tbuckley/cabot-search huggingface dataset:
Do Plaques Rapidly Progress Prior to Myocardial Infarction?
Authors: Amir Ahmadi, Jonathon Leipsic, Ron Blankstein, Carolyn Taylor, Harvey Hecht, Gregg W. Stone, Jagat Narula
Journal: Circulation Research (2015)

There is a common misperception in the cardiology community that most acute coronary events arise from ruptures of mildly stenotic plaques. This notion has emanated from multiple studies that had measured the degree of angiographic luminal narrowing in culprit plaques months to years before myocardial infarction. However, angiographic studies within 3 months before myocardial infarction, immediately after myocardial infarction with thrombus aspiration or fibrinolytic therapy, and postmortem pathological observations have all shown that culprit plaques in acute myocardial infarction are severely stenotic. Serial angiographic studies also have demonstrated a sudden rapid lesion progression before most cases of acute coronary syndromes. The possible mechanisms for such rapid plaque progression and consequent luminal obstruction include recurrent plaque rupture and healing and intraplaque neovascularization and hemorrhage with deposition of erythrocyte-derived free cholesterol. Moreover, recent intravascular and noninvasive imaging studies have demonstrated that plaques which result in coronary events have larger plaque volume and necrotic core size with greater positive vessel remodeling compared with plaques, which remain asymptomatic during several years follow-up, although these large atheromatous vulnerable plaques may angiographically seem mild. As such, it is these vulnerable plaques which are more prone to rapid plaque progression or are those in which plaque progression is more likely to become clinically evident. Therefore, in addition to characterizing plaque morphology, inflammatory activity, and severity, detection of the rate of plaque progression might identify vulnerable plaques with an increased potential for adverse outcomes.
Virus-mediated EpoR76E Therapy Slows Optic Nerve Axonopathy in Experimental Glaucoma
Authors: Wesley S Bond, Jessica Hines-Beard, YPaul L GoldenMerry, Mara Davis, Alma Farooque, Rebecca M Sappington, David J Calkins, Tonia S Rex
Journal: Molecular Therapy (2015)

Glaucoma, a common cause of blindness, is currently treated by intraocular pressure (IOP)–lowering interventions. However, this approach is insufficient to completely prevent vision loss. Here, we evaluate an IOP-independent gene therapy strategy using a modified erythropoietin, EPO-R76E, which has reduced erythropoietic function. We used two models of glaucoma, the murine microbead occlusion model and the DBA/2J mouse. Systemic recombinant adeno-associated virus–mediated gene delivery of EpoR76E (rAAV.EpoR76E) was performed concurrent with elevation of IOP. Axon structure and active anterograde transport were preserved in both models. Vision, as determined by the flash visual evoked potential, was preserved in the DBA/2J. These results show that systemic EpoR76E gene therapy protects retinal ganglion cells from glaucomatous degeneration in two different models. This suggests that EPO targets a component of the neurodegenerative pathway that is common to both models. The efficacy of rAAV.EpoR76E delivered at onset of IOP elevation supports clinical relevance of this treatment. Glaucoma, a common cause of blindness, is currently treated by intraocular pressure (IOP)–lowering interventions. However, this approach is insufficient to completely prevent vision loss. Here, we evaluate an IOP-independent gene therapy strategy using a modified erythropoietin, EPO-R76E, which has reduced erythropoietic function. We used two models of glaucoma, the murine microbead occlusion model and the DBA/2J mouse. Systemic recombinant adeno-associated virus–mediated gene delivery of EpoR76E (rAAV.EpoR76E) was performed concurrent with elevation of IOP. Axon structure and active anterograde transport were preserved in both models. Vision, as determined by the flash visual evoked potential, was preserved in the DBA/2J. These results show that systemic EpoR76E gene therapy protects retinal ganglion cells from glaucomatous degeneration in two different models. This suggests that EPO targets a component of the neurodegenerative pathway that is common to both models. The efficacy of rAAV.EpoR76E delivered at onset of IOP elevation supports clinical relevance of this treatment.
In Vivo Estimation of Size of Experimental Tumors
Authors: S D Morrison
Journal: JNCI Journal of the National Cancer Institute (1983)

