tbuckley/cabot-search huggingface dataset:
Estimates and Temporal Trend for US Nationwide 30-Day Hospital Readmission Among Patients With Ischemic and Hemorrhagic Stroke
Authors: Arvind B. Bambhroliya, John P. Donnelly, Eric J. Thomas, Jon E. Tyson, Charles C. Miller, Louise D. McCullough, Sean I. Savitz, Farhaan S. Vahidy
Journal: JAMA Network Open (2018)

Readmission reduction is linked to improved quality of care, saves cost, and is a desirable patient-centered outcome. Nationally representative readmission metrics for patients with stroke are unavailable to date. Such estimates are necessary for benchmarking performance.To provide US nationwide estimates and a temporal trend for overall, planned, and potentially preventable 30-day hospital readmission among patients with ischemic and hemorrhagic stroke; to investigate the association between hospitals' stroke discharge volume, teaching status, and 30-day readmission; and to highlight reasons for 30-day readmission and explore the association of 30-day readmission in terms of mortality, length of stay, and cost of care among patients with stroke.Cohort, year-wise analysis of the Nationwide Readmissions Database between January 1, 2010, and September 30, 2015. The setting was a population-based cohort study providing national estimates of 30-day readmission. The database represents 50% of all US hospitalizations from 22 geographically dispersed states. Participants were adult (≥18 years) patients with a primary discharge diagnosis of intracerebral hemorrhage, acute ischemic stroke, or subarachnoid hemorrhage. Hospitals were categorized by their annual stroke discharge volume and were classified as teaching hospitals if they had an American Medical Association-approved residency program or had a ratio of full-time equivalent interns and residents to beds of 0.25 or higher.Readmission was defined as any admission within 30 days of index hospitalization discharge. Using Centers for Medicare & Medicaid Services-defined algorithms, events were classified as planned or unplanned and as potentially preventable.Based on study criteria, 2 078 854 eligible patients were included (mean [SE] age, 70.02 [0.07] years; 51.9% female). Thirty-day readmission was highest for patients with intracerebral hemorrhage (13.70%; 95% CI, 13.40%-13.99%), followed by patients with acute ischemic stroke (12.44%; 95% CI, 12.33%-12.55%) and patients with subarachnoid hemorrhage (11.48%; 95% CI, 11.01%-11.96%). On average, there was a 3.3% annual decline in readmission between 2010 and 2014, which was statistically significant for the period of investigation (odds ratio, 0.96; 95% CI, 0.95-0.97). Patients discharged from nonteaching hospitals with high stroke discharge volume were at a significantly higher risk of 30-day readmission, and the top 2 reasons for readmission were acute cerebrovascular disease and septicemia.This study suggests that nationally representative readmission metrics can be used to benchmark hospitals' performance, and a temporal trend of 3.3% may be used to evaluate the effectiveness of readmission reduction strategies.
Abstract 9481: The Response of the Qt Interval and the T-wave Morphology to Sudden Tachycardia Provoked by Standing in Young Athletes
Authors: AndreaMenafoglio, MarcelloDi Valentino, AugustoGallino
Journal: Circulation (2012)

Background: the response of the QT interval to the sudden tachycardia provoked by standing can aid in the diagnosis of the long QT syndrome (LQTS). It is therefore important to know what is the normal response to this maneuver. The aim of this study was to characterise the response of the QT interval and the T-wave morphology following this provocation test in young healthy athletes. Methods: ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) athletes. ECG was performed after 5 minute of supine resting. Athletes without cardiac abnormalities, not taking drugs and with normal ECG (QTc for men  T1), notched G2 (T2>>T1)] were analysed at baseline and at maximal tachycardia. Results: ECG of 289 athletes was analysed (76 % men, mean age 18.4 ± 5.6 year...
Comparable outcomes of haploidentical, 10/10 and 9/10 unrelated donor transplantation in adverse karyotype AML in first complete remission
Authors: Francesca Lorentino, Myriam Labopin, Massimo Bernardi, Fabio Ciceri, Gerard Socié, Jan J. Cornelissen, Jordi Esteve, Annalisa Ruggeri, Liisa Volin, Ibrahim Yacoub‐Agha, Charles Craddock, Jacob Passweg, Didier Blaise, Tobias Gedde‐Dahl, Monica Poiani, Nathalie Fegueux, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2018)

