tbuckley/cabot-search huggingface dataset:
Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial
Authors: Ravindra Uppaluri, Ashley E. Winkler, Tianxiang Lin, Jonathan H. Law, Bruce H. Haughey, Brian Nussenbaum, Randal C. Paniello, Jason T. Rich, Jason A. Diaz, Loren P. Michel, Tanya Wildes, Gavin P. Dunn, Paul Zolkind, Dorina Kallogjeri, Jay F. Piccirillo, Farrokh Dehdashti, Barry A. Siegel, Rebecca D. Chernock, James S. Lewis, Douglas R. Adkins
Journal: Clinical Cancer Research (2016)

Purpose: Ras/MEK/ERK pathway activation is common in oral cavity squamous cell carcinoma (OCSCC). We performed a neoadjuvant (preoperative) trial to determine the biomarker and tumor response of OCSCC to MEK inhibition with trametinib.Experimental Design: Patients with stage II-IV OCSCC received trametinib (2 mg/day, minimum 7 days) prior to surgery. Primary tumor specimens were obtained before and after trametinib to evaluate immunohistochemical staining for p-ERK1/2 and CD44, the primary endpoint. Secondary endpoints included changes in clinical tumor measurements and metabolic activity [maximum standardized uptake values (SUVmax) by F-18 fluorodeoxyglucose positron emission tomography/CT), and in tumor downstaging. Drug-related adverse events (AE) and surgical/wound complications were evaluated.Results: Of 20 enrolled patients, 17 (85%) completed the study. Three patients withdrew because of either trametinib-related (n = 2: nausea, duodenal perforation) or unrelated (n = 1: constipation) AEs. The most common AE was rash (9/20 patients, 45%). Seventeen patients underwent surgery. No unexpected surgical/wound complications occurred. Evaluable matched pre- and posttrametinib specimens were available in 15 (88%) of these patients. Reduction in p-ERK1/2 and CD44 expression occurred in 5 (33%) and 2 (13%) patients, respectively. Clinical tumor response by modified World Health Organization criteria was observed in 11 of 17 (65%) evaluable patients (median 46% decrease, range 14%-74%). Partial metabolic response (≥25% reduction in SUVmax) was observed in 6 of 13 (46%) evaluable patients (median 25% decrease, range 6%-52%). Clinical-to-pathologic tumor downstaging occurred in 9 of 17 (53%) evaluable patients.Conclusions: Trametinib resulted in significant reduction in Ras/MEK/ERK pathway activation and in clinical and metabolic tumor responses in patients with OCSCC. Clin Cancer Res; 23(9); 2186-94. ©2016 AACR.
Atrial Fibrillation and Cancer—Validation in the Real World
Authors: Chang H. Kim, Sadeer G. Al-Kindi, Guilherme H. Oliveira
Journal: JAMA Cardiology (2016)

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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Cardiology journal
A Proposal for an Out-of-Range Glycemic Population Health Safety Measure for Older Adults With Diabetes
Authors: Leonard Pogach, Chin-Lin Tseng, Orysya Soroka, Miriam Maney, David Aron
Journal: Diabetes Care (2016)

OBJECTIVE To evaluate patient-level glycemic control and facility variation of a proposed out-of-range (OOR) measure (overtreatment [OT] [HbA1c &amp;lt;7% (53 mmol/mol)] or undertreatment [UT] [&amp;gt;9% (75 mmol/mol)]) compared with the standard measure (SM) (HbA1c &amp;lt;8% [64 mmol/mol]) in high-risk older adults. RESEARCH DESIGN AND METHODS Veterans Health Administration patients ≥65 years of age in 2012 who were taking antihyperglycemic agents in 2013 were identified. Patient-level rates and facility-level rates/rankings were calculated by age and comorbid illness burden. RESULTS We identified 303,097 patients who were taking antiglycemic agents other than metformin only. The study population comprised 193,689 patients with at least one significant medical, neurological, or mental health condition; 98.2% were taking a sulfonylurea and/or insulin; 55.2% were aged 65–75 years; and 44.8% were aged &amp;gt;75 years. The 47.4% of patients 65–75 years met the OOR measure (33.4% OT, 14% UT), and 65.7% met the SM. For patients aged &amp;gt;75 years, rates were 48.1% for OOR (39.2% OT; 8.9% UT) and 73.2% for SM. Facility-level rates for OOR for patients aged 65–75 years ranged from 33.7 to 60.4% (median 47.4%), with a strong inverse correlation (ρ = −0.41) between SM and OOR performance rankings. Among the best-performing 20% facilities on the SM, 14 of 28 ranked in the worst-performing 20% on the OOR measure; 12 of 27 of the worst-performing 20% facilities on the SM ranked in the best-performing 20% on the OOR measure. CONCLUSIONS Facility rankings that are based on an SM (potential benefits) and OOR measure (potential risks) differ substantially. An OOR for high-risk populations can focus quality improvement on individual patient evaluation to reduce the risk for short-term harms.
