tbuckley/cabot-search huggingface dataset:
CHARACTERISTICS AND OUTCOMES OF PULMONARY HYPERTENSION IN PATIENTS UNDERGOING TRICUSPID VALVE REPAIR OR REPLACEMENT
Authors: Mahima Vijavaraghavan, Kurt W. Prins, Sasha Z. Prisco, Ranjit John, Rochus Voeller, Andrew Shaffer, Stephen L. Archer, E. Kenneth Weir, Thenappan Thenappan
Journal: Journal of the American College of Cardiology (2020)
TRASTUZUMAB CARDIOTOXICITY SURVEILLANCE BY ARTIFICIAL INTELLIGENCE-AUGMENTED ELECTROCARDIOGRAPHY IN A MULTI SITE STUDY
Authors: Zachi Itzhak Attia, Suraj Kapa, Peter Noseworthy, Meir Tabi, Samuel Asirvatham, Patricia Pellikka, Gaurav Satam, Francisco Lopez-Jimemez, Paul Friedman, Joerg Herrmann
Journal: Journal of the American College of Cardiology (2020)
LOOK TO THE RIGHT: THE RIGHT VENTRICLE AS A POSSIBLE PLAYER INVOLVED IN CENTRAL ARTERIAL STIFFNESS PATHOGENESIS
Authors: Angela Su-Mei Koh, Liang Zhong, Shuang Leng, Fei Gao, Xiao-Dan Zhao, Ru San Tan, Bryan Keng, Louis Teo, Woon-Puay Koh
Journal: Journal of the American College of Cardiology (2020)
Correlation of PSMA ADC exposure with reduction in tumor growth rate determined using serial PSA measurements from a phase I clinical trial.
Authors: Yakov Rotshteyn, Francois Mercier, Rene Bruno, Nancy Stambler, Robert Joseph Israel, Vivien Wong
Journal: Journal of Clinical Oncology (2013)

e16047 Background: PSMA ADC is a fully humanized antibody to PSMA conjugated to the potent microtubule disrupting agent monomethyl auristatin E (MMAE). The safety and PK of PSMA ADC as well as changes in PSA levels were evaluated in a phase I dose escalation study in patients with taxane-refractory metastatic castration-resistant prostate cancer (mCRPC) (PSMA ADC 1301). Stein et al. (2010) has previously demonstrated correlation between growth rate derived from serial PSA measurements with survival in patients with mCRPC and suggested that growth rate could serve as a novel endpoint indicative of response to therapy and overall survival. Methods: The PK parameters for PSMA ADC, Total antibody (Ab) and free MMAE obtained from PSMA ADC Study 1301 (N=52) were calculated using non-compartmental analysis. The final data set contains 253 longitudinal PSA observations from 52 subjects dosed with 0.4-2.8 mg/kg PSMA ADC. The Stein model was re-expressed as a 7-parameter population model to describe the longitudinal PSA data which includes: Baseline PSA level (Y 0 ), PSA decrease rate (D), PSA increase rate (G), inter-patient variability for Y 0 , G and D respectively, and residual variance. Model parameters were estimated using Phoenix/NLME. Exposure-efficacy relationships and correlation between G and covariates were determined. Results: PSMA ADC, Total Ab, and MMAE exposure increased linearly with increasing PSMA ADC dose. Longitudinal PSA data were correctly fitted to the re-expressed Stein model. G continuously decreased with increasing PSMA ADC exposure, suggesting an exposure dependent drug effect. There was no apparent saturation of this effect at the maximum observed exposure, and no influence of age, baseline albumin and ALT/AST levels on G was evident. Conclusions: In a phase I study where PSMA ADC (0.4-2.8 mg/kg) was administered to patients with mCRPC, we observed a correlation of PSMA ADC exposure with the reduction of G, suggesting that PSMA ADC may provide dose-dependent therapeutic benefit to subjects with mCRPC.
