tbuckley/cabot-search huggingface dataset:
Phenotypic characterization of circulating tumor cells (CTCs) from neuroendocrine prostate cancer (NEPC) and metastatic castration-resistant prostate cancer (mCRPC) patients to identify a novel diagnostic algorithm for the presence of NEPC.
Authors: Himisha Beltran, Adam Jendrisak, Mark Landers, Juan Miguel Mosquera, Myriam Kossai, Jessica Louw, Rachel Krupa, David M. Nanus, Scott T. Tagawa, Dena Marrinucci, Mark A. Rubin, Ryan Vance Dittamore
Journal: Journal of Clinical Oncology (2015)

197 Background: NEPC is an aggressive variant of prostate cancer that most commonly arises in later stages of mCRPC, especially with visceral metastases in the setting of a low PSA. There are no reliable serum markers to identify patients that are transforming to NEPC and incidence of CTCs in these patients is unknown. Detection of NEPC has clinical implications as these patients are often treated with platinum chemotherapy rather than with androgen receptor (AR) targeted therapies such as abiraterone or enzalutamide. We sought to determine if phenotypic characterization of CTCs could differentiate NEPC from mCRPC. Methods: 24 pts (16 pts with tissue confirmed NEPC and 8 pts with mCRPC) had blood collection for CTC analysis utilizing the Epic Sciences platform. Epic analysis included identification of traditional CTCs (CK+, CD45- cells, with intact nuclei, morph distinct), CK- CTCs (CK-, CD45-, intact nuclei, morph distinct), small CTCs (CK+, CD45-, intact nuclei, small cell size), and CTC clusters. We examined CTCs at the single cell level for CTC size, shape, epithelial and AR expression. Advanced digital pathology algorithms measured size and shape measurements of CTCs. Results: CTCs from NEPC patients demonstrated strong statistical differentiation from mCRPC patients, with unique CTC morphology and protein chemistry that was not seen in mCRPC CTCs. NEPC CTCs had increase prevalence of unique CTC phenotypes including: small size, AR negativity, and presence of nucleoli. Unique cell types enabled a multivariate biomarker that is strongly associated with CTCs exclusive to tissue confirmed NEPC. Conclusions: CTCs from NEPC have unique phenotypes compared with those from mCRPC. If confirmed, the utilization of a liquid biopsy to diagnose NEPC may enable earlier identification of patients prone to visceral metastasis, and intervention to cytotoxic therapeutics. Additionally, identification of patients with NEPC could help for patient selection for AR vs. NEPC targeted therapeutics. [Table: see text]
Abstract 14358: Coronary Anatomy and Comorbidities in Stress-Induced Cardiomyopathy
Authors: Dustin Matel-Anderson, Andy Chau, Perry Krumenacher, Kwang Woo Ahn, Ronald Siegel, Seong Cheol Park, Hyun Seok Kim, Byung-il (Bill) W Choi
Journal: Circulation (2012)

BACKGROUND: Previous studies indicated patients with stress-induced cardiomyopathy (SIC) present with apical ballooning of the left ventricle during severe emotional stress. The psychosomatic mechanism explaining how emotional stress can cause myocardial dysfunction is hypothesized to be neurogenic coronary vasospasm causing ischemia despite normal coronary anatomy. METHOD: 50 patients (35 F, 15 M) with mean age 62 ±14 years, who were admitted with SIC from 2006 to 2012 were divided into groups by presence or absence of coronary stenosis(CS) for evaluation of coronary anatomy, LV function, risk factor profile, comorbidities, and stress type. RESULTS: 24 patients with mean age of 53 ±2 years without structural CS(Group A) were younger than 26 patients with mean age of 68 ±4 years with minimal, or insignificant CS(Group B): (P:0.015), with CS of LAD (35 ±5%), LCX (45 ±19%), and RCA (50 ±10%):(P:NS). Ejection fraction of 39 ±5 vs. 36 ±4%,Troponin of 9.4 ±2 vs. 6.5 ±6 ng/dl, LDL of 101±15 vs. 78 ±8 mg/dl, HDL...
Abstract 3847: Cardiac Contractility is Differentially Modulated by Isoforms 1 and 4 of the Plasma Membrane Calcium Pump
Authors: Mohamed A Shaheen, Tamer M Mohamed, Min Zi, Sukhpal Prehar, Nasser Alatwi, Zeinab Hegab, Florence Baudoin, Michael Emerson, Delvac Oceandy, Elizabeth J Cartwright, Ludwig Neyses
Journal: Circulation (2009)

