tbuckley/cabot-search huggingface dataset:
Propofol Sedation during Endoscopic Procedures: Safe and Effective Administration by Registered Nurses Supervised by Endoscopists
Authors: G. Tohda, S. Higashi, S. Wakahara, M. Morikawa, H. Sakumoto, T. Kane
Journal: Endoscopy (2006)

Background and Study Aims: Propofol has several attractive properties, including a rapid onset of action and rapid recovery. However, the administration of propofol sedation in the absence of anesthesiologists remains controversial. This report describes the safety profile of propofol sedation for endoscopy when administered by registered nurses under the supervision of endoscopists. Patients and Methods: The study was conducted in the endoscopic center of a Japanese private hospital. With assistance from an anesthesiologist, a protocol for administration of propofol by registered nurses was developed. Over the past 6 years, 27 500 patients received nurse-administered propofol sedation. The safety and patient satisfaction with this sedation procedure were evaluated. Results: Among the participating patients, 6.7 % developed hypoxemia (Spo2 < 90 %); 6.2 % required oxygen administration via a nasal cannula. Severe hypoxemia (Spo2 < 85 %) occurred in 121 patients (0.62 %) during upper gastrointestinal endoscopy and 20 patients (0.25 %) during colonoscopy, but neither mask ventilation nor endotracheal intubation was necessary. A decline in blood pressure (systolic blood pressure < 90 mm Hg) was seen in 3.5 % of the colonoscopy patients and 1.2 % of the upper endoscopy patients. However, hypotension was corrected immediately using an intravenous saline solution. Patients who received propofol sedation expressed overall satisfaction on a 10-point visual analogue scale (with an average of 9.4 points). Among patients who had previously received a combination of midazolam and pethidine for colonoscopy, 85 % preferred propofol sedation. The mean time from the end of the procedure to full recovery was 14.6 min. Conclusions: Administration of propofol by registered nurses under the supervision of endoscopists was safe, and resulted in high rates of patient satisfaction.
Immune Responses Against the Tumor-Associated Antigens WT1, MUC-1, PRAME and HER2/Neu in 114 Prospectively Screened Healthy Donors: Effects of Gender and Prior Pregnancy and Implications for Immunotherapy
Authors: Mathias Lutz, Andrea Worschech, Sabine Gahn, Laura Bernhard, Michael Schwab, Hermann Einsele, Ulrike Kämmerer, Peter Heuschmann, Erdwine Klinker, Christoph Otto, Stephan Mielke
Journal: Blood (2012)
Statins: we need an independent review
Authors: Fiona Godlee
Journal: BMJ (2016)

Statins are back in the news. A review published in the Lancet last week, covered in our news story (doi:10.1136/bmj.i4893), presents what its authors clearly consider to be a definitive account of the evidence on statins that should, they say, bring an end to a dangerous debate.

Not everyone agrees. Though the benefits of statins for secondary prevention or in people at high risk of cardiovascular disease are undisputed, proposals to offer them to large numbers of people at lower risk remain controversial, much to the frustration of the statin trialists who authored the Lancet review. …
Paracentesis
Authors: Todd W. Thomsen, Robert W. Shaffer, Benjamin White, Gary S. Setnik
Journal: New England Journal of Medicine (2006)

Abdominal paracentesis is performed as a diagnostic procedure to establish the etiology of new-onset ascites or to rule out spontaneous bacterial peritonitis in patients with preexisting ascites. Large-volume paracentesis is performed in hemodynamically stable patients with tense or refractory ascites to alleviate discomfort or respiratory compromise. Contraindications Many patients undergoing paracentesis will have baseline coagulopathy or thrombocytopenia. However, the incidence of clinically significant bleeding during paracentesis is extremely low, and routine use of fresh-frozen plasma or platelet concentrates is not recommended. Paracentesis should be avoided in patients with disseminated intravascular coagulation. The paracentesis needle should not pass through sites . . . .
Magnetic Enrichment of Dendritic Cell Vaccine in Lymph Node with Fluorescent-Magnetic Nanoparticles Enhanced Cancer Immunotherapy
Authors: Honglin Jin, Yuan Qian, Yanfeng Dai, Sha Qiao, Chuan Huang, Lisen Lu, Qingming Luo, Jing Chen, Zhihong Zhang
Journal: Theranostics (2016)

