tbuckley/cabot-search huggingface dataset:
Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non–Vitamin K Antagonist Oral Anticoagulants Before Stroke
Authors: Ying Xian, Jerome J. Federspiel, Adrian F. Hernandez, Daniel T. Laskowitz, Lee H. Schwamm, Deepak L. Bhatt, Eric E. Smith, Gregg C. Fonarow, Eric D. Peterson
Journal: Circulation (2017)

Intravenous rt-PA (recombinant tissue-type plasminogen activator) is effective in improving outcomes in ischemic stroke; however, there are few data on the use of rt-PA in patients who are receiving a non-vitamin K antagonist oral anticoagulant (NOAC).Using data from the American Heart Association Get With The Guidelines-Stroke Registry, we examined the outcomes of use of thrombolytic therapy in patients with ischemic stroke who received anticoagulation with NOACs versus those on warfarin (international normalized ratio <1.7) or not on anticoagulation from 1289 registry hospitals between October 2012 and March 2015.Of 42 887 patients with ischemic stroke treated with intravenous rt-PA within 4.5 hours, 251 were taking NOACs (dabigatran 87, rivaroxaban 129, and apixaban 35) before their stroke, 1500 were taking warfarin, and 41 136 were on neither. Patients on NOACs or warfarin were older, had more comorbid conditions, and experienced more severe strokes than did those who were not on anticoagulation (median National Institutes of Health Stroke Scale 12, 13, and 9, respectively). Unadjusted rates of symptomatic intracranial hemorrhage in the NOAC, warfarin, and none groups were 4.8%, 4.9%, and 3.9%, respectively (P=0.11). In comparison with those not on anticoagulation, the adjusted odds ratio for symptomatic intracranial hemorrhage for those on NOACs was 0.92 (95% confidence interval, 0.51-1.65) and for those on warfarin the adjusted odds ratio was 0.85 (95% confidence interval, 0.66-1.10). There were also no significant differences in the risk for life-threatening/serious systemic hemorrhage, any rt-PA complication, in-hospital mortality, and modified Rankin Scale at discharge across 3 groups. Similar results were also found after propensity score matching.Although experience of using rt-PA in patients with ischemic stroke on a NOAC is limited, these preliminary observations suggest that rt-PA appears to be reasonably well tolerated without prohibitive risks for adverse events among selected NOAC-treated patients. Future studies should evaluate the safety and efficacy of intravenous rt-PA in patients with ischemic stroke who are taking NOACs.
Population-Based Prevalence of Cerebral Cavernous Malformations in Older Adults
Authors: Kelly D. Flemming, Jonathan Graff-Radford, Jeremiah Aakre, Kejal Kantarci, Giuseppe Lanzino, Robert D. Brown, Michelle M. Mielke, Rosebud O. Roberts, Walter Kremers, David S. Knopman, Ronald C. Petersen, Clifford R. Jack
Journal: JAMA Neurology (2017)

<h3>Importance</h3> The prevalence of cerebral cavernous malformation (CCM) is unknown. Case ascertainment in most previous studies was based on autopsy data or clinical convenience samples, often without detailed clinical or radiologic information. <h3>Objective</h3> To determine the prevalence of CCM in a population-based sample of older adults. <h3>Design, Setting, and Participants</h3> This prospective imaging study included 4721 participants aged 50 to 89 years who were enrolled between January 1, 2004, and December 15, 2015, in the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. An age- and sex-stratified sampling strategy was used to randomly select participants from Olmsted County using the medical records linkage system of the Rochester Epidemiology Project. Participants were invited to undergo brain magnetic resonance imaging (MRI). Of the 4721 participants, 2715 had an evaluable MRI. All images were reviewed by a board-certified neuroradiologist, and MRI reports were searched for the terms<i>cavernous malformation, cavernous angioma,</i>and<i>cavernoma</i>. Two vascular neurologists reviewed MRIs, and potential CCMs were classified using Zabramski classification. Medical records of the identified individuals with CCM were reviewed along with their demographic information, medical history, and any symptoms referable to the identified CCM lesion. <h3>Main Outcomes and Measures</h3> Prevalence of CCM and clinical and radiologic characteristics of study participants with CCM. <h3>Results</h3> Of the 2715 participants who underwent MRI scans, 12 (0.44%) had CCM. With the use of inverse probability weights to adjust for participation bias, the overall prevalence was 0.46% (95% CI, 0.05-0.86). The age-adjusted prevalence was found to be 0.61% (95% CI, 0-1.47) for the 50- to 59-year age group, 0.17% (95% CI, 0-0.50) for the 60- to 69-year age group, 0.45% (95% CI, 0.09-0.81) for the 70- to 79-year age group, and 0.58% (95% CI, 0-1.29) for the 80- to 89-year age group. The sex-adjusted prevalence was 0.41% (95% CI, 0-1.00) for women and 0.51% (95% CI, 0-1.07) for men. Observed frequencies were similar in men and women, with a slight male predominance. Of the 12 participants with CCM, 9 (75%) had a single Zabramski type 2 lesion in a supratentorial location. Only 1 participant (0.037%) was symptomatic from the CCM during the study period. <h3>Conclusions and Relevance</h3> The findings and data from this study are important for determining the potential number of patients available for cohort studies and anticipated clinical trials in older patients with CCM.
Use of the qSOFA Score in the Emergency Department
Authors: Christian S. Scheer, Sven-Olaf Kuhn, Sebastian Rehberg
Journal: JAMA (2017)

