological mechanisms for ICIM. Conclusion: Taken together, we were able to identify CD8 and CD8-associated genes as specifically regulated transcripts in ICIM. Moreover, based on the variable clinical phenotype, we propose that analysis of CD8 and CD8-dependent genes will be important to identify ICIM patients and to potentially sub-differentiate different phenotypes.
Abstract 15884: Life-threatening Arrhythmias With Autosomal Recessive TECRL Variants
Authors: Gregory Webster, Elhadi H Aburawi, Marie Chaix, Stephanie Chandler, Roger Foo, A. K. M. Monwarul Islam, Janneke A Kammeraad, John D Rioux, Lihadh Al-Gazali, Md. Zahidus Sayeed, Tingting Xiao, Han Zhang, Lijian Xie, Cuilan Hou, Arthur A Wilde, Zahurul A Bhuiyan
Journal: Circulation (2020)

Introduction: Sudden death and aborted sudden death have been observed in patients with biallelic variants in TECRL . Phenotypes have only begun to be described and no data are available on medical therapy after long-term follow-up. Methods: An international, multicenter retrospective review was conducted. We report new cases associated with TECRL variants and long-term follow-up from previously published cases. Results: We present 10 cases and 37 asymptomatic heterozygous carriers. Median age at onset of cardiac symptoms was 8 years (range 1-22 years) and cases were followed for an average of 10.3 years (SD 8.3), right censored by death in 3 cases. All patients on metoprolol, bisoprolol or atenolol were transitioned to nadolol or propranolol due to failure of therapy. Phenotypes typical of both long QT syndrome and catecholaminergic polymorphic ventricular tachycardia were observed. We also observed divergent phenotypes in some cases despite identical homozygous variants. None of 37 heterozygous family members had a cardiac phenotype. Conclusions: Patients with biallelic pathogenic TECRL variants present with variable cardiac arrhythmia phenotypes, including those typical of long QT syndrome and catecholaminergic polymorphic ventricular tachycardia. Nadolol and propranolol may be superior beta-blockers in this setting. No cardiac disease or sudden death was present in patients with a heterozygous genotype.
18F-FDG PET/CT in a Rare Case of Poland Syndrome and Gastric Cancer
Authors: Sarvesh Loharkar, Gaurav Malhotra, Ramesh V. Asopa
Journal: Clinical Nuclear Medicine (2020)

Poland syndrome is a rare congenital anomaly characterized by unilateral aplasia of the sternoclavicular head of pectoralis major muscle with varying degree of same side upper limb anomalies. A 44-year-old man, with a case of adenocarcinoma of stomach, whose CECT chest revealed complete absence of pectoralis major and minor muscles on the left side, was diagnosed with Poland syndrome without presence of typical ipsilateral limb anomalies. Follow-up PET/CT revealed metabolically active recurrent disease with typical findings of Poland syndrome. It is important to be aware of oncologic association in a patient of Poland syndrome as highlighted in the present case.
Abstract 13442: Gabapentin as a Novel Adjunct for Postoperative Management After Superior Cavopulmonary Connection Operation in Children
Authors: Evan Z Ramsey, Hailey Collier, Deepthi Gunturi, Jen Faerber, Celine Thibault, Emily Schwartz, Jonathan Chen, David J Goldberg, Monique M Gardner
Journal: Circulation (2020)

Introduction: For infants with single ventricle congenital heart disease, the superior cavopulmonary connection (SCPC) stabilizes pulmonary blood flow but is associated with elevated pressure in the superior vena cava (SVC), often leading to irritability. We describe the off-label use of gabapentin for the treatment of irritability after SCPC. Methods: We reviewed our patients who underwent SCPC between 2011-2019. Patients were prescribed gabapentin at provider discretion. Total medication doses during the first seven postoperative days were aggregated in morphine and midazolam equivalents. For those who received gabapentin, maximum dose and use of post-discharge gabapentin were recorded. To determine if included infants were more likely to receive analgesic and anxiolytic medications, a propensity score outcome model was developed accounting for variables that may affect likelihood of gabapentin receipt or outcome risk. Inverse probability weighted logistic regression and linear regression models were used to estimate the effect of gabapentin receipt on morphine dosage and the odds of midazolam receipt. Results: The cohort included 323 infants; 61% male, 91% with prior cardiac surgery or intervention. Gabapentin was prescribed in 74 (23%), with a median (IQR) maximum dose of 10.7 mg/kg/day (5.5, 23.4), and was continued at discharge in 54 (73%). Infants prescribed gabapentin were younger at time of SCPC (median 137 days old vs 146 days, p=0.007), had longer postoperative intensive care (median 5.8 days vs 3.1 days, p&lt;0.001), and hospital length of stay (median 11.5 days vs 7 days, p&lt;0.001). Those who underwent SCPC from 2015-19 had increased odds of gabapentin receipt compared to 2011-14 (OR 5.3, 95% CI 2.8, 10.0). All patients received morphine postoperatively while 136 (42%) received midazolam equivalents. Infants prescribed gabapentin received 1 mg/kg more of morphine equivalents (p=0.05) and were twice as likely to be prescribed a midazolam equivalent (OR 2.2, CI 1.2, 4.1, p=0.01). Conclusions: Gabapentin was used with increasing frequency over the duration of the study period. Patients prescribed gabapentin tended to be younger and have longer hospital stays, but did not appear to be spared exposure to opioid or benzodiazepine medications.
Abstract 13093: Clinical Features and Prognosis of Acute Cardiac Injury in Hospitalized Patients With Covid-19: A Retrospective Cohort Study
Authors: Mingxing XIE, Li Zhang, yanting zhang, Wei Sun, CHUN WU, Bin Wang, Yuji Xie
Journal: Circulation (2020)