The precision and accuracy of various estimates of experimental tumor size from lineal dimensions were examined on capsules implanted subcutaneously and inflated to precisely known weights in Fischer 344 rats. The method of tying the final product of three dimensions to the measured excised weight gave a value with no significant systematic bias and the lowest error of estimate (root mean square of deviation=4.35 g).
A randomized placebo-controlled phase III study of granulocyte- macrophage colony-stimulating factor in adult patients (&gt; 55 to 70 years of age) with acute myelogenous leukemia: a study of the Eastern Cooperative Oncology Group (E1490)
Authors: JM Rowe, JW Andersen, JJ Mazza, JM Bennett, E Paietta, FA Hayes, D Oette, PA Cassileth, EA Stadtmauer, PH Wiernik
Journal: Blood (1995)
Cost-effectiveness of bronchial thermoplasty (BT) treatment relative to no BT treatment option for patients with severe asthma
Authors: Mariko Siyue Koh, Shin Yuh Ang, Shao Wei Lam, Ji Zhang, Hai V. Nguyen
Journal: European Respiratory Journal (2014)

Background: Bronchial Thermoplasty (BT) has been shown to be effective at reducing asthma exacerbations for patients with severe asthma. However, little is known about its cost effectiveness.

Aim: To evaluate the incremental cost-effectiveness of BT treatment option (a 3-time treatment episode) relative to no BT treatment option for patients with severe asthma.

Methods: We used a Markov model to estimate the costs and quality-adjusted life years (QALYs) gain for severe asthma patients with and without BT treatment. The model simulated transition among three health states (poorly controlled asthma, controlled asthma, and asthma-related death). We populated the model with data on costs and benefits from our study and from the published literature. We calculated costs from the social perspective which include one-time cost of BT treatment and its complications, costs of subsequent possible hospitalizations as well as costs of work absence.

Results: Over a 10-year time horizon, the average cost per patient is S$44,700 ( €25,690) with BT treatment and S$23,400 (€ 13,448) without BT treatment. The model predicted that the cohort with BT gained 6.28 QALYs per patient while the cohort without BT acquired 5.28 QALYs per patient. The BT treatment delivers incremental cost-effectiveness ratio of S$21,470 (€12,339) per QALY relative to no BT treatment. The findings were robust to probabilistic sensitivity analysis.

Conclusion: Bronchial Thermoplasty with an estimated cost of S$25,000 per treatment episode is cost effective compared with no BT treatment option at the conventional willingness-to-pay level of S$50,000.
In real life, one-quarter of patients with hormone receptor-positive metastatic breast cancer receive chemotherapy as initial palliative therapy: a study of the Southeast Netherlands Breast Cancer Consortium
Authors: D.J.A. Lobbezoo, R.J.W. van Kampen, A.C. Voogd, M.W. Dercksen, F. van den Berkmortel, T.J. Smilde, A.J. van de Wouw, F.P.J. Peters, J.M.G.H. van Riel, N.A.J.B. Peters, M. de Boer, P.G.M. Peer, V.C.G. Tjan-Heijnen
Journal: Annals of Oncology (2015)
Injury-Driven Stiffening of the Dermis Expedites Skin Carcinoma Progression
Authors: Venugopal R. Mittapalli, Josef Madl, Stefanie Löffek, Dimitra Kiritsi, Johannes S. Kern, Winfried Römer, Alexander Nyström, Leena Bruckner-Tuderman
Journal: Cancer Research (2015)