Allogeneic hematopoietic stem cell transplantation (HSCT) is the most powerful therapy preventing relapse in patients with adverse cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1). In the absence of a matched related donor, potential alternatives include 10/10, 9/10 HLA-matched unrelated (UD) or haploidentical (Haplo) donors. We analyzed clinical outcomes of patients undergoing T-cell repleted Haplo (n = 74), 10/10 UD (n = 433) and 9/10 UD HSCT (n = 123) from 2007 to 2015, reported to the EBMT Registry. Adverse risk AML was defined according to the 2017 ELN cytogenetic risk classification. The 2-year nonrelapse mortality was 19% for Haplo, 18% for 10/10 UD and 18% for 9/10 UD (P = .9). The relapse incidence was not significantly affected by donor source, with a 2-year incidence of 27% for Haplo HSCT, 39% for 10/10 UD and 37% for 9/10 UD SCT (P = .3). We show comparable probabilities of leukemia-free survival (LFS) and overall survival (OS) at 2 years among Haplo HSCT, 10/10 UD SCT and 9/10 UD SCT (53% and 59%, 43% and 50%, 44% and 50%, respectively, P = .5 for both parameters). The type of donor was not significantly associated with either acute or chronic graft-vs.-host disease incidence. Using multivariable Cox model, Haplo HSCT recipients experienced comparable OS and LFS to 10/10 and 9/10 UD. In the present series of adverse cytogenetics AML patients in CR1, Haplo HSCT recipients had comparable outcomes to those of 10/10 and 9/10 UDs, suggesting that all these types of HSCT may be considered a valid option in this high risk population.
Abstract 11990: LMNA Cardiomyopathy Mimicking Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Koichi Kato, Seiko Ohno, Takeru Makiyama, Minoru Horie
Journal: Circulation (2014)

Background and Objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by RV dilatation and ventricular arrhythmias. Desmosomal gene mutations are the major cause of ARVC. LMNA mutations have been known to lead dilated cardiomyopathy, other systemic diseases, and more recently, ARVC. In this study, we performed extensive genetic screening for LMNA in ARVC patients and assessed the clinical characteristics of patients with LMNA mutations. Methods: Study cohort consisted of 57 ARVC probands (definite; 45). Coding exons of LMNA, 4 desmosomal protein genes (PKP2, DSP, DSG2, DSC), and also 3 long QT syndrome related genes (KCNQ1, KCNH2, SCN5A) were amplified and sequenced by using illumina next generation sequencer. Clinical characteristics of LMNA mutation carriers and those of desmosomal mutation carriers were compared by using student t test. Results: Among 57 clinically-diagnosed ARVC probands, we identified desmosomal mutations in 32 probands (56.1%) and two LMNA mutations in two probands. The first LMNA mutation, p.M1K was detected in 62-year-old male, and the second one, p.W514X was in 70-year-old male. Both patients showed RV dilatation, non-sustained ventricular tachycardia, and complete atrioventricular block. His younger brother also died from ARVC. The proband’s daughter and son, who are currently in their 30s, have the same M1K mutation, however, have not had any signs of ARVC yet. In the family member with W514X mutant, the proband’s father suddenly died in his 40s and 45-year-old daughter who had the same W514X mutation, showed RV dilatation and brady-AF. In probands with LMNA mutations compared to those with desmosomal mutations, the age of onset was significantly older (38.6±18.1 vs 60.0±2.8), and their heart rate was significantly slower (61.1±12.5 vs 47±1.4). Both probands with LMNA mutations underwent pacemaker therapy, which is rare in patients with desmosomal mutations (2/2 vs 1/32 ). In family members with LMNA mutations, none of mutation carriers had showed ARVC until their 50s. Conclusion: Our patients with LMNA mutations developed ARVC with bradyarrhythmia after age of 50. Genetic screening for LMNA gene is important for ARVC, especially in cases with bradycardia.
Abstract LB-229: Mesothelin expression is a predict factor for peritoneal recurrence in gastric cancer
Authors: Su-Jin Shin, Hyunki Kim, Yoon Young Choi, Sejung Park, Chung Mo Nam, Hyun Cheol Chung
Journal: Cancer Research (2018)

