tbuckley/cabot-search huggingface dataset:
Abstract 13323: Identifying the Culprit Lesion in a Symptomatic Patient With Physiologically Corrected Transposition of the Great Arteries
Authors: Nael Aldweib, Ada Stefanescu, Ami Bhatt, Christopher P Learn, Doreen D Yeh
Journal: Circulation (2020)

Introduction: Physiologically corrected transposition of the great arteries [(S,L,L) TGA] is a rare congenital heart disease characterized by atrioventricular and ventriculoarterial discordance. Case Presentation: A 28-year-old man with (S,L,L) TGA, pulmonary valve (PV) stenosis, ventricular septal defect (VSD), and history of Kawasaki disease who presented for a gradual decline in exercise tolerance. Oxygen saturation was 96% at rest and dropped to 86% with ambulation. Hemoglobin was 17.7 g/dl, EKG showed no bradyarrhythmias. On stress test, peak heart rate was 159 beats/minute, and peak VO 2 22.6 ml/kg/min (83%, and 57% of predicted value respectively). Spirometry was normal. Transthoracic echocardiogram revealed biventricular hypertrophy with normal systolic function, a bicuspid PV with severe stenosis (peak and mean gradient of 155 and 90 mmHg respectively), large inlet VSD with bidirectional flow and mild systemic TV regurgitation. Coronary CTA showed no coronary artery aneurysms. Cardiac catheterization suggested hypoxia due to pulmonary-to-systemic shunting across the VSD with Q p /Q s = 0.86 (Figure). Consideration should be given to performing a high-risk surgical repair versus medical management. Conclusions: Natural history, symptoms, and timing of intervention are determined by the associated cardiac anomalies and the progressive dysfunction of the systemic right ventricle (SRV). Anatomic repair to restore the left ventricle as a systemic pump is a very high-risk procedure in adults. Functional repair maintains SRV, repair the VSD, and PV stenosis has a poor late outcome. Medical management ensures iron stores are repleted, provide empirical use of pharmacological heart failure therapy, and referral to heart transplantation when SRV systolic dysfunction ensues. Clinicians need to know the potential complications in both unoperated patients and following various surgical repairs to recommend appropriate treatment options.
Complications in Patients With COVID-19—Reply
Authors: Mohammad Madjid, Scott D. Solomon, Orly Vardeny
Journal: JAMA Cardiology (2020)

Complications in Patients With COVID-19To the Editor Madjid et al 1 recently reviewed the association between the cardiovascular system and infection with coronavirus disease 2019 (COVID-19).They point out the association between cardiovascular risk factors and the outcome of patients with COVID-19.However, the underlying risk associated with obesity was not listed among the risk factors.There are several lines of evidence that being overweight or obese is associated with risk of poor outcome (ie, admission to an intensive care unit or death) after infection with COVID-19.Recently, 72% of 775 patients with COVID-19 admitted to an intensive care unit in the UK were reported to have a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) greater than 25 and 38% had a BMI greater than 30, 2 a proportion higher than in the standard intensive care population.Obesity is also reported as a risk factor of poor outcome by the US Centers for Disease Control and Prevention. 3 A potential pathophysiological background exists linking the increasing severity of COVID-19 among patients with obesity.COVID-19 binds to angiotensin-converting enzyme 2 (ACE2), a surface molecule that allow the virus to enter the host cell.In this line, the role of angiotensin-conversing enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) in the pathogenicity of COVID-19 has been intensively debated. 4The level of ACE2 expression has been reported to be high in adipose tissue, therefore likely making the adipose tissue a reservoir for severe acute respiratory syndrome coronavirus 2. 5 In turn, the adipose tissue can trigger an increased inflammatory response to infection, potentially affecting all organs.Finally, patients with obesity can be at higher risk of hypoxemia due to altered thoracic compliance and the risk of lung atelectasis.I suggest that both BMI and treatment with ACEi or ARB be systematically reported in case series of patients with COVID-19 to further appreciate their interaction and association with outcome.Further research should then explore the impact of adipose tissue on the viral load, the systemic inflammatory response, and the outcome of patients with COVID-19.In the meantime, the potential risk of future deterioration should probably be appreciated in overweight patients developing COVID-19-related symptoms.
Association of Affordable Care Act Implementation With Ambulance Utilization for Asthma Emergencies in New York City, 2008-2018
Authors: Gregory A. Peters, Alexander J. Ordoobadi, Rebecca E. Cash, Matthew L. Wong, Paul Avillach, Carlos A. Camargo
Journal: JAMA Network Open (2020)

