tbuckley/cabot-search huggingface dataset:
Abstract 17157: Clinical Prediction of Incident Heart Failure in Type 2 Diabetes Mellitus in 507,637 Patients: a Systematic Review and Meta-analysis
Authors: Ying Wang, Tomoko Negishi, Kazuaki Negishi, Tomas H Marwick
Journal: Circulation (2014)

Background: Heart failure (CHF) is a major cause of death and disability in pts with type 2 diabetes mellitus (T2DM). Early treatment may improve the prognosis. This study sought to improve the ass...
AB1431-HPR Developing an evidence-based group programme for occupational therapy management of osteoarthritis
Authors: K McCausland
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with Hand OA form a significant proportion of Rheumatology referrals to Occupational Therapy. Occupational Therapy (OT) interventions for patients with Hand OA can reduce hand pain, and improve grip strength, hand function and quality of life. Under-resourcing of staff can mean that patients with Hand OA are waiting a long time for OT intervention. Providing OT interventions in a group setting for patients with arthritis has been used in Ireland and the UK with good results. <h3>Objectives</h3> To review the process of developing and piloting a group-based Occupational Therapy programme for patients with Hand Osteoarthritis. The programme would include self-management education, splinting and a hand exercise progamme. <h3>Methods</h3> The group programme was developed and piloted with 4 different patient groups between December 2016 and September 2017. The programme was delivered by two OTs and one OT Assistant, with between 3 and 9 patients per group. Outcome measures were taken at week 1 and at the end of the programme, week 13. <h3>Results</h3> Initial results are very positive, with the majority of patients who attended the group sessions showing improved grip strength, reduced hand pain, better hand function and they also reported increased confidence of how to manage their arthritis. <h3>Conclusions</h3> The development and commencement of a pilot group programme for OT management of Hand OA in Our Lady's Hospital, Navan, Ireland, has provided effective intervention, and also provides patient access to therapy in a more timely manner. <h3>References</h3> [1] Dziedzic K, et al. Self-Management approaches for osteoarthritis in the hand: a 2 × 2 factorial randomized trial. Ann Rheum Dis2015, 74 (1), 108–18 [2] Hennig T, et al. Effect of home-based hand exercises in women with hand osteoarthritis: a randomised controlled trial. Ann Rheum Dis2015, 74 (8), 1501–8 [3] Zhang W, et al. EULAR evidence based recommendations for the management of hand osteoarthritis: Report of a Task Force of the EULAR Standing Committe for International Clinial Studies Including Therapies (ESCISIT). Ann Rheum Dis2007, 66, 377–388 [4] Ye L, et al. Effects of rehabilitative interventions on pain, function and physical impairments in people with hand osteoarthritis. Arthritis Research &amp; Therapy2011, 13 (1) <h3>Acknowledgements</h3> I would like to acknowledge the support of my colleagues Michael Cureton, Dr Shawn Chavrimootoo and Dr SA Ramakrishnan. <h3>Disclosure of Interest</h3> None declared
Inconsistent Reporting of Potential Conflicts of Interest
Authors: Vinay Prasad
Journal: JAMA Internal Medicine (2018)

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Creatine Kinase Is the Main Target of Reactive Oxygen Species in Cardiac Myofibrils
Authors: HassaneMekhfi, VladimirVeksler, PhilippeMateo, VéroniqueMaupoil, LucRochette, RenéeVentura-Clapier
Journal: Circulation Research (1996)

Abstract Reactive oxygen species (ROS) have been reported to alter cardiac myofibrillar function as well as myofibrillar enzymes such as myosin ATPase and creatine kinase (CK). To understand their precise mode and site of action in myofibrils, the effects of the xanthine/xanthine oxidase (X/XO) system or of hydrogen peroxide (H2O2) have been studied in the presence and in the absence of phosphocreatine (PCr) in Triton X-100–treated cardiac fibers. We found that xanthine oxidase (XO), with or without xanthine, induced a decrease in maximal Ca2+-activated tension. We attributed this effect to the high contaminating proteolytic activity in commercial XO preparations, since it could be prevented by a protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), and it could be mimicked by trypsin. In further experiments, XO was pretreated with 1 mmol/L PMSF. Superoxide anion production by the X/XO system, characterized by electron paramagnetic resonance spin-trapping technique, was not altered by PMSF. A slight i...
Association of Endometrial Cancer Risk With Postmenopausal Bleeding in Women
Authors: Megan A. Clarke, Beverly J. Long, Arena Del Mar Morillo, Marc Arbyn, Jamie N. Bakkum-Gamez, Nicolas Wentzensen
Journal: JAMA Internal Medicine (2018)