High prevalence of nonalcoholic fatty liver disease in the middle east: Lifestyle and dietary habits
Authors: Ahad Eshraghian
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: I read with interest the recently published study by Younossi and colleagues demonstrating a steady rise in worldwide prevalence of nonalcoholic fatty liver disease (NAFLD).1 The Middle East has the highest prevalence rate of NAFLD among all other areas of the world. Three studies from Middle Eastern countries were included in this report. However, these studies are not concordant in terms of study design and population. The Iranian study which we performed dated back to 5 years ago and was conducted in a small town in Fars province.2 It should be noted that the study population was more similar to rural areas in terms of lifestyle. They had dietary habits that included less fast food and fewer foods enriched with saturated fatty acids as well as more daily physical activity. Therefore, the higher prevalence in urban areas with a more industrialized lifestyle is predictable and not surprising. The prevalence of NAFLD in urban areas was nearly 10% higher than that in rural areas in another Iranian study.3 The mentioned Turkish study was not a population‐based study. The study participants had been selected form outpatients returning to gastroenterology and internal medicine clinics affiliated to a university hospital. Therefore, the high reported prevalence of NAFLD (55%) in the study cannot be extrapolated to the general population.4 The study population in the third report was limited to participants aged 24‐70 years, which is different from the two other studies included in the meta‐analysis.5 Furthermore, it should be emphasized that estimation of NAFLD prevalence was not the primary aim in any of these three studies. On the other hand, NAFLD was diagnosed using ultrasound criteria in these studies, and there is still a lack of data regarding biopsy‐proven NAFLD including nonalcoholic steatohepatitis in the Middle East. Regardless of the designs of these studies, the change in dietary habits and lifestyle in Middle Eastern countries may be one of the main reasons for the high prevalence of NAFLD in this region. A recent review article showed that food and energy availability has increased over the past five decades in the Middle East. This increase in energy has been derived mainly from meat and vegetable oils, while the proportion of energy from fruits has decreased significantly.6 These changes have led to emerging epidemics of obesity and metabolic syndrome in this region and a subsequent rise in NAFLD. Therefore, we still need studies to focus specifically on the epidemiological aspects of NAFLD in Middle Eastern countries.
Knock-Down of CCAAT Displacement Protein (CDP) Restores Specific Granule Protein (SGP) Gene Expression in NB4 Acute Promyelocytic Leukemia Cells.
Authors: Jacqueline M. Tromp, Aimee L. Lucas, Julia Schaefer-Cutillo, Caryn St. Clair, Hong Sun, Arati Khanna-Gupta, Nancy Berliner
Journal: Blood (2005)
Four ABVD and Involved-Field Radiotherapy in Unfavorable Supradiaphragmatic Clinical Stages (CS) I-II Hodgkin’s Lymphoma (HL): Preliminary Results of the EORTC-GELA H9-U Trial.
Authors: Christophe Ferme, Marine Diviné, Andrej Vranovsky, Frank Morschhauser, Réda Bouabdallah, Jean Gabarre, Aspasia Bastard-Stamatoullas, Richard Delarue, Vittorina Zagonel, Jérôme Jaubert, Anton Hagenbeek, Mark Henri H. Kramer, Chantal Rieux, José Thomas, Michel Henry-Amar
Journal: Blood (2005)
The Histone Deacetylase Inhibitor (HDI) Depsipeptide Has Differential Activity in Core Binding Factor AML.
