tbuckley/cabot-search huggingface dataset:
Abstract 153: Creation of Cell Sheet-Based Bioengineered Cardiac Tissue Using Pluripotent Stem Cell-Derived Cells
Authors: Katsuhisa Matsuura, Shinako Aoki, Yuji Haraguchi, Tatsuya Shimizu, Nobuhisa Hagiwara, Teruo Okano
Journal: Circulation Research (2012)

Recent evidences have suggested that current cardiac cell therapy contributes to the improved cardiac function through mainly the paracrine effects. Thereby the bioengineered functional heart tissue is expected to function for repairing the broad injured heart. We have developed the cell sheet-based bioengineered vascularized cardiac tissue, however the system to collect the enough amount of cells from ES/iPS cells and the function of ES-derived cardiac tissue remain elusive. Recently we have established the cultivation system with the suitable conditions for expansion and cardiac differentiation of mouse ES cells and human iPS cells via embryoid body formation using three-dimensional bioreactor with the continuous perfusion system. For the cardiac differentiation experiments, we used several mouse ES cells that express EGFP or neomycin resistant gene under the control of αMHC promoter. At 10 days of differentiation, mouse ES cells increased up to 300 times (6.0×10 6 cells/mL). After the further 8 days of cultivation with the purification step, we collected around 5.0×10 8 cells in the 1L bioreactor culture and 99% of cells were positive for myosin heavy chain. The co-culture of ES-derived cardiomyocytes with the appropriate number of primary cultured fibroblasts on the temperature-responsive culture dishes enabled to form the cardiac cell sheets. Furthermore, when ES-derived cardiomyocytes were co-cultured with ES-derived endothelial cells, robust endothelial cell network was observed in the cardiac cell sheets. Mouse ES- or human iPS-derived cardiomyocytes in cell sheets beat spontaneously and synchronously and connexin43 was expressed at the edge of the adjacent cardiomyocytes. Furthermore the action potential propagation was observed between ES/iPS-derived cardiac cell sheets. These findings suggest that pluripotent stem cell-derived cardiomyocytes and endothelial cells might be useful for creating cell-sheet-based functional cardiac tissue and the layered stem cell-derived cardiac tissue might promote not only the cardiac regenerative medicine but also the understanding the molecular mechanisms of heart diseases.
LOW BACK PAIN PAIN RISK FACTORS IN OLYMPIC CLASS SAILORS OCCUR PRE-REGATTA AND WITHIN THE REGATTA
Authors: Shawn Hunt, Kathryn Roach, Ira Fiebert
Journal: British Journal of Sports Medicine (2017)

Background Hiking activity during sailing involves the hips, trunk, head, and upper extremities held in sustained, unsupported positions over the side of a boat to stabilize it at an optimal angle to the water, preventing velocity loss and overturn. Hiking requires high forces generated by lower extremities and trunk, potentially producing high lumbar spine compression and shear loads linked to acute Low Back Pain. Objective This study examined if competitive sailors performing hiking were at increased risk of developing low back pain (LBP) compared to non-hikers over the course of an Olympic class regatta. Design Prospective Cohort . Setting World Cup Regatta. Patients (or Participants) 172 Olympic class sailors completed a questionnaire concerning sailing activities, previous history of, and new LBP following a 6-day regatta. 152 subjects without LBP at the beginning of the regatta were classified as exposed (hikers) and unexposed (non-hikers) and new LBP cases were recorded for both groups. Interventions (or Assessment of Risk Factors) Relative risk ratios (RR) and CI 95% were calculated compared risk of new LBP in hikers and non-hikers. A priori hypothesis tested: hiking sailors are at increased risk for incident LBP versus non-hikers. Main Outcome Measurements Self-report LBP limiting sailing. Results Twenty-two subjects reported new LBP, 18 from hiking exposure group. Exposed (n=84) and unexposed (n=68) were no different in demographic/anthropometric variables across exposure and disease groups. Boat/equipment unloading time differences persisted across groups (P=0.0016, P=0.0022 respectively). Hikers' raw RR was 3.64 (CI 95% 1.29,10.26) times greater than non-hikers' for developing new LBP. Hikers' risk controlled for unloading time levels yielded an adjusted RR of 2.73 (CI 95% 1.05, 7.08). Hikers exposed to high unloading levels (&gt;2 hours) RR was 8.3 (CI 95% 1.05, 65.76) versus non-hikers. Conclusions Hiking and unloading forces may be risk factors for LBP prior to and during Olympic class regattas. Further study recommended.
Health Care in the New Millennium: Vision, Values, and Leadership.
Authors: David Woods
Journal: BMJ (2001)

