tbuckley/cabot-search huggingface dataset:
Transbronchial needle aspiration in peripheral pulmonary lesions: a systematic review and meta-analysis
Authors: Michele Mondoni, Giovanni Sotgiu, Martina Bonifazi, Simone Dore, Elena Maria Parazzini, Paolo Carlucci, Stefano Gasparini, Stefano Centanni
Journal: European Respiratory Journal (2016)

Fluoroscopy-guided transbronchial needle aspiration (TBNA) has long been used in the diagnosis of peripheral pulmonary lesions (PPLs), although its diagnostic performance varies considerably. We conducted a systematic review and meta-analysis evaluating the accuracy of TBNA in the diagnosis of PPLs, comparing its diagnostic yield with transbronchial biopsy (TBB) and assessing the main predictors of a successful aspirate. In 18 studies, the overall TBNA yield was 0.53 (95% CI 0.44–0.61). TBNA showed a higher accuracy when directly compared to TBB (0.60 (95% CI 0.49–0.71) versus 0.45 (95% CI 0.37–0.54)). The subgroup analyses documented a higher TBNA yield when the computed tomography (CT) bronchus sign was present (0.70 (95% CI 0.63–0.77) versus 0.51 (95% CI 0.38–0.64)), when rapid on-site evaluation (ROSE) was performed (0.62 (95% CI 0.43–0.79) versus 0.51 (95% CI 0.42–0.60)), in the case of malignant lesions (0.55 (95% CI 0.44–0.66) versus 0.17 (95% CI 0.11–0.24)) and for lesions &gt;3 cm (0.81 (95% CI 0.73–0.87) versus 0.55 (95% CI 0.47–0.63)). Conventional TBNA is a useful sampling technique for the diagnosis of PPL, with a higher diagnostic yield than TBB. The presence of CT bronchus sign, an underlying malignant process, lesion size &gt;3 cm and ROSE employment are predictors of a higher yield.
Integrative microRNA profiling in alcoholic hepatitis reveals a role for microRNA-182 in liver injury and inflammation
Authors: Delia Blaya, Mar Coll, Daniel Rodrigo-Torres, Maria Vila-Casadesús, José Altamirano, Marta Llopis, Isabel Graupera, Luis Perea, Beatriz Aguilar-Bravo, Alba Díaz, Jesus M Banales, Joan Clària, Juan José Lozano, Ramon Bataller, Juan Caballería, Pere Ginès, Pau Sancho-Bru
Journal: Gut (2016)

<h3>Objective</h3> MicroRNAs (miRNAs) are well-known regulators of disease pathogenesis and have great potential as biomarkers and therapeutic targets. We aimed at profiling miRNAs in alcoholic hepatitis (AH) and identifying miRNAs potentially involved in liver injury. <h3>Design</h3> MiRNA profiling was performed in liver samples from patients with AH, alcohol liver disease, non-alcoholic steatohepatitis, HCV disease and normal liver tissue. Expression of miRNAs was assessed in liver and serum from patients with AH and animal models. Mimic and decoy miR-182 were used in vitro and in vivo to evaluate miR-1829s biological functions. <h3>Results</h3> MiRNA expression profile in liver was highly altered in AH and distinctive from alcohol-induced cirrhotic livers. Moreover, we identified a set of 18 miRNAs predominantly expressed in AH as compared with other chronic liver conditions. Integrative miRNA-mRNA functional analysis revealed the association of AH-altered miRNAs with nuclear receptors, IGF-1 signalling and cholestasis. Interestingly, miR-182 was the most highly expressed miRNA in AH, which correlated with degree of ductular reaction, disease severity and short-term mortality. MiR-182 mimic induced an upregulation of inflammatory mediators in biliary cells. At experimental level, miR-182 was increased in biliary cells in mice fed with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet but not upregulated by alcohol intake or fibrosis. Inhibition of miR-182 in DDC-fed mice reduced liver damage, bile acid accumulation and inflammatory response. <h3>Conclusions</h3> AH is characterised by a deregulated miRNA profile, including miR-182, which is associated with disease severity and liver injury. These results highlight the potential of miRNAs as therapeutic targets and biomarkers in AH.
NCCN Guidelines Insights: Prostate Cancer Early Detection, Version 2.2016
Authors: Peter R. Carroll, J. Kellogg Parsons, Gerald Andriole, Robert R. Bahnson, Erik P. Castle, William J. Catalona, Douglas M. Dahl, John W. Davis, Jonathan I. Epstein, Ruth B. Etzioni, Thomas Farrington, George P. Hemstreet, Mark H. Kawachi, Simon Kim, Paul H. Lange, Kevin R. Loughlin, William Lowrance, Paul Maroni, James Mohler, Todd M. Morgan, Kelvin A. Moses, Robert B. Nadler, Michael Poch, Chuck Scales, Terrence M. Shaneyfelt, Marc C. Smaldone, Geoffrey Sonn, Preston Sprenkle, Andrew J. Vickers, Robert Wake, Dorothy A. Shead, Deborah A. Freedman-Cass
Journal: Journal of the National Comprehensive Cancer Network (2016)

