tbuckley/cabot-search huggingface dataset:
Abstract 14048: Diagnostic MRI Criteria for Identification of Intra-Mural Hematoma and Prediction of High Likelihood of Aortic Healing After Type B Acute Aortic Syndromes
Authors: Adeline Schwein, Matthew Bennett, Mohammad A Khan, Faisal Nabi, Dipan J Shah, Jean Bismuth
Journal: Circulation (2016)

Introduction:  Type B acute aortic syndromes (AAS) encompasses aortic dissection (AD) and intramural hematoma (IMH), whose diagnostic, evolution and treatment are subject to many controversies among cardio-vascular specialists. The aim of our study was to assess the ability of specific diagnostic MRI criteria to differentiate AD from IMH and predict optimal aortic remodeling following AAS.   Methods:  In this retrospective study, we included all patients presenting at our institution between 2008 and 2015 with type B AAS and who had a diagnostic MRI following their admission. Four diagnostic MRI criteria were established to identify IMH, which was hypothesized to predict high likelihood of aortic healing, defined as false lumen (FL)/mural hematoma (MH) shrinking and true lumen expansion over time: - No visualized entry tear - No contrast uptake in the FL/MH on first pass angiographic run - No contrast uptake in the FL/MH on equilibrium phase T1 weighted sequence - Less than 2.5 mm of maximal septal mobility on a cine acquisition. On each patient’s diagnostic MRI and last follow-up imaging study, we computed the volume of: 1) FL/MH, 2) total aorta, and 3) true lumen. Using paired t-test analysis, we compared the evolution of these volumes according to the presence or absence of the afore-mentioned MRI criteria.   Results:  Thirty seven patients were included in our study. Seven patients had all MRI criteria positive (IMH group), 30 had one or more negative criteria (AD group). There was no difference between both groups concerning patient gender, age or delay between onset of symptoms, diagnostic and follow up imaging study. 17 patients had a follow up imaging study (MRI or CT) after a mean (±SD) follow up of 14.2 ± 4 months: 6 patients in IMH group and 11 in AD group. FL/MH volume decrease and true lumen volume increase were statistically significant over time in IMH group (p = 0.043 and p = 0.029 respectively) In AD group, follow-up imaging study showed a significant increase of FL/MH volume (p = 0.016), without significant increase of true lumen.   Conclusion:  We established 4 diagnostic MRI criteria that aid in identification of IMH and are associated with high likelihood of aortic healing after type B AAS. This may have an impact on therapeutic decisions and imaging follow-up protocols.
Should This Patient Receive Aspirin?
Authors: Risa B. Burns, Kelly Graham, Mandeep S. Sawhney, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2017)

Aspirin exerts antiplatelet effects through irreversible inhibition of cyclooxygenase-1, whereas its anticancer effects may be due to inhibition of cyclooxygenase-2 and other pathways. In 2009, the U.S. Preventive Services Task Force endorsed aspirin for primary prevention of cardiovascular disease. However, aspirin's role in cancer prevention is still emerging, and no groups currently recommend its use for this purpose. To help physicians balance the benefits and harms of aspirin in primary disease prevention, the Task Force issued a guideline titled, “Aspirin Use for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer” in 2016. In the evidence review conducted for the guideline, cardiovascular disease mortality and colorectal cancer mortality were significantly reduced among persons taking aspirin. However, there was no difference in nonfatal stroke, cardiovascular disease mortality, or all-cause mortality, nor in total cancer mortality, among those taking aspirin. Aspirin users were found to be at increased risk for major gastrointestinal bleeding. In this Beyond the Guidelines, the guideline is reviewed and 2 experts discuss how they would apply it to a 57-year-old man considering starting aspirin for primary prevention. Our experts review the data on which the guideline is based, discuss how they would balance the benefits and harms of aspirin therapy, and explain how they would incorporate shared decision making into clinical practice.
Outcomes of Transanal Endoscopic Microsurgery (TEMS) for the Management of Adenomatous and Dysplastic Rectal Lesions in a Tertiary Referral Centre
Authors: D. Vukanic, P. Waters, A. Kiernan, P. Tsakkos, M. Lockhart, J. O'Riordan, P. Neary, D. Kavanagh
Journal: International Journal of Surgery (2017)
Pannexin 1 Channels as an Unexpected New Target of the Anti-Hypertensive Drug Spironolactone
Authors: Miranda E. Good, Yu-Hsin Chiu, Ivan K.H. Poon, Christopher B. Medina, Joshua T. Butcher, Suresh K. Mendu, Leon J. DeLalio, Alexander W. Lohman, Norbert Leitinger, Eugene Barrett, Ulrike M. Lorenz, Bimal N. Desai, Iris Z. Jaffe, Douglas A. Bayliss, Brant E. Isakson, Kodi S. Ravichandran
Journal: Circulation Research (2017)