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic skin fragility disorder characterized by injury-driven blister formation, progressive soft-tissue fibrosis, and a highly elevated risk of early-onset aggressive cutaneous squamous cell carcinoma (cSCC). However, the mechanisms underlying the unusually rapid progression of RDEB to cSCC are unknown. In this study, we investigated the contribution of injury-induced skin alterations to cSCC development by using a genetic model of RDEB and organotypic skin cultures. Analysis of RDEB patient samples suggested that premalignant changes to the dermal microenvironment drive tumor progression, which led us to subject a collagen VII hypomorphic mouse model of RDEB to chemical carcinogenesis. Carcinogen-treated RDEB mice developed invasive tumors phenocopying human RDEB-cSCC, whereas wild-type mice formed papillomas, indicating that the aggressiveness of RDEB-cSCC is mutation-independent. The inherent structural instability of the RDEB dermis, combined with repeated injury, increased the bioavailability of TGFβ, which promoted extracellular matrix production, cross-linking, thickening of dermal fibrils, and tissue stiffening. The biophysically altered dermis increased myofibroblast activity and integrin β1/pFAK/pAKT mechanosignaling in tumor cells, further demonstrating that cSCC progression is governed by pre-existing injury-driven changes in the RDEB tissue microenvironment. Treatment of three-dimensional organotypic RDEB skin cultures with inhibitors of TGFβ signaling, lysyl oxidase, or integrin β1-mediated mechanosignaling reduced or bypassed tissue stiffness and limited tumor cell invasion. Collectively, these findings provide a new mechanism by which RDEB tissue becomes malignant and offer new druggable therapeutic targets to prevent cSCC onset.
What's hot that the other lot got
Authors: Elizabeth Batalla-Duran
Journal: Thorax (2016)

Vitamin D is emerging as a possible factor in airways inflammation in chronic obstructive pulmonary disease (COPD) with deficiency thought to contribute to worsening lung function in COPD patients. A Korean study in Respiration (doi:10.1159/000445266) looked at whether vitamin D deficiency was associated with a more rapid decline in exercise capacity in male COPD patients. Multivariate analysis showed vitamin D deficiency was independently associated with a rapid decline in exercise capacity. The decrease in 6-minute walk distance (6MWD) in patients with severe vitamin D deficiency was more prominent (23.1 m/year) and the number of patients with moderate-to-severe deficiency was significantly higher in the rapid decliners (p=0.002). Vitamin D levels were significantly higher in those patients whose exercise capacity improved over the 3 years compared with those with no change or a decline. Studies are needed to ascertain if supplementation with vitamin D in those with deficiency would benefit the patient in terms of exercise capacity.

The Global Initiative for Obstructive Lung Diseases (GOLD) considers …
Association Between Child Poverty and Academic Achivement—In Reply
Authors: Nicole L. Hair, Jamie L. Hanson, Barbara L. Wolfe, Seth D. Pollak
Journal: JAMA Pediatrics (2015)

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 Pediatrics 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 Pediatrics journal
Feasibility, toxicity, and biologic response of interleukin-2 after consolidation chemotherapy for acute myelogenous leukemia: a report from the Children's Cancer Group.
Authors: E L Sievers, B J Lange, P M Sondel, M D Krailo, J Gan, W Liu-Mares, S A Feig
Journal: Journal of Clinical Oncology (1998)

PURPOSE Although remission can be achieved in 80% of children with acute myelogenous leukemia (AML), many patients experience relapse. Because interleukin-2 (IL-2) can induce remission in patients with overt evidence of AML, we hypothesized that IL-2 given to patients in first remission after intensive consolidation chemotherapy might prevent relapse. This study sought to determine whether such an approach was feasible. PATIENTS AND METHODS Twenty-one patients in complete remission received IL-2 after completion of treatment on Children's Cancer Group (CCG) protocol 2941. Recombinant IL-2 9 x 10(6) IU/m2 daily by continuous intravenous infusion (c.i.v.) was given for 4 days. After 4 days rest, IL-2 1.6 x 10(6) IU/m2 daily c.i.v. was resumed for 10 days. We monitored patients for toxicity and measured absolute lymphocyte count, the absolute count of cells that express CD56 and CD3 antigen, and soluble IL-2 receptor alpha-chain (sIL-2R alpha) levels before the start of IL-2 and after completion of each of the two courses of IL-2. RESULTS Observed toxicities included fever (57%), vascular leak (48%), hypotension (38%), tachycardia (14%), rash (29%), septicemia (5%), thrombocytopenia (29%), elevated transaminase (14%), electrolyte disturbance (29%), and hyperglycemia (10%). No patient required cardiac pressors or transfer to an intensive care unit. All patients studied developed an increase in lymphocyte count, CD56 count, CD3 count, and sIL-2R alpha levels after treatment with IL-2. CONCLUSION This schedule of IL-2 was reasonably well tolerated by children with AML in first remission. After treatment, increased levels of sIL-2R alpha were observed. CCG is conducting a randomized prospective trial to assess the efficacy of IL-2 to prevent the relapse of AML (CCG-2961).
Automatic Measurement of the Myocardial Interstitium
Authors: Thomas A. Treibel, Marianna Fontana, Viviana Maestrini, Silvia Castelletti, Stefania Rosmini, Joanne Simpson, Arthur Nasis, Anish N. Bhuva, Heerajnarain Bulluck, Amna Abdel-Gadir, Steven K. White, Charlotte Manisty, Bruce S. Spottiswoode, Timothy C. Wong, Stefan K. Piechnik, Peter Kellman, Matthew D. Robson, Erik B. Schelbert, James C. Moon
Journal: JACC. Cardiovascular imaging (2016)
Three weeks among the Korowai people
Authors: Maryke J Nielsen
Journal: BMJ (2015)