Emergency medical services (EMS) are an essential component of the health care system, but the effect of insurance expansion on EMS call volume remains unclear.This study investigated the association between health insurance expansion and EMS dispatches for asthma, an ambulatory care-sensitive condition. We hypothesized that insurance expansion under the Patient Protection and Affordable Care Act (ACA) would be associated with decreased EMS dispatches for asthma emergencies.This cohort study examined 14 865 267 ambulance calls dispatched within New York City from 2008 to 2018, including 217 303 calls for asthma-related emergencies, and used interrupted time series analysis to study the change in the annual incidence of EMS dispatches for asthma emergencies after implementation of the ACA. Multivariable linear regression examined the association between the uninsured rate and the incidence of asthma-related dispatches, controlling for population demographic characteristics and air quality index.Implementation of ACA on January 1, 2014.Incidence of EMS dispatches for asthma emergencies per 100 000 population per year (ie, asthma EMS dispatch rate) as classified by the 911 call-taker.In this study of 217 303 EMS dispatches for asthma-related emergencies, there was a decrease in the asthma EMS dispatch rate after implementation of the ACA, from a mean (SD) of 261 (24) dispatches per 100 000 population per year preintervention to 211 (47) postintervention (P = .047). This decrease in asthma EMS dispatch rate after ACA implementation was significant on interrupted time series analysis. Prior to 2014, the annual asthma EMS dispatch rate was increasing by 11.8 calls per 100 000 population per year (95% CI, 6.1 to 17.4). After ACA implementation, the asthma EMS dispatch rate decreased annually by 28.5 calls per 100 000 population per year (95% CI, -37.6 to -19.3), a significant change in slope from the preintervention period (P < .001). Multivariable linear regression, controlling for percentage of individuals younger than age 18 years, degree of racial/ethnic diversity, median household income, and air quality index, found that a 1% decrease in the citywide uninsured rate was associated with a decrease of 98.9 asthma dispatches per 100 000 population per year (95% CI, 5.72-192.10; P = .04).Insurance expansion within New York City under the ACA was associated with a significant reduction in the asthma EMS dispatch rate. Insurance expansion may be a viable method to reduce EMS utilization for ambulatory care-sensitive conditions such as asthma.
Abstract 15090: Direct Oral Anticoagulation vs Vitamin K Antagonist in Atrial Fibrillation With Liver Disease: A Systematic Review and Meta-analysis
Authors: Mahmoud El Iskandarani, Islam Shatla, Muhammad Khalid, Bara El Kurdi, Timir Paul, Marwan M Refaat
Journal: Circulation (2020)