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Treatment satisfaction and need for shared decision‐making in patients with psoriasis from Peru
Authors: J.C. Tapia, K. Chavez, G. Malaga, F. Bravo
Journal: British Journal of Dermatology (2017)

psoriasis is reported by the World Health Organization as a chronic skin disease with an elevated physical, emotional and socioeconomic burden. However, this burden is underestimated in developing countries, such as Peru, due the lack of epidemiological research in dermatology. This uncertainty hinders the development of appropriate patient-centered health care that prevent patients from unnecessary suffering.

This article is protected by copyright. All rights reserved.
Examining the effects of metformin on survival outcome in stage II/III colorectal cancer patients with diabetes mellitus.
Authors: Guek Eng Lee, Thinzar Aung, Kiat Hon Lim, Wah Siew Tan, Wai Meng David Tai, Nur-Afidah Binte Suhaimi, Min-Han Tan, Iain B. Tan
Journal: Journal of Clinical Oncology (2012)

3589 Background: Insulin resistance and deregulation of the insulin-like growth factor (IGF) axis is implicated in colonic carcinogenesis. Metformin inhibits hepatic gluconeogenesis and increases insulin sensitivity. It induces AMPK activation, thus inhibiting mTOR and downstream survival and proliferation pathways. We evaluated the effects of metformin on survival outcomes of patients with stage 2 and 3 colorectal cancer (CRC). Methods: Among 1455 patients with stage II or III colorectal cancer, we identified 344 patients with both CRC and diabetes mellitus. 219 diabetic patients received metformin and 125 diabetic patients were not receiving metformin. Patient’s demographics, clinical and histopathologic characteristics, overall survival, time to recurrence and relapse-free survival were evaluated. Molecular analysis for AMPK, and mTOR pathway on archival tissue is ongoing. Results: After a median follow-up of 78 months (6.5 years), there was no difference in survival outcomes between diabetic and non-diabetic patients. Among diabetic patients, there were 99 relapses and 90 deaths. Metformin use was associated with improved overall survival (HR 0.23; 95%CI: 0.15-0.35 p&lt;0.01), time to recurrence (HR 0.63; 95%CI: 0.41-0.96) and relapse-free survival (HR 0.47; 95%CI:0.33-0.67,p&lt;0.01). In multivariate analysis, after adjustment for T stage, N stage and patients' age, metformin use remained associated with improved overall survival (HR 0.18, p&lt;0.01); time to recurrence (HR 0.55; p&lt;0.04) and relapse-free survival (HR 0.44, p&lt;0.01). Results of molecular correlative studies performed on archival tissue will be presented at the meeting. Conclusions: Among patients with diabetes and colorectal cancer, use of metformin is associated with improved survival outcomes in both univariate and multivariate analysis lending support to the hypothesis that it may have anti-cancer activity.
Circulatory microRNA-142 as potential biomarker of disease progression in paediatric cystic fibrosis-associated liver disease
Authors: D.A. Calvopina, M.A. Coleman, M.A. Fernandez-Rojo, L.F. Wockner, C.J. McDonald, P.J. Lewindon, G.A. Ramm
Journal: Journal of Hepatology (2017)
Abstract 407: Modulation of Delta-Like Ligand-4 Signaling Improves Myocardial Revascularization Following Coronary Ischemia
Authors: S R Kumar, Christopher Yi, Timothy Martens, Sydney J Zagger, Antonio Duarte, Parkash S Gill
Journal: Circulation Research (2015)

