tbuckley/cabot-search huggingface dataset:
Inflammation and Mechanical Stretch Promote Aortic Stiffening in Hypertension Through Activation of p38 Mitogen-Activated Protein Kinase
Authors: Jing Wu, Salim R. Thabet, Annet Kirabo, Daniel W. Trott, Mohamed A. Saleh, Liang Xiao, Meena S. Madhur, Wei Chen, David G. Harrison
Journal: Circulation Research (2013)

Aortic stiffening commonly occurs in hypertension and further elevates systolic pressure. Hypertension is also associated with vascular inflammation and increased mechanical stretch. The interplay between inflammation, mechanical stretch, and aortic stiffening in hypertension remains undefined.Our aim was to determine the role of inflammation and mechanical stretch in aortic stiffening.Chronic angiotensin II infusion caused marked aortic adventitial collagen deposition, as quantified by Masson trichrome blue staining and biochemically by hydroxyproline content, in wild-type but not in recombination activating gene-1-deficient mice. Aortic compliance, defined by ex vivo measurements of stress-strain curves, was reduced by chronic angiotensin II infusion in wild-type mice (P<0.01) but not in recombination activating gene-1-deficient mice (P<0.05). Adoptive transfer of T-cells to recombination activating gene-1-deficient mice restored aortic collagen deposition and stiffness to values observed in wild-type mice. Mice lacking the T-cell-derived cytokine interleukin 17a were also protected against aortic stiffening. In additional studies, we found that blood pressure normalization by treatment with hydralazine and hydrochlorothiazide prevented angiotensin II-induced vascular T-cell infiltration, aortic stiffening, and collagen deposition. Finally, we found that mechanical stretch induces the expression of collagen 1α1, 3α1, and 5a1 in cultured aortic fibroblasts in a p38 mitogen-activated protein kinase-dependent fashion, and that inhibition of p38 prevented angiotensin II-induced aortic stiffening in vivo. Interleukin 17a also induced collagen 3a1 expression via the activation of p38 mitogen-activated protein kinase.Our data define a pathway in which inflammation and mechanical stretch lead to vascular inflammation that promotes collagen deposition. The resultant increase in aortic stiffness likely further worsens systolic hypertension and its attendant end-organ damage.
S69 Troponin levels and risk of death following a myocardial infarction in people with and without copd
Authors: KJ Rothnie, N Ahmed, JK Quint
Journal: Thorax (2016)

<h3>Introduction</h3> Myocardial Infarction (MI) is a common comorbidity and cause of death in people with COPD, and COPD is associated with increased risk of death following acute MI.<sup>1,2</sup> We aimed to: 1) compare levels of peak troponin following MI between people with and without COPD; and 2) investigate differences in the prognostic value of peak troponin between those with and without COPD. <h3>Methods</h3> Patients from the Myocardial Ischaemic National Audit Project (MINAP) database who had linked Office of National Statistics (ONS) mortality data from 2003–2013 were included in the study. COPD was defined as the presence of obstructive airway disease and smoking history. We used linear regression to compare levels of peak troponin I and T between people with and without COPD followed by logistic regression to investigate the prognostic value of peak troponin level in predicting 180 day mortality separately for those with and without COPD. All models were adjusted for age, sex, smoking, peripheral vascular disease, cerebrovascular disease, chronic renal failure and previous angina. <h3>Results</h3> We included 300,146 patients with a first MI, 34,027 (11.3%) with COPD. Peak troponin T &amp; I was lower for those with COPD following both STEMI (troponin T: 0.51 ng/mL lower, adjusted% 17% lower (95% CI: 6–18%); troponin I: 5.49 ng/mL lower, adjusted% 12% lower (6–18%)) and non-STEMI (troponin T: 0.07 ng/mL lower, adjusted% 20% lower (95% CI: 16–25%); troponin I: 0.34 ng/mL lower, adjusted% 19% lower (15–23%)). The prognostic value of increased peak troponin was higher for COPD patients than those without COPD for troponin T, p-value for interaction = 0.02 (Table 1), but this was not apparent for troponin I p-value for interaction = 0.520. <h3>Conclusion</h3> Cardiac Troponin T appears a better prognostic indicator for long-term outcome amongst COPD patients following an MI compared to Troponin I. Clinicians should not be reassured by relative lower troponin levels in COPD patients at the time of an MI. <h3>References</h3> Rothnie KJ, <i>et al</i>. Risk of myocardial infarction (MI) and death following MI in people with chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis. <i>BMJ Open</i> 2015;<b>5</b>(9):e007824. Rothnie KJ, <i>et al</i>. Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease. <i>Heart</i> 2015;<b>101</b>(14):1103–10.
Integrative Analysis of the Mutational Landscape of Mouse and Human AML Identifies Functionally Relevant Leukemia Disease Alleles
Authors: Megan A. Hatlen, Kanika Arora, Vladimir Vacic, Ewa A. Grabowska, Willey Liao, Bridget Riley-Gillis, Dayna M. Oschwald, Lan Wang, Jacob E. Joergens, Alan H. Shih, Franck Rapaport, Shengqing Gu, Francesca Voza, Takashi Asai, Benjamin Neel, Michael G. Kharas, Mithat Gonen, Ross L. Levine, Stephen D. Nimer
Journal: Blood (2015)
Mediterranean diet in UK shows positive effects in study
Authors: Jacqui Wise
Journal: BMJ (2016)