Rationale: Resistant hypertension is a major health concern with unknown cause. Spironolactone is an effective antihypertensive drug, especially for patients with resistant hypertension, and is considered by the World Health Organization as an essential medication. Although spironolactone can act at the mineralocorticoid receptor (MR; NR3C2), there is increasing evidence of MR-independent effects of spironolactone. Objective: Here, we detail the unexpected discovery that Panx1 (pannexin 1) channels could be a relevant in vivo target of spironolactone. Methods and Results: First, we identified spironolactone as a potent inhibitor of Panx1 in an unbiased small molecule screen, which was confirmed by electrophysiological analysis. Next, spironolactone inhibited α-adrenergic vasoconstriction in arterioles from mice and hypertensive humans, an effect dependent on smooth muscle Panx1, but independent of the MR NR3C2. Last, spironolactone acutely lowered blood pressure, which was dependent on smooth muscle cell expression of Panx1 and independent of NR3C2. This effect, however, was restricted to steroidal MR antagonists as a nonsteroidal MR antagonist failed to reduced blood pressure. Conclusions: These data suggest new therapeutic modalities for resistant hypertension based on Panx1 inhibition.
Staphylococcus aureus et MRSA dans les hôpitaux autrichiens, 1995
Authors: W Koller
Journal: Eurosurveillance (1997)

En 1996, le ministere federal autrichien de la sante et de la protection des consommateurs demanda a 327 hopitaux de soins intensifs et autres institutions de soins de rapporter le nombre de patients hospitalises en 1995 qui avaient eu une culture positive a Staphylococcus aureus (SA). Il demanda egalement la proportion de SA resistantes a la methicilline (MRSA) et de EMRSA ( MRSA epidemique caracterisee par un profil particulier de multiresistance aux antibiotiques*) ainsi que les sites ou les souches avaient ete isolees.
Contact Precautions for Multidrug-Resistant Organisms
Authors: Lance R. Peterson
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Individualized treatment approaches for Langerhans cell histiocytosis
Authors: E. Roider, C. Signer, B. Fehrenbacher, G. Metzler, M. Schaller, J. Kamarachev, K. Kerl, S. Balabanov, W. Jochum, W. Hoetzenecker, A. Cozzio, L.E. French, R. Dummer, E. Guenova
Journal: British Journal of Dermatology (2017)

Langerhans cell histiocytosis (LCH) belongs to the rare histiocytic disorders, and has an estimated incidence of 1-2 cases per million adults [1]. Myeloid dendritic cells that express the same antigens (CD1a, CD207) as epidermal Langerhans cell seem to be the precursor cells for LCH [2]. Clinical presentation of patients with LCH may vary in site and extent of involvement. In 45% of patients LCH manifests as a multisystem disease including 77% bone, 39% skin, 19% lymph node, 16% liver, 13% spleen, 13% oral mucosa, 10% lung, and 6% CNS involvement [3]. This article is protected by copyright. All rights reserved.
Abstract 52: Dynamic rewiring of apoptotic signaling networks by combined EGFR/FRGR inhibition enhances killing of head and neck squamous tumor by DNA damage
Authors: Yogesh Dayma, Michael B. Yaffe
Journal: Clinical Cancer Research (2017)