Delta-like ligand-4 (DLL4) is an arterial-specific Notch ligand and balanced signaling by DLL4 is required for functional neovascularization. We hypothesized that modest inhibition of DLL4 signaling improves myocardial revascularization following coronary ischemia. Myocardial infarction was induced by ligation of mid-left anterior descending (LAD) artery via rapid left thoracotomy in 6-8 week-old male mice with inducible endothelial-specific knockout or overexpression of DLL4. DLL4 silencing in homozygous mice on the day of or 5 days prior to LAD ligation resulted in significant reduction in revascularization. At four weeks, explanted hearts showed 1.8-fold fewer vessels in LAD territory, 3-fold greater myocardial hypoxia, 1.7-fold larger fibrotic scar and 17% increased perfusion defect in the left ventricle (LV) by scintigraphy. CT angiography confirmed fewer collateral vessels. Echocardiography showed increased LV dilation (37% higher end-diastolic volume) and 12% greater reduction in ejection fraction (EF) compared to baseline (all p&lt;0.001). Overexpression of DLL4 showed a similarly worse outcome. Conversely, partial DLL4 knockout in heterozygous animals resulted in improved outcomes in all parameters. For translational application, animals were systemically administered 1.5mg/kg or 3mg/kg DLL4-Fc intraperitoneally three times a week beginning the day of ligation. RT-PCR analysis of downstream molecules confirmed that systemic DLL4-Fc partially inhibits Notch signaling in endothelial cells in the ischemic LV. When LAD was ligated very proximally, DLL4-Fc improved survival. With mid-LAD ligation, DLL4-Fc induced a dose-dependent increase in number of CD 31-positive vessels and by CT angiography. There was a dose-dependent reduction in hypoxic myocardial area, scar burden, and scintigraphic perfusion defect. DLL4-Fc treated mice had lower end-diastolic LV volume and preserved or improved EF. In an ischemia-reperfusion model, DLL4-Fc increased the number of vessels in the ischemic zone. Our data suggests that balanced DLL4 signaling is crucially required for myocardial angiogenic recovery following coronary ischemia. Modulation of DLL4 signaling has translational therapeutic potential.
TWIST1-WDR5-<i>Hottip</i> Regulates <i>Hoxa9</i> Chromatin to Facilitate Prostate Cancer Metastasis
Authors: Reem Malek, Rajendra P. Gajula, Russell D. Williams, Belinda Nghiem, Brian W. Simons, Katriana Nugent, Hailun Wang, Kekoa Taparra, Ghali Lemtiri-Chlieh, Arum R. Yoon, Lawrence True, Steven S. An, Theodore L. DeWeese, Ashley E. Ross, Edward M. Schaeffer, Kenneth J. Pienta, Paula J. Hurley, Colm Morrissey, Phuoc T. Tran
Journal: Cancer Research (2017)

TWIST1 is a transcription factor critical for development that can promote prostate cancer metastasis. During embryonic development, TWIST1 and HOXA9 are coexpressed in mouse prostate and then silenced postnatally. Here we report that TWIST1 and HOXA9 coexpression are reactivated in mouse and human primary prostate tumors and are further enriched in human metastases, correlating with survival. TWIST1 formed a complex with WDR5 and the lncRNA Hottip/HOTTIP, members of the MLL/COMPASS-like H3K4 methylases, which regulate chromatin in the Hox/HOX cluster during development. TWIST1 overexpression led to coenrichment of TWIST1 and WDR5 as well as increased H3K4me3 chromatin at the Hoxa9/HOXA9 promoter, which was dependent on WDR5. Expression of WDR5 and Hottip/HOTTIP was also required for TWIST1-induced upregulation of HOXA9 and aggressive cellular phenotypes such as invasion and migration. Pharmacologic inhibition of HOXA9 prevented TWIST1-induced aggressive prostate cancer cellular phenotypes in vitro and metastasis in vivo This study demonstrates a novel mechanism by which TWIST1 regulates chromatin and gene expression by cooperating with the COMPASS-like complex to increase H3K4 trimethylation at target gene promoters. Our findings highlight a TWIST1-HOXA9 embryonic prostate developmental program that is reactivated during prostate cancer metastasis and is therapeutically targetable. Cancer Res; 77(12); 3181-93. ©2017 AACR.
Epigenetic reprogramming in hepatitis C virus-induced liver fibrosis: DNA methylation as a biomarker to identify susceptibility
Authors: A. Vasanthakumar, J.W. Davis, K. Idler, E. Dilmukhametova, L. Hazelwood, M. Abunimeh, P. Dorr, M. Charafeddine, D.E. Cohen, S. England, J. Waring
Journal: Journal of Hepatology (2017)
Hepatic LGR5 stem cells contribute to liver carcinogenesis
Authors: W. Cao, M. Li, P. Liu, J. Liu, M. Bolkestein, K. Chen, L.J.W. Van Der Laan, D. Sprengers, H.J. Metselaar, J. Kwekkeboom, R. Smits, M.P. Peppelenbosch, Q. Pan
Journal: Journal of Hepatology (2017)
An approach to hepatitis C Virus epidemiology: analysis in 7602 patients of orthopaedic surgery
Authors: M. Pipa-Muniz, M.I. Romero, E.B. Alonso, M.C. Luengo, P.V. Trastoy, A.M. Mata, L. Franco, R.G. López, E.F. Ruiz, I.P. Muñiz, C. de la Coba Ortiz, R.T. Gozález, A.C.G. Bernal, A.Á. Álvarez, J.P. Pariente, C.G. Suárez, L.O. Guerra, F.J.R. Llorente
Journal: Journal of Hepatology (2017)
Dose variation in metastatic breast cancer: Are European Medicines Agency summary of product characteristics (SmPC) being followed?
Authors: James Charnock, Alec Bruce, Caroline Anger
Journal: Journal of Clinical Oncology (2015)

