tbuckley/cabot-search huggingface dataset:
Risk of venous and arterial thromboembolic events in patients with metastatic breast cancer treated with bevacizumab: A meta-analysis.
Authors: V. Calvo, N. Ramirez, C. Saura, M. Vidal, A. Velasco, A. Llombart-Cussac, H. Cortes-Funes, D. Miles, J. Baselga, J. Cortes
Journal: Journal of Clinical Oncology (2010)

1043 Background: The use of bevacizumab, a vascular endothelial growth factor inhibitor, has been associated with an increase in risk of arterial thromboembolic events (ATE) and venous thromboembolic events (VTE) in some clinical trials. The aim of this systematic review and meta-analysis of randomized trials was to assess the overall risk of both grade 3-5 ATE and VTE associated with bevacizumab in patients with metastatic breast cancer (MBC). Methods: We selected all randomized phase III trials which compared chemotherapy with or without bevacizumab in MBC. For the analysis, we used a fixed-effects and random effects models to calculate the pooled event-based relative risk ratios (RR) with 95% confidence interval (CI). The Cochran's Q statistic and I2 statistics were first calculated to assess the heterogeneity among the proportions of the included trials. For this study, we collected all grade 3-5 events reported in these trials. We analyzed the overall RR for vascular events (ATE + VTE) because differentiation between ATE and VTE was not clearly defined in some studies. Results: Five trials were included in the meta-analysis: E2100, AVADO, RIBBON-1, RIBBON-2 and AVF-2119g. In total, 2,368 patients received bevacizumab-based therapy and 1,416 chemotherapy alone. Vascular events were reported in 72 and 41 patients, respectively. There was a tendency for heterogeneity (p=0.082) considering all trials, so both the fixed-effects and the random-effects models were used. Patients treated with bevacizumab-containing regimens had a RR for vascular events of 1.095 (95% CI, 0.747-1.606; p=COPY fixed-model) and 1.066 (95% CI, 0.596-1.908; p=0.829) (random-model). Conclusions: Although patients with MBC treated with chemotherapy present a remarkable risk of vascular events, the addition of bevacizumab to chemotherapy did not increase the risk of VTE and ATE in this patient population. No significant financial relationships to disclose.
The relation between alcohol problems and the anxiety disorders
Authors: M G Kushner, K J Sher, B D Beitman
Journal: American Journal of Psychiatry (1990)

The idea that people suffering from anxiety have a proclivity to consume alcohol to relieve their symptoms is supported by reports showing high comorbidity rates of alcohol and anxiety problems. The authors reviewed relevant epidemiologic surveys, family studies, and field studies and conclude that the relationship between alcohol problems and anxiety appears to be variable among the anxiety disorders. In agoraphobia and social phobia, alcohol problems appear more likely to follow from attempts at self-medication of anxiety symptoms, but panic disorder and generalized anxiety disorder may be more likely to follow from pathological alcohol consumption. Simple phobia does not appear to be related to alcohol problems in any meaningful way.
<i>PRDM16</i> (1p36) translocations define a distinct entity of myeloid malignancies with poor prognosis but may also occur in lymphoid malignancies.
Authors: F. P. Duhoux, G. Ameye, K. Bahloula, M. Mozziconacci, S. Laibe, I. Wlodarska, L. Michaux, P. Talmant, S. Richebourg, E. Lippert, F. Speleman, C. Herens, S. Struski, S. Raynaud, N. Nadal, M. Lafage, N. Auger, J. Libouton, J. Demoulin, H. A. Poirel
Journal: Journal of Clinical Oncology (2011)