In 2014, I was offered the chance to join an expedition to West Papua, Indonesia, to assess the healthcare needs of the Korowai people. Reported to be the world’s only tree dwelling people, their first contact with the Western world was in the 1970s. Because of the inaccessibility of the rain forests where they live, they have retained their traditional semi-nomadic way of life. The expedition was commissioned by Tribal Survival, a new charity established to promote the health and wellbeing of remote indigenous tribes.

Although excited by the possibility of venturing into the medical unknown, I had reservations. During previous experiences volunteering in resource constrained settings, I had observed the risk of causing inadvertent harm while trying to do good. I debated whether any benefit could be achieved by such a short trip and what role there might be for this well financed but inexperienced organisation.

As medical students in the early 2000s my generation had unprecedented opportunities to explore global health. Riding high on the optimism of the millennium development goals and record levels of philanthropy, I found this a charismatic and captivating area of medicine. I fundraised hard during term time to spend my summer holidays volunteering with a student charity in Kenya, returning to the same area three times over four years. Over that time, I saw many successful projects established in partnership with local non-government organisations (NGOs). Yet the effectiveness and sustainability of some of them seemed doubtful.

Over the years, the former medical student charity has evolved into a successful and innovative organisation (child.org). Grass roots organisations, I concluded, can have a vital role, firstly, by identifying and highlighting unmet needs and, secondly, through innovative programmes that, if successful, can be scaled up. The trustees of Tribal Survival assured me that the Korowai people …
The PARSC trial, a prospective study for the assessment of recurrence risk in stage II colon cancer patients using ColoPrint.
Authors: Ramon Salazar, John Marshall, Jaume Capdevila, Bengt Glimelius, Jan Willem de Waard, Jacobus Van Der Hoeven, Joost Klaase, Frédéric Bibeau, Thomas Bachleitner-Hofmann, Rachel A Midgley, Edward Allen Levine, Wai Lun Law, Michio Asano, George J. Chang, Stephen M Cohen, Robert W. Beart, Paul M. Goldfarb, Martin McCarter, Lisette Stork-Sloots, Robert Rosenberg
Journal: Journal of Clinical Oncology (2012)

TPS10632 Background: An 18-gene expression profile, ColoPrint, has been developed for identifying colon cancer patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. The gene signature was validated in public datasets and independent patient cohorts (stage II and III patients). Uni-and multivariate analysis was performed on the pooled stage II patient set (n=320) (median follow-up 70 months). ColoPrint classifies 65% of stage II patients as Low Risk. The 3-year RFS was 91% for Low Risk and 74% for High Risk patients with a HR of 2.9 (p=0.001). ColoPrint was the only significant prognostic marker in the subgroup of patients with T3-MSS phenotype (Tabernero, ASCO GI 2012). Methods: A blinded prospective trial, PARSC (Prospective study for the Assessment of Recurrence risk in Stage II colon cancer patients) using ColoPrint has been initiated. Objectives are: (1)To validate the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage II colon cancer. (2) To compare the risk assessment in stage II patients using the ColoPrint profile vs a clinical risk assessment based on Investigator’s assessment of risk and ASCO high-risk recommendations. (3) To investigate therapy as a potential confounding factor for ColoPrint results. (4) To assess the performance of ColoPrint in estimating the 3-year relapse rate in patients with stage III colon cancer. Inclusion criteria: age ≥ 18 years, adenocarcinoma of the colon, stage II and III, no prior neo-adjuvant therapy, no synchronous tumors, fresh tumor sample, and written informed consent. The treatment of the patient is at the discretion of the physician adhering to National Comprehensive Cancer Network (NCCN)-approved regimens or a recognized alternative (blinded for ColoPrint result). The trial started in Sept. 2008 with currently 32 participating sites in 11 countries. Thus far, 340 eligible stage II and 280 stage III patients have been enrolled. The aim is to enroll 575 stage II patients. Clinical trial registry number: NCT00903565.
Parliamentary privilege—mortality in members of the Houses of Parliament compared with the UK general population: retrospective cohort analysis, 1945-2011
Authors: John Dennis, Tim Crayford
Journal: BMJ (2015)