Authors: Olatoyosi M. Odenike, Serhan Alkan, Dorie Sher, John E. Godwin, Dezheng Huo, Stephen J. Brandt, Jingping Xie, Yanming Zhang, David H. Vesole, Richard A. Larson, Wendy Stock
Journal: Blood (2006)
T Cell Depleted Allogeneic Stem Cell Transplants for Hematological Malignancies: A 20 Year Experience Shows No Relationship Between Choice of Transplanted T Cell Dose or Delayed T Cell Add-Back on Major Outcomes
Authors: Prathima Anandi, Xin Tian, Puja D. Chokshi, Noelle Watters, Sawa Ito, Minoo Battiwalla, Austin John Barrett
Journal: Blood (2015)
Abstract 15011: Intravenous Immunoglobulin for Acute Myocarditis is Associated With Increased Resource Utilization but Equivalent Survival: An Outcome Analysis Amongst U.S. Children’s Hospitals
Authors: Pirouz Shamszad, Deipanjan Nandi, Matthew J O'Connor, Kimberly Y Lin, Andrew T Costarino, Robert E Shaddy, Joseph W Rossano
Journal: Circulation (2015)

Introduction: Intravenous immunoglobulin (IVIg) is frequently utilized in the treatment of pediatric acute myocarditis (AM) though the data surrounding the efficacy of intravenous immunoglobulin (IVIg) are equivocal. Hypothesis: IVIg utilization does not improve survival in pediatric AM but is associated with increased resource utilization. Methods: A retrospective review of the Pediatric Health Information System database was performed for children &lt;18 years hospitalized with AM between 2004 and 2014. A 1:1 propensity matched case control design was used to compare children who received IVIg (IVIg-group) to those who did not receive IVIg (no IVIg-group). The propensity score was based on a model including treatment with mechanical ventilation (MV), inotropes, or mechanical circulatory support (MCS). High- and low-use hospitals were defined by quartiles of percent usage of IVIg. Results: A total of 1802 children with AM were identified (median age 8y [IQR 1 - 15]; 60% male, 60% IVIg given, 65% inotrope use, 46% MV use, 16% MCS use). After matching, 552 children were included in both the IVIg-group and no IVIg-group. Overall median follow-up of the matched cohort was 1.4y [IQR 0.4-3.4]. Unadjusted in-patient mortality was similar between groups (6% vs. 9%, p=0.09). On multivariable Cox regression, there was no association between IVIg and follow-up mortality (OR 1.0, 95%CI 0.3- 2.9). Although in-patient cardiac transplantation occurred more frequently in the IVIg-group (2% vs. 0%, p&lt;0.001), there was no association between IVIg and cardiac transplantation during the follow up period (OR 0.5, 95%CI 0.2-1.1). Mortality was similar between high- and low-use centers (6% vs. 8%, p=0.316) as was length of stay (7d [IQR 8-18] vs. 7d [4-18], p=0.771). Total charges, as well as pharmacy charges, were significantly higher in the IVIg-group ($125k vs. $77k, $32k vs. $2.8k; p&lt;0.001 for both) and high-use centers ($125k vs. $112k, p=0.025; $27k vs. $5.1k, p&lt;0.001). Conclusions: IVIg is frequently utilized in children for the treatment of AM. Overall survival was similar in patients treated and not treated with IVIg, though resource utilization was significantly increased. Further study is needed to assess the most optimal, cost-effective treatment for AM in children.
Fibrin Generation in Heparin-Induced Thrombocytopenia (HIT): Pathomechanistic Background for Novel Therapy and Prophylaxis
Authors: Valerie Tutwiler, Hyun Sook Ahn, Rudy Fuentes, Vincent M. Hayes, Sergei V. Zaytsev, X. Long Zheng, Douglas B. Cines, Steven E. McKenzie, John W. Weisel, Mortimer Poncz, Lubica Rauova
Journal: Blood (2012)
The detection of microbial DNA but not cultured bacteria is associated with increased mortality in patients with suspected sepsis—a prospective multi-centre European observational study
Authors: M.J. O’Dwyer, M.H. Starczewska, J. Schrenzel, K. Zacharowski, D.J. Ecker, R. Sampath, D. Brealey, M. Singer, N. Libert, M. Wilks, J.-L. Vincent
Journal: Clinical Microbiology and Infection (2016)
Safety, tolerability, and efficacy of repeated doses of dihydroartemisinin-piperaquine for prevention and treatment of malaria: a systematic review and meta-analysis
Authors: Julie Gutman, Stephanie Kovacs, Grant Dorsey, Andy Stergachis, Feiko O ter Kuile
Journal: The Lancet Infectious Diseases (2016)