Aims: The fatalities case due to coronavirus disease 2019 (COVID-19) is escalating. However, information on critical complications in hospitalized patients of COVID-19 is scant. We aimed to explore the prevalence of acute cardiac injury and its association with in-hospital mortality in COVID-19 patients. Methods: This retrospective study analyzed COVID-19 patients in Union Hospital (Wuhan, China) from Jan 24 to March 18, 2020. Clinical outcomes (discharge, or death) were monitored to April 9, 2020, the latest date of follow-up. Demographic, clinical, laboratory, echocardiographic data, treatment and prognosis were analyzed. Results: A total of 235 COVID-19 patients were included in the final analysis. Their median age was 66 years (interquartile range 57 - 73), and 131 (55.7%) were men. 98 (41.7%) patients were diagnosed with acute cardiac injury, of whom 60 (61.2%) died. There were more comorbidities in those who with acute cardiac injury than those without. A higher proportion of patients with acute cardiac injury received glucocorticoid therapy (68.0% vs 37.0%; P &lt; 0.001), immunoglobulin (53.1% vs 30.1%; P &lt; 0.001) and invasive mechanical ventilation (40.8% vs 6.6%; P &lt; 0.001) than those without. The percentage of patients who were admitted to intensive care unit (39.8 % vs 8.0%; P &lt; 0.001) or died during hospitalization (61.2% vs 8.0%, P &lt; 0.001) were also higher in those with acute cardiac injury. Plasma high-sensitivity troponin I level correlated significantly with plasma interleukin -6, procalcitonin and C-reactive protein levels in COVID-19 patients. Echocardiography showed that cardiac function was attenuated in acute cardiac injury patients. Multivariable Cox proportional hazards regression analysis showed acute cardiac injury was an independent risk factor for higher in-hospital mortality in COVID-19 patients (HR, 3.393; 95% CI, 1.647- 6.987, P &lt;0.001). Conclusions: Acute cardiac injury is a common condition and may be related to inflammatory response in COVID-19 patients. In addition, our study highlights an association between acute cardiac injury and a higher risk of in-hospital mortality. It is suggested that clinicians should be alert to acute cardiac injury in COVID-19 patients and take prompt treatments to improve outcomes.
Malakoplakia Presenting as a Mass in the Transplanted Kidney
Authors: Lokeshwaran Madurai Kalimuthu, Manish Ora, Aftab Hasan Nazar, Sanjay Gambhir
Journal: Clinical Nuclear Medicine (2020)

Abstract Malakoplakia is a rare inflammatory condition that can affect many organ systems, including the genitourinary tract. It is associated with impaired immune function. Isolated renal parenchymal involvement has been reported in very few cases. Urinary tract and digestive malakoplakia have been reported in transplant recipients, but the involvement of transplant itself is rare. Variable clinical manifestations and nonspecific radiological appearance make the diagnosis difficult. The differential diagnosis includes infective etiologies and malignancy. We report a case of renal allograft malakoplakia, mimicking as a malignancy on 18 F-FDG PET/CT.
Advanced Prostate Cancer with ATM Loss: PARP and ATR Inhibitors
Authors: Antje Neeb, Nicolás Herranz, Sara Arce-Gallego, Susana Miranda, Lorenzo Buroni, Wei Yuan, Alejandro Athie, Teresa Casals, Juliet Carmichael, Daniel Nava Rodrigues, Bora Gurel, Pasquale Rescigno, Jan Rekowski, Jon Welti, Ruth Riisnaes, Veronica Gil, Jian Ning, Verena Wagner, Irene Casanova-Salas, Sarai Cordoba, Natalia Castro, Maria Dolores Fenor de la Maza, George Seed, Khobe Chandran, Ana Ferreira, Ines Figueiredo, Claudia Bertan, Diletta Bianchini, Caterina Aversa, Alec Paschalis, Macarena Gonzalez, Rafael Morales-Barrera, Cristina Suarez, Joan Carles, Amanda Swain, Adam Sharp, Jesus Gil, Violeta Serra, Christopher Lord, Suzanne Carreira, Joaquin Mateo, Johann S. de Bono
Journal: European Urology (2020)