Ian Morrison 

Jossey-Bass, £29.50, pp 260

ISBN 0 7879 5115 3

Rating: ![Graphic][1] ![Graphic][2] ![Graphic][3] 

In Glasgow, where Ian Morrison grew up, health care is a right while carrying a machine gun is a privilege. “Somehow,” he writes, “America got it the wrong way round.”

Morrison, a former president of the US Institute for the Future, doesn't think Americans are well served by their $1 trillion a year, market driven system—which leaves some 45 million people uninsured and in which high costs don't necessarily translate into higher quality outcomes. Infant mortality, for example, is …

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Primary (1°) tumor location as an independent prognostic marker from molecular features for overall survival (OS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB / SWOG 80405 (Alliance).
Authors: Alan P. Venook, Fang-Shu Ou, Heinz-Josef Lenz, Omar Kabbarah, Xueping Qu, Donna Niedzwiecki, Tyler Zemla, Richard M. Goldberg, Howard S. Hochster, Bert H. O'Neil, Hanna Kelly Sanoff, Robert J. Mayer, Monica M. Bertagnolli, Charles David Blanke, Federico Innocenti
Journal: Journal of Clinical Oncology (2017)

3503 Background: 80405 found no OS or Progression Free Survival (PFS) difference when bevacizumab (BV) or cetuximab (Cet) was added to 1st-line FOLFOX or FOLFIRI in All RAS wild type (wt) mCRC pts. There was a significant 1° side by biologic interaction (P int: OS = 0.008, PFS = 0.001) favoring pts with left-sided (L) 1°. Analyses of 1° tumors beyond All RAS includes Consensus Molecular Subtype (CMS), BRAF and MSI. (CMS results - see Lenz et al; BRAF -see Innocenti et al) We asked whether 1° tumor location - L vs right (R) - is an independent prognostic marker when these other molecular features are considered. Methods: We used a Cox proportional hazard model stratified by prior XRT and +/- adjuvant chemo; adjusted for age, gender, synchronous vs metachronous, CMS, MSI and BRAF status. Pts with transverse (T) tumors were excluded in this analysis. Results: Sidedness was determined in 782 pts (L - 472; R - 256; T -54). Molecular data from 728 pts (with L - and R-sided 1°s) was available as follows: KRAS -- 291, NRAS -393, BRAF - 393, MSI - 378, CMS - 533. L vs R mOS: 32.9 v 19.6 months (mo) (p &lt; 0.0001). See Table for OS results in All RAS / BRAF wt and BRAF mutant (mut) pts. Sidedness (R vs L) is an independent prognostic marker even after adjusting for all these molecular features: HR = 1.392 (1.032, 1.878), p = 0.031. Conclusions: Primary tumor location is an independent prognostic factor when adjusted for age, gender, synchronous/metachronous, CMS, MSI and BRAF status. We are exploring clinical variables such as tumor burden, metastatic sites and measurability of disease in an attempt to explain the impact of sidedness. Support: U10CA188021, U10CA180882. Eli Lilly and Co, Genentech/Roche, Pfizer, Sanofi. Clinical trial information: NCT002655850. [Table: see text]
Randomized phase III trial of adjuvant pazopanib versus placebo after nephrectomy in patients with locally advanced renal cell carcinoma (RCC) (PROTECT).
Authors: Robert J. Motzer, Naomi B. Haas, Frede Donskov, Marine Gross-Goupil, Sergei Varlamov, Evgeny Kopyltsov, Jae-Lyun Lee, Bohuslav Melichar, Brian I. Rini, Toni K. Choueiri, Milada Zemanova, Lori A Wood, Dirk Fahlenkamp, Martin Neil Reaume, Arnulf Stenzl, Weichao Bao, Paola Aimone, Christian Doehn, Paul Russo, Cora N. Sternberg
Journal: Journal of Clinical Oncology (2017)