Abstract We have previously shown that a subset of triple-negative breast cancers can be dramatically sensitized to killing by DNA-damaging chemotherapy by time-staggered inhibition of EGFR. This sensitization effect results from dynamic re-wiring of apoptotic signaling pathways to engage a caspase-8-dependent cell death mechanism (Figure 1). Here we explored whether combined EGFR and/or FGFR inhibition could enhance the killing of head and neck squamous cell cancers by DNA damaging treatments through a similar re-wiring mechanism. The epidermal growth factor receptor (EGFR) and FGFR pathways are two of the most dysregulated molecular pathways in human head-and-neck squamous cell carcinoma (HNSCC). Despite overexpression in approximately 90% of HNSCC tumors, EGFR inhibitors alone have not exerted a major therapeutic impact on tumor response or patient survival. A recent study provides evidence that the insensitivity of the majority of HNSCC to EGFR inhibitors is mediated by dominant activity of alternative receptor tyrosine kinase (RTK) systems such as FGFR signaling (Clinical Cancer Research 2011). We have found that time-staggered administration of either EGFR inhibitors, or FGFR inhibitors, can dramatically enhance the apoptotic response of HNSCCs to DNA damage from doxorubicin. Importantly, combined inhibition of both the EGFR and FGFR pathways was more effective than inhibition of either pathway alone, at inducing sensitization to cytotoxic chemotherapy through dynamic network re-rewiring. Enhanced cell death by dual EGFR/FGFR inhibition and subsequent genotoxic injury results from greater activation of Caspase-8 than that seen by either EGFR or FGFR inhibitors alone. This enhanced Caspase-8 acitivty, together with Caspase-9 activation, accounts for the majority of apoptotic death. Our data further suggest that Src family kinases are a critical downstream node of EGFR/FGFR activity since treatment of HNSCC cell lines with Src kinase inhibitors resulted in similar sensitization to doxorubicin treatment. In summary, our data extend the utility of therapeutic dynamic rewiring for the targeting of tumors with redundant receptor signaling pathways as well as their critical downstream nodes. Citation Format: Yogesh Dayma, Michael B. Yaffe. Dynamic rewiring of apoptotic signaling networks by combined EGFR/FRGR inhibition enhances killing of head and neck squamous tumor by DNA damage [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 52.
Effect of High-Intensity Treadmill Exercise on Motor Symptoms in Patients With De Novo Parkinson Disease
Authors: Margaret Schenkman, Charity G. Moore, Wendy M. Kohrt, Deborah A. Hall, Anthony Delitto, Cynthia L. Comella, Deborah A. Josbeno, Cory L. Christiansen, Brian D. Berman, Benzi M. Kluger, Edward L. Melanson, Samay Jain, Julie A. Robichaud, Cynthia Poon, Daniel M. Corcos
Journal: JAMA Neurology (2017)

Parkinson disease is a progressive neurologic disorder. Limited evidence suggests endurance exercise modifies disease severity, particularly high-intensity exercise.To examine the feasibility and safety of high-intensity treadmill exercise in patients with de novo Parkinson disease who are not taking medication and whether the effect on motor symptoms warrants a phase 3 trial.The Study in Parkinson Disease of Exercise (SPARX) was a phase 2, multicenter randomized clinical trial with 3 groups and masked assessors. Individuals from outpatient and community-based clinics were enrolled from May 1, 2012, through November 30, 2015, with the primary end point at 6 months. Individuals with idiopathic Parkinson disease (Hoehn and Yahr stages 1 or 2) aged 40 to 80 years within 5 years of diagnosis who were not exercising at moderate intensity greater than 3 times per week and not expected to need dopaminergic medication within 6 months participated in this study. A total of 384 volunteers were screened by telephone; 128 were randomly assigned to 1 of 3 groups (high-intensity exercise, moderate-intensity exercise, or control).High-intensity treadmill exercise (4 days per week, 80%-85% maximum heart rate [n = 43]), moderate-intensity treadmill exercise (4 days per week, 60%-65% maximum heart rate [n = 45]), or wait-list control (n = 40) for 6 months.Feasibility measures were adherence to prescribed heart rate and exercise frequency of 3 days per week and safety. The clinical outcome was 6-month change in Unified Parkinson's Disease Rating Scale motor score.A total of 128 patients were included in the study (mean [SD] age, 64 [9] years; age range, 40-80 years; 73 [57.0%] male; and 108 [84.4%] non-Hispanic white). Exercise rates were 2.8 (95% CI, 2.4-3.2) days per week at 80.2% (95% CI, 78.8%-81.7%) maximum heart rate in the high-intensity group and 3.2 (95% CI, 2.8-3.6; P = .13) days per week at 65.9% (95% CI, 64.2%-67.7%) maximum heart rate in the moderate-intensity group (P < .001). The mean change in Unified Parkinson's Disease Rating Scale motor score in the high-intensity group was 0.3 (95% CI, -1.7 to 2.3) compared with 3.2 (95% CI, 1.4 to 5.1) in the usual care group (P = .03). The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group. Anticipated adverse musculoskeletal events were not severe.High-intensity treadmill exercise may be feasible and prescribed safely for patients with Parkinson disease. An efficacy trial is warranted to determine whether high-intensity treadmill exercise produces meaningful clinical benefits in de novo Parkinson disease.clinicaltrials.gov Identifier: NCT01506479.
Cryopreservation: Hydrogel Encapsulation Facilitates Rapid‐Cooling Cryopreservation of Stem Cell‐Laden Core–Shell Microcapsules as Cell–Biomaterial Constructs (Adv. Healthcare Mater. 23/2017)
Authors: Gang Zhao, Xiaoli Liu, Kaixuan Zhu, Xiaoming He
Journal: Advanced Healthcare Materials (2017)
Abstract P233: Prevalence of Healthy Lifestyles by Country of Origin and Level of Acculturation among Diverse Hispanic/Latino Men and Women: Results from the Hispanic Community Health Study / Study of Latinos
Authors: Juan P Bustos, Amber Pirzada, Thanh Huyen T Vu, Aida Giachello, Linda Van Horn, Martha L Daviglus
Journal: Circulation (2013)