Ca2+ plays a crucial role in excitation-contraction coupling as well as in cardiac signal transduction. Two isoforms of the plasma membrane calcium pump (PMCA), PMCA1 and 4, are expressed in the my...
Surgical Pathology and Management of Anorectal Crohn's Disease
Authors: L E Hughes
Journal: Journal of the Royal Society of Medicine (1978)

The anorectal manifestations of Crohn's disease comprise a complex and heterogeneous group of conditions which fall into two main categories: primary lesions of the active disease process and secondary lesions resulting from healing of, or infective complications of, the primary lesions. The lesions are classified into distinct clinicopathological entities which may be used in assessing prognosis and determining appropriate treatment. A basic principle of management is that surgery should be avoided as far as possible in the presence of disease activity, but will frequently be necessary, and satisfactory, for secondary complications.
Abstract 20075: Mutations in NEXN, a Novel Z-disc Gene, are Associated with Hypertrophic Cardiomyopathy
Authors: Hu Wang, Zhaohui Li, Jizheng Wang, Kai Sun, Qiqiong Cui, Lei Song, Yubao Zou, Xiaojian Wang, Xuan Liu, Rutai Hui, Yuxin Fan
Journal: Circulation (2010)

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by increased ventricular wall thickness that cannot be explained by any underlying condition, cadiomyocyte hypertrophy and disarray,...
Abstract 14350: Trend in Acute Myocardial Infarction Mortality among Elderly People in China, 2002-2008
Authors: Chaoying Cui, Yuanchen Cui, Yida Tang, Yun Wang, Harlan M Krumholz
Journal: Circulation (2010)

Background:  In the US and China cardiovascular disease is the leading cause of death, but the trends may be distinctly different. In the US hospitalizations for AMI have declined by more than 20% since 2002. We sought to determine recent changes in death caused by AMI in China based on data available from the China Ministry of Health.   Methods:  The data source was the China Ministry of Health 2002-2008 annual reports. Mortality was defined as death caused by AMI, and the population at risk was defined as individuals aged 65 years or older. Mortality rates for each year were calculated per 100,000 person-years. Descriptive analysis was conducted for overall trend and sub-group analysis was conducted by gender, age and urban/rural to understand potential disparities in mortality.   Results:  From 2002-2008, the overall AMI mortality rate increased from 248 per 100,000 person-years in 2002 to 391 in 2008 for patients aged 65 or older, a 58% relative increase. The increase in AMI mortality was not uniformly observed across age groups, urban/rural and gender. The relative increases were 24% and 72% for age 65-69 and 85 or older groups, respectively. Large urban areas had a relative increase of 36% vs. 150% for rural areas. The relative increases were 31% (large urban) vs. 111% (rural) and 28% (large urban) vs. 210% (rural) for age 65-69 and 85 or older groups, respectively. Female who lived in an urban environment had a higher relative increase than male (38% vs. 32%).   Conclusions:  Based on Chinese Ministry of Health 2002-2008 annual reports, the observed AMI mortality rates between 2002 and 2008 have increased by relative 58% for the elderly population in China. Further work is necessary to determine if the changes are the result of better diagnostic methods or a changing epidemiology.
Abstract 9922: Pentraxin 3 is a Local Inflammatory Marker in Atrial Fibrillation
Authors: Takeshi Soeki, Sachiko Bando, Toshiyuki Niki, Hiromu Yamazaki, Akira Takashima, Kozue Ogasawara, Mika Bando, Takayuki Ise, Hidekazu Takeuchi, Noriko Tomita, Yuka Ueda, Kenya Kusunose, Koji Yamaguchi, Yoshio Taketani, Takashi Iwase, Hirotsugu Yamada, Tetsuzo Wakatsuki, Masataka Sata
Journal: Circulation (2011)