Health Status Changes and Outcomes in Patients With Heart Failure and Mitral Regurgitation
Authors: Suzanne V. Arnold, Gregg W. Stone, Michael J. Mack, Adnan K. Chhatriwalla, Bethany A. Austin, Zixuan Zhang, Ori Ben-Yehuda, Saibal Kar, D. Scott Lim, JoAnn Lindenfeld, William T. Abraham, David J. Cohen
Journal: Journal of the American College of Cardiology (2020)
ELECTROCARDIOGRAPHIC CHARACTERISTICS IN HYPERTROPHIC CARDIOMYOPATHY WITH LEFT VENTRICULAR APICAL ANEURYSM
Authors: Nandini Mehra, Anthony Kashou, Christopher DeSimone, Alexander C. Egbe, Rick A. Nishimura, Hartzell Schaff, Abhishek Deshmukh
Journal: Journal of the American College of Cardiology (2020)
PLASMA B-TYPE NATRIURETIC PEPTIDE LEVELS IS A PREDICTOR OF ADVERSE EVENTS IN PATIENTS WITH LEFT VENTRICULAR NON-COMPACTION
Authors: Jay Ramchand, Pooja Podugu, Michael Chetrit, Serge Harb, Alex Milinovich, Brian P. Griffin, Leslie Cho, Scott D. Flamm, Deborah Kwon, Wai Hong Wilson Tang
Journal: Journal of the American College of Cardiology (2020)
Leptomeningeal disease as a manifestation of CLL.
Authors: Aisha Salman Zaidi, Eric Christopher Burton, Mitesh Lotia
Journal: Journal of Clinical Oncology (2012)

e17019 Background: Chronic Lymphocytic Leukemia is a lymphoproliferative disorder which can have variable course from being indolent to aggressive. Reported annual incidence of Chronic Lymphocytic Leukemia is 3:100000. The most common manifestation is Lymphadenopathy and Leptomeningeal involvement is very rare with only a few reported cases in literature. Methods: This is an observational case report. Results: We report a case of 57 year old White male who presented with CNS disease as his first manifestation of CLL. He reported a 6 week history of cognitive decline with inability to perform complex tasks, difficulty with calculations, word finding trouble, progressive clumsiness of right arm and leg and a weight loss. MRi revealed Left sided Leptomeningeal enhancement. As part of his work up; patient received LP, PET scans, Infectious and autoimmune studies and eventually brain biopsy which initially showed Lymphocytic predominance.On further review by NIH immunohistochemical stains for CD5, CD20 and CD23 were positive on the leptomeningeal and parenchymal lymphocytes. His bone marrow showed CLL involvement both morphologically and immunophenotypically by means of flow cytometric analysis. He was started on treatment with High dose methotrexate and Rituximab and showed remarkable improvement in his cognitive function by the completion of his second cycle. His bone marrow repeat biopsy showed complete remission and no involvement of lymphoma. Conclusions: CLL is an indolent disease and direct CNS invasion is extremely rare. Our case becomes unique in terms of its presentation. It highlights the importance of timely diagnosis and management of leptomeningeal disease in CLL can lead to resolution of neurologic symptoms.
Communication of diagnosis in elderly lung cancer patients: Who is informed, what information is given, and what patients know and want to know.