6531 Background: The PRDM16 gene on chromosome 1p36 is reported to be rearranged in sparse cases of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with t(1;3)(p36;q21). Methods: We report the largest series to date of 39 cases of hematological malignancies with PRDM16 alterations out of a series of 120 cases with 1p36 rearrangements screened by fluorescence in situ hybridization (FISH). Results: PRDM16 was found to be rearranged with the RPN1 locus (3q21) in 30 cases and with other loci in 9 cases. The PRDM16 rearrangements are not restricted to myeloid malignancies, as we characterized two cases of lymphoid proliferation with translocations involving PRDM16. We identified novel translocation partners of PRDM16, including transcription factors ETV6 and IKZF1. This is the first report of a translocation involving IKZF1 in a myeloid malignancy. Translocations involving PRDM16 are original in that they lead to its over-expression through 2 different mechanisms (transcriptional upregulation by promoter switch or formation of a chimeric gene). Survival data interestingly suggest that patients with AML/MDS and PRDM16 translocations have a poor prognosis whatever the partner gene, RPN1 versus others. The 32 patients with available survival data had a poor prognosis, as the median overall survival (OS) was 18 months [95% CI, 6 to 31 months] and 5-year OS was 25.7% [95% CI, 8.4-43.0%]. Conclusions: Our study confirms that AML/MDS with PRDM16 translocations share numerous characteristics with AML/MDS associated with translocations involving EVI1 (3q26), which is another transcription factor with a PR domain. If this poor prognosis is confirmed, we propose the addition of a “PRDM16”-entity in the WHO classification of AML/MDS, as is already the case for AML with EVI1 translocations. This new entity could later be broadened to a “PR domain gene rearrangements” subgroup to encompass the AML with EVI1 translocations.
Abstract 14385: c-Src Tyrosine Kinase Mediates the Effect of Mitochondrial Oxidative Stress on Gap Junctional Remodeling and Ventricular Tachycardia
Authors: Ali A Sovari, Euy-Myoung Jeong, Elena Dolmatova, Alex Tan, Shadi Zandieh, Man Liu, Gu Lianzhi, Divya Arasu, Marcelo G Bonini, Heather S Duffy, Samuel C Dudley
Journal: Circulation (2011)

Introduction:  Reactive oxygen species (ROS) are thought to play a central role in the genesis of arrhythmia. Mitochondria are the major source of cardiac ROS. Studies suggest ROS activates c-Src tyrosine kinase, which reduces Cx43 at the gap junctions by competing with Cx43 for binding to Zonula Occludence-1. We sought to determine the role of mitochondria oxidative stress in the genesis of ventricular arrhythmia in a manganese superoxide dismutase (MnSOD) knock out mouse model. We hypothesized that excess ROS in this model would activate c-Src and reduce Cx43 levels and that inhibition of c-Src would prevent Cx43 remodeling and the risk of arrhythmia.   Method:  Wild type and MnSOD+/- mice with and without treatment with the c-Src inhibitor PP1 (1.5 mg/kg IP three times/week x 2 weeks) were studied. Western blotting and immunohistochemistry staining for Cx43 were performed. Mitochondrial ROS was measured by confocal microscopy and flow cytometry from isolated cardiomyocytes using mitoSOX red. In-vivo epicardial mapping was performed using a 30-channel bipolar electrode array with 1 mm resolution.   Results:  MnSOD+/- myocytes showed a 66% increase in the level of mitochondrial ROS compared to the control (by mitoSOX, P    Conclusion:  Mitochondrial oxidative stress is associated with increased risk of ventricular arrhythmia and a significant reduction in Cx43 at the gap junctions, providing the impaired conduction substrate for reentry arrhythmia. c-Src tyrosine kinase seems to mediate the effect of mitochondrial ROS on Cx43 and may be an effective antiarrhythmic target in oxidative stress states.
TNF-a induces cPLA2 expression via Jak2/PDGFR-dependent Elk-1/p300 activation in human lung epithelial cells
Authors: Chuen-Mao Yang
Journal: European Respiratory Journal (2014)