As the worldwide burden of endometrial cancer continues to rise, interest is growing in the evaluation of early detection and prevention strategies among women at increased risk. Focusing efforts on women with postmenopausal bleeding (PMB), a common symptom of endometrial cancer, may be a useful strategy; however, PMB is not specific for endometrial cancer and is often caused by benign conditions.To provide a reference of the prevalence of PMB in endometrial cancers and the risk of endometrial cancer in women with PMB.For this systematic review and meta-analysis, PubMed and Embase were searched for English-language studies published January 1, 1977, through January 31, 2017.Observational studies reporting the prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB in unselected populations were selected.Two independent reviewers evaluated study quality and risk of bias using items from the Newcastle-Ottawa Quality Assessment Scale and the Quality Assessment of Diagnostic Accuracy Studies tool. Studies that included highly selected populations, lacked detailed inclusion criteria, and/or included 25 or fewer women were excluded.The pooled prevalence of PMB in women with endometrial cancer and the risk of endometrial cancer in women with PMB.A total of 129 unique studies, including 34 432 unique patients with PMB and 6358 with endometrial cancer (40 790 women), were analyzed. The pooled prevalence of PMB among women with endometrial cancer was 91% (95% CI, 87%-93%), irrespective of tumor stage. The pooled risk of endometrial cancer among women with PMB was 9% (95% CI, 8%-11%), with estimates varying by use of hormone therapy (range, 7% [95% CI, 6%-9%] to 12% [95% CI, 9%-15%]; P < .001 for heterogeneity) and geographic region (range, 5% [95% CI, 3%-11%] in North America to 13% [95% CI, 9%-19%] in Western Europe; P = .09 for heterogeneity).Early detection strategies focused on women with PMB have the potential to capture as many as 90% of endometrial cancers; however, most women with PMB will not be diagnosed with endometrial cancer. These results can aid in the assessment of the potential clinical value of new early detection markers and clinical management strategies for endometrial cancer and will help to inform clinical and epidemiologic risk prediction models to support decision making.
Randomized Comparison of Paclitaxel-Eluting Balloon and Stenting Versus Plain Balloon Plus Stenting Versus Directional Atherectomy for Femoral Artery Disease (ISAR-STATH)
Authors: Ilka Ott, Salvatore Cassese, Philipp Groha, Birgit Steppich, Martin Hadamitzky, Tareq Ibrahim, Sebastian Kufner, Karl Dewitz, Regina Hiendlmayer, Karl-Ludwig Laugwitz, Heribert Schunkert, Adnan Kastrati, Massimiliano Fusaro
Journal: Circulation (2017)

Background: Atherosclerosis in the superficial femoral artery is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting, and directional atherectomy (DA) have provided new options for the treatment of superficial femoral artery disease; however, the comparative efficacy of these interventional strategies remains uncertain. Methods: One hundred and fifty-five patients with symptomatic peripheral artery disease due to de novo superficial femoral artery stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA and stenting (n=52), or DA with distal protection and bailout stenting (n=55). The primary end point of the study was percentage diameter stenosis after 6 months measured by angiography. Other end points included target lesion revascularization, thrombosis, ipsilateral amputation, binary restenosis, and all-cause mortality at 6 and 24 months. Results: Baseline and lesion characteristics were comparable in all groups with a mean lesion length of 65.9±46.8 mm and 56% total occlusions. At 6 months angiography, the percent diameter stenosis was significantly lower in patients treated by PEB angioplasty and stenting (34±31%) as compared with BA angioplasty and stenting (56±29%, P =0.009) or DA (55±29%, P =0.007). Similarly, binary restenosis was significantly lower after treatment with PEB and stenting as compared with BA and stenting or DA. Clinical follow-up at 24 months revealed a lower risk for target lesion revascularization after PEB angioplasty and stenting as compared with BA and stenting or DA. We found no difference in terms of target lesion thrombosis and mortality among groups, and no patient underwent amputation. Conclusions: Treatment of de novo superficial femoral artery lesions with PEB angioplasty and stenting is superior to BA angioplasty and stenting or DA in terms of angiographic diameter stenosis at 6 months and target lesion revascularization at 24 months. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00986752.
Abstract 585: Exosomal EphA2 transmits chemoresistance and predicts pancreatic cancer patient responses to therapy
Authors: Jia Fan, Qian Wei, Eugene J. Koay, Yang Liu, Zhen Zhao, Ye Hu
Journal: Cancer Research (2018)