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection provide recommendations for prostate cancer screening in healthy men who have elected to participate in an early detection program. The NCCN Guidelines focus on minimizing unnecessary procedures and limiting the detection of indolent disease. These NCCN Guidelines Insights summarize the NCCN Prostate Cancer Early Detection Panel's most significant discussions for the 2016 guideline update, which included issues surrounding screening in high-risk populations (ie, African Americans, BRCA1/2 mutation carriers), approaches to refine patient selection for initial and repeat biopsies, and approaches to improve biopsy specificity.
A phase I dose-escalation trial of GliaSite brachytherapy for recurrent glioblastoma multiforme
Authors: T. Mikkelsen, L. Kleinberg, K. Judy, X. Ye, V. Stieber, S. Desideri, J. D. Fisher, S. A. Grossman
Journal: Journal of Clinical Oncology (2005)

1548 Background: NABTT opened trial 2106 to determine the maximum tolerated dose (MTD) of GliaSite Brachytherapy (GSBT) in the treatment of recurrent GBM. This trial closed 2004 without reaching the MTD. Methods: Patients with recurrent resectable GBM were enrolled in cohorts of 5 to receive postoperative brachytherapy. A DLT was defined as CTC 2.0 grade 3/4 toxicity not resolved within 1 month of onset or 3 months from end of brachytherapy (whichever was longer), any Grade 5 toxicity, or radiation necrosis requiring craniotomy within 3 months from completion of brachytherapy. Progressive disease (PD) was defined as progressive neurologic abnormalities not explained by causes unrelated to tumor progression; greater than 25% increase in the volume of enhancing tumor; or new enhancement on MRI scan. Results: 12 patients were screened. 7 did not receive GSBT. Of the remaining 5, 1 was taken off study prior to the evaluation endpoint to start new therapy.The median patient age was 56 years (43–67). The median KPS was 90 (60–100). 3 patients had a diagnosis of GBM (WHO IV), 1 had AA (WHO III) and 1 had AO (WHO III). The median number of cycles of previous chemotherapy was 3 (1–6). The median previous external beam radiation therapy dose was 60 Gy (56–63). The median balloon size was 3.0 cm (2.0–4.0). All patients received a dose of 80 Gy @ 1 cm. The median dwell time 116 hrs (115–168). The median delivered radioactivity was 429 mCi (237–661). No DLT was encountered. At the endpoint, 2 had SD, and 2 had PD. The patient taken off study to start a new treatment had a PR. 2 patients were alive at last follow up. The median time of survival will be presented as the data mature. Conclusions: At this time, it was determined that this trial could not complete accrual. Analysis of the early PD suggested that some of the radiographic findings may have represented a reaction to treatment. It was thus decided that the trial would be closed and replaced by a Phase II trial using a fixed dose of GSBT with an endpoint designed to characterize the imaging changes associated with GSBT and correlate these with biologic and pathologic findings at the time of imaging progression. No significant financial relationships to disclose.
Residual Kidney Function Decline and Mortality in Incident Hemodialysis Patients
Authors: Yoshitsugu Obi, Connie M. Rhee, Anna T. Mathew, Gaurang Shah, Elani Streja, Steven M. Brunelli, Csaba P. Kovesdy, Rajnish Mehrotra, Kamyar Kalantar-Zadeh
Journal: Journal of the American Society of Nephrology (2016)