Cytosolic phospholipase A2 (cPLA2) plays a pivotal role in mediating agonist-induced arachidonic acid (AA) release for prostaglandin (PG) synthesis during inflammation triggered by tumor necrosis factor-a (TNF-a). However, the mechanisms underlying TNF-a-induced cPLA2 expression in human lung epithelial cells (HPAEpiCs) were not completely understood. Here, we demonstrated that TNF-a induced cPLA2 mRNA and protein expression, promoter activity, and PGE2 secretion in HPAEpiCs. TNF-a-inducedresponses were inhibited by the inhibitor of Jak2 (AG490), PDGFR (AG1296), PI3K (LY294002), or MEK1/2 (PD98059) and transfection with siRNA of Jak2, PDGFR, Akt, or p42. TNF-a also stimulated Jak2, PDGFR, Akt, and p42/p44 MAPK phosphorylation, which were attenuated by their respective inhibitors. TNF-a stimulated Akt activation via a Jak2/PDGFR pathway. In addition, TNF-a-induced p42/p44 MAPK phosphorylation was reduced by AG1296 or LY294002. Moreover, TNF-a could induce Akt and p42/p44 MAPK translocation from the cytosol into the nucleus, which was inhibited by AG490, AG1296, or LY294002. Finally, TNF-a-stimulated Elk-1 phosphorylation was reduced by LY294002 or PD98059. We also observed that TNF-a time-dependently induced p300/Elk-1 and p300/Akt complex formation, which was reduced by AG490, AG1296, or LY294002. The activity of cPLA2 protein up-regulated by TNF-a was reflected on the PGE2 release which was reduced by AG490, AG1296, LY294002, or PD98059.These results demonstrated that TNF-a-induced cPLA2 expression and PGE2 release was mediated through a Jak2/PDGFR/PI3K/Akt/p42/p44 MAPK/Elk-1 pathway in HPAEpiCs.
Recommendation of adjuvant chemotherapy and trastuzumab in older adults with HER2-positive breast cancer: A survey of oncologists
Authors: S. K. Pal, A. Naeim, F. L. Wong, C. T. Chung, S. Bhatia, J. Mortimer, G. Somlo, S. Hurvitz, D. Villaluna, A. Hurria
Journal: Journal of Clinical Oncology (2009)

9547 Background: Though substantial evidence supports the use of adjuvant trastuzumab in patients with HER2-positive breast cancer, a lesser amount of data is available to guide use of this therapy in older adults. The objective of the current study is to understand how patient age and health status impact the oncologists' decision to recommend adjuvant therapy in older women with HER2-positive breast cancer. Methods: Medical oncologists (n=151) participated in an online survey comprised of case scenarios with patients of varying age (70, 75, 80, 85) and health status (good, average, poor) with a T2(4 cm) N2(4+ LN) ER(-), HER2(+) breast cancer. Oncologists could offer the hypothetical patient treatment with chemotherapy and trastuzumab, chemotherapy alone, trastuzumab alone, or no therapy. The influence of age and health status on treatment recommendations was assessed using a generalized linear mixed-effects model. Results: With increasing age and deterioration of health status, the recommendation for chemotherapy with trastuzumab decreased (P&lt;0.0001 for both). In contrast, recommendation for trastuzumab alone or no therapy increased with advancing age (P&lt;0.0001 for both) and deteriorating health status (P&lt;0.0035 and P=0.059, respectively). Chemotherapy alone was not frequently recommended, irrespective of age or health status. Conclusions: Given the relative dearth of evidence-based data for adjuvant treatment of HER2-positive breast cancer in older adults of varying health, oncologists recommend a diverse array of therapeutic approaches for this subgroup. Increasing age and declining health status lead to more frequent recommendation of trastuzumab alone or no therapy, and less frequent recommendation of chemotherapy with trastuzumab. [Table: see text] [Table: see text]
Atypical presentation in adults in the largest community outbreak of leishmaniasis in Europe (Fuenlabrada, Spain)
Authors: L Horrillo, J V San Martín, L Molina, E Madroñal, B Matía, A Castro, J García-Martínez, A Barrios, N Cabello, I G Arata, J M Casas, J M Ruiz Giardin
Journal: Clinical Microbiology and Infection (2014)
Sildenafil Treatment of Women With Antidepressant-Associated Sexual Dysfunction
Authors: H George Nurnberg, Paula L Hensley, Julia R Heiman, Harry A Croft, Charles Debattista, Susan Paine
Journal: JAMA (2008)

Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women.To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors (SRIs) in women.An 8-week prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 1, 2003, and January 1, 2007, at 7 US research centers that included 98 previously sexually functioning, premenopausal women (mean [SD] age 37.1 [6] years) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction.Forty-nine patients were randomly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity.The primary outcome measure was the mean difference in change from baseline to study end (ie, lower ordinal score) on the Clinical Global Impression sexual function scale. Secondary measures included the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale-female version, the University of New Mexico Sexual Function Inventory-female version, a sexual activity event log, and the Hamilton Depression Rating scale. Hormone levels were also assessed.In an intention-to-treat analysis, women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 (95% confidence interval [CI], 1.6-2.3) compared with those taking placebo (1.1; 95% CI, 0.8-1.5), with a mean end point difference of 0.8 (95% CI, 0.6-1.0; P = .001). Assigning baseline values carried forward to the 22% of patients who prematurely discontinued resulted in a mean end point in the sexual function score of 1.5 (95% CI, 1.1-1.9) among women taking sildenafil compared with 0.9 (95% CI, 0.6-1.3) among women taking placebo with a mean end point difference of 0.6 (95% CI, 0.3-0.8; P = .03). Baseline endocrine levels were within normal limits and did not differ between groups. The mean (SD) Hamilton scores for depression remained consistent with remission in both groups (4.0 [3.6]; P = .90). Headache, flushing, and dyspepsia were reported frequently during treatment, but no patients withdrew because of serious adverse effects.In this study population, sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects.clinicaltrials.gov Identifier: NCT00375297.
National outbreak of Salmonella Enteritidis phage type 14b in England, September to December 2009: case–control study
Authors: K Janmohamed, D Zenner, C Little, C Lane, J Wain, A Charlett, B Adak, D Morgan
Journal: Eurosurveillance (2011)

Binary file ES_Abstracts_Final_ECDC.txt matches
How Accurate is Urine Cytology?
Authors: Marigold Curling, G Broome, W F Hendry
Journal: Journal of the Royal Society of Medicine (1986)

Exfoliative urinary cytology was performed on 260 new cases of histologically proven urothelial cancer. The site, size, shape and histological grade of the tumours were documented, and they were classified by the TNM system. Overall, urine cytology was positive in 135 (52%), suspicious in 28 (11%) and negative in 97 (38%) cases. Malignant cells were found most often when the urothelial tumours were large, papillary and solid, moderately or poorly differentiated and invasive (T2-4). Most upper tract tumours and those situated in bladder diverticula had positive urinary cytology. This study confirms that exfoliative urinary cytology is useful in detecting the more malignant bladder tumours including in-situ carcinoma, and other tumours in less accessible parts of the urinary tract.
Multilayered, Hyaluronic Acid‐Based Hydrogel Formulations Suitable for Automated 3D High Throughput Drug Screening of Cancer‐Stromal Cell Cocultures
Authors: Brian J. Engel, Pamela E. Constantinou, Lindsey K. Sablatura, Nathaniel J. Doty, Daniel D. Carson, Mary C. Farach‐Carson, Daniel A. Harrington, Thomas I. Zarembinski
Journal: Advanced Healthcare Materials (2015)

Validation of a high-throughput compatible 3D hyaluronic acid hydrogel coculture of cancer cells with stromal cells. The multilayered hyaluronic acid hydrogels improve drug screening predictability as evaluated with a panel of clinically relevant chemotherapeutics in both prostate and endometrial cancer cell lines compared to 2D culture. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Exaggerated IDO1 expression and activity in Langerhans cells from patients with atopic dermatitis upon viral stimulation: a potential predictive biomarker for high risk of Eczema herpeticum
Authors: A. Staudacher, T. Hinz, N. Novak, D. von Bubnoff, T. Bieber
Journal: Allergy (2015)