Abstract Background: Mesothelin is overexpressed in many solid tumors. Recent studies showed that mesothelin expression is associated with poor outcome in several malignant tumors and it may play a role of cancer cell proliferation, local invasion and metastasis. Clinical trials of mesothelin-targeted immunotherapies are currently in progress. However, the correlation between mesothelin expression and prognosis of gastric cancer is still conflicting. Patients and Methods: Mesothelin expression in tumour cells were immunohistochemically evaluated in 964 advanced gastric cancer patients, and their associations with clinical outcome were analysed. The prediction model for recurrence was developed by cox proportional hazard models. Results: High mesothelin expression was observed in 49.6% and significantly associated with a high stage (P = 0.022) and the presence of recurrence with peritoneal carcinomatosis (P = 0.002). In univariate survival analysis, high mesothelin expression was significantly associated with shorter recurrent-free survival (RFS) (P=0.003) and overall survival (OS) (P=0.006). Multivariate survival analysis revealed that high mesothelin expression was independently associated with poor RFS and OS (P=0.001; P=0.002, respectively) in addition to stage, lymphovascular invasion and Lauren classification (all, P&amp;lt;0.001). In multivariate analysis for recurrence with peritoneal carcinomatosis, high mesothelin expression was also independent prognostic factors in all advanced gastric cancer patients (P&amp;lt;0.001) and in intestinal (P=0.017) and diffuse/mixed type (P=0.005) subgroups. The overall discrimination ability of prediction model for recurrence, the model with mesothelin was better than model without mesothelin. Conclusions: High mesothelin expression was correlated with poor outcome. And, mesothelin expression, along with Lauren classification was meaningful predict factor for peritoneal recurrence. Citation Format: Su-Jin Shin, Hyunki Kim, Yoon Young Choi, Sejung Park, Chung Mo Nam, Hyun Cheol Chung. Mesothelin expression is a predict factor for peritoneal recurrence in gastric cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-229.
Abstract 3398: Analysis of whole transcriptome RNA-seq of large numbers of clinical FFPE samples
Authors: Yulia Newton, Justin Golovato, Mark Johnson, Shahrooz Rabizadeh, Zack Sanborn, Steve Benz, Charles J. Vaske
Journal: Cancer Research (2018)

Abstract Background: We evaluate the feasibility, quality, and analytical potential of whole-transcriptome RNA-seq on over one thousand clinical FFPE tumor samples. Transcriptional profiling of RNA is used for clinical decision making in many tumor types. Clinical analysis of RNA is complicated by the common use of formalin-fixed paraffin-embedded (FFPE) tissue storage, which can cause low yield and RNA degradation. Methods: RNA was extracted from FFPE material using commercially available kits using an RNAseH based ribodeplete. Multiple libraries per sample are sequenced using standard Illumina sequencing. Bowtie2, RSEM, and custom software are used for alignment, transcript quantification, fusion detection, and variant expression analysis. Results: We observe a &amp;gt;85% success rate on whole transcriptome RNA-seq on our cohort of more than 1000 samples. We find reliable transcript quantification upon successful sequencing, and on a subset of samples quantify differences between FFPE and fresh-frozen material when using ribodeplete. We also compare transcriptional profiles of clinical FFPE samples to an independent set of fresh frozen, poly-A capture samples from The Cancer Genome Atlas (TCGA) and show differences between poly-A capture and ribodeplete RNA isolation methods as well as FFPE vs. FF effects. We present a robust mapping methodology for comparison of public FF poly-A dataset to our FFPE ribodeplete samples. We demonstrate that we are able to utilize this joint gene expression space to perform site of origin prediction on FFPE samples. This is especially important for clinical application in analyzing Cancer of Unknown Primary (CUP) samples as well as detecting outlier samples whose molecular features may suggest additional therapeutic avenues. Finally, we show reliable detection of fusion transcripts from FFPE RNA-seq material from whole-transcriptome analysis and expression of somatic tumor variants detected from DNA sequencing. Conclusions: Large scale sequencing of RNA from clinical FFPE materials provides reliable transcriptomic results comparable to existing public databases of RNA, enabling research on cohorts of tumors that are FFPE-banked and unavailable as frozen tissue. Citation Format: Yulia Newton, Justin Golovato, Mark Johnson, Shahrooz Rabizadeh, Zack Sanborn, Steve Benz, Charles J. Vaske. Analysis of whole transcriptome RNA-seq of large numbers of clinical FFPE samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3398.
Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial Kidney Disease
Authors: Siu Chiu Chan, Ying Zhang, Annie Shao, Svetlana Avdulov, Jeremy Herrera, Karam Aboudehen, Marco Pontoglio, Peter Igarashi
Journal: Journal of the American Society of Nephrology (2018)