Dendritic cell (DC) migration to the lymph node is a key component of DC-based immunotherapy. However, the DC homing rate to the lymphoid tissues is poor, thus hindering the DC-mediated activation of antigen-specific T cells. Here, we developed a system using fluorescent magnetic nanoparticles (α-AP-fmNPs; loaded with antigen peptide, iron oxide nanoparticles, and indocyanine green) in combination with magnetic pull force (MPF) to successfully manipulate DC migration in vitro and in vivo. α-AP-fmNPs endowed DCs with MPF-responsiveness, antigen presentation, and simultaneous optical and magnetic resonance imaging detectability. We showed for the first time that α-AP-fmNP-loaded DCs were sensitive to MPF, and their migration efficiency could be dramatically improved both in vitro and in vivo through MPF treatment. Due to the enhanced migration of DCs, MPF treatment significantly augmented antitumor efficacy of the nanoparticle-loaded DCs. Therefore, we have developed a biocompatible approach with which to improve the homing efficiency of DCs and subsequent anti-tumor efficacy, and track their migration by multi-modality imaging, with great potential applications for DC-based cancer immunotherapy.
Palmoplantar keratoderma and Charcot-Marie-Tooth disease: combination of two independent genetic diseases? Identification of two point mutations in the <i>MPZ</i> and <i>KRT1</i> genes by whole-exome sequencing
Authors: S. Gagliardi, I. Ricca, A. Ferrarini, M. Valente, G.S. Grieco, G. Piccolo, E. Alfonsi, M. Delledonne, C. Cereda
Journal: British Journal of Dermatology (2016)
Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area: results of the prospectively randomized GAIN study
Authors: J. Furlanetto, W. Eiermann, F. Marmé, T. Reimer, M. Reinisch, S. Schmatloch, E. Stickeler, C. Thomssen, M. Untch, C. Denkert, G. von Minckwitz, B. Lederer, V. Nekljudova, K. Weber, S. Loibl, V. Möbus
Journal: Annals of Oncology (2016)
Profiling of caspase signalling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas (DLBCL)
Authors: J Muris, S Cillessen, [No Value] van Houdt, H Kluin-Nelemans, G Ossenkoppele, H van Krieken, C Meijer, J Oudejans
Journal: Annals of Oncology (2005)
Efficacies of biological therapies at week 12 in patients with plaque psoriasis in real-world academic clinical practice: a Canadian multicentre retrospective study
Authors: A. Shahbaz, J. Qiang, J.E.C. Marinas, W.B. Kim, S. Greaves, J. Yeung
Journal: British Journal of Dermatology (2016)

Psoriasis is a chronic inflammatory condition for which biologic therapies have been proven as effective therapies.1 However, considerable variation in the real world efficacy of these agents is observed in clinical practice.2 Given the treatment choices available, it is vital that dermatologists have access to the necessary information for optimal treatment selection in daily clinical practice. In this large, multi-centre study, we examine the real world effectiveness of, etanercept (ETN), adalimumab (ADA), ustekinumab (UST), infliximab (IFX) and validated assessment tools of response to these treatments.

