tbuckley/cabot-search huggingface dataset:
Insights from Europe related to pandemic influenza A(H1N1)2009 have international relevance
Authors: H A Kelly, B J Cowling
Journal: Eurosurveillance (2011)

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Abstract 16746: Lower Fluoroscopy Frame Rate During Device Implantation Reduces Radiation Exposure
Authors: John T Duell, Hiroko Beck, Stephen Synowski, Benjamin Remo, Thomas Klein, Anastasios Saliaris, Vincent See, Ramarao Vunnam, Rui Huang, Steven Shorofsky, Timm Dickfeld
Journal: Circulation (2013)

Introduction: Radiation exposure is related in a dose-dependent fashion to long-term risk of a variety of malignancies for both patients and operators in the electrophysiology laboratory. All attempts to reduce the dose without compromising care should be taken. Hypothesis: We examined whether decreasing fluoroscopy frame rate from 3 frames per second (FPS) to 2 FPS during permanent pacemaker (PPM) and implantable cardiac defibrillator (ICD) implantation can safely reduce radiation exposure without a detrimental impact in clinical outcomes. Methods: Single or dual chamber device implantations performed at a single tertiary center from July 2011 to June 2013 were identified and enrolled into the study. Average fluoroscopy dose, fluoroscopy duration, case length, major complication rate, and procedure-related mortality were compared retrospectively. Complications were defined as any event requiring re-accessing the pocket, removal of hardware, additional procedures or medication changes. Results: Out of a t...
NOX2 Activation of Natural Killer T Cells Is Blocked by the Adenosine A<sub>2A</sub> Receptor to Inhibit Lung Ischemia–Reperfusion Injury
Authors: Ashish K. Sharma, Damien J. LaPar, Matthew L. Stone, Yunge Zhao, Christopher K. Mehta, Irving L. Kron, Victor E. Laubach
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Ischemia–reperfusion (IR) injury after lung transplantation, which affects both short- and long-term allograft survival, involves activation of NADPH oxidase 2 (NOX2) and activation of invariant natural killer T (iNKT) cells to produce IL-17. Adenosine A2A receptor (A2AR) agonists are known to potently attenuate lung IR injury and IL-17 production. However, mechanisms for iNKT cell activation after IR and A2AR agonist–mediated protection remain unclear.Objectives: We tested the hypothesis that NOX2 mediates IL-17 production by iNKT cells after IR and that A2AR agonism prevents IR injury by blocking NOX2 activation in iNKT cells.Methods: An in vivo murine hilar ligation model of IR injury was used, in which left lungs underwent 1 hour of ischemia and 2 hours of reperfusion.Measurements and Main Results: Adoptive transfer of iNKT cells from p47phox−/− or NOX2−/− mice to Jα18−/− (iNKT cell-deficient) mice significantly attenuated lung IR injury and IL-17 production. Treatment with an A2AR agonist attenuated IR injury and IL-17 production in wild-type (WT) mice and in Jα18−/− mice reconstituted with WT, but not A2AR−/−, iNKT cells. Furthermore, the A2AR agonist prevented IL-17 production by murine and human iNKT cells after acute hypoxia–reoxygenation by blocking p47phox phosphorylation, a critical step for NOX2 activation.Conclusions: NOX2 plays a key role in inducing iNKT cell–mediated IL-17 production and subsequent lung injury after IR. A primary mechanism for A2AR agonist–mediated protection entails inhibition of NOX2 in iNKT cells. Therefore, agonism of A2ARs on iNKT cells may be a novel therapeutic strategy to prevent primary graft dysfunction after lung transplantation.
Potential Simpson's Paradox in Multicenter Study of Intraperitoneal Chemotherapy for Ovarian Cancer
Authors: Gerhard B. Holt
Journal: Journal of Clinical Oncology (2016)

