tbuckley/cabot-search huggingface dataset:
The extended Toronto criteria for liver transplantation in patients with hepatocellular carcinoma: A prospective validation study
Authors: Gonzalo Sapisochin, Nicolas Goldaracena, Jerome M. Laurence, Martin Dib, Andrew Barbas, Anand Ghanekar, Sean P. Cleary, Les Lilly, Mark S. Cattral, Max Marquez, Markus Selzner, Eberhard Renner, Nazia Selzner, Ian D. McGilvray, Paul D. Greig, David R. Grant
Journal: Hepatology (2016)

The selection of liver transplant candidates with hepatocellular carcinoma (HCC) relies mostly on tumor size and number. Instead of relying on these factors, we used poor tumor differentiation and cancer-related symptoms to exclude patients likely to have advanced HCC with aggressive biology. We initially reported similar 5-year survival for patients whose tumors exceeded (M+ group) and were within (M group) the Milan criteria. Herein, we validate our original data with a new prospective cohort and report the long-term follow-up (10-years) using an intention-to-treat analysis. The previously published study (cohort 1) included 362 listed (294 transplanted) patients from January 1996 to August 2008. The validation cohort (cohort 2) includes 243 listed (105 M+ group, 76 beyond University of California San Francisco criteria; 210 transplanted) patients from September 2008 to December 2012. Median follow-up from listing was 59.7 (26.8-103) months. For the validation cohort 2, the actuarial survival from transplant for the M+ group was similar to that of the M group at 1 year, 3 years, and 5 years: 94%, 76%, and 69% versus 95%, 82%, and 78% (P = 0.3). For the combined cohorts 1 and 2, there were no significant differences in the 10-year actuarial survival from transplant between groups. On an intention-to-treat basis, the dropout rate was higher in the M+ group and the 5-year and 10-year survival rates from listing were decreased in the M+ group. An alpha-fetoprotein level >500 ng/mL predicted poorer outcomes for both the M and M+ groups.Tumor differentiation and cancer-related symptoms of HCC can be used to select patients with advanced HCC who are appropriate candidates for liver transplantation; alpha-fetoprotein level limitations should be incorporated in the listing criteria for patients within or beyond the Milan criteria. (Hepatology 2016;64:2077-2088).
In vivo delivery of Akt1 siRNA to tumors and their vasculature
Authors: Paula Ofek, Anat Grossman-Jonish, Merav Yoeli-Lerner, Wiebke Fischer, Rainer Haag, Ronit Satchi-Fainaro
Journal: Cancer Research (2008)