Following a Mediterranean-type diet in the United Kingdom is linked to a lower incidence of cardiovascular disease and mortality, a study has found.

The European Prospective Investigation of Cancer (EPIC) Norfolk study is an ongoing UK prospective cohort and part of the Europe-wide EPIC study. The research, published in the journal BMC Medicine , included 23 902 initially healthy people who were assessed at baseline from 1993 to 1997 and followed up for an average of 12-17 …
Comparison of upstream tirofiban and eptifibatide use in patients with moderate and high risk acute coronary syndromes: An ACUITY substudy
Authors: Ajay J Kirtane, Helen Parise, Roxana Mehran, Jeffrey W Moses, Martin Fahy, Philip E Aylward, Angel R Cequier, Harald Darius, Walter Desmet, Ramin Elbrahimi, Marital Hamon, Lars Hvilsted Rasmussen, Hans-Juerrgen Rupprecht, Gregg W Stone
Journal: Circulation (2007)
The Addition of Gemtuzumab Ozogamicin to Low Dose Ara-C Improves Remission Rates but Not Survival: Results of the UK LRF AML14 and NCRI AML16 “Pick a Winner” Comparison
Authors: Alan Burnett, Robert Hills, Ann Elizabeth Hunter, Donald Milligan, William J. Kell, Keith Wheatley, John Yin, Mary Frances McMullin, Helen Dignum, David Bowen, Nigel H. Russell
Journal: Blood (2010)
Efficacy of idelalisib in CLL subpopulations harboring del(17p) and other adverse prognostic factors: Results from a phase 3, randomized, double-blind, placebo-controlled trial.
Authors: Jeff Porter Sharman, Steven E. Coutre, Richard R. Furman, Bruce D. Cheson, John M. Pagel, Peter Hillmen, Jacqueline Claudia Barrientos, Andrew David Zelenetz, Thomas J. Kipps, Ian Flinn, Paolo Ghia, Michael J. Hallek, Bertrand Coiffier, Susan Mary O'Brien, Eugen Tausch, Karl A Kreuzer, Wendy Jiang, Thomas Michael Jahn, Mirella Lazarov, Stephan Stilgenbauer
Journal: Journal of Clinical Oncology (2014)

7011^ Background: Idelalisib (IDELA) is a potent and selective inhibitor of PI3Kδ, which is critical for activation, proliferation and survival of B cells and their homing and retention in lymphoid tissues. An unmet need exists for effective therapies in patients with CLL positive for del(17p) and other adverse prognostic factors. This report describes the efficacy of IDELA in combination with rituximab (R) in such high-risk relapsed patients. Methods: Samples for del(17p), del(11q), TP53mut, IGHVmut, ZAP70 and CD38 expression, and β2-microglobulin were collected prospectively and tested using standard methods. Patients were stratified based on presence of del(17p) and/or TP53mut, and on IGHV mutational status. The endpoints evaluated in the high-risk subpopulations in the preplanned 1st interim analysis include progression-free-survival (PFS) and overall response rate (ORR). The primary study analysis was reported in NEJM 2014. Results: IDELA+R retained robust efficacy across all high-risk subpopulations (see Table). Importantly, IDELA+R achieved 76.5% ORR and PFS HR 0.13 in the highest risk patients who were positive for both del(17p) and TP53mut, compared to 80.4% ORR and PFS HR 0.17 in those who had neither present. Conclusions: These results confirm the retained robust efficacy of IDELA in high-risk CLL subpopulations and support IDELA as a potentially important novel treatment for patients with CLL positive for del(17p) and other adverse prognostic factors. Clinical trial information: NCT01539512. PFS ORR IDELA+R IDELA+R Placebo+R HR 95%CI n %ORR n %ORR Overall 0.15 0.08,0.28 88 80.7 88 12.5 Rai stage III or IV 0.12 0.05,0.27 52 75.0 60 11.7 Binet Stage C 0.13 0.06,0.30 47 74.5 51 13.7 Del(17p) 0.14 0.04,0.47 20 80.0 24 0.0 TP53mut 0.11 0.04,0.31 34 79.4 30 10.0 Del(17p) and/or TP53mut : Both 0.13 0.04,0.47 17 76.5 15 0.0 : Either one alone 0.09 0.02,0.42 20 85.0 24 12.5 : Neither 0.17 0.07,0.43 51 80.4 49 16.3 Del(11q) 0.10 0.02,0.46 28 82.1 29 6.9 IGHV unmutated 0.13 0.06,0.27 71 78.9 72 12.5 ZAP70+ 0.13 0.06,0.26 77 79.2 74 12.2 CD38+ 0.13 0.05,0.34 43 83.7 34 17.6 β2-microglobulin > 4mg/L 0.14 0.07,0.27 75 77.3 68 10.3
Harmonisation des données nationales de morbidité d'EISS pour la surveillance de la grippe : un index simple
Authors: H Uphoff, J M Cohen, D M Fleming, A Noone
Journal: Eurosurveillance (2003)