TO THE EDITOR: Wright et al used a propensity score matched sample approach to evaluate overall survival and treatment-related toxicities of intraperitoneal (IP)/intravenous (IV) relative to IV-only adjuvant treatment protocols for ovarian cancer. The authors found substantial differences between institutions in raw IP usage rates. In addition, non-negligible differences between treatment groups were found even after propensity score matching (compare Appendix Table A1 in Wright et al) in several variables, including institution at which patients received treatment, Charlson comorbidity scale, age, primary tumor site, and histology. IP treatment was administered to a low percentage of patients in some institutions (4% at institution 3), and to a high percentage in others (67% and 63% at institutions 1 and 2, respectively). Is there a potential for Simpson’s paradox in the authors’ analysis? Even with propensity matching, patients who received IV-only treatment tended to be older and poorer and have more comorbidities than other patients. Did the matcher try compensating for differences between institutions in percentage of IP treatment by assigning sicker, higher-risk patients receiving IV-only treatment to match patients receiving IP treatment from low IP rate institutions? Unfortunately, even percentage data on the institutional distribution of propensity score matched patients receiving IV-only versus IP/IV treatment was not presented. More broadly, can we be confident that the observed mortality differences were not largely attributable to differences between institutions—unrelated to the selection of IP/IV versus IV-only treatment? For example, if institutions with a large number of patients receiving IV-only treatment had an overall higher mortality rate, then might this pose a threat of distortion via Simpson’s paradox? I am concerned that there might have been differences between institutions that were not directly related to the choice of treatment protocol; for example, differences in surgical treatments, differences in patient selection, differences in outpatient and community factors, differences in monitoring approaches, or other hospital factors. It would be useful to see if there were any substantial differences between centers in overall survival rates (adjusted and/or unadjusted) within a treatment protocol. For example, were the overall survival rates in the IV-only treatment condition comparable across institutions? What was the range of overall survival rates in the IV-only treatment condition across institutions? Wright et al provide a useful examination of the clinical use of IP/IV chemotherapy at six National Comprehensive Cancer Network institutions. I am hopeful that additional data and analysis can be provided by the authors to further clarify their findings.
General Practitioners' Use of Non-Steroidal Anti-Inflammatory Drugs in Tayside and Fife Regions
Authors: J Keys, P H G Beardon, C Jau, C C Lang, D G McDevitt
Journal: Journal of the Royal Society of Medicine (1992)

The objectives of this study were to assess the prescribing of non-steroidal anti-inflammatory drugs (NSAIDs) by general practitioners and to determine their attitudes to problems caused by this class of drugs. The study consisted of two parts. The first was a questionnaire survey among general practitioners in Fife and Tayside, and the second was an analysis of NSAID prescribing over 12 months among the doctors in the Carnoustie Health Centre, using duplicate prescriptions. In the questionnaire survey 61% of the general practitioners responded. The three most preferred drugs were buprofen (56%), naproxen (20%) and mefenamic acid (7%); choice of drug was determined by efficacy and personal experience. Gastrointestinal side effects were most frequently encountered, although there was little consensus amongst respondents as to their management. The duplicate prescription study showed that 14% of patients (1607 individuals) received at least one NSAID prescription in the year of study Ibuprofen (31%), naproxen (20%) and piroxicam (15%) were most frequently prescribed and up to 16% of the patients were co-prescribed a gastroprotective agent; ranitidine (75%) was the most commonly prescribed. Despite the introduction of newere NSAIDs, ibuprofen and naproxen are still the most commonly prescribed drugs. Furthermore, although gastrointestinal side effects are commonly encountered, there is some uncertainty about their management.
Accumulated cyclin B1 by RASSF1A enhances microtubule damaging agent-induced cell death through the mediation of hyperphosphorylated Cdc25C and Cdc2
Authors: Young Mi Whang, Jun Seok Jung, Won Beak You, Jae Sook Sung, Yeul Hong Kim
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3758 