Objectives: Increasing evidence indicates that inflammation contributes to the pathogenesis of atrial fibrillation (AF), but their role remains poorly defined. Pentraxin 3 (PTX3), which has C-terminal sequence homology with the classic pentraxin C-reactive protein (CRP), is produced abundantly from local inflammatory lesion while CRP is mainly produced in the liver. In this study, we investigated whether the local level of PTX3 might be a sensitive marker for the local inflammation of AF. Methods: Sampling of blood in periphery and left atrial appendage (LAA) was performed in 18 patients with AF undergoing pulmonary vein isolation and 10 control subjects with atrial septal defect or WPW syndrome. We measured the concentrations of CRP, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and PTX3 in plasma of periphery and LAA. Results: Plasma PTX3 concentrations both in periphery and LAA were higher in patients with AF than control subjects. PTX3 concentration was significantly higher in LAA than periphery in patients with AF (3.3±0.7 vs 2.8±0.5 ng/ml, p&lt;0.01) but not in control subjects (2.4±0.5 vs 2.4±0.5 ng/ml, NS). On the other hand, there was no significant difference of CRP, IL-6, and TNF-alpha concentrations in periphery and LAA between AF patients and control subjects. Plasma PTX3 concentartion did not differ between patients with paroxysmal AF and persistent AF. However, there was a significantly positive correlation between plasma concentration of PTX3 in LAA and left atrial diameter (r=0.47, p&lt;0.05). Conclusion: Local production of PTX3 in left atrium might reflect the local inflammation of AF. In addition, PTX3 might be superior to other inflammatory markers which are reported to be elevated in AF.
Abstract P276: Differential Association of D-dimer with Stroke and Coronary Heart Disease: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Neil A Zakai, George Howard, Leslie A McClure, Suzanne E Judd, Brett M Kissela, Monika M Safford, Mary Cushman
Journal: Circulation (2013)

Introduction: D-dimer, a marker of coagulation activation, has higher levels in blacks than whites and has been variably associated with stroke and coronary heart disease (CHD). Methods: REGARDS recruited 30,239 participants in their homes across the continental US between 2003-07; by design 55% were female, 41% black, and 56% lived in the southeast. In a case-cohort study, D-dimer was measured in 646 participants with incident stroke, 515 with incident CHD, and 1104 in a cohort random sample. D-dimer was log transformed and modeled per 1-unit increase. Cox models were used to determine the HR for vascular disease for D-dimer and the difference in HR (95% CI) by race and vascular disease calculated by bootstrapping with 1000 replicate samples and using the 2.5 and 97.5 percentiles of the distribution (see Table for model variables). Results: Median D-dimer was higher in blacks (0.45 mcg/mL; IQR 0.26, 0.85) than whites (0.38 mcg/mL; IQR 0.23, 0.69); p &lt;0.001. D-dimer was higher with increasing age, female gender, diabetes, hypertension and prebaseline cardiovascular disease (all p &lt;0.05). The table shows the HR of stroke and CHD by baseline D-dimer. In minimally-adjusted models, D-dimer was associated with both stroke and CHD. Accounting for Framingham stroke and CHD risk factors, D-dimer remained associated with CHD (HR 1.45; 95% CI 1.18, 1.79), but was marginally associated with stroke (HR 1.20; 95% CI 0.99, 1.45). The difference in the HR of D-dimer between CHD and stroke was 0.22 in the basic model and 0.25 in the Framingham model, but this difference was of marginal statistical significance (Table). There was no difference in the HRs for stroke or CHD for D-dimer in blacks compared to whites (Table). Discussion: The association of D-dimer with stroke appeared smaller than for CHD with similar associations by race. Findings suggest that hemostasis activation may play a greater role in pathogenesis of CHD than stroke. Further study is needed to confirm these findings and evaluate the association of D-dimer with different stroke subtypes.
Prognostic influences of delay in patients treated for non-small cell lung cancer
Authors: Gunnar Myrdal, Mats Lambe, Gunnar Hillerdal, Kristina Lamberg, Thorhallur Agustsson, Elisabeth Ståhle
Journal: Thorax (2003)