Deleterious ATM alterations are found in metastatic prostate cancer (PC); PARP inhibition has antitumour activity against this subset, but only some ATM loss PCs respond. To characterise ATM-deficient lethal PC and to study synthetic lethal therapeutic strategies for this subset. We studied advanced PC biopsies using validated immunohistochemical (IHC) and next-generation sequencing (NGS) assays. In vitro cell line models modified using CRISPR-Cas9 to impair ATM function were generated and used in drug-sensitivity and functional assays, with validation in a patient-derived model. ATM expression by IHC was correlated with clinical outcome using Kaplan-Meier curves and log-rank test; sensitivity to different drug combinations was assessed in the preclinical models. Overall, we detected ATM IHC loss in 68/631 (11%) PC patients in at least one biopsy, with synchronous and metachronous intrapatient heterogeneity; 46/71 (65%) biopsies with ATM loss had ATM mutations or deletions by NGS. ATM IHC loss was not associated with worse outcome from advanced disease, but ATM loss was associated with increased genomic instability (NtAI:number of subchromosomal regions with allelic imbalance extending to the telomere, p = 0.005; large-scale transitions, p = 0.05). In vitro, ATM loss PC models were sensitive to ATR inhibition, but had variable sensitivity to PARP inhibition; superior antitumour activity was seen with combined PARP and ATR inhibition in these models. ATM loss in PC is not always detected by targeted NGS, associates with genomic instability, and is most sensitive to combined ATR and PARP inhibition. Of aggressive prostate cancers, 10% lose the DNA repair gene ATM; this loss may identify a distinct prostate cancer subtype that is most sensitive to the combination of oral drugs targeting PARP and ATR.
Abstract 13753: Early and Late Outcomes of Ambulatory Counter Pulsation Device: Novel Intravascular Ventricular Assist Device vs Conventional Axillary Intra-aortic Balloon Pump
Authors: Hidefumi Nishida, Yojiro Koda, Tae Song, David Onsager, Ann Nguyen, Jonathan Grinstein, Chung Bow, Bryan Smith, Sara Kalantari, Nitasha Sarswat, Gene Kim, Valluvan Jeevanandam, Takeyoshi Ota
Journal: Circulation (2020)

Introduction: Intravascular ventricular assist device (iVAS; NuPulse CV, North Carolina, USA) is a newly developed ambulatory and portable counter pulsation heart assist system. Hypothesis: Early and late clinical outcomes of iVAS is comparable to those of conventional axillary intra-aortic balloon pump (IABP) as a bridge to heart transplantation(BTT). Methods: Between April 2016 and January 2020, 33 patients underwent iVAS implantation (Group A) and 69 patients underwent axillary IABP (Group B) as a BTT. We reviewed perioperative data and late clinical outcomes including survival. Long-term survival was assessed with the Kaplan-Meier analysis. Results: The patients in Group A was significantly older than Group B (A: 58.8±8.1 vs B: 53.3±14.7 p=0.048). The use of inotropes at the time of device implantation was similar between two groups (A:22/33(66.7%) vs B: 47/69(68.1%), p=0.88). Almost all patients were able to ambulate and participate in physical therapy (A:100% vs B:97.1%, p=0.21). The duration of device support in Group A was significantly longer than Group B (A:83.3±93.7 vs B:19.0±13.3 days, p &amp;lt;0.01). After a FDA approval, eleven patients (44%) in Group A was able to be discharged with an iVAS. While waiting for transplantation, 3 patients expired in Group A and none in Group B. Two patients in Group A required an escalation of support (ECMO N=1, LVAD N=1) and 1 patients in Group B (percutaneous LVAD N=1). Balloon exchange due to device related complications was required less frequently in Group A compared to Group B (A: 2/33, 6.1% vs B: 20/69, 29.0% p &amp;lt;0.01). Adverse events during balloon exchange included aortic rupture (N=1) and type A aortic dissection (N=1) (all in Group B). The success rate of BTT was not significantly different between groups (A:27/32(84.4%), B: 64/68(94.1%),p=0.13). The long-term survival after heart transplantation did not differ between the groups (A: 78.1% at 3 years vs B: 83.8% at 3 years, log-rank=0.07). Conclusions: Both iVAS and conventional axillary IABP showed comparable long-term survival and decent success rates of BTT. The iVAS featured with the portable mechanism might be a promising option as a BTT.