4507 Background: PROTECT (NCT01235962) evaluated the efficacy and safety of pazopanib (PAZ) versus placebo in patients (pts) with locally advanced renal cell carcinoma (RCC) post nephrectomy. Methods: 1538 pts with resected pT2 (high grade), pT3 or greater clear cell RCC were randomly assigned to PAZ or placebo for 1 year. The starting dose (800 mg) following treatment of 403 pts was lowered to 600 mg to improve tolerability and primary endpoint was changed to disease-free survival (DFS) with PAZ 600 (N = 1135). Primary analysis was performed after 350 DFS events in intent-to-treat (ITT) PAZ 600, and DFS follow-up analysis was performed after an additional 12 months. Secondary endpoints included DFS with ITT PAZ 800 and ITT ALL, and safety. Results: Disease characteristics were similar between arms. The primary analysis results of DFS ITT 600 were not significant [HR: 0.862; 95% CI, 0.699, 1.063; p = 0.165] (Table). The secondary endpoint of DFS in ITT PAZ 800 and ITT ALL yielded 31% and 20% risk reduction, respectively. Updated DFS analysis in ITT 600 showed a higher HR with longer follow up. Increased ALT and AST were the most common adverse events leading to treatment discontinuation in the PAZ 600 (ALT 16% and AST 5%) and PAZ 800 (ALT 18% and AST 7%) groups. Conclusions: The study did not meet the primary DFS endpoint in ITT 600; however, a 31% decrease in the risk of recurrence was observed in ITT 800. The safety profiles in the 600 mg and 800 mg groups were similar and consistent with PAZ prior experience. Clinical trial information: NCT01235962. [Table: see text]
Incremental Value of Circulating MiR-122-5p to Predict Outcome after Out of Hospital Cardiac Arrest
Authors: Yvan Devaux, Antonio Salgado-Somoza, Josef Dankiewicz, Adeline Boileau, Pascal Stammet, Anna Schritz, Lu Zhang, Mélanie Vausort, Patrik Gilje, David Erlinge, Christian Hassager, Matthew P. Wise, Michael Kuiper, Hans Friberg, Niklas Nielsen
Journal: Theranostics (2017)

Rationale.The value of microRNAs (miRNAs) as biomarkers has been addressed in various clinical contexts.Initial studies suggested that miRNAs, such as the brain-enriched miR-124-3p, might improve outcome prediction after out-of-hospital cardiac arrest.The aim of this study is to determine the prognostic value of miR-122-5p in a large cohort of comatose survivors of out-of-hospital cardiac arrest.Methods.We analyzed 590 patients from the Targeted Temperature Management trial (TTM-trial).Circulating levels of miR-122-5p were measured in serum samples obtained 48 hours after return of spontaneous circulation.The primary end-point was poor neurological outcome at 6 months evaluated by the cerebral performance category score.The secondary end-point was survival at the end of the trial.Results.Forty-eight percent of patients had a poor neurological outcome at 6 months and 43% were dead at the end of the trial.Levels of miR-122-5p were lower in patients with poor neurological outcome compared to patients with good neurological outcome (p<0.001),independently of targeted temperature management regimen.Levels of miR-122-5p were significant univariate predictors of neurological outcome (odds ratios (OR), 95% confidence intervals (CI): 0.71 [0.57-0.88]).In multivariable analyses, miR-122-5p was an independent predictor of neurological outcome and improved the predictive value of a clinical model including miR-124-3p (integrated discrimination improvement of 0.03 [0.02-0.04]).In Cox proportional hazards models, miR-122-5p was a significant predictor of survival at the end of the trial. Conclusion.Circulating levels of miR-122-5p improve the prediction of outcome after out-of-hospital cardiac arrest.
Abstract 5325A: Fruit and vegetable intake and risk of breast cancer: Pooled analysis of the Nurses’ Health Study and the Nurses’ Health Study II
Authors: Maryam S. Farvid, Walter C. Willett, A. Heather Eliassen
Journal: Cancer Research (2017)