e11581 Background: Breast cancer represents the highest cancer burden in the EU and is a high profile treatment area. We identify variation in treatment length and dosing of bevacizumab (BV) and capecitabine (CP) in France, Germany, Italy, Spain and UK (EU5) compared to European Medicines Agency (EMA) SmPC dosing recommendations for metastatic breast cancer (mBC). Methods: This study used IMS Oncology Analyzer, an anonymised patient database collected through quarterly physician panel survey, which provides information on patterns of cancer care. Inclusion criteria of mBC patients currently receiving BV or CP collected within the last 3 years (October 2011 – September 2014). Correct dosing defined as (+/- 10%): BP – 10 mg/kg over 2 weeks or 15 mg/kg over 3 weeks; CP – 1,250 mg/m2 over 2 weeks with 1 week rest. Results: 84% (513/612) of BV patients received correct cycle length, with 77% of these patients (397) dosed correctly. 97 patients (19%) were under dosed with less than half over 60 years old and 70% presenting with an ECOG score of 1-2. While the remaining 16% of BV patients did not receive the recommended cycle length, 82% (81/99) did receive either 10 or 15 mg/kg EMA recommended doses. Although 90% of CP treated patients (619/686) received the correct cycle length, only 23% of those patients were dosed at the recommended 1,250 mg/m2. 60% (372/619) were under dosed; of which 70% are over 60 years old and 83% presented with an ECOG status of 1-2, with 244 patients receiving 1,000 mg/m2. While this dosage is commonly prescribed in combination in colorectal and gastric cancer, panel physicians were of the opinion that lower doses in mBC have similar efficacy and reported reducing doses to increase tolerability, as supported by the proportion of over 60 year olds being under dosed in the data. Conclusions: This study has identified variation in dosing and cycle duration of both BV and CV from those recommended by the EMA. It therefore appears that physicians are actively tailoring dosage and cycle length to patients’ fitness as opposed to strictly following EMA SmPC.
Abstract 290: Circulating miRNAs as Biomarkers in Acute Coronary Syndrome
Authors: Lina Cordeddu, Anna P Pilbrow, Vicky A Cameron, Richard W Troughton, Mark A Richards, Roger S Foo
Journal: Circulation Research (2012)