Epidermal growth factor receptor (EGFR)/HER1 is expressed at high levels in ∼20% of breast cancers and correlates with poor disease prognosis. One mechanism that contributes to the generation and maintenance of cancerous cells is the disruption of the cellular cytoskeleton. Microtubule associated proteins (MAPs) are major components of cytoskeleton proteins associated with microtubule assembly and its stabilization. MAP-2, a component of the MAP family, is a marker for neurons and its immunoreactivity has been demonstrated in several neoplasms. We hypothesized that MAP-2 expression is deregulated in EGFR overexpressing breast cancers thus rendering them resistant to conventional therapy. Here we show that loss of MAP-2 expression in breast cancer cells during sustained activation of the EGFR results in resistance to chemotherapeutic drugs. We first evaluated the expression of MAP-2 in a range of breast cancer cells and found that all cell lines expressed varying degrees of MAP-2. However when compared on the basis of their EGFR status, we observed higher expression of MAP-2 in EGFR overexpressing cells than in non-EGFR overexpressing cells both at protein and mRNA levels. To investigate whether the expression of MAP-2 is regulated by the expression of EGFR we selected two cell lines based on their responsiveness to EGF. MCF-7 and MCF-10A cells were challenged with increasing doses of EGF (25-150 ng/ml) and examined for the expression of phosphorylated EGFR. We observed that MCF-7 cells were weakly and MCF-10A cells were strongly stimulated when challenged by increasing doses of EGF. We next examined the expression of MAP-2 in cell lines challenged with EGF and observed that although MAP-2 expression increased with increasing doses of EGF, its expression was almost completely lost at concentrations >100 ng/ml of EGF treatment. This observation suggested a possible mechanism of resistance in breast cancer patients with EGFR overexpression. Based on these observations we conclude that with constant EGF stimulation, cells lose their MAP-2 expression that is required for microtubule stabilization and subsequent cell cycle arrest. In next series of experiments we sought to understand how MAP-2 expression would change in EGFR expressing cells that are challenged with EGF and then treated with microtubule disrupting agents. We found increasing resistance to growth inhibition by docetaxel in cells that were challenged with higher concentrations of EGFR (>50 ng/ml). This suggested that over expression of EGFR signaling in breast cancers could, in fact, be responsible for resistance to therapeutic agents. The loss of MAP-2 expression could have implications in treatment of breast cancers overexpressing the EGFR and exhibiting resistance to conventional therapy.
Tinzaparin vs Warfarin for Acute Venous Thromboembolism—Reply
Authors: Alok A. Khorana, Agnes Y. Y. Lee
Journal: JAMA (2016)

In Reply Ms Maruyama and colleagues question the conclusions of the CATCH trial of tinzaparin vs warfarin for the treatment of cancer-associated venous thromboembolism and raise concerns with the reporting of serious adverse events and mortality. We note that the CATCH trial was the largest study of treatment of acute venous thromboembolism in patients with active malignancy ever conducted and included a diverse study population, thereby increasing its generalizability and validity in the real-world setting. All safety and efficacy analyses were conducted with intention to treat, capturing all 900 randomized patients.
Abstract 9132: Balloon Aortic Valvuloplasty Performed Without Heparin is Associated with a Reduction in Vascular and Bleeding Complications rates
Authors: Florence LeClercq, Delphine Delseny, Erika Nogues, Nicolas Nagot, Jean christophe Macia, Richard Gervasoni, Christophe Piot, FranÇois Roubille
Journal: Circulation (2012)