Abstract Fruit and vegetable intake has been hypothesized to protect against breast cancer, but the overall evidence has not been supportive. Using pooled data from the Nurses’ Health Study and the Nurses’ Health Study II cohorts, we evaluated fruit and vegetable intake in relation to breast cancer risk. Diet was assessed every 4 years using semi-quantitative food frequency questionnaires. Cox proportional hazards regression, adjusting for multiple breast cancer risk factors, was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs)for each category, using the lowest quintile of intake as the reference category. Among 182,204 women aged 27 to 66 years, we prospectively identified 10,973 invasive breast cancer cases during follow-up from 1980 through 2012 for the Nurses’ Health Study and from 1991 through 2013 for the Nurses’ Health Study II. Fruit and vegetable intake was significantly associated with a lower risk of breast cancer. The pooled multivariate HR (95% CIs) for highest (3.2 servings/day) versus lowest (0.4 serving/day) quintile intake of total fruit intake was 0.93 (0.86-0.99; Ptrend=0.03) and for highest (4.9 servings/day) versus lowest (1.5 servings/day) quintile intake of total vegetable was 0.92 (0.86-0.99; Ptrend=0.02). We also observed that a higher intake of yellow/orange vegetables, cruciferous vegetable, fruits and vegetables rich in vitamin C, fruits and vegetables rich in α-carotene, fruits and vegetables rich in β-carotene, and fruits and vegetables rich in lutein was each associated with a lower breast cancer risk. In addition, the association with vegetable intake was stronger for both estrogen and progesterone receptor negative (HR=0.91; 95%CIs=0.87-0.95) than both estrogen and progesterone receptor positive cancers (HR=0.98; 95%CIs=0.96-1.00; Pheterogeneity=0.003). Our findings support an association of a higher fruit and vegetable intake with a lower breast cancer risk. Citation Format: Maryam S. Farvid, Walter C. Willett, A. Heather Eliassen. Fruit and vegetable intake and risk of breast cancer: Pooled analysis of the Nurses’ Health Study and the Nurses’ Health Study II [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5325A. doi:10.1158/1538-7445.AM2017-5325A
FRI0234 Choice of biologic therapy following rituximab: influencing factors in a french multicenter cohort of rheumatoid arthritis
Authors: G Vial, A De Pouilly, L Scouppe, B Pereira, C Lukas, C Daien, A Ruyssen-Witrand, P Vergne-Salle, A Tournadre, C Richez
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> In rheumatoid arthritis (RA), the long lasting effect of rituximab (RTX) on B lymphocyte depletion may influence the choice of biologic after RTX failure but there is currently no specific recommendation about the optimal strategy. <h3>Objectives</h3> We assessed factors which may have influenced the choice of biologic following failure to RTX in RA patients and analysed the effectiveness of these biologics. <h3>Methods</h3> A retrospective study of RA patients, who had started a new biologic during the year after RTX discontinuation, was conducted between 2009 and 2016 in 5 French rheumatology centers. We collected at baseline (at the time the biologic was introduced after RTX) and during follow-up (3, 6 and 12 months), data about patients and disease. Characteristics of the patients receiving tocilizumab (TCZ), abatacept (ABA) or anti-TNF following RTX, the EULAR response and retention rate were compared using univariate and multivariate analyses. <h3>Results</h3> 152 RA patients (117 women, mean age 56.9±13 years) were analysed. RA duration was 14.3 years [IQR 7.8–19.8], mean DAS28 ESR at baseline 4.8±1.3. 57 patients (37.5%) received TCZ, 47 (31%) anti-TNF and 48 (31.2%) ABA following RTX. 87% had received anti-TNF prior to RTX. No significant difference in the biologics prescription profile was noted across centers. At baseline, sex, disease characteristics and activity, use of concomitant DMARDs or prednisone were not different between the 3 groups. There was no difference in the number of cycles or dose of RTX received and the number of previous anti-TNF treatment. Patients receiving ABA were slightly older (59.8 years vs 54 years for TCZ and 57.8 years for anti-TNF, p=0.06). Multimorbidity index (MMI) assessing the number of comorbidities was higher in the group ABA but not significantly (MMI count 2±1.7 for ABA, 1.6±1.5 for TCZ, 1.7±1.4 for anti-TNF, p=0.5). At 3, 6 and 12 months, DAS28ESR was lower in patients with TCZ as compared to those with anti-TNF or ABA (Table) but tender and swollen joint counts did not differ. The EULAR good-or-moderate response rates were similar across groups (Table). After adjustment on age, sex, disease duration, MMI count, number of previous anti-TNF, use of concomitant DMARDs and prednisone, drug retention rate at 1 year was significantly better for ABA compared to anti-TNF (p=0.02) and for TCZ compared to anti-TNF (p=0.04), but no difference was found between TCZ and ABA (p=0.62) (Figure). <h3>Conclusions</h3> Patients who received ABA following failure of RTX, seem to be older and with more comorbidities. Similar rate of good-or-moderate EULAR response was observed between patients receiving TCZ, ABA or anti-TNF. However, drug retention rate was better with TCZ and ABA compared to anti-TNF after RTX discontinuation. <h3>Disclosure of Interest</h3> None declared
Adjuvant hepatic arterial infusion chemotherapy is beneficial for selective patients with Hepatocellular carcinoma undergoing surgical treatment
Authors: Jui-Hu Hsiao, Cheng-Chung Tsai, Tsung-Jung Liang, Chia-Ling Chiang, Huei-Lung Liang, I-Shu Chen, Yu-Chia Chen, Po-Ming Chang, Nan-Hua Chou, Being-Whey Wang
Journal: International Journal of Surgery (2017)
Abstract 91: Interdependence of Mitochondrial Fission and Mitophagy in Adult Mouse Hearts
Authors: Moshi Song, Yan Burelle, Gerald W Dorn
Journal: Circulation Research (2015)