Intermittent preventive treatment (IPT) for malaria is used in infants, children, adults, and pregnant women. Dihydroartemisinin-piperaquine (DP) is an effective, well tolerated artemisinin-based combination therapy. The long half-life of piperaquine makes it attractive for IPT. We conducted a systematic review and meta-analysis to establish the efficacy and safety of repeated treatment with DP.Following PRISMA guidelines, we searched multiple databases on Sept 1, 2016, with the terms: "human" AND "dihydroartemisinin-piperaquine" OR "DHA-PPQ". Studies were eligible if they were randomised controlled trials (RCTs) or prospective cohort studies involving repeat exposures to standard 3-day courses of DP for either seasonal malaria chemoprevention, mass drug administration, or treatment of clinical malaria, conducted at any time and in any geographic location. Random-effects meta-analysis was used to generate pooled incidence rate ratios and relative risks, or risk differences.11 studies were included: two repeat treatment studies (one in children younger than 5 years and one in pregnant women), and nine IPT trials (five in children younger than 5 years, one in schoolchildren, one in adults, two in pregnant women). Comparator interventions included placebo, artemether-lumefantrine, sulfadoxine-pyrimethamine (SP), SP+amodiaquine, SP+piperaquine, SP+chloroquine, and co-trimoxazole. Of 14 628 participants, 3935 received multiple DP courses (2-18). Monthly IPT-DP was associated with an 84% reduction in the incidence of malaria parasitaemia measured by microscopy compared with placebo. Monthly IPT-DP was associated with fewer serious adverse events than placebo, daily co-trimoxazole, or monthly SP. Among 56 IPT-DP recipients (26 children, 30 pregnant women) with cardiac parameters, all QTc intervals were within normal limits, with no significant increase in QTc prolongation with increasing courses of DP.Monthly DP appears well tolerated and effective for IPT. Additional data are needed in pregnancy and to further explore the cardiac safety with monthly dosing.Bill & Melinda Gates Foundation and NIH.
AB0293 Carotid Intima Media Thickness and Interleukin -17 Level in Rheumatoid Arthritis Patients
Authors: S.S. Shaharir, N. Sulaiman Sahari, A. Abdul Wahab, M.S. Mohamed Said, M.R. Ismail
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid Arthritis (RA) patients are at risk of cardiovascular disease (CVD) and carotid intima media thickness (cIMT) is an excellent marker of subclinical atherosclerosis. However, cIMT and the CVD biomarkers among RA patients with low disease activity and remission are not well studied. <h3>Objectives</h3> To assess the carotid intima media thickness (cIMT) in RA patients who were in low disease activity state and lacking concomitant co-morbidities potentially influencing cIMT. This study was also aimed to determine the correlation between serum IL-17 with cIMT. <h3>Methods</h3> Rheumatoid Arthritis patients who were in low disease activity or remission (DAS28&lt;3.2) from Rheumatology Clinic, National University of Malaysia Medical Centre were recruited. Patients with traditional CVD risk factors were excluded. Carotid ultrasound was performed in RA patients and their age and gender-matched healthy controls to determine the cIMT thickness. Serum IL-17 was measured using ELISA method. <h3>Results</h3> A total of 76 patients were screened and 22 RA patients who were in low disease activity or remission were included. Patients with RA had significantly higher median cIMT, 0.53 (IQR0.13) mm compared to controls, 0.47 (IQR 0.14) mm, p=0.01. In RA patients, the cIMT had significant positive correlation with age (r<sub>s</sub>=0.84, p=0.00), systolic BP (r<sub>s</sub>=0.45, p=0.04), waist circumference (r<sub>s</sub>=0.43, p=0.04), total cholesterol (r<sub>s</sub>=0.54, p=0.01), BMI (r<sub>s</sub>=0.45, p=0.04) and serum IL-17 (r<sub>s</sub>=0.45, p=0.03) but negative correlation with total HDL (r<sub>s</sub>=-0.43, p=0.05). <h3>Conclusions</h3> Patients with RA had significantly higher cIMT as compared to healthy controls despite minimal disease activity and lack of traditional CV risk factors, suggesting that the vascular injury due to previous inflammation may not be reversible. Serum IL-17 was also found to be correlated significantly with cIMT, suggesting that it may play a role in atherogenesis among RA patients. <h3>References</h3> van Sijl AM et al, Carotid intima media thickness in rheumatoid arthritis as compared to control subjects: a meta-analysis. Semin Arthritis Rheum. 2011;40(5):389–97 Targonska-Stepniak B et al. The relationship between carotid intima media thickness and the activity of rheumatoid arthritis. J Clin Rheumatol. 2011;17(5):249–55 <h3>Disclosure of Interest</h3> None declared
