tbuckley/cabot-search huggingface dataset:
Hybrid minimally invasive versus open oesophagectomy for patients with oesophageal cancer: A multicenter, open-label, randomized phase III controlled trial, the MIRO trial.
Authors: Christophe Mariette, Bernard Meunier, Denis Pezet, Cecile Dalban, Denis Collet, Pascal-Alexandre Thomas, Cecile Brigand, Thierry Perniceni, Nicolas Carrere, Franck Bonnetain, Guillaume Piessen
Journal: Journal of Clinical Oncology (2015)

5 Background: Surgical resection is regarded as the only curative option for resectable oesophageal cancer. Postoperative morbidity, in particular pulmonary complications, continues to be of great concern and occurs in more than half of patients after open oesophagectomy (OO). We assessed whether hybrid minimally invasive oesophagectomy (HMIO) reduces morbidity compared with OO. Methods: We performed a multicentre, open-label, randomised controlled trial at 12 study centres between October 2009 and April 2012. Patients aged 18-75 years old with resectable cancers of the middle or lower third of the oesophagus were assigned by a computer-generated randomisation sequence to undergo either transthoracic OO or HMIO. Surgical technique was standardised by both on site visits and the use of videos, and was based on an Ivor Lewis procedure with laparoscopic gastric mobilisation and open right thoracotomy. Randomisation was stratified by centre. The primary outcome was 30 day grade II-IV postoperative morbidity as defined by the Dindo-Clavien classification. Analysis was by intention to treat. Results: We randomly assigned 104 patients to the OO group and 103 to the HMIO group. Sixty-seven (64.4%) patients in the OO group had major postoperative morbidity compared with 37 (35.9%) in the HMIO group (OR 0·31, 95% CI 0·18-0·55; p=0·0001). Thirty-one (30.1%) patients in the OO had major pulmonary complications compared with 18 (17.7%) in the minimally invasive group p=0·037), whereas 30-day mortality was 5 (4.9%) vs. 5 (4.9%), respectively. Conclusions: These findings provide evidence for the short-term benefits of HMIO for patients with resectable oesophageal cancer (NCT00937456 ClinicalTrials.gov). Clinical trial information: NCT00937456.
LP04 : A phase 3, open-label, single-arm study to evaluate the efficacy and safety of 12 weeks of simeprevir (SMV) plus sofosbuvir (SOF) in treatment-naïve or -experienced patients with chronic HCV genotype 1 infection and cirrhosis: Optimist-2
Authors: E. Lawitz, G. Matusow, E. DeJesus, E. Yoshida, F. Felizarta, R. Ghalib, E. Godofsky, R. Herring, G. Poleynard, A. Sheikh, H. Tobias, M. Kugelmas, R. Kalmeijer, M. Peeters, O. Lenz, B. Fevery, G. De La Rosa, J. Scott, R. Sinha, J. Witek
Journal: Journal of Hepatology (2015)
What indication, morbidity and mortality for central pancreatectomy in oncological surgery? A systematic review
Authors: Michele Santangelo, Anna Esposito, Vincenzo Tammaro, Armando Calogero, Carmen Criscitiello, Giuseppe Roberti, Maria Candida, Niccolò Rupealta, Antonio Pisani, Nicola Carlomagno
Journal: International Journal of Surgery (2015)
Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent
Authors: Jerald L Cohen, Jorge Cheirif, Douglas S Segar, Linda D Gillam, John S Gottdiener, Eva Hausnerova, Denise E Bruns
Journal: Journal of the American College of Cardiology (1998)