Introduction Acute coronary syndrome is characterized by the active, inflamed and unstable atherosclerotic plaque that is vulnerable to rupture, predisposing to lumen occlusion and varying extents of myocardial injury. Plasma microRNA have been examined in the hope of identifying an easily accessible biomarker for acute coronary syndrome. But so far studies have taken a candidate approach and screened only for miRNA that are potentially released from the injured myocardium. Even so, data from these studies are inconsistent and a consensus is yet to be reached. Aim We set out to screen for circulating plasma microRNAs to serve as biomarkers for patients with Acute Coronary Syndrome. Methods and results We selected patients who suffered from 2 ends of the severity spectrum of acute coronary syndrome vs age-matched healthy controls. These were 20 μsevere” (STEMI: troponin-positive with subsequent rapid deterioration in left ventricular function or death within 5 years), 20 μmild” (unstable angina: troponin-negative with sustained normal left ventricular function and survival at 5 years), and 20 normal healthy volunteers. Blood samples were obtained from patients within 2 weeks of the acute event. We took a non-constrained approach and screened using an array panel consisting of 379 miRNA. We found 32 miRNA that were significantly upregulated (29/32) or downregulated (3/32) in the comparison between patient vs. control (sum of t-statistic&gt;2). We have made a preliminary analysis of these in relation to a full panel of other classical biomarkers and patient clinical details. We selected 4 candidate microRNAs (miR-27b, -103, -323-3p, -652) and proceeded to test the plasma levels of these in a validation cohort of 100 troponin-positive, 100 troponin-negative patients and 100 normal healthy volunteers. miR 27b, -323-3p, -652 were significantly upregulated in disease and hence robustly validated. Conclusion miR 27b, -323-3p, -652 strongly associates with the event of acute coronary syndrome. Further work will be required to determine the origin and physiological function of these candidate miRNA, and whether their plasma levels can be used for prognostication purposes.
Hepatic fibrosis is associated with histological activity in nonalcoholic steatohepatitis: an analysis from a large database of screening biopsies in the CENTAUR trial
Authors: V. Ratziu, V.W.-S. Wong, N. Lanthier, J. Boursier, W. Alazawi, J. Kluwe, J. Genesca, P. Andreone, L. Serfaty, R. Skoien, B.L. Wiens, P. Vig, E. Lefebvre, S. Seyedkazemi, Z. Kayali, F. Poordad, A. Sanyal, F. Tacke, Z. Goodman
Journal: Journal of Hepatology (2017)
56 Performance of a novel molecular stool screening test, the faecal cologuard® in a cohort of irish symptomatic and surveillance patients
Authors: A Alakkari, BM Ryan
Journal: Gut (2017)

Background  Screening tests for precancerous polyps and early CRC reduce mortality. Cologuard is a stool-based, commercially available, molecular screening tool that detects occult blood in combination with multiple DNA abnormalities released from neoplastic colonic cells (from small polyps to cancers). Previous population-based studies reported a sensitivity and specificity of 69%–92% and 87% respectively for detection of polyps.  Aim  To evaluate the Cologuard in asymptomatic low risk surveillance and symptomatic patients.  Method  Ethics approval was obtained and patients were recruited from endoscopy referrals and the colonoscopy surveillance waiting list. Inclusion and exclusion criteria in Table 1. Participants provided stool for Cologuard prior to colonoscopy. Cologuard and Colonoscopy results were correlated to calculate NPV, PPV, sensitivity and specificity.  Results  60 patients were recruited. To date 40 have completed the study. 22 (55%) female. Median age 60 years (range 42–80). 18 (45%) patients were symptomatic. Colonoscopy adenoma detection rate was 28% (n=11). Cologuard was positive in 10 (25%) patients, 4 of whom had adenomatous polyps, 1>10 mm size and 3 1 cm in size, 1=7 mm and 5 5 mm. No CRC was diagnosed.  Conclusions  Cologuard seems reliable for excluding CRC and adenomatous polyps>5 mm in size, and maybe useful in triaging surveillance patients for Colonoscopy.
Induction of Chondrogenic Differentiation of Human Mesenchymal Stem Cells by Biomimetic Gold Nanoparticles with Tunable RGD Density
Authors: Jingchao Li, Xiaomeng Li, Jing Zhang, Naoki Kawazoe, Guoping Chen
Journal: Advanced Healthcare Materials (2017)

Nanostructured materials have drawn a broad attention for their applications in biomedical fields. Ligand‐modified nanomaterials can well mimic the dynamic extracellular matrix (ECM) microenvironments to regulate cell functions and fates. Herein, ECM mimetic gold nanoparticles (Au NPs) with tunable surface arginine‐glycine‐aspartate (RGD) density are designed and synthesized to induce the chondrogenic differentiation of human mesenchymal stem cells (hMSCs). The biomimetic Au NPs with an average size of 40 nm shows good biocompatibility without affecting the cell proliferation in the studied concentration range. The RGD motifs on Au NPs surface facilitate cellular uptake of NPs into monolayer hMSCs through integrin‐mediated endocytosis. The biomimetic NPs have a promotive effect on cartilaginous matrix production and marker gene expression in cell pellet culture, especially for the biomimetic Au NPs with high surface RGD density. This study provides a novel strategy for fabricating biomimetic NPs to regulate cell differentiation, which holds great potentials in tissue engineering and biomedical applications.
3 times higher healthcare cost in chronic hepatitis B patients compared to non-chronic hepatitis B controls especially those with decompensated liver disease: United States real world healthcare utilization and cost analysis
Authors: M.H. Nguyen, J. Lim, A.B. Ozbay, S. Shreay, I. Liou, N. Meyer, G. Dusheiko, S. Gordon
Journal: Journal of Hepatology (2017)