Background: Current guidelines recommend against the use of direct oral anticoagulation (DOAC) therapy in patients with atrial fibrillation (AF) in the setting of significant liver disease (LD) due to lack of evidence in safety and efficacy studies. However, recently studies have investigated the role of DOAC in comparison to Vitamin K antagonist (VKA) in this category of patients. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of this approach. Hypothesis: DOAC is safe and effective compared to VKA in AF with LD patients. Method: Unrestricted search of the PubMed, EMBASE, and Cochrane databases performed from inception until June 1, 2020 for studies comparing DOAC with VKA including more than 100 AF patients with LD. Relevant data were extracted and analyzed using Revman 5.3 software. Hazard ratio (HR) and 95% Confidence interval (CI) were calculated using the random-effects model. Result: A total of 5 studies (3 retrospective and 2 post hoc analysis) were included examining 39,064 patients with AF and LD (25,398 DOAC vs 13,669 VKA). DOAC is associated with lower risk of major bleeding compared to VKA with a HR of 0.68 (95% CI 0.47-0.98; I 2 =53%), all-cause mortality (HR 0.74;95% CI 0.59-0.94; I 2 =61%), and intracranial bleeding (HR 0.48; 95% CI 0.40-0.58; I 2 =0). There was no significant difference in ischemic stroke risk (HR 0.73; 95% CI 0.47-1.14; I 2 =72%) and gastrointestinal bleeding risk (0.96; 95% CI 0.61-1.51; I 2 =41%) between DOAC and VKA. Conclusion: DOAC is non-inferior to VKA regarding ischemic stroke prevention in AF patients with LD. Moreover, DOAC is associated with a lower risk of major bleeding, intracranial bleeding and all-cause mortality. Further randomized trials are needed to validate our findings.
Depression Is Associated With Progression of Diabetic Nephropathy in Type 1 Diabetes
Authors: Aila J. Ahola, Valma Harjutsalo, Carol Forsblom, François Pouwer, Per-Henrik Groop
Journal: Diabetes Care (2020)

To investigate the relationship between depression and diabetic nephropathy progression in type 1 diabetes.Data from 3,730 participants without end-stage renal disease (ESRD) at baseline, participating in the Finnish Diabetic Nephropathy Study, were included. Depression was assessed in three ways. Depression diagnoses were obtained from the Finnish Care Register for Health Care. Antidepressant agent purchase data were obtained from the Drug Prescription Register. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Based on their urinary albumin excretion rate (AER), participants were classified as those with normal AER, microalbuminuria, and macroalbuminuria. Progression from normal AER to microalbuminuria, macroalbuminuria, or ESRD; from microalbuminuria to macroalbuminuria or ESRD; or from macroalbuminuria to ESRD, during the follow-up period, was investigated.Over a mean follow-up period of 9.6 years, renal status deteriorated in 18.4% of the participants. Diagnosed depression and antidepressant purchases before baseline were associated with 53% and 32% increased risk of diabetic nephropathy progression, respectively. Diagnosed depression assessed during follow-up remained associated with increased risk of disease progression (32%). BDI-derived symptoms of depression showed no association with the progression, but the total number of antidepressant purchases modestly reduced the risk (hazard ratio 0.989 [95% CI 0.982-0.997]), P = 0.008). With the sample divided based on median age, the observations followed those seen in the whole group. However, symptoms of depression additionally predicted progression in those age ≤36.5 years.Diagnosed depression and antidepressant purchases are associated with the progression of diabetic nephropathy in type 1 diabetes. Whether successful treatment of depression reduces the risk needs to be determined.
DCE-MRI assessment of responses to hormonotherapy in preclinical breast and prostate cancer, models in rat
Authors: Olivier Duchamp, Paul Walker, Amendine Bataille, Philippe Genne, François Brunotte, Francis Bichat, Nathalie Just, Nicolas Guilbaud
Journal: Cancer Research (2004)