To examine mortality in members of the two UK Houses of Parliament compared with the general population, 1945-2011.Retrospective cohort analysis of death rates and predictors of mortality in Members of Parliament (MPs) and members of the House of Lords (Lords).UK.4950 MPs and Lords first joining the UK parliament in 1945-2011.Standardised mortality ratios, comparing all cause death rates of MPs and Lords from first election or appointment with those in the age, sex, and calendar year matched general population.Between 1945 and 2011, mortality was lower in MPs (standardised mortality ratio 0.72, 95% confidence interval 0.67 to 0.76) and Lords (0.63, 0.60 to 0.67) than in the general population. Over the same period, death rates among MPs also improved more quickly than in the general population. For every 100 expected deaths, 22 fewer deaths occurred among MPs first elected in 1990-99 compared with MPs first elected in 1945-49. Labour party MPs had 19% higher death rates compared with the general population than did Conservative MPs (relative mortality ratio 1.19, 95% confidence interval 1.01 to 1.40). The effect of political party on mortality disappeared when controlling for education level.From 1945 to 2011, MPs and Lords experienced lower mortality than the UK general population, and, at least until 1999, the mortality gap between newly elected MPs and the general population widened. Even among MPs, educational background was an important predictor of mortality, and education possibly explains much of the mortality difference between Labour and Conservative MPs. Social inequalities are alive and well in UK parliamentarians, and at least in terms of mortality, MPs are likely to have never had it so good.
Inhibition of the T cell oxygen sensing machinery promotes anti-tumor efficacy
Authors: David Clever, Rahul Roychoudhuri, Nicholas P Restifo
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Mechanisms of immune tolerance can also be co-opted by tumors to subvert anti-tumor effector T cell responses. The lung represents a unique anatomic tissue of pronounced immune tolerance where T lymphocytes do not mount effector responses under steady state conditions despite
The impact of definition of ILD on WHO group Classification of PH in scleroderma
Authors: Stephen Mathai, Mohamed Gashouta, Rachel Damico, Paul Hassoun
Journal: European Respiratory Journal (2013)

Background:Patients with scleroderma (SSc) can develop several forms of pulmonary hypertension (PH). However, while guidelines for classification of PH distinguish between WHO Group I and II disease, they fail to distinguish between PH-ILD [group III] and PAH with thresholds of pulmonary function or chest radiographic findings that define PH-ILD. Therefore, we applied various definitions of “significant” ILD to our population of SSc patients with known PH to determine the impact on PH classification.

Methods: 150 consecutive patients with SSc and either Group I or III PH documented by RHC were retrospectively reviewed. We applied 3 definitions of “significant” ILD:

1) TLC  “minimal” fibrosis (clinical trial definition)

2) Limited/Extensive staging system: extent of lung involvement>20% of lung fields or <20% with FVC<70% predicted

3) FVC<70% predicted.

Patients were then reclassified as Group I or III based upon these criteria.

Results: Using the clinical trial definition, 73% of patients had Group I disease; however, when applying the limited/extensive staging system or FVC criteria, only 39% patients had Group I disease. No differences in demographics or hemodynamics were noted between groups based upon ILD definition.

Conclusions: We found a substantial impact upon the WHO group classification of patients with SSc-PH based upon criteria used to define ILD with changes in >40% of patients. Given the differences in response to therapy and outcomes in SSc between Group I and Group III disease, the changes in PH classification based upon definition of ILD demonstrated in this study have important implications for clinical trials and clinical practice.