From being a rare disease in the early 1900s, lung cancer is today the most common forms of cancer worldwide. This development is due to the gradual uptake of cigarette smoking in different populations and birth cohorts during the past 75 years. In spite of different modes of treatment, survival is still poor and surgery remains the prerequisite for cure. National data from the Swedish Cancer Register for the 35-year period 1958-1994 were analysed to estimate the effects of birth cohort, year of diagnosis (period) and age at diagnosis on the time trends in lung cancers. Early mortality, complications, major morbidity during the first 30 days, quality of life and long term survival after lung cancer surgery were assessed to estimate the significance of pre-surgical and tumour-related risk factors. Also, effects of delay in diagnosis and treatment among patients with non-small cell lung cancer were examined.The main results indicate that the overall age-adjusted incidence of lung cancer in Sweden has stabilised in men during the last two decades but has been increasing continuously in women. The fastest rate increase was noted among the youngest women and the incidence of adenocarcinoma is increasing in both sexes. Our results show low early mortality and morbidity after lung cancer surgery. Furthermore, quality of life was comparable with that of CABG patients postoperatively. However, patients with reduced lung capacity and those undergoing pneumonectomy should be treated with great care, as they run a considerable risk of major complications, impaired quality of life or death during the first 30 days postoperatively. Tumour stage (TNM) is the best prognostic indicator for long-term survival following radical surgery, underlying the importance of accurate surgical staging. Factors such as impaired preoperative lung function, older age, and major complications after surgery all negatively influence survival. Current smokers as a group run a significant risk of an adverse outcome (major complication or death), impaired mental health and shortened survival after lung cancer surgery. Waiting time for diagnosis and treatment of lung cancer was longer than recommended; especially among those surgically treated, but prolonged delay did not influence survival adversely.
Abstract 19541: Impaired Calcium Release, Prolonged Action Potentials and Early Afterdepolarizations in Ventricular Myocytes from Mice Harboring a Ryanodine Receptor 2 Loss-of-Function Mutation Associated with Catecholaminergic Polymorphic Ventricular Tachycardia
Authors: Yan-Ting Zhao, Randall Loaiza, Carmen R Valdivia, Francisco Alvarado, Cong Li, Patricia Powers, Héctor H Valdivia
Journal: Circulation (2012)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) patients harboring the cardiac ryanodine receptor (RyR2) mutation RyR2-A4860G exhibit sympathetically-driven idiopathic ventricular fibrillation without cardiac structural defects. In sharp contrast to other CPVT mutations characterized to date, RyR2-A4860G fails to activate in response to increasing luminal [Ca 2+ ] and, when expressed in HEK293 or HL-1 cells, it exhibits attenuated store overload-induced Ca 2+ release. Thus, RyR2-A4860G is the first loss-of-function mutation linked to CPVT, but the arrhythmogenic mechanisms are unknown. We used homologous recombination to generate a mouse harboring the RyR2-A4860G mutation and used isolated ventricular myocytes to investigate the cellular mechanisms by which this mutation generates ventricular arrhythmias. Mice heterozygous for the mutation (RyR2-A4860G +/- ) display no apparent cardiac structural defects. Whole cell current-clamp combined with confocal Ca 2+ imaging to simultaneously record actions potential (AP) and intracellular Ca 2+ transient ([Ca 2+ ] i ) revealed that AP duration at 90% repolarization (APD 90 ) in RyR2-A4860G +/- was longer than in WT cardiomyocytes at 1 Hz (209±51 vs. 118±37 ms, n=12 and 7, respectively). As a result of prolonged APs, RyR2-A4860G +/- cells exhibited early afterdepolarizations (EADs) at significantly greater frequency than WT (50% vs 14%, respectively). Ca 2+ imaging of RyR2-A4860G +/- cells showed that during the longer APs, Ca 2+ release events are often interspaced between two successive AP-triggered Ca 2+ transients. Since the [Ca 2+ ] i amplitude in RyR2-A4860G +/- cells is significantly lower than in WT (3.5±0.6 , 2.5±0.3, and 2.5±0.2 vs. 3.8±0.3, 4.3±0.5, and 4.4±0.7, at 1, 2 and 3 Hz, respectively), the presence of Ca 2+ release suggests decreased Ca 2+ -dependent inactivation, and subsequent re-activation, of L-type Ca 2+ current during the AP plateau. In conclusion, our results demonstrate that RyR2-A4860G mutation is accompanied by profound impairment of SR Ca 2+ release, which leads to AP prolongation and EADs. This is a novel mechanism of arrhythmias in CPVT, distinct from delayed afterdepolarizations that are commonly detected in all gain-of-function RyR2 mutations.
Clinical outcome of endoscopic mucosal resection (EMR) in clinical stage I (cSt I ) esophageal cancer
Authors: T. Yoshii, S. Tamai, N. Aoyama, J. Minamide, S. Takagi, O. Motohashi, N. Nakayama, K. Nishimura, K. Takata, Y. Kameda
Journal: Journal of Clinical Oncology (2009)