Atopic dermatitis (AD) is a heterogenous and highly complex disease characterized by an increased microbial colonization. For unknown reasons, a subgroup of patients with AD develops Eczema herpeticum (EH), a severe viral complication due to spreading of herpes simplex virus (HSV). Indoleamine 2,3-dioxygenase (IDO1) is a tryptophan (Trp)-catabolizing enzyme which is assumed to be instrumental in the antibacterial and antiviral defence mechanisms.Comparative investigation of the IDO1 expression and activity in freshly isolated monocytes, plasmacytoid DC (pDC) and in vitro-generated Langerhans cells (LC) obtained from AD patients with HSV infections and EH and nonatopic controls.We demonstrate an increase in Trp degradation in the serum of patients during acute EH episodes. Circulating pDC from patients with history of EH display an increased IDO1 expression. An increased Trp degradation is detected in the supernatants of circulating monocytes from AD patients with acute EH. Mature LC from AD patients with history of EH and with acute EH display an increased IDO1 expression and activity, respectively. In LC from patients with history of EH, viral signals induce an exaggerated IDO1 expression and activity.IDO1 expression and activity in LC seem to be involved in the pathophysiology of EH in AD and could represent a predictive biomarker for patients with risk to develop EH and other viral complications.
On the spot treatment needed
Authors: F A I Riordan, O Marzouk, A P J Thomson, J A Sills, C A Hart
Journal: BMJ (1994)

damage in both clinical studies and animal models of meningitis.Diagnosing meningococcal meningitis in the community may be extremely difficult.General practitioners should not give dexamethasone in the home as many patients would be treated inappropriately.There have been no placebo controlled trials of dexamethasone to support its use in meningococcal septic shock, but trials of steroids in adult patients with other forms of Gram negative sepsis have shown no benefit.3We stand by our recent recommendation that general practitioners should give parenteral anti- biotics before admission to all patients suspected of having meningococcal disease.4In all five health districts that participated in a study there was a trend towards increased survival when benzylpenicillin was given before admission, with greatest benefit in the patients who were most ill- those with a haemorrhagic rash.5We therefore endorse the chief medical officer's advice.During the winter general practitioners should ensure that they carry benzylpenicillin among their emergency drugs.If they see a patient in whom they suspect meningococcal disease, especially if a rash is present, they should give a dose, ideally intravenously, before urgently arranging admission to hospital.Admitting paediatricians can remind general practitioner colleagues over the telephone of the value of this treatment.Whether or not benzylpenicillin is given, immediate transfer to hospital is the next urgent priority.
Pakistan authorities trade blame as heatwave deaths exceed 800
Authors: J. Clark
Journal: BMJ (2015)

Pakistan has declared a state of emergency as the death toll from an unprecedented heatwave exceeded 800. The declaration came amid criticism of the country’s management of the crisis and power failures that had prevented people from using water pumps, electric fans, and air conditioning.

Temperatures reached 44°C in the past week, which coincided with Ramadan, the holy month during which Muslims are required to fast daily until sundown. Most of those who have died …
Empirical Comparison of Commonly Used Measures to Evaluate Pain Treatment in Cancer Patients With Chronic Pain
Authors: Rianne de Wit, Frits van Dam, Huda Huijer Abu-Saad, Simone Loonstra, Linda Zandbelt, Anneke van Buuren, Karin van der Heijden, Gerleen Leenhouts
Journal: Journal of Clinical Oncology (1999)

PURPOSE: There is limited consensus about the most appropriate measures to evaluate the adequacy of pain treatment in cancer patients. There are no known studies describing commonly used measures to simultaneously evaluate the adequacy of cancer pain treatment. The purpose of this study was to compare measures, which are frequently reported in the literature, to assess the adequacy of pain treatment in cancer patients with chronic pain. This study was part of a randomized controlled trial. PATIENTS AND METHODS: In total, 313 cancer patients with a pain duration of at least 1 month were evaluated. After a baseline measure in the hospital, patients were followed up at 2, 4, and 8 weeks after discharge at home. Adequacy of cancer pain treatment was evaluated by means of four different types of outcome measures. The four types included three pain intensity markers based on patients' pain intensity, a pain relief scale, a patient satisfaction scale, and three pain management indexes that related patients' pain medication with pain intensity. RESULTS: The proportion of inadequately treated pain patients varied extremely. Depending on the outcome measure used, the percentage of inadequately treated patients ranged from 16% to 91%. The choice of measure, rather than pain treatment itself, determined the proportion of inadequacy. CONCLUSION: There is an urgent need for consensus about how to evaluate the effectiveness of pain treatment. Studies that evaluate adequacy of pain treatment should be interpreted with caution. Further research is necessary to elucidate the validity and reliability of outcome measures simultaneously.