1941  The assessment of tumor morphology and microvascular permeability in breast and prostate cancers is of importance as a key indicator of survival and response to therapy. Hormone deprivation is one of the commonly used clinical treatment. In order to study the impact of hormonotherapy on tumor angiogenesis, tumor vascular permeability (Ktrans), extracellular leakage space and tumor growth parameters were assess by dynamic contrast enhanced (DCE)-MRI in vivo in hormono-dependent chemically DMBA-induced rat mammary carcinoma and in the Dunning R3327-H rat prostate cancer model. We have previouly demonstrated the anti-tumor efficiency of different hormone deprivation protocols (surgical ablation or clinically active drugs) performed in these breast and prostate cancer models. Tumor images were performed at 1.5T on a clinical MR scanner prior and at different time points after hormone deprivation. Hormone deprivation (D0) significantly inhibited the growth of breast and prostate tumors as determined via tumor volume measurements (T/C values ranging from 15 to 30%) using thin slice Turbo Spin Echo T2-weighted MR imaging (TR/TE : 4500/54). Kinetic model analysis of DCE-MRI (T1-weighted gradient echo imaging) using Gadomer (Schering, Germany) as contrast agent, demonstrated that hormone deprivation significantly decreased tumor vascular permeability-related parameters between D0 and D14-D28 after hormone deprivation (Ktrans decrease ranging from 1.5 to 2.5 fold) whereas these parameters increased with the tumor progression in the control rats (Ktrans increase ranging from 1.5 to 3.5 fold). Interestingly, at D28 after castration of the R3327-H bearing-rats the Ktrans and the leakage space values returned to the level of the control rats. The tumor volume was stabilized in the castrated rats but significantly increased in the control rats. At D28, in the castrated rats, the plasma circulating testosterone levels remained very low (1723 ± 434 and 1.4 ± 0.1 ng/ml in control and castrated rats respectively). Tumor related-angiogenesis parameters were also modified in the DMBA-breast model when a tumor regrowth was observed in the ovarectomized rats. In order to know if these results could be used to early detect the tumor hormono-independency switch, a similar technological approach is currently performed using Nude rats bearing hormono-dependent and non hormono-dependent human tumors. We therefore conclude that MR imaging is a useful technology to demonstrate changes in tumor volume and vascular permeability related-angiogenesis parameters and to compare pharmacological effects induced by clinically applied or investigating hormonal cancer treatments.
Abstract 17471: Outcome of Acute Myocardial Injury in COVID-19 Patients
Authors: Magdi Zordok, Muhammad Etiwy, Shruti Hegde, Michael Maysky
Journal: Circulation (2020)

Background: Acute myocardial injury has been reported in approximately 20% of patients with Coronavirus disease 2019 (COVID-19). Little is known about the outcome of this subset of patients. We are testing the hypothesis of higher morbidity and mortality in patients with COVID-19 who have acute myocardial injury. Methods: In this retrospective study, we analyzed data from patients admitted to Steward Healthcare hospitals in Massachusetts between March 22 and April 24, who tested positive for COVID-19 confirmed by serology and found to have elevated troponin levels (&gt;0.01). The sociodemographic information, clinical data, and outcomes of these critically ill patients were retrospectively extracted from the medical records. The primary outcome was in-hospital death. Data were analyzed using JMP statistical analysis software. Results: Two hundred eighty-three COVID-19 positive patients were found to have troponin levels &gt;0.01 on admission. Of these 183 patients (64.6%) were males, 49.1% were Caucasian and 32.1% were African Americans. The mean age of the patients was 70.7 ± 13.8. The prevalence of comorbid conditions was as follows: hypertension, 69.7%; hyperlipidemia, 46.9%; diabetes mellitus, 42.6%; chronic kidney disease, 28.3%; heart failure, 19.3%; atrial fibrillation, 22.1%; coronary artery disease, 17.1%; cerebrovascular accident, 10.2%; obesity, 38%; chronic obstructive pulmonary disease or asthma 20.8%, obstructive sleep apnea, 4.9%. One hundred thirty-seven patients (48.4%) noted to have acute kidney injury on presentation,128 (45.2%) required ICU level of care, 41% required invasive mechanical ventilation for a mean of 10.4 ± 7.9 days, and 38.8% required vasopressors. The average length of stay (LOS) in the medical intensive care unit and the hospital was 11.5 ± 8.3 days and 11.4 ± 9.5 days respectively. The overall in-hospital mortality rate was 45.6%. Conclusion: Patients with COVID-19 and elevated Troponin levels had high morbidity and mortality
Abstract 14395: Abnormal Regulation of P53-mTOR Pathway by MRNA-binding Protein ZFP36L2 in Peri-partum Cardiomyopathy
Authors: Yuki Tatekoshi, Hidemichi Kouzu, Hsiang-Chun Chang, Jason S Shapiro, Adam D Jesus, Warren A McGee, Issam Ben-Sahra, Chunlei Chun, Hossein Ardehali
Journal: Circulation (2020)