In patients with ESRD, residual kidney function (RKF) contributes to achievement of adequate solute clearance. However, few studies have examined RKF in patients on hemodialysis. In a longitudinal cohort of 6538 patients who started maintenance hemodialysis over a 4-year period (January 2007 through December 2010) and had available renal urea clearance (CLurea) data at baseline and 1 year after hemodialysis initiation, we examined the association of annual change in renal CLurea rate with subsequent survival. The median (interquartile range) baseline value and mean±SD annual change of CLurea were 3.3 (1.9-5.0) and -1.1±2.8 ml/min per 1.73 m2, respectively. Greater CLurea rate 1 year after hemodialysis initiation associated with better survival. Furthermore, we found a gradient association between loss of RKF and all-cause mortality: changes in CLurea rate of -6.0 and +3.0 ml/min per 1.73 m2 per year associated with case mix-adjusted hazard ratios (95% confidence intervals) of 2.00 (1.55 to 2.59) and 0. 61 (0.50 to 0.74), respectively (reference: -1.5 ml/min per 1.73 m2 per year). These associations remained robust against adjustment for laboratory variables and ultrafiltration rate and were consistent across strata of baseline CLurea, age, sex, race, diabetes status, presence of congestive heart failure, and hemoglobin, serum albumin, and serum phosphorus levels. Sensitivity analyses using urine volume as another index of RKF yielded consistent associations. In conclusion, RKF decline during the first year of dialysis has a graded association with all-cause mortality among incident hemodialysis patients. The clinical benefits of RKF preservation strategies on mortality should be determined.
Methylphenidate for Attention-Deficit/Hyperactivity Disorder in Children and Adolescents
Authors: Ole J. Storebø, Erik Simonsen, Christian Gluud
Journal: JAMA (2016)

<h3>Clinical Question</h3> Is treatment with methylphenidate associated with benefits or harms for children and adolescents with attention-deficit/hyperactivity disorder (ADHD)? <h3>Bottom Line</h3> Methylphenidate is associated with improvement in ADHD symptoms, general behavior, and quality of life; however, due to the very low quality of the evidence, the magnitude of the associated improvement is uncertain. Methylphenidate was associated with an increased risk of nonserious adverse events. There are too few data to assess the association with serious adverse events.
Genotype‐phenotype correlation of CTNNB1 mutations reveals different ß‐catenin activity associated with liver tumor progression
Authors: Sandra Rebouissou, Andrea Franconi, Julien Calderaro, Eric Letouzé, Sandrine Imbeaud, Camilla Pilati, Jean‐Charles Nault, Gabrielle Couchy, Alexis Laurent, Charles Balabaud, Paulette Bioulac‐Sage, Jessica Zucman‐Rossi
Journal: Hepatology (2016)

CTNNB1 mutations activating ß-catenin are frequent somatic events in hepatocellular carcinoma (HCC) and adenoma (HCA), particularly associated with a risk of malignant transformation. We aimed to understand the relationship between CTNNB1 mutation types, tumor phenotype, and level of ß-catenin activation in malignant transformation. To this purpose, CTNNB1 mutation spectrum was analyzed in 220 HCAs, 373 HCCs, and 17 borderline HCA/HCC lesions. ß-catenin activation level was assessed in tumors by quantitative reverse-transcriptase polymerase chain reaction and immunohistochemistry (IHC), in cellulo by TOP-Flash assay. Overall, ß-catenin activity was higher in malignant mutated tumors, compared to adenomas, and this was related to a different spectrum of CTNNB1 mutations in HCCs and HCAs. In benign tumors, we defined three levels of ß-catenin activation related to specific mutations: (1) S45, K335, and N387 mutations led to weak activation; (2) T41 mutations were related to moderate activity; and (3) highly active mutations included exon 3 deletions and amino acid substitutions within the ß-TRCP binding site (D32-S37). Accordingly, in vitro, K335I and N387K mutants showed a lower activity than S33C. Tumors with highly active mutations demonstrated strong/homogeneous glutamine synthase (GS) staining and were associated with malignancy. In contrast, weak mutants demonstrated heterogeneous pattern of GS staining and were more frequent in HCAs except for the S45 mutants identified similarly in 20% of mutated HCAs and HCCs; however, in most of the HCCs, the weak S45 mutant alleles were duplicated, resulting in a final high ß-catenin activity.High ß-catenin activity driven by specific CTNNB1 mutations and S45 allele duplication is associated with malignant transformation. Consequently, HCAs with S45 and all high/moderate mutants should be identified with precise IHC criteria or mutation screening. (Hepatology 2016;64:2047-2061).
Phase I clinical results of intralesional injection of tetra-o-methy nordihydroguaiaretic acid (M4N) in refractory head and neck cancer
Authors: F. R. Dunphy, K. K. Dukelow, J. Provenzal, J. Crawford
Journal: Journal of Clinical Oncology (2004)