Le Programme europeen de surveillance de la grippe (European Influenza Surveillance Scheme, EISS), avec 18 pays participants en 2001-2002, surveille l'activite et l'impact de la grippe en recueillant chaque annee les donnees de morbidite et virologiques aupres des centres de soins primaires pendant toute la duree de l'hiver. Bien qu'ils soient semblables en principe dans le concept de surveillance, les indicateurs utilises et les observations faites sont tres differents. Des systemes de soins et des organisations differents influencent le comportement face a une consultation (besoin d'un certificat du medecin pour l'employeur, par exemple). De plus, et c'est du en partie aux differences dans les systemes de soins, les definitions utilisees pour le numerateur et le denominateur dans le calcul des taux de morbidite sont differents. Ceci rend l'interpretation comparative des donnees de morbidite des pays participants extremement delicate. 
L'harmonisation des collectes de donnees par l'utilisation de numerateurs et denominateurs equivalents est une option possible, mais difficile a realiser a court terme. De plus, d'autres elements devrait etre consideres, comme le besoin d'une continuite de la surveillance et savoir si de telles demarches auraient effectivement pour resultat une comparabilite directe, etc. 
Un index simple a ete teste, qui permet de comparer l'impact de la morbidite de la grippe d'une annee donnee avec ce qui est considere comme une epidemie  normale  dans ce pays. En principe, pour chaque pays, l'index donne un apercu chiffre de la relation de la morbidite attribuable a la grippe dans l'epidemie en cours et de la morbidite typique pour une epidemie de grippe. 
Dans cette etude pilote, l'utilite d'un tel index a ete exploree en prenant huit pays en exemple pendant les saisons 1999/2000 et 2000/2001. Une mise au point plus precise de la methode n'a pas encore ete effectuee.
Can color Doppler myocardial imaging identify chronically ischemic myocardium during dobutamine stress echocardiography ? An experiment study
Authors: Monika Szilard, Frank Weidemann, F Jamal, Bart Bijnens, Y.M Huang, X.S Liu, T Kukulski, Jan D'hooge, Eric Verbeken, G.R Sutherland, Ivan De Scheerder
Journal: Circulation (2000)
Comparing the Prognostic Value of Risk stratifying Models for Patients with Lower-Risk Myelodysplastic Syndromes: Is one model better?
Authors: Amer M Zeidan, Mikkael A. Sekeres, Xiao-Feng Wang, Najla Al Ali, Guillermo Garcia-Manero, David P. Steensma, Gail Roboz, John Barnard, Eric Padron, Amy Dezern, Jaroslaw P. Maciejewski, Alan F List, Rami S Komrokji
Journal: American Journal of Hematology (2015)