Authors: Regina Girones, Jorge Aparicio, Maria Dolores Torregrosa
Journal: Journal of Clinical Oncology (2013)

e20643 Background: Lung cancer chemotherapy decisions in patients &gt; 70 years old are complex; in order to integrate patients in the decision-making process, they must be informed. To assess the modes of communication with older lung cancer patients, we prospectively collected data in order to assess patients’ level of knowledge about diagnosis and prognosis. We examined who informed the patient, the information given and what the patient knew and wanted to know. Relationships, among other parameters were presented. Methods: 83 patients diagnosed with lung cancer from January 2006 to February 2008 were recruited from a single center. Logistic regression and multiple imputation methods were used to assess associations between patient information and independent variables. Results: In the majority of cases, families received the diagnosis of lung cancer (92.8%). Family was more protective when the patients were elderly (p: 0,036), depressed (p: 0,054), had dementia (p: 0,03), had poor performance status (p: 0,03) or complied with frailty criteria (p: 0,014). At our institution, physicians who gave cancer diagnoses were not oncologists. We received the patient diagnosed yet. We found that they usually gave cancer diagnosis preferably to family members. Only 27,7% of patients were informed that they had tumors. There was a correlation between age and more protective attitudes on the part of physicians. 73,5% of patients actively solicited information, however elderly and frail patients tended to do so less. Conclusions: A large proportion of elderly lung cancer patients do not receive adequate information about their disease prior to contact with oncologists however they do actively ask for information and speak about cancer with oncologists. Information about cancer is difficult to provide, even in elderly patients.
MECHANICAL CIRCULATORY SUPPORT IN INFANTS WITH CONGENITAL HEART DISEASE
Authors: Jonathan Edelson, Joseph Rossano, Heather Griffis, Matthew J. O'Connor, Hannah Katcoff, Oluwatimilehin Okunowo, Kimberly Lin, Christopher Mascio, J. William Gaynor, Jonathan Michael Chen, Stephanie Fuller, Danielle Burstein
Journal: Journal of the American College of Cardiology (2020)
THE INTERACTION OF DESPHOPHO-UNCARBOXYLATED MATRIX GLA PROTEIN AND GROWTH DIFFERENTIATION FACTOR 15 IN TERMS OF ADDITIVE RISK OF STABLE CORONARY HEART DISEASE PATIENTS
Authors: Otto Mayer, Jitka Seidlerova, Jan Bruthans, Julius Gelžinský, Radek Kučera
Journal: Journal of the American College of Cardiology (2020)
The Novel Coronavirus Disease (COVID-19) Threat for Patients With Cardiovascular Disease and Cancer
Authors: Sarju Ganatra, Sarah P. Hammond, Anju Nohria
Journal: JACC CardioOncology (2020)

A s the novel coronavirus severe acute respira- tory syndrome coronavirus-2 (SARS-CoV-2) continues to spread across the globe, millions of people may be affected (1,2).Although knowledge regarding the complications and fatality rate associated with SARS-CoV-2 (COVID-19) infection is evolving, preliminary data from China suggests that patients with pre-existing comorbidities, particularly cardiovascular disease (CVD) and cancer, may be among those at highest risk of not just acquiring the infection but also having worse outcomes (1-3).The risk of adverse outcomes may be even higher for those afflicted with a dual diagnosis, particularly the elderly.This is extremely concerning from a public health perspective since cancer and CVD are amongst the most prevalent diseases worldwide (4), and the impact of the current pandemic of coronavirus disease 2019 (COVID-19) could be devastating for these patients.The World Health Organization (WHO) has recently declared COVID-19 a public health emergency of international concern (2).COVID-19 caused by SARS-CoV-2 originated in Wuhan, in the Hubei province of China, but it is spreading rapidly and efficiently (2).SARS-CoV-2 is a novel enveloped RNA betacoronavirus, similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), pathogens responsible for the severe acute respiratory syndrome (SARS) outbreaks in 2002 to 2003 in Guangdong Province, China, and severe respiratory disease outbreaks in 2012 in the Middle East, respectively (5).Although there are phylogenetic similarities between the coronaviruses responsible for SARS and COVID-19, the transmission is exponential with COVID-19, and