Objectives. The echocardiographic contrast-enhancing effects and safety profile of ALBUNEX (a suspension of air-filled albumin microspheres) were compared with the new contrast agent OPTISON (formerly FS069: a suspension of albumin microspheres containing the gas perfluoropropane) in 203 patients with inadequate noncontrast echocardiograms. Background. The efficacy of ALBUNEX has been limited by its short duration of action. By using perfluoropropane instead of air within the microsphere, its duration of action is increased. Methods. Each patient received ALBUNEX (0.8 and 0.22 mL/kg) and OPTISON (0.2, 0.5, 3.0, and 5.0 mL) on separate days a minimum of 48 hours apart. Echocardiograms were evaluated for increase in left ventricular (LV) endocardial border length, degree of LV opacification, number of LV endocardial border segments visualized, conversion from a nondiagnostic to a diagnostic echocardiogram, and duration of contrast enhancement. A thorough safety evaluation was conducted. Results. Compared with ALBUNEX, OPTISON more significantly improved every measure of contrast enhancement. OPTISON increased well-visualized LV endocardial border length by 6.0 ± 5.1, 6.9 ± 5.4, 7.5 ± 4.7, and 7.6 ± 4.8 cm, respectively, for each of the four doses, compared with only 2.2 ± 4.5 and 3.4 ± 4.6 cm, respectively, for the two ALBUNEX doses (p < 0.001). 100% LV opacification was achieved in 61%, 73%, 87%, and 87% of the patients with the four doses of OPTISON, but in only 16% and 36% of the patients with the two ALBUNEX doses (p < 0.001). Conversion of nondiagnostic to diagnostic echocardiograms with contrast occurred in 74% of patients with the optimal dose of OPTISON (3.0 mL) compared with only 26% with the optimal dose of ALBUNEX (0.22 mL/kg) (p < 0.001). The duration of contrast effect was also significantly greater with OPTISON than with ALBUNEX. In a subset of patients with potentially poor transpulmonary transit of contrast (patients with chronic lung disease or dilated cardiomyopathy), OPTISON more significantly improved the same measures of contrast enhancement compared with ALBUNEX and did so to the same extent as in the overall population. Side effects were similar and transient with the two agents. Conclusion. OPTISON appears to be a safe, well-tolerated echocardiographic contrast agent that is superior to ALBUNEX.
Mass spectral analysis of mouse serum proteome to predict tumor clearance
Authors: Norman Woller, Heinrich Roder, Sarah Knocke, Krista Meyer, Julia Grigorieva, Senait Asmellash, Kevin Sayers, Caroline Maher
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts A novel transposon tumor induction model was used to induce cholangiocarcinoma tumors in C57BL/6 mice. In this system, it is possible to drive immune related activities that will lead to 1) large tumors, no clearance or response by tumor-directed CD8+ T cells, 2) large tumors, no
Prognostic factors for positive surgical staging in patients with Hodgkin's disease.
Authors: P Mauch, D Larson, R Osteen, B Silver, B Yeap, G Canellos, H Weinstein, D Rosenthal, G Pinkus, M Jochelson
Journal: Journal of Clinical Oncology (1990)

Staging laparotomy was performed as part of the routine recommended diagnostic evaluation following clinical staging (CS) in 692 patients presenting with supradiaphragmatic Hodgkin's disease (HD). Various clinical factors were analyzed by multivariate analysis for prediction of abdominal involvement. Factors that were statistically significant for predicting disease below the diaphragm included CS III-IV disease (P less than .001), B symptoms (P less than .001), mixed cellularity (MC) or lymphocytic depletion (LD) histology (P = .017), number of supradiaphragmatic sites greater than or equal to 2 (P = .001), male sex (P = 0.034) and age greater than or equal to 40 years (P = .004). Separate analyses were performed for various subgroups of CS IA-IIA, CS IB-IIB, CS IIIA-IVA, and CS IIIB-IVB patients. Upstaging was seen in 0% to 55% of CS I-II patients based on subgroup. Male sex, B symptoms, and number of sites above the diaphragm greater than or equal to 2 all independently predicted for positive surgical staging in CS I-II patients. Sixty-four percent of CS I-II patients who were upstaged had extensive abdominal disease by positive lower abdominal nodes or multiple splenic nodules (greater than or equal to 5). Downstaging (to pathological stage [PS] I-II) was seen in 9% to 68% of patients with CS III-IV disease based on subgrouping. Age greater than or equal to 40, MC or LD histology, and B symptoms all independently predicted for positive surgical staging in CS III-IV patients. Downstaging was more frequently seen in CS IIIA-IVA patients (55%) than in patients who were CS III-IVB (22%). Four subgroups of patients who had a low probability (less than 10%) of stage or treatment change following laparotomy were identified. These included CS IA female patients, CS IA male patients with lymphocyte predominance histology or high neck presentations, and patients with CS IIIB-IVB disease and account for 21% of the study population. Staging laparotomy altered the stage and treatment of a significant number of the remaining 79% patients and should continue to be recommended for this group of patients.
Erratum. Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study. Diabetes Care 2014;37:1854–1862
Authors: Monique van Nielen, Edith J.M. Feskens, Marco Mensink, Ivonne Sluijs, Esther Molina, Pilar Amiano, Eva Ardanaz, Beverly Balkau, Joline W.J. Beulens, Heiner Boeing, Françoise Clavel-Chapelon, Guy Fagherazzi, Paul W. Franks, Jytte Halkjaer, José Maria Huerta, Verena Katzke, Timothy J. Key, Kay Tee Khaw, Vittorio Krogh, Tilman Kühn, Virginia V.M. Menéndez, Peter Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, Olov Rolandsson, Isabelle Romieu, Carlotta Sacerdote, Maria-José Sánchez, Matthias B. Schulze, Annemieke M.W. Spijkerman, Anne Tjonneland, Rosario Tumino, Daphne L. van der A, Anne M.L. Würtz, Raul Zamora-Ros, Claudia Langenberg, Stephen J. Sharp, Nita G. Forouhi, Elio Riboli, Nicholas J. Wareham
Journal: Diabetes Care (2015)
A more pluralist typology of selection processes
Authors: Bence Nanay
Journal: Behavioral and Brain Sciences (2001)