Some patients classified as having lower-risk (LR)-disease by the International Prognostic Scoring System (IPSS) fare more poorly than predicted. We examined the prognostic utility of IPSS, the MD Anderson LR-Prognostic System (LR-PSS), and the revised IPSS (IPSS-R) in a large cohort of patients classified as having IPSS LR-MDS in the MDS Clinical Research Consortium database. Actual overall survival (OS) was assessed in patients with IPSS LR-MDS (i.e. low and intermediate-1) using Kaplan–Meier methods. Harrell's c index (HCI) and Akaike information criteria (AIC) were used to compare the models. Median OS of 1,140 eligible patients was 47 months (95% CI, 44–52). Median follow-up was 62 months. HCI values indicating the discriminatory power of the models (higher is better) were better for LR-PSS (0.74, 95% CI, 0.70–0.78) than IPSS-R (0.64, 95% CI, 0.60–0.67) and IPSS (0.64, 95% CI, 0.60–0.68). Similarly, AIC values indicating the goodness of the fit were better for LR-PSS than IPSS-R and IPSS (8,110, 8,147, and 8,150, respectively, lower is better). LR-PSS assigned 25.1% and 37.4% of patients with IPSS LR-MDS into LR-PSS Category 3 and IPSS-R Categories ≥Intermediate, respectively. Of 291 patients (25.5%) who survived ≤24 months from diagnosis, only 37.1% and 45% were classified as LR-PSS category 3 and IPSS-R categories ≥Intermediate, respectively (P = 0.06). While both LR-PSS and IPSS-R distinguish groups with varied survival outcome among patients with IPSS LR-MDS, both tools fail to identify a significant subset with poor OS. Future studies should assess whether patients identified as at increased risk will benefit from earlier interventions with disease-modifying therapies. Am. J. Hematol. 90:1036–1040, 2015. © 2015 Wiley Periodicals, Inc.
Intravenous busulfan test dose clearance comparison with first and thirteenth dose systemic exposure in allogenic bone marrow transplantation patients
Authors: R. D. Harvey, T. Shea, C. Walko, C. Krasnow, L. Patel, J. Serody, D. Gabriel, T. Comeau, C. Lindley
Journal: Journal of Clinical Oncology (2005)

6658 Background: The area-under-the concentration-time curve (AUC) or steady state concentration (Css) of high dose busulfan (HD-Bu) has correlated with toxicity and engraftment and a number of investigators have reported that frequent dose adjustments are needed to maintain the desired AUC. Using the oral formulation, we found that a test dose failed to predict the first dose and steady state systemic exposure of busulfan due to significant intrasubject variability. Intravenous (IV)busulfan has demonstrated predictable intrasubject variability. The objective of this study is to evaluate the ability of an IV test dose to predict systemic exposure of IV HD-Bu. Methods: The day prior to HD-Bu, seven patients received a single test dose of intravenous busulfan (0.8 mg/kg) by two hour infusion with blood concentrations obtained at 0, 2, 3, 4, 5, 6, 8 and 10 hours. Busulfan 0.8 mg/kg/dose IV q 6h x 15 doses was then administered. Following the first and thirteenth doses, blood samples were also collected at 0, 2, 3, 4, 5 and 6 hours. Serum concentrations were analyzed using GC-MS and noncompartmental pharmacokinetic analysis to determine clearance was performed using WIN-NONLIN. The systemic clearance (dose/AUC) of the test dose was compared with the first and thirteenth doses. Results: Mean (range) clearance for the test, first and thirteenth doses were 15869 mL/hr (9642–28228), 15673 mL/hr (10483–29707) and 12958 mL/hr (8067–21269), respectively. Bias and precision for the test compared with the first dose were 2% and 7%, respectively. Bias and precision for the test compared with the thirteenth dose were both 22%, indicating a significant decrease in clearance from the first and test doses to the thirteenth dose. Conclusions: The utilization of a test dose demonstrated bioequivalence (<10% variability) with the first HD-Bu dose, but not the thirteenth dose (>20% variability). The decrease in clearance between the test and thirteenth dose may be secondary to changes in liver glutathione S-transferase (GST) activity. Alpha-GST samples have been collected for all patients and will be analyzed to investigate this relationship. No significant financial relationships to disclose.
PET imaging with of prostate-specific membrane antigen (PSMA) for staging of primary prostate cancer with <sup>68</sup>Ga-HBED-PSMA.
Authors: Tobias Maurer, Juergen Gschwend, Hans-Juergen Wester, Michael Souvatzoglou, Ambros Beer, Konstantin Holzapfel, Gregor Weirich, Bernhard Haller, Hubert Kübler, Markus Schwaiger, Matthias Eiber
Journal: Journal of Clinical Oncology (2015)