e15569 Background: When a tumor invades to the muscularis mucosa or submucosal layer (T1a-MM or T1b, in Japan), cSt I esophageal cancer(EC) has 10–50%. risk of lymph node metastasis (LNM). Surgery, though very invasive, is the standard radical therapy for the patients(pts.) with such stage EC. Endoscopic mucosal resection (EMR), which conserves the esophagus, is a minimally invasive and attractive therapeutic modality for such pts. However, the clinical outcomes of EMR for these pts. have been not fully elucidated. Methods: We conducted retrospective analysis of the clinical courses of 44 pts. who underwent EMR for newly diagnosed T1a-MM or T1bcN0M0 EC between 1994 and 2007at our hospital, and who could be followed up for at least 1 year. Statistical analysis was performed by the Kaplan-Meier methods and the Cox proportional hazard model. Results: Patients decided on the following treatments immediately after EMR based on informed consent and their general condition; 2 underwent surgery, one underwent prophylactic chemotherapy(CHT) and 41 selected follow-up without any additional therapy. Of the 41, 20 selected this course by choice, 12 because of severe concurrent disease; 2 because of poor performance status and 7 because of other multiple primary cancers (MPCs). Twelve pts. died; 2 were cause specific; (4.5%), 8 from MPCs and, 2 from unknown causes. Median age was 67 years old (range 53–80), and 5 were female. No critical comlications were noted. Median follow-up time was 1542days (375–3786). 5 developed LNM. One with prophylactic CHT, was followed by surgery, and another was followed by CHT, who showed cause specific deaths later. Other 3 pts. followed by chemoradiotherapy, did not show cause specific death. Overall and cause specific survival rates at 5 years were 67.3% and 91.8%, respectively. Multivariate analysis revealed that either severe concurrent disease or MPCs significanctly influenced survival (p=0.041, HR 5.437(95%CI 1.073–25.542)). 8 and 6 pts. developed metachronous EC and local recurrence, respectively. Apart from one, they could be retreated endoscopicaly. Conclusions: EMR is a very useful therapeutic modality for cSt I EC, not only for local control but also as a clinically sufficient treatment; especially in pts. with severe concurrent disease. No significant financial relationships to disclose.
Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009-2010
Authors: A Kilander, R Rykkvin, S G Dudman, O Hungnes
Journal: Eurosurveillance (2010)

Infection with the recently emerged pandemic influenza A(H1N1) virus causes mild disease in the vast majority of cases, but sporadically also very severe disease. A specific mutation in the viral haemagglutinin (D222G) was found with considerable frequency in fatal and severe cases in Norway, but was virtually absent among clinically mild cases. This difference was statistically significant and our data are consistent with a possible causal relationship between this mutation and the clinical outcome.
Abstract 1098: Effect of Hypercholesterolemia on Myocardial Necrosis and Apoptosis in Response to Ischemia Reperfusion Injury
Authors: Robert M Osipov, Cesario Bianchi, Jun Feng, Yuhong Liu, Richard T Clements, Neel Sodha, Frank W Sellke
Journal: Circulation (2008)

OBJECTIVE: Myocardial ischemia-reperfusion(I/R) injury often results in necrosis and apoptosis and may lead to cardiac dysfunction or death. This study investigates impact of hypercholesterolemia in the setting of I/R injury on myocardium. METHODS: The mid-left anterior descending coronary artery in normocholesterolemic (NCn=7) and hypercholesterolemic (HCn=7) Yucatan males were occluded for 60 min, followed by reperfusion for 120 min. Hemodynamic values were recorded. Monastryl blue/TTC staining was utilized to assess the area-at-risk (AAR) and necrosis. The expression of Bcl2, apoptosis inducing factor (AIF), total &amp; cleaved caspase3, total &amp; cleaved PARP, bad, BNIP3, Akt and phospho-Akt measured. The TUNEL staining utilized to assess the magnitude of apoptosis. RESULTS: Hemodynamic values of MAP (p&lt;0.01), DLVP (p&lt;0.01), +dP/pt (p&lt;0.01), and −dP/pt (p&lt;0.01) were increased 1.2 fold in HC. In HC longitudinal and horizontal segmental shortening in the AAR decreased by 49% vs. 26% (p&lt;0.01) and 68% vs. 48% (p&lt;0.01) at the end. The AAR was similar in both groups (36% vs. 34%, p=0.61) whereas infarct size increased 45% in HC (42% vs. 61%, p=0.01). The expression of anti-apoptotic Bcl2 decreased 2.3-fold (p&lt;0.01) whereas pro-apoptotic PARP and BNIP3 increased 2.8-fold (p&lt;0.01) and 1.9 fold (p&lt;0.01) respectively in HC. Ischemia decreased Akt expression 1.6-folds (p&lt;0.01) and phospho-Akt 1.5 fold (p&lt;0.01) in HC, whereas increased phospho-Akt 1.9 fold (p&lt;0.01) in NC. In HC the TUNEL+ cells increased 3.8 fold (p=0.03) in the AAR. CONCLUSIONS: This study demonstrated that hypercholesterolemia have positive ionotropic effect on myocardial function, increase infarct size in AAR, mediate pro-apoptosis and attenuate survival pathway after I/R injury.