This article is protected by copyright. All rights reserved.
P3-049: Body-frame based Fractionated Stereotactic Radiosurgery on Consecutive Days for Stage I Non-small Cell Lung Cancer
Authors: Sang Min Yoon, Eun Kyung Choi, Jung Shin Lee, Woo-Sung Kim, Seung Il Park, Jin Sook Ryu, Jae Woo Song, Si Yeol Song, Jong Hoon Kim, O-Kyu Noh
Journal: Journal of Thoracic Oncology (2007)
P2-231: Palliative Chemotherapy for Pulmonary Pleomorphic Carcinoma
Authors: Hyun-Mi Bae, Hye Sook Min, Yu Jung Kim, Se-Hoon Lee, Dong-Wan Kim, Doo Hyun Chung, Jong-Seok Lee, Young Whan Kim, Dae Seog Heo
Journal: Journal of Thoracic Oncology (2007)
Results of a phase II trial on individualized radiation dose-escalation based on normal tissue constraints in concurrent chemo-radiation for stage III non-small cell lung cancer (NSCLC)
Authors: Angela Van Baardwijk, Bart Reymen, Rinus Wanders, Jacques Borger, Anne-Marie C Dingemans, Gerben Bootsma, Cordula Pitz, Ragnar Lunde, Wiel Geraedts, Frank Peters, Philippe Lambin, Dirk De Ruysscher
Journal: Journal of Thoracic Oncology (2011)
P1-115: Carcinosarcoma of the lung with soft tissues metastases. A case report
Authors: Luis M. Domínguez Parra, José F. Corona Cruz, Edgardo Jiménez Fuentes, Oscar G. Arrieta Rodríguez, Ana M. Cano Valdéz, Jaime G. DelaGarzaSalazar
Journal: Journal of Thoracic Oncology (2007)
P1-130: Multimodality therapy for patients with invasive thymoma disseminated into the pleural cavity: the role of extrapleural pneumonectomy.
Authors: Yoshinori Ishikawa, Haruko Suzuki, Rie Nakahara, Tetsuro Kondo, Haruhisa Matsuguma, Yukari Kamiyama, Kiyoshi Mori, Naoto Miyazawa, Tetsuro Kodama, Kohei Yokoi
Journal: Journal of Thoracic Oncology (2007)
Personalised Hip Therapy: development of a non-operative protocol to treat femoroacetabular impingement syndrome in the FASHIoN randomised controlled trial
Authors: Peter DH Wall, Edward J Dickenson, David Robinson, Ivor Hughes, Alba Realpe, Rachel Hobson, Damian R Griffin, Nadine E Foster
Journal: British Journal of Sports Medicine (2016)

Femoroacetabular impingement (FAI) syndrome is increasingly recognised as a cause of hip pain. As part of the design of a randomised controlled trial (RCT) of arthroscopic surgery for FAI syndrome, we developed a protocol for non-operative care and evaluated its feasibility.In phase one, we developed a protocol for non-operative care for FAI in the UK National Health Service (NHS), through a process of systematic review and consensus gathering. In phase two, the protocol was tested in an internal pilot RCT for protocol adherence and adverse events.The final protocol, called Personalised Hip Therapy (PHT), consists of four core components led by physiotherapists: detailed patient assessment, education and advice, help with pain relief and an exercise-based programme that is individualised, supervised and progressed over time. PHT is delivered over 12-26 weeks in 6-10 physiotherapist-patient contacts, supplemented by a home exercise programme. In the pilot RCT, 42 patients were recruited and 21 randomised to PHT. Review of treatment case report forms, completed by physiotherapists, showed that 13 patients (62%) received treatment that had closely followed the PHT protocol. 13 patients reported some muscle soreness at 6 weeks, but there were no serious adverse events.PHT provides a structure for the non-operative care of FAI and offers guidance to clinicians and researchers in an evolving area with limited evidence. PHT was deliverable within the National Health Service, is safe, and now forms the comparator to arthroscopic surgery in the UK FASHIoN trial (ISRCTN64081839).ISRCTN 09754699.
Addition of bevacizumab to chemotherapy in advanced non-small cell lung cancer: A systematic review and meta-analysis.
Authors: A. B. Lima, L. T. Macedo, A. D. Sasse
Journal: Journal of Clinical Oncology (2010)

e18087 Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Treatment with chemotherapy prolongs survival with a positive impact on quality of life. Recently, studies have demonstrated that the addition of bevacizumab to chemotherapy is associated with better outcomes in patients with advanced NSCLC. However, the benefit seems to be dependent of the drugs used in the chemotherapy regimens. This systematic review evaluated the efficacy of the addition of bevacizumab to chemotherapy in advanced NSCLC. Methods: PubMed, EMBASE, and Cochrane databases were searched. Eligible studies were randomized clinical trials (RCTs) that evaluated chemotherapy with or without bevacizumab in patients with advanced NSCLC. The primary outcome was overall survival (OS). Secondary outcomes included response rate (RR) and progression-free survival (PFS). Hazard ratio (HR) and odds ratio (OR) with fixed effect model were used for meta-analysis and were expressed with 95% confidence intervals (CI). Results: We included results reported from four RCTs, with a total of 1,995 patients, all of them using platinum-based chemotherapy regimens. Compared to chemotherapy alone (n = 812), the addition of bevacizumab to chemotherapy (n = 1,183) resulted in a significant longer OS (HR 0.87; 95% CI 0.78 to 0.98; p = 0.02), longer PFS (HR 0.73; 95% CI 0.66 to 0.80; p < 0.00001) and higher response rates (OR 2.07; 95% CI 1.71 to 2.50; p = 0.00001). There was a slight increase in toxicities in the combination group, without increase of treatment- related mortality. Conclusions: The addition of bevacizumab to chemotherapy in patients with advanced NSCLC prolongs OS, PFS and RR. Considering the toxicities added, bevacizumab plus platinum-based chemotherapy can be considered a standard option in selected patients with advanced NSCLC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Proximal Tubule CD73 Is Critical in Renal Ischemia-Reperfusion Injury Protection
Authors: Sun-sang J. Sung, Li Li, Liping Huang, Jessica Lawler, Hong Ye, Diane L. Rosin, Issah S. Vincent, Thu H. Le, Jing Yu, Nicole Görldt, Jürgen Schrader, Mark D. Okusa
Journal: Journal of the American Society of Nephrology (2016)