1108   In recent years it has become clear that angiogenesis, new capillary blood vessel growth from pre-existing vasculature, is crucial for tumor progression and metastases. Consequently, the microvascular endothelial cell, recruited by a tumor, has become an important target in cancer therapy. Akt, a serine/threonine protein kinase, has been implicated in the vascular endothelial growth factor (VEGF) signaling pathway of many tumor types promoting VEGF secretion. Akt is chronically activated not only in tumor cells, but also in VEGF-stimulated tumor endothelial cells, and induces angiogenesis via its downstream effectors. For that reason, Akt has become an attractive drug target for cancer therapy. Several Akt inhibitors are today in clinical trials but they all suffer from lack of selectivity and specificity.  In order to overcome those limitations, we propose to inhibit the overexpressed Akt1 in tumors and their surrounding endothelial cells by using RNA interference. Still, this highly specific approach bears a formidable obstacle: siRNA intracellular delivery to target cells  in vivo . Naked siRNAs are not only poorly taken up by most cells, but are also readily degraded by RNAses and rapidly eliminated from circulation. Our novel approach, to specifically deliver Akt1 siRNA in vivo to tumor epithelial and endothelial cells, is based on targeted nanoparticles. We generated dendritic core-shell architectures based on poly(ethylene-imine) or polyglycerol. The negatively charged Akt1 siRNA is entrapped in the positively charged dendritic architectures. These nanoparticles have an approximate MW of 15 kDa, and thus accumulate in the tumor environment due to the enhanced permeability and retention effect by virtue of their size, and are taken up by tumor endothelial cells by endocytosis. Moreover, a pH-sensitive controlled release based on cleavage at low pH ( In vivo  experiments targeting luciferase siRNA-nanocarrier conjugates to luciferase-infected tumor-bearing mice are currently ongoing. These preliminary experiments point at our novel nanocarriers as a revolutionary vehicle for siRNA specific delivery to tumor epithelial and endothelial cells. We predict that  in vivo  silencing of an important angiogenesis regulator such as Akt1, in a selective manner, will warrant this approach as a successful anticancer therapy.
A phase II study of continuous infusion recombinant human granulocyte- macrophage colony-stimulating factor as an adjunct to autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma in first remission
Authors: SJ O'Day, SN Rabinowe, D Neuberg, AS Freedman, RJ Soiffer, NA Spector, MJ Robertson, K Anderson, M Whelan, K Pesek
Journal: Blood (1994)
Intra-Tumoral Heterogeneity In Multiple Myeloma Gleaned From Gene Expression Profiling Analysis Of Plasma Cells and Bone Marrow Biopsies: Comparison Of Random Bone Marrow Samples and CT-Guided Fine Needle Aspirations Of MRI-Defined Focal Lesions
Authors: Bart Barlogie, Emily Hansen, Sarah Waheed, Jameel Muzaffar, Monica Grazziutti, Donald Johann, Frits van Rhee, Qing Zhang, Christoph Heuck, Joshua Epstein
Journal: Blood (2013)
Abstract 1642: Head-to-Head Comparison of Myocardial Perfusion SPECT Imaging and Delayed Enhancement Magnetic Resonance Imaging to Detect Myocardial Infarction
Authors: Marcus Carlsson, Hakan Arheden
Journal: Circulation (2007)

PURPOSE: Direct visualization of myocardial infarction is possible by delayed enhancement MRI (DE-MRI). The method has been validated in animal studies and patients and is considered to be the reference method for infarct assessment. However, myocardial perfusion SPECT has remained the most common method to depict stress induced ischemia and gives simultaneous information on myocardial infarction. The accuracy of gated SPECT for infarction assessment has been under debate stating that SPECT has limited sensitivity. Therefore, the aim of this study was to determine the sensitivity and specificity of gated SPECT for infarct assessment using MRI as reference method. METHODS: 96 patients (32 females) referred for myocardial perfusion SPECT imaging were included. A body weight adjusted dose of technetium labelled tetrofosmin was injected at rest and during adenosine infusion and gated SPECT images were aquired in all but 2 patients where SPECT were acquired without ECG-gating. In all patients, DE-MRI were performed the same day. All images were evaluated visually with the observers blinded to all clinical data and to the results of the other imaging study. RESULTS: In 29 patients infarcts were visualized by MRI. Of these, 25 patients had infarct detected by gated SPECT. Thus, the sensitivity and specificity for infarct detection by gated SPECT on patient basis were 86% and 97%, respectively. CONCLUSION:. This study has showed high sensitivity and very high specificity for gated SPECT on a patient basis for infarct detection. Thus, gated SPECT can be used for infarct detection with good accuracy in patients with suspected ischemic heart disease.
Familial and Acquired Hemophagocytic Lymphohistiocytosis
Authors: G.E. Janka
Journal: Annual Review of Medicine (2011)

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome in which an uncontrolled and ineffective immune response, triggered in most cases by infectious agents, leads to severe hyperinflammation. Familial forms of HLH (FHL), which are increasingly found also in adolescents and adults, are due to genetic defects leading to impaired function of natural killer cells and cytotoxic T cells. These mutations occur either in the perforin gene or in genes important for the exocytosis of cytotoxic granules. Cytotoxic granules contain perforin and granzymes, which induce apoptosis upon entering (infected) target cells. Additionally, perforin is important for the downregulation of the immune response. Acquired forms of HLH are encountered in association with (usually) viral infections, autoinflammatory/autoimmune diseases, malignant diseases, and acquired immune deficiency states (e.g., after organ transplantation). Treatment of HLH includes immune-suppressive and immune-modulatory agents, cytostatic drugs, and biological response modifiers. For patients with FHL, stem cell transplantation is indicated and can be curative.
Seasonal Changes in the Prevalence of Gestational Diabetes Mellitus
Authors: Robert G. Moses, Veronica C.K. Wong, Kelly Lambert, Gary J. Morris, Fernando San Gil
Journal: Diabetes Care (2016)