Objectives: Bleeding and vascular complications are currently the main adverse events associated with balloon aortic valvuloplasty (BAV). We assessed the hypothesis that BAV performed without heparin may be associated with lower complication rates. Methods We conducted a retrospective analysis of all consecutive patients who had undergone BAV in our center between 2008 and 2011. We evaluated 3 groups: patients included between 2008 and 2009 when BAV was performed with large sheaths (10 to 12 French) and injection of unfractionated heparin (UH) (50IU/kg bolus IV) (group 1); patients included after 2009, for whom smaller size sheaths (8 or 9 French) were used, were divided into 2 groups: group 2 (with UH bolus) and group 3 (without UH bolus). We collected all major in-hospital adverse events, bleeding (≥ BARC 3), vascular access complications (including pseudoanerysm or arterio venous fistula) and acute limb ischemia. Results Overall, 140 patients were included in this study. The 3 groups had similar median age (84 years) and preceding lower extremity artery disease (overall n= 36, 27%, p=0.79). Vascular access and bleeding complications were observed in 16 patients (11.4%) and were lower in group 3 compared to group 1 and group 2 (table 1). The use of heparin was associated with an increased risk of vascular access and bleeding complications [relative risk (IC) 2.85 (1.28 to 9.13] whereas absence of heparin did not increase ischemic complications as acute limb ischemia (p=0.82), stroke (1 patient in group 2) or other major in- hospital adverse events (p=0.5). Vascular and bleeding complications were comparable among patients who received heparin with no influence of the used sheath’ s size (table 1). In conclusion, we showed in this study that balloon aortic valvuloplasty performed without heparin is safe and leads to a dramatic reduction of vascular and bleeding events. Although randomization was not used, this marked difference is difficult to explain by confounding factors. .
Intraperitoneal cisplatin and cytarabine in the treatment of refractory or recurrent ovarian carcinoma.
Authors: M Markman, T Hakes, B Reichman, W Hoskins, S Rubin, W Jones, L Almadrones, E L Yordan, J Eriksson, J L Lewis
Journal: Journal of Clinical Oncology (1991)

Preclinical evaluation has suggested impressive concentration-dependent cytotoxic synergy between cisplatin and cytarabine in ovarian carcinoma. To further evaluate the clinical relevance of these observations, 39 patients with refractory or recurrent ovarian carcinoma were entered onto a phase II trial of intraperitoneal (IP) cisplatin (100 to 105 mg/m2 per course) plus cytarabine (600 to 900 mg per course). Treatment was administered over 2 or 3 days for a maximum of five monthly courses, followed by surgical reevaluation in patients without clinical evidence of disease. The 3-day regimen was discontinued secondary to the development of severe thrombocytopenia (five of 12 courses platelets decreased to less than 50,000/mm3). Additional toxicities included abdominal pain (moderate to severe at some time during therapy in 46% of patients), fever without evidence of infection (44%), and bacterial peritonitis (10%). Three patients declined surgical reassessment. Fourteen of 36 (39%; 95% confidence interval [CI], 23% to 55%) assessable patients demonstrated surgically defined responses, including 12 of 23 (52%; 95% CI, 32% to 72%) patients with tumor nodules less than 1 cm in diameter and only two of 13 (15%; 95% CI, 0% to 34%) patients with any lesion greater than 1 cm. There were seven (30%; 95% CI, 11% to 49%) surgically defined complete responses (CRs) in patients with less than 1 cm disease and none in patients with larger tumor nodules. IP cisplatin/cytarabine results in a high surgically defined response rate in patients with minimal residual ovarian carcinoma, but activity is low in patients with bulky intraabdominal disease.
Image-Guided Ablation of Malignant Liver Tumors: Recommendations for Clinical Validation of Novel Thermal and Non-Thermal Technologies - A Western Perspective
Authors: Riccardo Lencioni, Thierry de Baere, Robert C. Martin, Charles W. Nutting, Govindarajan Narayanan
Journal: Liver Cancer (2015)