Introduction: A loss of function mutation in the mRNA binding protein ZFP36L2 has been associated with congenital heart diseases in humans, although the mechanism remains unclear. Objectives: We sought to elucidate the role of ZFP36L2 in the heart using mice with cardiac-specific ZFP36L2 deletion. Results: Cardiac-specific Zfp36l2 knockout (cs-L2KO) female mice exhibit a dramatic phenotype in which the majority of mice die after repeated pregnancies due to heart failure. We performed RNA-seq in H9c2 cells with ZFP36L2 KD, and found the expression of multiple mTOR pathway genes were altered, including marked repression of Redd1 and Sesn2 . Consistent with the RNA-seq data, the activity of mTORC1 was increased in cs-L2KO mouse hearts and in ZFP36L2 KD H9c2 cells. Loss of TSC2 mitigated mTORC1 hyperactivity in ZFP36L2 KD cells, indicating that ZFP36L2 regulates mTORC1 activity through the TSC2 complex. Overexpression of REDD1 rescued increased mTORC1 activity with ZFP36L2 KD, suggesting that ZFP36L2 regulates mTORC1, in-part through REDD1. Under total amino acid starvation, we observed higher p-S6K T389 levels in ZFP36L2 KD cells, and SESN2 overexpression mitigated p-S6K T389 , indicating loss of ZFP36L2 also regulates mTORC1 through amino acid sensing. p53 is a transcriptional activator of both REDD1 and SESN2, and we found that ZFP36L2 was required to maintain p53 levels by directly destabilizing MDM2 mRNA. Accordingly, administration of Nutlin3, an MDM2 inhibitor, reversed the reduction in p53, REDD1 and SESN2 protein levels, and prevented the increase in S6K phosphorylation in response to ZFP36L2 KD. Next, we treated pregnant mice with rapamycin, and cs-L2KO mice treated with rapamycin displayed significantly improved cardiac function after delivery. Finally, we analyzed human heart samples from patients with peri-partum cardiomyopathy and found ZFP36L2 protein to be significantly decreased and p-S6K T389 levels increased, compared to healthy controls. Conclusions: Our studies demonstrate that ZFP36L2 regulates mTORC1 activity through modifying p53 stability, and that the disruption of this pathway induces peri-partum cardiomyopathy. Inhibition of mTORC1 hyperactivity with rapamycin can be a potential therapy for this disease.
Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: An observational cohort study
Authors: Giorgio Bozzi, Davide Mangioni, Francesca Minoia, Stefano Aliberti, Giacomo Grasselli, Laura Barbetta, Valeria Castelli, Emanuele Palomba, Laura Alagna, Andrea Lombardi, Riccardo Ungaro, Carlo Agostoni, Marina Baldini, Francesco Blasi, Matteo Cesari, Giorgio Costantino, Anna Ludovica Fracanzani, Nicola Montano, Valter Monzani, Antonio Pesenti, Flora Peyvandi, Marcello Sottocorno, Antonio Muscatello, Giovanni Filocamo, Andrea Gori, Alessandra Bandera
Journal: Journal of Allergy and Clinical Immunology (2020)
Bladder Cancer
Authors: Andrew T. Lenis, Patrick M. Lec, Karim Chamie, MD, MSHS
Journal: JAMA (2020)

Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality.Advanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non-muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non-muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease.Improved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non-muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.