To determine the effect of different seasons on the prevalence of gestational diabetes mellitus (GDM) by using World Health Organization criteria.The results of all pregnancy glucose tolerance tests (GTTs) were prospectively collected over a 3-year period in a temperate climate, and the results were grouped by season.The results of 7,369 pregnancy GTTs were available for consideration. In winter, the median 1-h and 2-h glucose results after GTT were significantly (P < 0.0001) lower than the overall 1-h and 2-h results. The prevalence of GDM at the 1-h diagnostic level was 29% higher in summer and 27% lower in winter than the overall prevalence (P = 0.02). The prevalence of GDM at the 2-h diagnostic level was 28% higher in summer and 31% lower in winter than the overall prevalence (P = 0.01).The prevalence of GDM varies according to seasons, which leads to the possible overdiagnosis of GDM in summer and/or underdiagnosis in winter. Further research into standardization of the GTT or seasonal adjustment of the results may need to be considered.
Prepregnancy Diabetes and Offspring Risk of Congenital Heart Disease
Authors: Nina Øyen, Lars J. Diaz, Elisabeth Leirgul, Heather A. Boyd, James Priest, Elisabeth R. Mathiesen, Thomas Quertermous, Jan Wohlfahrt, Mads Melbye
Journal: Circulation (2016)

Maternal diabetes mellitus is associated with an increased risk of offspring congenital heart defects (CHD); however, the causal mechanism is poorly understood. We further investigated this association in a Danish nationwide cohort.
A subset of human CD34+ hematopoietic progenitors express low levels of CD4, the high-affinity receptor for human immunodeficiency virus-type 1
Authors: G Zauli, G Furlini, M Vitale, MC Re, D Gibellini, L Zamai, G Visani, P Borgatti, S Capitani, M La Placa
Journal: Blood (1994)
Acute pulmonary embolism: mortality prediction by the 2014 European Society of Cardiology risk stratification model
Authors: Cecilia Becattini, Giancarlo Agnelli, Mareike Lankeit, Luca Masotti, Piotr Pruszczyk, Franco Casazza, Simone Vanni, Cinzia Nitti, Pieter Kamphuisen, Maria Cristina Vedovati, Maria Grazia De Natale, Stavros Konstantinides
Journal: European Respiratory Journal (2016)

The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients' risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in "high-risk" (95% CI 14.0-29.8), 7.7% in "intermediate-high-risk" (95% CI 4.5-10.9) and 6.0% in "intermediate-low-risk" patients (95% CI 3.4-8.6). One of the 196 "low-risk" patients died (0.5%, 95% CI 0-1.0; negative predictive value 99.5%).By using the 2014 ESC model, RVD or troponin tests would be avoided in about 20% of patients (sPESI 0), preserving a high negative predictive value. Risk stratification in patients at intermediate risk requires further improvement.
Surgery for the Zollinger–Ellison Syndrome
Authors: Samuel A. Wells
Journal: New England Journal of Medicine (1999)

In 1955, Zollinger and Ellison described the clinical syndrome of virulent peptic ulcer disease associated with marked gastric hyperacidity and pancreatic islet-cell tumors.1 A year earlier, Wermer had reported a familial disease characterized by hyperparathyroidism, pituitary tumors, and pancreatic islet-cell tumors: the disease is now known as multiple endocrine neoplasia type 1 (MEN-1).2 Since these two landmark discoveries in endocrine oncology, we have learned a great deal about the pathophysiology, clinical presentation, diagnosis, and treatment of the Zollinger–Ellison syndrome.The most important advance was the discovery that gastrin, a polypeptide hormone and potent acid secretagogue, is the cause of the . . .
Ticagrelor is no better than aspirin at preventing cardiovascular events after acute stroke or TIA, study finds
Authors: Susan Mayor
Journal: BMJ (2016)