Background Mutation of HNF1B , the gene encoding transcription factor HNF-1 β , is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in renal function. HNF-1 β has also been implicated in epithelial–mesenchymal transition (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not known. Methods To explore the mechanism of fibrosis, we created HNF-1 β –deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal differentially expressed genes in wild-type and HNF-1 β –deficient mIMCD3 cells, and performed cell lineage analysis in HNF-1 β mutant mice. Results The HNF-1 β –deficient cells exhibited properties characteristic of mesenchymal cells such as fibroblasts, including spindle-shaped morphology, loss of contact inhibition, and increased cell migration. These cells also showed upregulation of fibrosis and EMT pathways, including upregulation of Twist2, Snail1, Snail2, and Zeb2, which are key EMT transcription factors. Mechanistically, HNF-1 β directly represses Twist2 , and ablation of Twist2 partially rescued the fibroblastic phenotype of HNF-1 β mutant cells. Kidneys from HNF-1 β mutant mice showed increased expression of Twist2 and its downstream target Snai2 . Cell lineage analysis indicated that HNF-1 β mutant epithelial cells do not transdifferentiate into kidney myofibroblasts. Rather, HNF-1 β mutant epithelial cells secrete high levels of TGF- β ligands that activate downstream Smad transcription factors in renal interstitial cells. Conclusions Ablation of HNF-1 β in renal epithelial cells leads to the activation of a Twist2-dependent transcriptional network that induces EMT and aberrant TGF- β signaling, resulting in renal fibrosis through a cell-nonautonomous mechanism.
Noninvasive Detection of Myocardial Ischemia From Perfusion Reserve Based on Cardiovascular Magnetic Resonance
Authors: NidalAl-Saadi, EikeNagel, MichaelGross, AxelBornstedt, BernhardSchnackenburg, ChristophKlein, WaldemarKlimek, HelmutOswald, EckartFleck
Journal: Circulation (2000)

Background—Myocardial perfusion reserve can be noninvasively assessed with cardiovascular MR. In this study, the diagnostic accuracy of this technique for the detection of significant coronary artery stenosis was evaluated. Methods and Results—In 15 patients with single-vessel coronary artery disease and 5 patients without significant coronary artery disease, the signal intensity–time curves of the first pass of a gadolinium-DTPA bolus injected through a central vein catheter were evaluated before and after dipyridamole infusion to validate the technique. A linear fit was used to determine the upslope, and a cutoff value for the differentiation between the myocardium supplied by stenotic and nonstenotic coronary arteries was defined. The diagnostic accuracy was then examined prospectively in 34 patients with coronary artery disease and was compared with coronary angiography. A significant difference in myocardial perfusion reserve between ischemic and normal myocardial segments (1.08±0.23 and 2.33±0.41; P...
Bidirectional Glenn Procedure Improves the Mechanical Efficiency of a Total Cavopulmonary Connection in High-Risk Fontan Candidates
Authors: YoshihisaTanoue, AkiraSese, YasutakaUeno, KunitakaJoh, TakayukiHijii
Journal: Circulation (2001)

Background—A total cavopulmonary connection (TCPC) is a widely performed surgical procedure for Fontan candidates. High-risk candidates who have undergone the bidirectional Glenn procedure (BDG) before TCPC have shown good results. The exact mechanism of this procedure, however, is still poorly understood. We hypothesized that a volume reduction with BDG improved ventricular contractility, thereby optimizing mechanical efficiency after TCPC. Methods and Results—We measured percent normal systemic ventricular end-diastolic volume (%N-EDV), contractility (end-systolic elastance; Ees), afterload (effective arterial elastance; Ea), and mechanical efficiency (ventriculoarterial coupling; Ea/Ees) on the basis of the cardiac catheterization data before and after TCPC. Eighteen patients who underwent staged TCPC after BDG (staged group) were compared with 29 patients who underwent primary TCPC (primary group). Ees and Ea were approximated as follows: Ees=mean arterial pressure/minimal ventricular volume, and Ea=m...
Performance of the Simplified American Academy of Pediatrics Table to Screen Elevated Blood Pressure in Children
Authors: Yuanyuan Zhang, Liu Yang, Yaping Hou, Min Zhao, Pascal Bovet, Bo Xi
Journal: JAMA Pediatrics (2018)

because NEDS does not report on hospital costs, payments, or out-of-pocket expenses, these data could not be evaluated.Notwithstanding these limitations, our study demonstrated a substantial clinical and financial burden associated with firearm-related injuries among pediatric patients.Moving forward, additional resources and funds should be allocated to the study of firearm-related injuries.Only through further understanding of the social, political, and health-related risk factors for these injuries can we develop and implement effective policies to address this public health concern.
Homologous recombination is independently regulated by BRCA1 and p53
Authors: Zhihui Feng, Henning Willers, Alejandro Treszezamsky, Simon Powell
Journal: Cancer Research (2005)