it can be transmitted by people who are just mildly ill or even asymptomatic, leading to 10 times as many cases as SARS in one-quarter of the time (2,5,6).Although our understanding about the risk of infection with SARS-CoV-2 and its impact is limited, we examine its interaction with the 2 most common disease entities: cancer and CVD. PRE-EXISTING CANCER AND CARDIOVASCULAR DISEASEPatients with cancer are typically at higher risk of infection due to compromised host defenses and the sequelae of antineoplastic treatment, namely, leukopenia, disruption in barriers to infection, and shifts in microbial flora.The current COVID-19 pandemic is particularly concerning, given the potential of spread from asymptomatic carriers (1-3).A report from China suggests that among those confirmed infected with SARS-CoV-2, approximately 1% of patients had cancer (3): 5-fold higher than the general incidence of cancer in China (201.7 per 100,000 persons) (7).A retrospective analysis of MERS-CoV infection has demonstrated that it was more likely to occur in
ASSOCIATION BETWEEN BIVENTRICULAR REMODELLING AND PEAK EXERCISE PERFORMANCE: THREE-DIMENSIONAL ECHOCARDIOGRAPHIC STUDY IN A LARGE ATHLETIC COHORT
Authors: Bálint Károly Lakatos, Marton Tokodi, Orsolya Kiss, Nora Sydo, Emese Csulak, Alexandra Fábián, Mate Babity, Csaba Bognár, Bela Merkely, Attila Kovács
Journal: Journal of the American College of Cardiology (2020)
COMPARING SEDATION VERSUS GENERAL ANESTHESIA IN TRANSESOPHAGEAL ECHOCARDIOGRAPHY-GUIDED PERCUTANEOUS TRANSCATHETER MITRAL VALVE REPAIR: A META-ANALYSIS
Authors: Sandeep Banga, Abdul Moiz Hafiz, Youssef Chami, Darrel Gumm, Preeti Banga, Carmen Howard, Minchul Kim, Partho Sengupta
Journal: Journal of the American College of Cardiology (2020)
Pharmacokinetics of PT523, a novel aminopterin analogue, in patients with solid tumors
Authors: J. G. Supko, X. He, N. Sao, F. D’Amato, L. Blaszkowsky, J. R. Clark, G. I. Shapiro, P. Bhargava, L. J. Appleman, J. P. Eder
Journal: Journal of Clinical Oncology (2006)

2052 Background: N α -(4-Amino-4-deoxypteroyl)-N 5 -hemiphthaloyl)-L-ornithine (PT523) is a nonpolyglutamatable aminopterin analogue selected for clinical evaluation based upon properties that confer potential therapeutic advantages over classic and nonclassic antifolates. This report describes the pharmacokinetic (PK) behavior of PT523 in cancer patients as determined in the first phase I trial of the drug. Methods: Adult patients with refractory solid tumors received PT523 as a 5 min iv infusion every 7 days for 3 weeks. Plasma samples were obtained at -5, 4, 10, 15, 20, 30, 45 min; 1, 2, 3, 4, 6, 8, 24, and 48 h after starting the first weekly infusion. Urine was collected and pooled from 0–8, 8–24, and 24–48 h. An LC/MS assay was used to measure PT523 in plasma and urine. Interday accuracy and precision were both &lt;15% at the lowest concentrations measured in plasma (0.50 ng/mL) and urine (50 ng/mL). PK parameters were estimated by standard noncompartmental methods. Results: The PK of PT523 was characterized in 24 patients with normal renal and hepatic function, and a median age of 52 years (range, 28 - 77 years). Data was obtained from groups of at least three patients receiving doses of 5, 6.7, 9, 12, and 16 mg/m 2 . The PT523 concentration in plasma decreased in a polyexponential manner and the terminal log-linear phase was achieved 4–6 h after dosing. In the 7 patients receiving doses of 16 mg/m 2 , the mean peak drug concentration in plasma (C max ) was 5,650 ± 300 ng/mL and the median plasma concentration 48 h after dosing was 1.7 ng/mL (range, 1.0 - 23.4 ng/mL). The apparent biological half-life (t 1/2,z ), total body clearance (CL) and apparent volume of distribution at steady-state (V ss ) were all independent of the dose. Mean ± SD values of PK parameters for the entire cohort of 24 patients were: CL, 1.16 ± 0.31 L/h/m 2 ; t 1/2,z , 5.3 ± 1.2 h; V ss , 7.7 ± 1.5 L/m 2 . The mean amount of the dose excreted as unchanged drug in urine over 48 h was 40 ± 15%. Conclusions: PT523 exhibits linear PK with moderate interpatient variability when administered as a 5 min iv infusion at doses of 5 - 16 mg/m 2 . Renal clearance is a major route of elimination. Association between the CL of PT523 and creatinine clearance should be evaluated in a future study to assess whether dose modification is warranted for patients with diminished renal function. No significant financial relationships to disclose.