Ticagrelor, a direct acting antiplatelet agent, is no more effective than aspirin at preventing recurrent stroke, myocardial infarction, or death in patients who have an ischaemic stroke or transient ischaemic attack (TIA), a randomised trial has shown.1

The risk of a further ischaemic event is high in the first 90 days after a stroke or TIA, so aspirin is commonly used to reduce thrombotic risk. But a risk …
H-TArget model: Early technology assessment for ext generation sequencing in oncology.
Authors: Valesca Retel, Manuela A Joore, Bram Ramaekers, Michel M van den Heuvel, Michiel Simon Van Der Heijden, Wim van Harten
Journal: Journal of Clinical Oncology (2015)

6604 Background: Next Generation Sequencing (NGS) promises to find mutations (targets) in individual cancer patients, to subsequently prescribe targeted therapy. Currently, NGS is in development, the effects on choice of therapy and prognosis are still unclear, and the costs for targeted therapies are high. To accelerate the reimbursement process of NGS and potential new targeted therapies, and have a NGS-panel available for patients in the earliest possible stage, early Technology Assessment (TA) is performed to inform policy making around NGS in the Netherlands. One of the aims of the TA was to conduct a cost-effectiveness analysis. Methods: We constructed a target-based decision model (H-TArget) to estimate the cost-effectiveness of NGS versus single- and no testing. Standard- and targeted therapies in first and second line for 9 targets (BRAF, KRAS, NRAS, EGFR, ERBB/HER, MET, ROS, ALK, RET) over 3 tumor types (melanoma, non-small-cell lung cancer (NSCLC), colorectal cancer (CRC)) were incorporated. A Dutch healthcare perspective and a 5-year time horizon were adopted. Outcomes were incremental cost-effectiveness ratios (ICER) expressed in €/quality adjusted life year (QALY). The threshold for cost-effectiveness is 80k in the Netherlands, which means that the concerning technology is cost-effective if the ICER is below this threshold. Expected Value of Partial Perfect Information (EVP(P)I) was calculated to quantify the value of further research into particular subsets of uncertain parameters. Results: The expected ICER was €65k/QALY for melanoma, €188k/QALY for NSCLC, and €103k/QALY for CRC. As a weighted average to the three populations, the overall ICER yielded €160k/QALY. The EVPI was €25M for melanoma, the subsets of parameters to focus on in future research were: €2M together for failures, prevalence, survival, and €23M for costs. Conclusions: At the moment, using NGS is only cost-effective for melanoma. This is mostly due to the high costs of targeted therapies and the fact that the effects are still small. Based on our findings, industry should strive for a significant cost reduction of targeted therapies or achieve a spectacular improvement in effectiveness, which could improve the cost-effectiveness.
Spectrin Tunis (Sp alpha I/78), an elliptocytogenic variant, is due to the CGG----TGG codon change (Arg----Trp) at position 35 of the alpha I domain
Authors: L Morle, F Morle, AF Roux, J Godet, BG Forget, L Denoroy, M Garbarz, D Dhermy, R Kastally, J Delaunay
Journal: Blood (1989)
Abstract 3577: Thickness of mitral annular calcification is directly associated with cardiovascular morbidity and mortality. The Northern Manhattan Study.
Authors: Shun Kohsaka, Ralph L Sacco, Zhezhen Jin, Rui Liu, Tatjana Rundek, Bernadette Boden-Albala, Shunichi Homma, Marco R Di Tullio
Journal: Circulation (2007)