&lt;b&gt;&lt;i&gt;Background: &lt;/i&gt;&lt;/b&gt;Image-guided ablation is used to treat patients with unresectable malignant hepatic tumors that are limited in number and size, especially hepatocellular carcinoma (HCC) and colorectal hepatic metastases. While radiofrequency ablation (RFA) has been the most popular technique, several alternate options for focal tissue destruction have recently attracted attention. These technologies appear to be able to overcome some specific limitations of RFA. Currently, there is no accepted algorithm for the use of the different techniques for image-guided ablation. &lt;b&gt;&lt;i&gt;Summary: &lt;/i&gt;&lt;/b&gt;A panel of physicians practicing in North America or Europe met to develop a set of recommendations aimed at providing directions for clinical validation of energy-based, thermal and non-thermal image-guided ablation technologies in the treatment of malignant liver tumors. The recommendations were developed through a critical appraisal of potential advantages and disadvantages of each ablation technology, based on experimental findings and available data, as well as on critical considerations for their clinical validation in hepatic tumor treatment from a Western perspective. &lt;b&gt;&lt;i&gt;Key Messages: &lt;/i&gt;&lt;/b&gt;Significant variability appears to exist among the different equipment and devices within each type of technology. A comprehensive understanding of the data and a critical appraisal of the efficacy and safety profile of each ablation system is required. Clinical practice guidelines should include specific information of the recommended techniques and protocols instead of a generic indication of the technology.
Cancer Survivorship Research: The Best Is Yet to Come
Authors: David J. Vaughn, Anna T. Meadows
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.4.888 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11844806 Cancer Survivorship Research: The Best Is Yet to Come David J. VaughnxDavid J. VaughnSearch for articles by this author , Anna T. MeadowsxAnna T. MeadowsSearch for articles by this author Show More Abramson Family Cancer Research Institute, at the University of Pennsylvania Cancer Center; The Children’s Hospital of Philadelphia, Philadelphia, PA https://doi.org/10.1200/JCO.2002.20.4.888 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
‘D’ Excision for Sacrococcygeal Pilonidal Sinus Disease
Authors: C V Mann, R Springall
Journal: Journal of the Royal Society of Medicine (1987)

A new procedure is described for treating pilonidal sinus by an excision and primary suture technique, and the results reported in 30 consecutive patients so treated--28 with chronic sinuses and 2 with an acute abscess. Seventeen patients (Group 1) had had no previous surgery, while 13 (Group 2) had had multiple previous operations. A total of 24 patients (80%) healed after the operation, their mean hospital stay being 16 days. In Group 1 the success rate was 88% with a mean hospital stay of 15 days; in Group 2 the comparable figures were 69% and 17 days. After additional procedures (usually curettage) all patients healed.
Outcomes After a Sequential Clofarabine/Arac-C Chemotherapy Followed By Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) In Pediatrics Patients With JMML Or Primary/Relapsed Refractory AML: A Pilot Study
Authors: Grain Audrey, Anne Sirvent, Marion Strullu, Francoise Mechinaud, Mohamad Mohty, Patrice Chevallier, Thierry Guillaume, Fanny Rialland
Journal: Blood (2013)
Evaluation of antithymocyte globulin pharmacokinetics and pharmacodynamics in children
Authors: Naïm Bouazza, Saik Urien, Bénédicte Neven, Despina Moshous, Jennifer Nisoy, Aurélie Gabrion, Marina Cavazzana, Stéphane Blanche, Jean-Marc Tréluyer, Fabien Touzot
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract 12771: When Auto-Antibodies Potentiate: The Paradoxical Signalling Role of Anti-HSP27 Auto-Antibody Immune Complexes Improves Athero-Protection
Authors: Chunhua Shi, Yongxiang Chen, Yumei Li, Edward R O’Brien
Journal: Circulation (2014)

Introduction: While we recently demonstrated that elevated serum levels of the Heat Shock Protein (HSP27) are athero-protective (JACC 2013), we are cognizant of the presence of anti-HSP27 auto-antibodies in human serum that, intuitively, might attenuate the salutary functions of this protein. Interestingly, we note higher levels of anti-HSP27 auto-antibodies in healthy controls compared to CAD patients.

Hypothesis: Taking an iconoclastic perspective, we posit that auto-antibodies to HSP27 function to enhance the athero-protective effects of HSP27.

Methods / Results: Briefly, we reassessed a number of the mechanistic published parameters of the athero-protective effects of HSP27 but now in the presence of anti-HSP27 auto-antibodies. 

Conclusion: Anti-HSP27 auto-antibodies enhance the athero-protective effects of HSP27 by augmenting internalization of the protein, increasing NF-kB signalling and unexpectedly producing a less inflammatory cellular milieu. Hence, there is the potential to develop HSP27 immunization strategies for the prevention and/or treatment of atherosclerosis.