DEBUNKING THE JULY EFFECT IN TRANSCATHETER INTERVENTIONS IN STRUCTURAL HEART DISEASE: MYTH OR TRUTH? IMPLICATIONS ON RESIDENT CLINICAL TRAINING IN THE CURRENT ERA
Authors: Sameer Hirji, Supreet Singh, Alexis Okoh, Alexandra Malarczyk, Edward Percy, Morgan Harloff, Ahmed Kolkailah, Cheryl Zogg, Emefah Loccoh, Farhang Yazdchi, Mark Russo, Pinak Shah, Patrick O’Gara, Tsuyoshi Kaneko
Journal: Journal of the American College of Cardiology (2020)
ECG-AGE FROM ARTIFICIAL INTELLIGENCE: A NEW PREDICTOR FOR MORTALITY? THE CODE (CLINICAL OUTCOMES IN DIGITAL ELECTROCARDIOGRAPHY) STUDY
Authors: Gabriela Miana Paixão, Antonio Horta Ribeiro, Emilly Lima, Bruna Seewald, Manoel Horta Ribeiro, Derick Oliveira, Paulo Gomes, Nathalia Castro, Wagner Meira, Thomas Schön, Antonio L. Ribeiro
Journal: Journal of the American College of Cardiology (2020)
PREDICTING SUDDEN CARDIAC DEATH BY MACHINE LEARNING OF VENTRICULAR ACTION POTENTIALS
Authors: Anojan Selvalingam, Mahmood Alhusseini, Albert J. Rogers, David Krummen, Firas M. Abuzaid, Tina Baykaner, Paul Clopton, Peter Bailis, Matei Zaharia, Paul Wang, Sanjiv Narayan
Journal: Journal of the American College of Cardiology (2020)
Association of childhood obesity with risk of early all-cause and cause-specific mortality: A Swedish prospective cohort study
Authors: Louise Lindberg, Pernilla Danielsson, Martina Persson, Claude Marcus, Emilia Hagman
Journal: PLoS Medicine (2020)

Pediatric obesity is associated with increased risk of premature death from middle age onward, but whether the risk is already increased in young adulthood is unclear. The aim was to investigate whether individuals who had obesity in childhood have an increased mortality risk in young adulthood, compared with a population-based comparison group.In this prospective cohort study, we linked nationwide registers and collected data on 41,359 individuals. Individuals enrolled at age 3-17.9 years in the Swedish Childhood Obesity Treatment Register (BORIS) and living in Sweden on their 18th birthday (start of follow-up) were included. A comparison group was matched by year of birth, sex, and area of residence. We analyzed all-cause mortality and cause-specific mortality using Cox proportional hazards models, adjusted according to group, sex, Nordic origin, and parental socioeconomic status (SES). Over 190,752 person-years of follow-up (median follow-up time 3.6 years), 104 deaths were recorded. Median (IQR) age at death was 22.0 (20.0-24.5) years. In the childhood obesity cohort, 0.55% (n = 39) died during the follow-up period, compared to 0.19% (n = 65) in the comparison group (p < 0.001). More than a quarter of the deaths among individuals in the childhood obesity cohort had obesity recorded as a primary or contributing cause of death. Male sex and low parental SES were associated with premature all-cause mortality. Suicide and self-harm with undetermined intent were the main cause of death in both groups. The largest difference between the groups lay within endogenous causes of death, where children who had undergone obesity treatment had an adjusted mortality rate ratio of 4.04 (95% CI 2.00-8.17, p < 0.001) compared with the comparison group. The main study limitation was the lack of anthropometric data in the comparison group.Our study shows that the risk of mortality in early adulthood may be higher for individuals who had obesity in childhood compared to a population-based comparison group.