Instead of using only one notion of selection I argue for a broader typology of different types of selection. Three such types are differentiated, namely simple one-step selection, iterated one-step selection, and multi-step selection. It is argued that this more general and more inclusive typology might face more effectively the possible challenges of a general account of selection.
Differential antiplatelet efficacy for various GPIIb/IIIa antagonists Role of plasma calcium levels
Authors: S Mousa
Journal: Cardiovascular Research (2000)

Objectives: The present study was undertaken to determine the effects of free ionized calcium influenced by either the anticoagulant used (citrate vs. heparin) or directly varying the calcium levels after treatment of blood with citrate on the antiplatelet efficacy of two classes of GPIIb/IIIa antagonists. Methods: The platelet effects of changes in plasma [Ca++] with the different GPIIb/IIIa antagonists were determined using light transmittance aggregometry, direct binding kinetics, and 125I-fibrinogen binding to activated human platelets. Results: A significantly higher IC50s was shown with heparin (free ionized calcium=1.1 mM) as compared to that with citrate (free ionized calcium=0.12 mM) with class II GPIIb/IIIa antagonists (P<0.01) such as Orbofiban, and Integrilin. In contrast, class I GPIIb/IIIa antagonists such as Roxifiban and Abciximab showed no significant changes in their IC50s in either citrate or heparin. Similar data were shown with other non-calcium chelating anticoagulant such as PPACK as compared to that with heparin. Additionally, similar data were shown with regard to the [Ca++] sensitivity for GPIIb/IIIa antagonists from Class II but not Class I in the changes in IC50 values required for the inhibition of 125I-fibrinogen binding to activated human gel filtered platelets. Additionally, examples from Class I GPIIb/IIIa antagonists such as 3H-active form of Roxifiban showed no significant changes in its platelet binding affinity in response to change in [Ca++]. In contrast, GPIIb/IIIa antagonists from class II such as 3H-active form of Orbofiban demonstrated significant changes (P<0.01) in its platelet binding kinetics and antiplatelet efficacy in response to changes in Ca++ concentrations. Conclusions: These data suggest the impact of the method of blood collection or changes in plasma calcium levels on the antiplatelet efficacy for class II but not class I GPIIb/IIIa antagonists depending on their platelet binding kinetics.
Role of Mitochondrial DNA in Septic AKI via Toll-Like Receptor 9
Authors: Naoko Tsuji, Takayuki Tsuji, Naro Ohashi, Akihiko Kato, Yoshihide Fujigaki, Hideo Yasuda
Journal: Journal of the American Society of Nephrology (2015)

Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. However, the mechanisms that activate the TLR9 pathway and cause kidney injury during sepsis remain unknown. To determine the role of mitochondrial DNA (mtDNA) in TLR9-associated septic AKI, we established a cecal ligation and puncture (CLP) model of sepsis in wild-type (WT) and Tlr9 -knockout ( Tlr9 KO) mice. We evaluated systemic circulation and peritoneal cavity dynamics and immune response and tubular mitochondrial dysfunction to determine upstream and downstream effects on the TLR9 pathway, respectively. CLP increased mtDNA levels in the plasma and peritoneal cavity of WT and Tlr9 KO mice in the early phase, but the increase in the peritoneal cavity was significantly higher in Tlr9 KO mice than in WT mice. Concomitantly, leukocyte migration to the peritoneal cavity increased, and plasma cytokine production and splenic apoptosis decreased in Tlr9 KO mice compared with WT mice. Furthermore, CLP-generated renal mitochondrial oxidative stress and mitochondrial vacuolization in the proximal tubules in the early phase were reversed in Tlr9 KO mice. To elucidate the effects of mtDNA on immune response and kidney injury, we intravenously injected mice with mitochondrial debris (MTD), including substantial amounts of mtDNA. MTD caused an immune response similar to that induced by CLP, including upregulated levels of plasma IL-12, splenic apoptosis, and mitochondrial injury, but this effect was attenuated by Tlr9 KO. Moreover, MTD-induced renal mitochondrial injury was abolished by DNase pretreatment. These findings suggest that mtDNA activates TLR9 and contributes to cytokine production, splenic apoptosis, and kidney injury during polymicrobial sepsis.
Validation of a kinetic analysis of renal cancer regression and growth following treatment with sunitinib and interferon-alfa (IFN-α): Analysis of the pivotal randomized trial.
Authors: J. Wilkerson, W. D. Stein, S. T. Kim, X. Huang, R. J. Motzer, A. T. Fojo, S. E. Bates
Journal: Journal of Clinical Oncology (2010)

4597 Background: We developed a novel method to analyze the response of tumors to therapy, quantifying the rate of tumor regression (decay, d) and growth (g), based on tumor measurements obtained while patients are receiving therapy. Previous data suggested that g correlates strongly with survival and clinical benefit. We sought to validate this method using tumor measurements obtained by CT scans from a randomized phase 3 trial in patients with metastatic renal cell carcinoma (RCC) treated with sunitinib or IFN-α [Motzer et al, N Eng J Med 356:115; 2007]. Methods: Data were analyzed using our kinetic equation that extracts the rate of tumor regression (d) and the rate of growth (g) [Stein et al, Oncologist. 13:1046; 2008]. Results: In patients treated with sunitinib, overall survival (OS) was strongly correlated with the rate of tumor growth (log g, R =0.75); less so with the rate of regression (log d, R = 0.22). The median growth rate constant of tumors in patients treated with sunitinib (0.00109 days-1; log g = -2.96) was half that (p < 0.001) of tumors in patients treated on the IFN-α arm (0.00268 days-1; log g = -2.57). With IFN- α, the correlation of OS with both log g (R = 0.29) and log d (R = 0.068) was weaker. The median g value with IFN-α was not significantly different from that of tumors in a similar population receiving placebo in another clinical trial (0.00278 days-1, Stein et al, Oncologist. 13:1055; 2008). Notably, tumor growth rate constants determined using radiological measurements obtained by either study investigators or independent reviewers were highly correlated (R = 0.87). There was no significant advantage in including data from independent review when regressing OS with the tumor growth rate constants. Conclusions: Determining the growth rate constant of renal cancers during drug therapy provides a robust method to assess the results of clinical trials. We also noted that, in patients who died early, the data were consistent with an increase in the growth rate constant after sunitinib was discontinued, suggesting that continuation of treatment with sunitinib beyond study criteria for progression might have extended survival. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Risks of Death and Stroke in Patients Undergoing Hemodialysis With New-Onset Atrial Fibrillation
Authors: Chia-Jen Shih, Shuo-Ming Ou, Pei-Wen Chao, Shu-Chen Kuo, Yi-Jung Lee, Chih-Yu Yang, Der-Cherng Tarng, Chih-Ching Lin, Po-Hsun Huang, Szu-Yuan Li, Yung-Tai Chen
Journal: Circulation (2016)

Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia.This nationwide, population-based, propensity score-matched cohort study used data from Taiwan's National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13-1.43), all-cause death (aHR, 1.59; 95% CI, 1.52-1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71-1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17-1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76-2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45-1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA2DS2-VASc score for ischemic stroke was diminished in the competing-risk model.The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.
Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations
Authors: Thomas F Eleveld, Derek A Oldridge, Virginie Bernard, Jan Koster, Leo Colmet Daage, Sharon J Diskin, Linda Schild, Nadia Bessoltane Bentahar, Angela Bellini, Mathieu Chicard, Eve Lapouble, Valérie Combaret, Patricia Legoix-Né, Jean Michon, Trevor J Pugh, Lori S Hart, JulieAnn Rader, Edward F Attiyeh, Jun S Wei, Shile Zhang, Arlene Naranjo, Julie M Gastier-Foster, Michael D Hogarty, Shahab Asgharzadeh, Malcolm A Smith, Jaime M Guidry Auvil, Thomas B K Watkins, Danny A Zwijnenburg, Marli E Ebus, Peter van Sluis, Anne Hakkert, Esther van Wezel, C Ellen van der Schoot, Ellen M Westerhout, Johannes H Schulte, Godelieve A Tytgat, M Emmy M Dolman, Isabelle Janoueix-Lerosey, Daniela S Gerhard, Huib N Caron, Olivier Delattre, Javed Khan, Rogier Versteeg, Gudrun Schleiermacher, Jan J Molenaar, John M Maris
Journal: Nature Genetics (2015)
Influence of obesity and nasal polyps on severe asthma
Authors: Federica Novelli, Giulia Lenzini, Manuela Latorre, Veronica Seccia, Maria Laura Bartoli, Laura Malagrinò, Federico Lorenzo Dente, Pier Luigi Paggiaro
Journal: European Respiratory Journal (2013)

Background: Asthma is often associated with comorbidities that can influence its control, phenotype and response to treatment. Aim of this study is to evaluate the influence of two common comorbidities (obesity and nasal polyps, NP) on pulmonary function, inflammation, asthma control and quality of life in patients with severe asthma (SA).  Method: We studied 64 patients with SA. All patients performed spirometry, collection of induced sputum for inflammatory cells, measurement of exhaled nitric oxide (eNO) and ENT visit. Asthma control was evaluated according to GINA guidelines and by ACT questionnaire, quality of life by AQLQ.  Results: The percentage of patients with uncontrolled asthma was high (46.9%). Obese asthmatics had a similar functional data than non-obese, but worse asthma control (ACT score: 16 (7-25) vs 21 (10-25), p  Conclusion: In patients with SA, NP is associated with increased eosinophilic airway inflammation and with worse lung function, but has less impact on asthma control and quality of life than obesity.
Diagnosis of Aerococcus urinae infections: Importance of matrix-assisted laser desorption ionization time-of-flight mass spectrometry and broad-range 16S rDNA PCR
Authors: O. Opota, G. Prod'hom, C. Andreutti-Zaugg, M. Dessauges, L. Merz, G. Greub, J.-P. Chave, K. Jaton
Journal: Clinical Microbiology and Infection (2015)
Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer
Authors: J. O'Shaughnessy, M. Campone, E. Brain, P. Neven, D. Hayes, I. Bondarenko, T.W. Griffin, J. Martin, P. De Porre, T. Kheoh, M.K. Yu, W. Peng, S. Johnston
Journal: Annals of Oncology (2015)

Androgen receptor (AR) signaling and incomplete inhibition of estrogen signaling may contribute to metastatic breast cancer (MBC) resistance to a nonsteroidal aromatase inhibitor (NSAI; letrozole or anastrozole). We assessed whether combined inhibition of androgen biosynthesis with abiraterone acetate plus prednisone and estradiol synthesis with exemestane (E) may be of clinical benefit to postmenopausal patients with NSAI-pretreated estrogen receptor-positive (ER+) MBC. Patients (N = 297) were stratified by the number of prior therapies for metastatic disease (0–1 versus 2) and by prior NSAI use (adjuvant versus metastatic), and randomized (1:1:1) to receive oral once daily 1000 mg abiraterone acetate plus 5 mg prednisone (AA) versus AA with 25 mg E (AAE) versus 25 mg E alone (E). Each treatment arm was well balanced with regard to the proportion of patients with AR-positive breast cancer. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, clinical benefit rate, duration of response, and overall response rate. There was no significant difference in PFS with AA versus E (3.7 versus 3.7 months; hazard ratio [HR] = 1.1; 95% confidence interval [CI] 0.82–1.60; P = 0.437) or AAE versus E (4.5 versus 3.7 months; HR = 0.96; 95% CI 0.70–1.32; P = 0.794). Increased serum progesterone concentrations were observed in both arms receiving AA, but not with E. Grade 3 or 4 treatment-emergent adverse events associated with AA, including hypokalemia and hypertension, were less common in patients in the E (2.0% and 2.9%, respectively) and AA arms (3.4% and 1.1%, respectively) than in the AAE arm (5.8% for both). Adding AA to E in NSAI-pretreated ER+ MBC patients did not improve PFS compared with treatment with E. An AA-induced progesterone increase may have contributed to this lack of clinical activity. NCT01381874.