Cardiorespiratory fitness and death from cancer: a 42-year follow-up from the Copenhagen Male Study
Authors: Magnus Thorsten Jensen, Andreas Holtermann, Hans Bay, Finn Gyntelberg
Journal: British Journal of Sports Medicine (2016)

Poor cardiorespiratory fitness (CRF) is associated with death from cancer. If follow-up time is short, this association may be confounded by subclinical disease already present at the time of CRF assessment. This study investigates the association between CRF and death from cancer and any cause with 42 years and 44 years of follow-up, respectively.Middle-aged, employed and cancer-free Danish men from the prospective Copenhagen Male Study, enrolled in 1970-1971, were included. CRF (maximal oxygen consumption (VO2max)) was estimated using a bicycle ergometer test and analysed in multivariable Cox models including conventional risk factors, social class and self-reported physical activity. Death from cancer and all-cause mortality was assessed using Danish national registers. Follow-up was 100% complete.In total, 5131 men were included, mean (SD) age 48.8 (5.4) years. During 44 years of follow-up, 4486 subjects died (87.4%), 1527 (29.8%) from cancer. In multivariable models, CRF was highly significantly inversely associated with death from cancer and all-cause mortality ((HR (95% CI)) 0.83 (0.77 to 0.90) and 0.89 (0.85 to 0.93) per 10 mL/kg/min increase in estimated VO2max, respectively). A similar association was seen across specific cancer groups, except death from prostate cancer (1.00 (0.82 to 1.2); p=0.97; n=231). The associations between CRF and outcomes remained essentially unchanged after excluding subjects dying within 10 years (n=377) and 20 years (n=1276) of inclusion.CRF is highly significantly inversely associated with death from cancer and all-cause mortality. The associations are robust for exclusion of subjects dying within 20 years of study inclusion, thereby suggesting a minimal influence of reverse causation.
AB0110 The Proteasome Is Related To Muscle Wasting in Experimental Arthritis and Is Altered by Etanercept Treatment
Authors: V.D.O.N. Teixeira, P.V.G. Alabarse, K. Ghannan, J.M.S. Silva, L. Martinez-Gamboa, L.I. Filippin, E. Feist, R.M. Xavier
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis is an autoimmune inflammatory disease associated with systemic complications like fatigue and muscle wasting. Muscle wasting could be related to the activation of the ubiquitin-proteasome system. <h3>Objectives</h3> To evaluate muscle loss and involvement of the proteasome in collagen-induced arthritis (CIA), with or without treatment with methotrexate or a TNF inhibitor (etanercept). <h3>Methods</h3> Male DBA1/J mice were divided into 4 groups (n=8 each): CIA (saline); ETN (etanercept, 5.5 mg/kg) and MTX (methotrexate, 35 mg/kg), treated twice a week for 6 weeks, and a healthy control group (CO). Treatments started one week after booster injection. Clinical score, hind paw oedema, and body weight were analysed during the experimental period. Gastrocnemius muscles (GA) were weighted after death and used to quantify proteasome activity, protein levels and mRNA expression of its subunits by Western blot and rtPCR. Significance was considered when p≤0.05. <h3>Results</h3> Treatments slowed disease development, observed through smaller clinical score and hindpaw edema in ETN and MTX. ETN presented higher body weight (21±1.0g) compared to MTX (19±1.3) at weeks 5 and 7. GA weight was heavier in ETN (105±12g) than CIA and MTX (80±10 and 79±10g, respectively), a result also observed after normalization of muscle with body weight. Of note, the catalytic properties of 26S proteasome showed an increase of caspase-like activity in CIA and MTX groups (150 and 200% of activity, respectively). Furthermore, muscles of MTX treated animals showed higher protein levels for proteasomal subunits PSMB8 and PSMB9 and increased gene expression for Psmb5, Psmb8 and Psmb9. In contrast, expression of Psmb6 was decreased and of Psmb9 was enhanced in CIA. <h3>Conclusions</h3> Although both drugs improved the disease score, ETN presented a stronger anti-arthritic effect and was the only treatment able to partially prevent muscle wasting. In contrast to ETN, MTX treatment did not prevent muscle loss due to CIA accompanied by persistent up-regulation of proteasome expression and activity. <h3>Acknowledgement</h3> Financial support: CAPES, CNPq, FIPE-HCPA. <h3>Disclosure of Interest</h3> None declared