5679   Both BRCA1 and p53 are tumor suppressors and are involved in a gamut of cellular processes ranging from DNA repair to cell cycle arrest, apoptosis, and transcriptional regulation. A direct functional link between BRCA1 and p53 was initially suggested by the observation that loss of p53 can partially rescue embryonic lethality in BRCA1 knockout mice. Recent studies suggested that BRCA1 directs a selective p53-dependent transcriptional response towards cell replication and DNA repair targets. Our previous results showed that BRCA1 was exported from the nucleus in response to DNA damage and that it was p53 dependent. Therefore, we sought to determine whether there was a direct functional link between BRCA1 and p53 in their roles in DNA repair. First we found that, in contrast to BRCA1, p53 status does not have a significant effect on IR- or MMC-induced cytotoxicity. Next, using a plasmid substrate, pDR-GFP, integrated into genome of the breast cancer cell line MCF7, we demonstrated that the frequency of homology directed recombinational repair (HR) was decreased by p53 and increased by BRCA1. The knock down of BRCA1 by siRNA decreased HR to the same extent in p53 positive and p53 negative cells suggesting that BRCA1 and p53 independently regulate the HR pathway. HR frequency was not significantly affected when p53 positive cells were treated with Leptomycin B, a nuclear export receptor (CRM1) inhibitor, which causes BRCA1 to accumulate in the nucleus. We also found that BRCA1 status regulated ionizing radiation (IR)-induced RAD51 focus formation, whereas p53 did not, again suggesting that BRCA1 regulates HR by a RAD51 dependent pathway while p53 regulates HR by a mechanism independent of the formation of RAD51 foci. In conclusion, our data suggests that BRCA1 and p53 regulate HR through independent mechanisms, which implies that the two proteins could cooperate in producing genomic instability by separate mechanisms.
Abstract 3986: HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells
Authors: Bok-Soon Lee, Yeon Soo Kim, Jeon Yeob Jang, Hyo Jeong Kim, Myeong-Hoon Lee, Jae Won Chang, Bon Seok Koo, Ho-Ryun Won, Yong-Sung Kim, Chul-Ho Kim
Journal: Cancer Research (2018)

Abstract Purpose: Although TRAIL can directly induce death in cancer cells via DR4 and DR5 receptors, it appears that TRAIL resistance exists in many cancers. This study focuses on anti-cancer drugs for TRAIL-resistant head and neck cancer (HNC) to provide a further step toward effective cancer therapy. Materials and Methods: The combined effects of TRAIL and VPA on cell viability were assessed via MTT and flow cytometric assays. Western blotting was used to determine cell death signaling. Results: The results indicate that combined TRAIL and VPA treatment greatly reduced the cell viability and thus induced cell death relative to treatment with TRAIL or VPA alone in TRAIL-resistant HNC cells. A caspase-dependent signaling pathway was shown, and combined treatment with TRAIL and VPA also significantly decreased the expression of HDAC4. When we pretreated cells with z-VAD followed by combined treatment with TRAIL and VPA, the cell death was blocked with no decreased expression of HDAC4. To confirm the cell death involved in HDAC4 in HNC cells, we pretreated siRNA of the HDAC 4, followed by treating the TRAIL and VPA. The results showed that the knock down of HDAC4 sensitized the TRAIL-resistant HNC cells to apoptotic cell death. Finally, we showed a high expression of HDAC4 in HNC tissues compared to normal tissues obtained from the same patients. Conclusion: Combined VPA and TRAIL treatment may be a promising therapy for HNC via HDAC4 degradation. Citation Format: Bok-Soon Lee, Yeon Soo Kim, Jeon Yeob Jang, Hyo Jeong Kim, Myeong-Hoon Lee, Jae Won Chang, Bon Seok Koo, Ho-Ryun Won, Yong-Sung Kim, Chul-Ho Kim. HDAC4 degradation by combined TRAIL and valproic acid treatment induces apoptotic cell death of TRAIL-resistant head and neck cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3986.