Introduction: Hispanics/Latinos experience a high burden of CVD risk factors, particularly diabetes and obesity, and CVD is a leading cause of death in this ethnic group. Individual healthy lifestyle factors (HLF) - ideal weight, healthy diet, moderate alcohol consumption and physical activity, and non-smoking are associated with favorable levels of CVD risk factors. Little data exist on prevalence of combined HLF among diverse Hispanics/Latinos with varying levels of acculturation. Hypothesis: Prevalence of all 5 HLF varies among Hispanic/Latino men and women of different backgrounds and levels of acculturation. Number of HLF will be higher with lower acculturation. Methods: HCHS/SOL participants (6164 men, 9356 women) ages 18-74. Five HLF were considered: BMI[[Unable to Display Character: &amp;#706;]]25kg/m2, healthy diet (highest sex-specific 40% of Alternate Healthy Eating Index), moderate physical activity (moderate-vigorous activity [[Unable to Display Character: &amp;#707;]]150 min/week; or vigorous activity [[Unable to Display Character: &amp;#707;]] 75 min/week), not currently smoking, and moderate alcohol consumption (men ≤30g/day; women ≤15g/day). Measures of acculturation included nativity, years resided in the US, and language preference. Prevalence of HLF was examined by gender, Hispanic/Latino background, and level of acculturation. Results: Prevalence of having all 5 HLF was low, i.e., only 3.0% in men and 4.4% in women; 18.3% and 22.0% had any four HLF. Among women, prevalence of 5 HLF was highest among Mexicans (7% of 3910), followed by Central (3.8% of 993) and South Americans (3.8% of 609), Cubans (2.3% of 1177), Dominicans (1.6% of 913), and Puerto Ricans (0.7% of 1497). Proportion of those US-born or who had resided in the US [[Unable to Display Character: &amp;#707;]]10 years was lower with higher number of HLF; proportion preferring Spanish was higher with higher number of HLF. For example, 17% of women with 5HLF (n=354) were US-born, vs. 40% of those with 0-1 HLF (n=444, all p-values: [[Unable to Display Character: &amp;#706;]]0.0001). Among men, Mexicans had highest prevalence of all 5 HLF (4.7% of 2333), followed by Central Americans (4.4% of 648), South Americans (2.4% of 411), Dominicans (1.5% of 474), Puerto Ricans (1.3% of 1057), and Cubans (1.2% of 1036). Among all men, there were no differences in number of HLF by levels of acculturation (p-values: 0.0007-0.019). Conclusions: Having all 5 HLF was low among all Hispanics/Latinos although this differed by Hispanic/Latino background. For women only, greater acculturation was associated with lower prevalence of having all 5 HLF; the lower the acculturation the higher the number of HLF. Public health efforts targeting adverse lifestyles are required to prevent cardiovascular risk factors and disease among Hispanic/Latinos.
Abstract #5649: Pharmakokinetic/phamacodynamic relationship of the HSP90 inhibitor NVP-AUY922 in human xenografts and patients in a clinical Phase I trial
Authors: Michael Jensen, Susan Ide, Josef Brueggen, Joseph Schoepfer, Xiaofeng Wang, Cornelia Quadt, Carlos Garcia-Echeverria
Journal: Cancer Research (2009)