BACKGROUND: Mitral annular calcification (MAC) is common in the elderly, and is associated with atherosclerotic risk factors. We sought to determine the magnitude of association between MAC and vascular events in the multiethnic prospective cohort of northern Manhattan. METHODS: MAC was assessed by transthoracic 2D-echocardiography as binary (yes/no) and continuous (mm) variable. Subjects were aged ≥40 years at enrollment, and were free of prior myocardial infarction (MI) and stroke. The association between MAC and MI, ischemic stroke, and vascular death was examined, adjusting for established cardiovascular risk factors and for carotid artery stenosis (&gt;60%) by means of Cox regression analysis. RESULTS: Of 1,958 subjects, 502 (25.7%) had MAC. MAC was significantly associated with age, systolic blood pressure, male gender and history of atrial fibrillation. During a mean follow-up of 7.4 ± 2.5 months, there were 100 MI, 104 ischemic stroke and 156 vascular deaths recorded. After adjustment for other risk factors, MAC was associated with an increased risk of MI (HR 1.72, 95%CI 1.13–2.63; p=0.012) and vascular death (HR 1.57, 95%CI 1.12–2.20; p=0.008), but not of ischemic stroke (HR 1.36, 95%CI 0.89 –2.06; p=0.16). When MAC was categorized into mild to moderate (1– 4mm, n=253; 13.1%) or severe (≥4mm, n=245; 12.7%), severe MAC remained as a strong and independent predictor of vascular events, but not stroke (Table ). CONCLUSION: MAC was a strong and independent predictor for MI and vascular death in this multiethnic cohort especially when its thickness is more than 4mm. Its predictive value for ischemic stroke was not independent of other cardiovascular risk factors. Table. Association of MAC severity with clinical vascular outcomes.
Finding the Right t-PA Dose for Asians with Acute Ischemic Stroke
Authors: Cathy Sila
Journal: New England Journal of Medicine (2016)

The efficacy of intravenous thrombolysis with tissue plasminogen activator (t-PA) for improving outcomes in patients with acute ischemic stroke has driven the infrastructure development for acute stroke care delivery in the United States, Europe, and Australia for the past 20 years. The early implementation was slow and cautious; 60% of U.S. neurologists cited safety concerns regarding the risk of symptomatic intracerebral hemorrhage, but only 9% cited cost as a barrier.1 That may change, because the average cost of a standard dose of alteplase increased by 111%, from $3,050 to $6,430, during the past decade.2In Asia, where 50% of the . . .
Polypharmacy and functional status in older patients with breast, colon, and lung cancers.
Authors: G. K. Prithviraj, R. Bagai, S. M. Koroukian, N. A. Berger, C. Owusu
Journal: Journal of Clinical Oncology (2010)

9087 Background: To evaluate the prevalence of polypharmacy and the inappropriate prescribing of medications (IPM), and to determine the relation between polypharmacy, IPM, and functional status in older cancer patients. Methods: Between April 2008 and September 2009 patients aged ≥65 years with incident breast, colon, or lung cancer seen at an academic center were enrolled. At study entry patients completed a functional assessment [Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Karnofsky Performance Scale (KPS), Vulnerable Elderly Survey (VES), and Timed-up and Go (TUG) Test] and a geriatric assessment including review of current medications. Data sources for medication review included patient self-report and medical records. Polypharmacy was defined as current use of ≥7 medications. IPM was defined as use of ≥1 medication included in the Beer's Criteria (Yes/No). Using bivariate analysis with chi-squared testing, associations between polypharmacy, IPM and measures of functional status were examined. Results: Of 91 participants the median age was 74 years. Fifty-two percent and 34% of participants were identified with polypharmacy and IPM, respectively. The median number of medications per patient was 7. Patients with polypharmacy were more likely to have ADL disability at cancer diagnosis (76% vs. 23%, P=0.04), to have KPS scores ≤70 (85% vs. 15%, p = 0.02), to score ≥3 on the VES (64% vs. 36%, p = 0.02), to take >14 seconds to complete the TUG test (78% vs. 22%, p = 0.03), to score ≥2 on the Charlson Comorbidity Index (74% vs. 26%, p = 0.003) and to have ≥1 geriatric syndrome (dementia, depression, falls, visual and hearing impairments) (63% vs. 37%, p = 0.05). Although patients with polypharmacy were more likely to have IPM (77% vs. 23%, p = 0.0005), there was no statistically significant association between IPM and functional outcomes. Conclusions: Polypharmacy and IPM were highly prevalent in this group of older patients with breast, colon, or lung cancer; and polypharmacy was associated with poorer functional status at diagnosis. Interventions for polypharmacy may improve functional status, treatment tolerance and cancer outcomes among older patients and are therefore warranted. No significant financial relationships to disclose.
The Hypertrichosis of Esau
Authors: Charles M. Phillips
Journal: JAMA Dermatology (2016)

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