The role of Drp1-mediated mitochondrial fission in normal hearts is controversial. Cardiomyocyte mitochondria are hypo-dynamic, but mitochondrial dynamism factors are abundantly expressed. Cardiac-specific Drp1 gene deletion (KO) provokes mitochondrial enlargement, MPTP-dependent cardiomyocyte loss, and dilated cardiomyopathy (Song et al Cell Metab, 2015). We postulated that Drp1-dependent mitochondrial fission is essential for triage and elimination of damaged cardiomyocyte mitochondria by Parkin-mediated mitophagy. Others described no benefit of Parkin KO in mice with perinatal cardiac Drp1 KO (Kageyama et al EMBO J, 2014), but these Parkin KO mice have little basal phenotype due to germ-line compensation. Here, we assessed the individual and interactive roles of Parkin and Drp1 in adult mouse hearts by conditionally ablating each gene (Cre-Lox at 8 wks), separately and in combination. Parkin KO hearts appeared normal; as reported, Drp1 KO caused lethal cardiomyopathy after 6-7 wks. Cardiac-specific Parkin KO concomitant with Drp1 KO ameliorated the underlying cardiomyopathy by: 1. Increasing survival (94% vs 56%; P&lt;0.0001); 2. Enhancing cardiac contractility (LV FS 36.2±4.0 vs 23.2±1.7%; P=0.01); 3. Decreasing adverse remodeling (LV r/h 5.0±0.5 vs 6.3±0.4; P=0.05); 4. Reducing cardiomyocyte necrosis (1.9±0.5 vs 5.0±1.2%; P=0.05) and replacement fibrosis (33.3±5.3 vs 13.0±1.5%; P=0.02); 5. Attenuating mitochondrial deficiency (5.7±0.4 vs 4.7±0.6 μg/mg; P=0.20). Deleting Parkin did not affect mitochondrial enlargement or respiratory function in Drp1 KO cardiomyocytes, but normalized mitochondrial-associated LC3 and p62, mitophagy markers increased in cardiac Drp1 KO. These studies show how Drp1-mediated mitochondrial fission and Parkin-mediated mitophagy interact to maintain the quality of cardiac mitochondria: Interrupting mitochondrial fission (Drp1 KO) prevents segregation of damaged mitochondrial components into daughter organelles normally targeted for mitophagy; mitophagy thus ultimately consumes fission-defective parent organelles. Parkin KO suppresses generalized mitophagy, postponing (but not preventing) the Drp1 KO cardiomyopathy.
Usefulness of Statistical Models To Assess the Benefit of Breast Cancer Screening: Reply
Journal: JNCI Journal of the National Cancer Institute (1979)

Usefulness of Statistical Models To Assess the Benefit of Breast Cancer Screening: Reply Get access Sam Shapiro Sam Shapiro Director Health Services Research and Development CenterBaltimore, Maryland 21205 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 63, Issue 5, November 1979, Page 1110, https://doi.org/10.1093/jnci/63.5.1110 Published: 01 November 1979
What Is Medicaid? More Than Meets the Eye
Authors: Benjamin D. Sommers, David C. Grabowski
Journal: JAMA (2017)

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