NVP-AUY922 is a synthetic inhibitor of Heat Shock Protein 90 (HSP90) ATPase activity. HSP90 is a ubiquitously expressed molecular chaperone which plays an important role in the conformational maturation and activation of a large number of \#8220;client\#8221; proteins that have been implicated in oncogenesis. HSP90 has attracted considerable interest as a therapeutic target for cancer treatment since HSP90 ATPase inhibition induces the simultaneous degradation of multiple oncogenic proteins. Antitumor activity and tolerability of NVP-AUY922 was determined in preclinical cancer animal models. The pharmacokinetic profile of NVP-AUY922 in plasma and tumor tissues was evaluated at well tolerated, efficacious dose levels. We observed tumor specific compound retention and rapid tissue and plasma clearance. Ex vivo PK/PD analyses of tumor tissues upon acute dose or after termination of in vivo efficacy studies showed a time-dependent association between compound concentration and down-regulation of target proteins. The receptor tyrosine kinase ErbB2 is a well described Hsp90 client protein which is often overexpressed in breast cancer. The combination of NVP-AUY922 and an ErbB2 inhibitor was evaluated in the ErbB2 overexpressing human breast cancer model BT-474. We demonstrate significantly better in vivo antitumor effect when trastuzumab is combined with the ErbB2 inhibitor trastuzumab compared to either inhibitor alone. Disruption of the HSP90 chaperone hetero-complex, resulting in a loss of Heat Shock Factor-1 (HSF-1) repression and induction of Heat Shock Protein 70 (HSP70) is considered to be one of the most robust biomarkers to detect inhibition of Hsp90 ATPase activity in clinical trials. In the current dose escalation study in patients with solid tumors, induction of HSP70 is being evaluated for pharmacodynamic effect of AUY922 treatment in a surrogate tissue, peripheral blood monocytes (PBMC), at multiple time-points. In order to determine whether Hsp70 can be used as a reliable biomarker in combination trials, we generated an A375 melanoma cell line expressing luciferase under the control of the human Hsp70 promoter (A375/Hsp70-luc). Using Xenogen imaging technology we were able to monitor the effect of various antitumor agents on Hsp70 induction. Among the compounds evaluated in this model only administration of Hsp90 inhibitors and to a lesser degree the HDAC inhibitor NVP-LBH589 resulted in Hsp70 induction. These data indicate that Hsp70 may be used as a reliable biomarker in clinical trials where Hsp90 inhibitors are combined with conventional anticancer agents.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5649.
Pazopanib Sensitivity in a Patient With Breast Cancer and <i>FGFR1</i> Amplification
Authors: Fiona Tsui-Fen Cheng, Fu Ou-Yang, Nina Lapke, Kai-Che Tung, Yen-Kung Chen, Yuh-Yu Chou, Shu-Jen Chen
Journal: Journal of the National Comprehensive Cancer Network (2017)

Treatment options for patients with hormone receptor–positive (HR+), HER2-negative (HER2−) breast cancer and resistance to endocrine therapy remain limited. An interesting therapeutic target in these patients is fibroblast growth factor receptor 1 (FGFR1). FGFR1 is amplified in approximately 11% of patients with breast cancer, especially those with HR+ disease. This report presents a patient with metastatic HR+ HER2− breast cancer harboring an FGFR1 amplification who was resistant to endocrine therapy but responded to pazopanib, a multi–tyrosine kinase inhibitor with FGFR-inhibiting activity. Upon pazopanib treatment, the patient's brain lesions nearly disappeared, and she experienced therapeutic changes in the lung and an improvement of liver function. This case suggests that pazopanib may be a promising agent for the treatment of patients with breast cancer and FGFR1 amplifications.