c-Rel gain in B cells drives germinal center reactions and autoantibody production
Authors: Maike Kober-Hasslacher, Hyunju Oh-Strauß, Dilip Kumar, Valeria Soberon, Carina Diehl, Maciej Lech, Thomas Engleitner, Eslam Katab, Vanesa Fernández-Sáiz, Guido Piontek, Hongwei Li, Björn Menze, Christoph Ziegenhain, Wolfgang Enard, Roland Rad, Jan P. Böttcher, Hans-Joachim Anders, Martina Rudelius, Marc Schmidt-Supprian
Journal: Journal of Clinical Investigation (2020)

Single-nucleotide polymorphisms and locus amplification link the NF-κB transcription factor c-Rel to human autoimmune diseases and B cell lymphomas, respectively. However, the functional consequences of enhanced c-Rel levels remain enigmatic. Here, we overexpressed c-Rel specifically in mouse B cells from BAC-transgenic gene loci and demonstrate that c-Rel protein levels linearly dictated expansion of germinal center B (GCB) cells and isotype-switched plasma cells. c-Rel expression in B cells of otherwise c-Rel-deficient mice fully rescued terminal B cell differentiation, underscoring its critical B cell-intrinsic roles. Unexpectedly, in GCB cells transcription-independent regulation produced the highest c-Rel protein levels among B cell subsets. In c-Rel-overexpressing GCB cells this caused enhanced nuclear translocation, a profoundly altered transcriptional program, and increased proliferation. Finally, we provide a link between c-Rel gain and autoimmunity by showing that c-Rel overexpression in B cells caused autoantibody production and renal immune complex deposition.
Trends in Parity and Breast Cancer Incidence in US Women Younger Than 40 Years From 1935 to 2015
Authors: Sarah M. Lima, Rebecca D. Kehm, Katrina Swett, Lou Gonsalves, Mary Beth Terry
Journal: JAMA Network Open (2020)

<h3>Importance</h3> During the past several decades, breast cancer incidence has been increasing for women younger than 40 years. The increase matches the decrease in parity, an established breast cancer risk factor, but secular trends in incidence have not been examined prior to the 1970s. <h3>Objective</h3> To examine whether secular trends in parity explain the increase in breast cancer incidence among US women aged 25 to 39 years from 1935 to 2015. <h3>Design, Setting, and Participants</h3> This population-based cohort study used population-based aggregate-level data from the Connecticut Tumor Registry (CTR) to examine breast cancer incidence and age-standardized rates among women aged 25 to 39 years from 1935 to 2015. National mean live births were calculated using birth data from the National Vital Statistics System (NVSS) from 1930 to 2015 (allowing for 5-year lag). Linear regression was used to compare a baseline model of year estimating age-adjusted breast cancer incidence rate with a model that adjusted for parity constructs. <h3>Main Outcomes and Measures</h3> Breast cancer incidence rates among women aged 25 to 39 years from 1935 to 2015. <h3>Results</h3> Among women in Connecticut aged 25 to 39 years from 1935 to 2015, incidence of breast cancer for women aged 25 to 39 years increased 0.65% (95% CI, 0.53%-0.77%) per year, from 16.3 breast cancer diagnoses per 100 000 women in 1935 to 38.5 breast cancer diagnoses per 100 000 women in 2015. This increase began nearly 4 decades before the secular decrease in parity (mean [SD] parity peaked at 2.26 [0.87] live births per woman in 1966 and in 2010 had decreased to 1.41 [0.71] live births per woman). Age-specific parity trends explained only 0% to 4% of the variability in incidence over time. <h3>Conclusion and Relevance</h3> These findings suggest that breast cancer incidence for women aged 25 to 39 years has been significantly increasing since the 1930s and cannot be attributed to changes in parity over time.