5614 Background:Patients with relapsed-refractory Head and Neck cancer have a poor prognosis with a 10% 2- year survival. Novel treatments are being explored in this poor prognostic group. M4N, a derivative from the plant, Larrea tridentata, has shown activity in murine models after intratumornal injection. Methods: Intratumor injections were administered at the same dose each week x 3 weeks with a target dose of 20mg/cm3 tumor volume. Three patients (1 female and 2 males) were treated, median age 65 (54–82). The first received 10mg/cm3 x 3 weeks, the second received 15mg/cm3 x 3 weeks, the third received 15mg/cm3 x 1 week. Using fanning intratumoral injection technique a total of 7 intratumoral injections were performed. Pharmocokinetics were obtained preinjection and 1,2,4,8,24 hours post-injection on the first and last week of intratumoral injection. Results: Major toxicity was brief heart-block requiring two hospitalizations in one patient observed after day 8 and day 15 injection. One patient developed a tracheal-cutaneous fistula one week after day 1 injection which necessitated removal from study. All patients experienced pain at the intratumoral injection site requiring intravenous morphine, median 25mg (range 10–40mg). In all three patients, injected tumor volumes were observed to respond by crusting within one week of the first injection, followed within two weeks by necrosis and ulceration. Two patients that completed 3 weeks of intratumoral injection were observed to have total necrosis of the injected tumor site, followed by disease progression outside the boundaries of the injected tumor volume. Conclusions: M4N intratumor injection was feasible and showed promising antitumor activity in relapsed-refractory squamous cell cancer. Pain was the major complication, but was less intense as injection technique experience was acquired.This approch is worthy of futher investigation Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration BioCure Medical LLC
Geographic Variation in Trends and Disparities in Acute Myocardial Infarction Hospitalization and Mortality by Income Levels, 1999-2013
Authors: Erica S. Spatz, Adam L. Beckman, Yun Wang, Nihar R. Desai, Harlan M. Krumholz
Journal: JAMA Cardiology (2016)

During the past decade, the incidence and mortality associated with acute myocardial infarction (AMI) in the United States have decreased substantially. However, it is unknown whether these improvements were consistent across communities of different economic status and geographic regions since efforts to improve cardiovascular disease prevention and management may have had variable impact.
Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients
Authors: Amy K LeBlanc, Christina Mazcko, Diane E Brown, Jennifer W Koehler, Andrew D Miller, C Ryan Miller, R Timothy Bentley, Rebecca A Packer, Matthew Breen, C Elizabeth Boudreau, Jonathan M Levine, R Mark Simpson, Charles Halsey, William Kisseberth, John H Rossmeisl, Peter J Dickinson, Timothy M Fan, Kara Corps, Kenneth Aldape, Vinay Puduvalli, G Elizabeth Pluhar, Mark R Gilbert
Journal: Neuro-Oncology (2016)

On September 14–15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed.
A Randomized, Controlled Trial of Financial Incentives for Smoking Cessation
Authors: Kevin G. Volpp, Andrea B. Troxel, Mark V. Pauly, Henry A. Glick, Andrea Puig, David A. Asch, Robert Galvin, Jingsan Zhu, Fei Wan, Jill DeGuzman, Elizabeth Corbett, Janet Weiner, Janet Audrain-McGovern
Journal: New England Journal of Medicine (2009)