e16038 Background: Prostate-specific membrane antigen (PSMA) shows increased expression on most prostate cancers (PCa). Aim of this retrospective analysis of consecutive pts was to evaluate the accuracy of Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBED-CC)] (68Ga-HBED-PSMA) a recently developed ligand of PSMA, for the preoperative staging of lymph node (LN) involvement in primary PCa. Methods: 92 consecutive pts with intermediate to high-risk PCa received 68Ga-HBED-PSMA-PET/MR and were included in this analysis. One nuclear medicine physician and one radiologist reviewed PET/MRI imaging in consensus. Pelvine LN dissection was performed according to a predefined template. LN involvement was evaluated according to a 5-point scale on a patient- and field-based manner and correlated to postoperative histological analysis. Results: Due to lacking PSMA expression of the primary PCa 4 pts were excluded from further analysis. In total, 20 pts showed metastatic LN. 68Ga-HBED-PSMA-PET/MR detected 15 out of 20 pts with histological proven metastatic LN (sens: 75.0%) and correctly classified all 68 pts without histological evidence of LN metastases (spec: 100%; acc. 94.3%; PPV: 100%; NPV: 93.2%). 5 pts without evidence of metastatic LN on imaging showed only micrometastases in single LNs. In total, 470 anatomical fields were analysed (52 with LN metastases). Sens, spec, acc, PPV and NPV for the field-based analysis were calculated as 73.1%, 98.6%, 95.7%, 86.4% and 96.7%, respectively. Conclusions: 68Ga-HBED-PSMA-PET/MR shows overall accuracy for LN staging in primary PCa surpassing reported results of standard imaging. Thus, 68Ga-HBED-CC PSMA-PET/MR has the potential to replace current imaging modalities in primary PCa staging in the future.
The Trade-off Between Speed and Safety in Drug Approvals
Authors: Anupam B. Jena, Jie Zhang, Darius N. Lakdawalla
Journal: JAMA Oncology (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 Oncology 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 Oncology journal
Open-label, dose confirmation and dosimetry study of Interstitial <sup>131</sup>I-chTNT-1/B MAb for the treatment of recurrent glioblastoma multiforme (GBM)
Authors: S. Shen, R. Lustig, K. D. Judy, J. B. Fiveash, J. S. Shan
Journal: Journal of Clinical Oncology (2008)

2072 Background: 131I-chTNT-1/B MAb (Cotara [C]) is a radioiodinated chimeric monoclonal antibody specific for DNA and histone H1 complex, which becomes exposed in the necrotic areas of gliomas. This is the first report on biodistribution and dosimetry of C for treatment of recurrent glioma. In a prior phase I trial with a single catheter, C was infused over ∼25 hrs using convection enhanced delivery (CED). This current trial assesses the use of 2 interstitial catheters to deliver C via CED. Methods: Patients with recurrent GBM and tumor volume of 5–60 cc are eligible. Patients receive 3 mCi of C for imaging and dosimetry followed 2–4 weeks later with a therapy dose. Cohorts of 3–6 patients will be enrolled to receive a therapy dose of 1.5, 2.0 or 2.5 mCi/cc. Biodistribution and dosimetry of C is determined using 5 sequential whole body images and counting 9 blood samples. Uptake and clearance of C in tissues were quantified and radiation doses were determined based on Medical Internal Radiation Dose schema. Results: Three patients received an imaging dose and then a therapy dose at 1.5 mCi/cc, both infused over ∼25 hrs with 2 interstitial catheters. The administered therapeutic radiation dose ranged from 17- 74 mCi and no dose limiting toxicities (DLT) were observed. From images acquired immediately and up to 168 hours post infusion, Cotara was concentrated only in tumor. Minimal uptake of Cotara could be faintly visualized only in stomach, heart, and thyroid. The peak uptake ranged from 1.1–3.3 %ID for stomach, 0.4–1.2 %ID for heart, 0.05–0.26 %ID for thyroid, 0.0009–0.0017 %ID/mL for blood, and 30–55.7 %ID for tumor. Radiation doses ranged 1.8–3.3 cGy/mCi for stomach, 0.9–1.6 cGy/mCi for heart, 0.7–4.4 cGy/mCi for thyroid, 0.9–1.6 cGy/mCi for contralateral healthy brain, 0.64–1.1 cGy/mCi for marrow from radioactivity in blood, and 179–598 cGy/mCi for tumor. Mean tumor-to-body dose ratio was 551 and ranged 223–732. Conclusions: CED administered C specifically localized only in tumor with minimal systemic radiation exposure. No DLTs were observed at the 1.5 mCi/cc dose level. These clinical and biodistribution/dosimetry findings are encouraging and support further dose escalation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Peregrine Pharmaceuticals Peregrine, Inc Peregrine, Inc
Integrated Molecular and Pharmacogenetic Profiles in Prediction of Early Response to Therapy in Children with Acute Lymphoblastic Leukemia (ALL): A Report From Malaysia-Singapore ALL Study Group.
Authors: Yi Lu, Shirley Kow Yin Kham, Hany Ariffin, Ah Moy Tan, Hai Peng Lin, Thuan Chong Quah, Allen Eng Juh Yeoh
Journal: Blood (2009)