CD73-derived adenosine plays an anti-inflammatory role in various organs. However, its role in renal ischemia-reperfusion injury (IRI) is controversial. We targeted CD73 mutant mice to determine the function of CD73 expressed by various renal cell types under mild IRI conditions. Mice with CD73 deletion in proximal tubules exhibited exacerbated IRI, comparable with that of CD73−/− mice compared with WT mice. Mice with CD73 deletions in other cell types, including cortical type 1 fibroblast–like cells, mesangial cells, macrophages, and dendritic cells, showed small or no increases in injury above control mice when subjected to threshold levels of ischemia. Results from adoptive transfer experiments between WT and CD73−/− mice and pharmacologic studies modulating enzymatic activity of CD73 and extracellular adenosine levels supported a critical role of adenosine generated by proximal tubule CD73 expression in abrogating IRI. Renal adenosine levels were lower before and after ischemia in CD73-deficient mice. However, reduction in total acid–extractable renal adenosine levels was inadequate to explain the marked difference in kidney injury in these CD73-deficient mice. Furthermore, CD73 inhibition and enzyme replacement studies showed no change in total kidney adenosine levels in treated mice compared with vehicle-treated controls. Protection from IRI in neutrophil–depleted WT recipients was sustained by repopulation with bone marrow neutrophils from WT mice but not by those lacking adenosine 2a receptors (from Adora2a−/− mice). These data support the thesis that local adenosine generated by cells at the injury site is critical for protection from IRI through bone marrow–derived adenosine 2a receptors.
Incidence and prognostic role of cumulative toxicity by tyrosine kinase inhibitors (TKI) in metastatic renal cell carcinoma (mRCC)
Authors: R. Iacovelli, M. Cossu Rocca, D. Cullurà, G. Aurilio, E. Verri, C. Crescio, S. Detti, O. De Cobelli, F. Nolè
Journal: Annals of Oncology (2015)
Rethinking the Primary Care Workforce — An Expanded Role for Nurses
Authors: Thomas Bodenheimer, Laurie Bauer
Journal: New England Journal of Medicine (2016)

Interview with Dr. Thomas Bodenheimer on the evolving roles of physicians and nurses in the provision of primary care. (08:23)Download In the U.S. primary care practice of the future, the physician's role will increasingly be played by nurse practitioners, and the 150 million adults with one or more chronic conditions will receive some of their care from registered nurses functioning as care managers.
Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia
Authors: Thomas B. Alexander, Norman J. Lacayo, John K. Choi, Raul C. Ribeiro, Ching-Hon Pui, Jeffrey E. Rubnitz
Journal: Journal of Clinical Oncology (2016)

Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m2 and cytarabine 2 g/m2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m2, three at 40 mg/m2, six at 55 mg/m2, and five at 70 mg/m2. The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.
Preeclampsia Associates with Asthma, Allergy, and Eczema in Childhood
Authors: Jakob Stokholm, Astrid Sevelsted, Ulrik D. Anderson, Hans Bisgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Preeclampsia reflects an unusual increase in systemic inflammation during pregnancy.Objectives: We studied associations between preeclampsia and asthma, allergy, and eczema in Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) and in national registries.Methods: COPSAC2000 is a high-risk birth cohort of 411 Danish children. Asthma, allergy, and eczema were diagnosed prospectively, and lung function measured at age 1 month and 7 years. Sensitization was evaluated at age 6 months, 18 months, 4 years, and 6 years by skin prick tests and IgE measurements. The register-based cohort included 1.7 million children from Danish national registries in the 35-year period 1977–2012. Children born to mothers with preeclampsia were analyzed regarding risk of asthma, allergy, and eczema.Measurements and Main Results: In the COPSAC2000 cohort, 5.6% (n = 23) were diagnosed with preeclampsia. Preeclampsia was associated with increased risk of treatment with inhaled corticosteroids at age 7 years (adjusted odds ratio, 4.01 [95% confidence interval (CI), 1.11–14.43]; P = 0.0337), increased bronchial responsiveness to methacholine (adjusted β-coefficient log-μmol, −0.80 [95% CI, −1.55 to −0.06]; P = 0.0348), and allergic rhinitis (adjusted odds ratio, 4.83 [95% CI, 1.58–14.78]; P = 0.0057) in the 7-year-old children. Furthermore, the children had an increased risk of sensitization to both aeroallergens and food allergens, and increased amount of total IgE during childhood. In the registry-based cohort, 3.7% (n = 62,728) were born to mothers with preeclampsia. Preeclampsia was associated with increased risk of asthma, eczema, and aeroallergen and food allergy, especially pronounced after a duration of preeclampsia of 14 days or more. Maternal asthma increased the risk of preeclampsia.Conclusions: Preeclampsia is a shared prenatal risk factor for asthma, eczema, and allergy in childhood pointing toward in utero immune programming of the child.
Proto-Oncogenic Src Phosphorylates EB1 to Regulate the Microtubule-Focal Adhesion Crosstalk and Stimulate Cell Migration
Authors: Yijun Zhang, Youguang Luo, Rui Lyu, Jie Chen, Ruming Liu, Dengwen Li, Min Liu, Jun Zhou
Journal: Theranostics (2016)

Cell migration, a complex process critical for tumor progression and metastasis, requires a dynamic crosstalk between microtubules (MTs) and focal adhesions (FAs). However, the molecular mechanisms underlying this event remain elusive. Herein we identify the proto-oncogenic protein Src as an important player in the regulation of the MT-FA crosstalk. Src interacts with and phosphorylates end-binding protein 1 (EB1), a member of MT plus end-tracking proteins (+TIPs), both in cells and in vitro. Systematic mutagenesis reveals that tyrosine-247 (Y247) is the primary residue of EB1 phosphorylated by Src. Interestingly, both constitutively activated Src and Y247-phosphorylated EB1 localize to the centrosome and FAs. Src-mediated EB1 phosphorylation diminishes its interactions with other +TIPs, including adenomatous polyposis coli (APC) and mitotic centromere associated kinesin (MCAK). In addition, EB1 phosphorylation at Y247 enhances the rate of MT catastrophe and significantly stimulates cell migration. These findings thus demonstrate that the Src-EB1 axis plays a crucial role in regulating the crosstalk between MTs and FAs to promote cell migration.
A randomized, parallel-group, phase II study to evaluate the efficacy and safety of three doses of the integrin inhibitor cilengitide compared with docetaxel in patients with stage IV non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy
Authors: Christian Manegold, Johan Vansteenkiste, Felipe Cardenal, Wolfgang Schutte, Penella Woll, Ernst Ulsperger, Bjorn Ruter, Martin Picard, Josef Eckmayr, Joachim von Pawel
Journal: Journal of Thoracic Oncology (2009)
Small-Scale Mass Spectrometry-Based Phosphoproteomic Analysis of Primary Hematopoietic Stem and Progenitor Cells to Identify Critical Regulators of HSPC Mobilization and Leukemogenesis
Authors: Leo D. Wang, Phi Nguyen, Scott B Ficarro, John Hutchinson, Oliver Hofmann, Jarrod A Marto, Amy J. Wagers
Journal: Blood (2014)
Antipsychotic-like Effects of M 4 Positive Allosteric Modulators Are Mediated by CB 2 Receptor-Dependent Inhibition of Dopamine Release
Authors: Daniel J. Foster, Jermaine M. Wilson, Daniel H. Remke, M. Suhaib Mahmood, M. Jashim Uddin, Jürgen Wess, Sachin Patel, Lawrence J. Marnett, Colleen M. Niswender, Carrie K. Jones, Zixiu Xiang, Craig W. Lindsley, Jerri M. Rook, P. Jeffrey Conn
Journal: Neuron (2016)