Smoking is the leading preventable cause of premature death in the United States. Previous studies of financial incentives for smoking cessation in work settings have not shown that such incentives have significant effects on cessation rates, but these studies have had limited power, and the incentives used may have been insufficient.We randomly assigned 878 employees of a multinational company based in the United States to receive information about smoking-cessation programs (442 employees) or to receive information about programs plus financial incentives (436 employees). The financial incentives were $100 for completion of a smoking-cessation program, $250 for cessation of smoking within 6 months after study enrollment, as confirmed by a biochemical test, and $400 for abstinence for an additional 6 months after the initial cessation, as confirmed by a biochemical test. Individual participants were stratified according to work site, heavy or nonheavy smoking, and income. The primary end point was smoking cessation 9 or 12 months after enrollment, depending on whether initial cessation was reported at 3 or 6 months. Secondary end points were smoking cessation within the first 6 months after enrollment and rates of participation in and completion of smoking-cessation programs.The incentive group had significantly higher rates of smoking cessation than did the information-only group 9 or 12 months after enrollment (14.7% vs. 5.0%, P<0.001) and 15 or 18 months after enrollment (9.4% vs. 3.6%, P<0.001). Incentive-group participants also had significantly higher rates of enrollment in a smoking-cessation program (15.4% vs. 5.4%, P<0.001), completion of a smoking-cessation program (10.8% vs. 2.5%, P<0.001), and smoking cessation within the first 6 months after enrollment (20.9% vs. 11.8%, P<0.001).In this study of employees of one large company, financial incentives for smoking cessation significantly increased the rates of smoking cessation. (ClinicalTrials.gov number, NCT00128375.)
Abstract 3115: Prolonged QRS Duration is a Significant Predictor of Low Cardiac Output Syndrome Development After Isolated Coronary Artery Bypass Grafting in Patients with Impaired Left Ventricular Systolic Function
Authors: Tayfun Acil, Riza Turkoz, Meltem Acil, Alpay T Sezgin, Mehmet Baltali, Oner Gulcan, Bulent Ozin, Haldun Muderrisoglu
Journal: Circulation (2006)
Risk factors for lung cancer worldwide
Authors: Jyoti Malhotra, Matteo Malvezzi, Eva Negri, Carlo La Vecchia, Paolo Boffetta
Journal: European Respiratory Journal (2016)

Lung cancer is the most frequent malignant neoplasm in most countries, and the main cancer-related cause of mortality worldwide in both sexes combined.The geographic and temporal patterns of lung cancer incidence, as well as lung cancer mortality, on a population level are chiefly determined by tobacco consumption, the main aetiological factor in lung carcinogenesis.Other factors such as genetic susceptibility, poor diet, occupational exposures and air pollution may act independently or in concert with tobacco smoking in shaping the descriptive epidemiology of lung cancer. Moreover, novel approaches in the classification of lung cancer based on molecular techniques have started to bring new insights to its aetiology, in particular among nonsmokers. Despite the success in delineation of tobacco smoking as the major risk factor for lung cancer, this highly preventable disease remains among the most common and most lethal cancers globally.Future preventive efforts and research need to focus on non-cigarette tobacco smoking products, as well as better understanding of risk factors underlying lung carcinogenesis in never-smokers.
Imported chikungunya cases in an area newly colonised by Aedes albopictus: mathematical assessment of the best public health strategy
Authors: Thomas Sochacki, Frédéric Jourdain, Yvon Perrin, Harold Noel, Marie-Claire Paty, Henriette de Valk, Alexandra Septfons, Frédéric Simard, Didier Fontenille, Benjamin Roche
Journal: Eurosurveillance (2016)

We aimed to identify the optimal strategy that should be used by public health authorities against transmission of chikungunya virus in mainland France. The theoretical model we developed, which mimics the current surveillance system, predicted that without vector control (VC), the probability of local transmission after introduction of viraemic patients was around 2%, and the number of autochthonous cases between five and 15 persons per hectare, depending on the number of imported cases. Compared with this baseline, we considered different strategies (VC after clinical suspicion of a case or after laboratory confirmation, for imported or autochthonous cases): Awaiting laboratory confirmation for suspected imported cases to implement VC had no significant impact on the epidemiological outcomes analysed, mainly because of the delay before entering into the surveillance system. However, waiting for laboratory confirmation of autochthonous cases before implementing VC resulted in more frequent outbreaks. After analysing the economic cost of such strategies, our study suggested implementing VC immediately after the notification of a suspected autochthonous case as the most efficient strategy in settings where local transmission has been proven. Nevertheless, we identified that decreasing reporting time for imported cases should remain a priority.