Abstract Exosomes are small extracellular vesicles secreted by most cells that are found in blood and other bodily fluids, and which contain cytoplasmic material and membrane factors corresponding to their cell type of origin. Exosome membrane factors and contents have been reported to alter adjacent and distant cell behavior in multiple studies, but the impact of cancer-derived exosomes on chemoresistance is less clear. We therefore analyzed exosomes from the human pancreatic cancer (PC) cell lines PANC-1, MIA PaCa-2 and BxPC-3 for their ability to transmit chemoresistance, finding that PANC-1 exosomes increased the gembicitabine (GEM) resistance of MIA PaCa-2 and BxPC-3 cell cultures. Comparative proteomics determined that PANC-1 exosomes overexpressed Ephrin type-A receptor 2 (EphA2) versus exosomes of less chemoresistant PC cell lines MIA PaCa-2 and BxPC-3. EphA2-knockdown in PANC-1 cells inhibited their ability to transmit exosome-mediated chemoresistance to MIA PaCa-2 and BxPC-3, while treatment of MIA PaCa-2 and BxPC-3 cells with soluble EphA2 did not promote chemoresistance, indicating that membrane carried EphA2 was important for the EphA2 chemoresistance effect. EphA2 levels on circulating exosomes were markedly increased in mice bearing PANC-1 tumors and PC patients who subsequently revealed poor responses to treatment. We thus concluded that exosomal EphA2 expression could transmit chemoresistance and may serve as a minimally-invasive predictive biomarker for PC treatment response. Further work should address whether additional exosomal factors regulate resistance to other cancer therapeutic agents for PC or other cancer types. Citation Format: Jia Fan, Qian Wei, Eugene J. Koay, Yang Liu, Zhen Zhao, Ye Hu. Exosomal EphA2 transmits chemoresistance and predicts pancreatic cancer patient responses to therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 585.
Abstract 11679: Post-resuscitation Care and Survival After In-hospital Cardiac Arrest
Authors: Saket Girotra, Brahmajee K Nallamothu, Yunshu Zhou, Mary Vaughan-Sarrazin, Paul S Chan
Journal: Circulation (2016)

Background: More than 40% of in-hospital cardiac arrest (IHCA) deaths occur in patients during the post-resuscitation period following return of spontaneous circulation (ROSC). However, the degree to which post-resuscitation survival varies across hospitals and whether this variation is explained by hospital characteristics is unknown. Methods: We identified 80,201 patients within Get with the Guidelines-Resuscitation who achieved ROSC following IHCA. Using a multivariable hierarchical regression model, we calculated risk adjusted rates of post-resuscitation survival for each hospital and quantified hospital variation in post-resuscitation survival using median odds ratio (OR). We also assessed the association of hospital characteristics with post-resuscitation survival. Results: The mean age was 65.5 years, 57% were men, and 23% were black. Nearly 1 in 4 (23.0%) patients had an initial shockable rhythm. Overall, 33.5% of patients with ROSC survived to discharge, but the rate of post-resuscitation survival varied across hospitals (median hospital rate: 33.3%; interquartile range: 29.9%-36.7%; total range: 18.9%-55.1%). The median OR was 1.35 (95% CI: 1.30, 1.39, Figure), which suggests that post-resuscitation survival for 2 patients with similar covariates at 2 randomly selected hospitals varied by 35%. Except U.S. census region (P&lt;0.001), no hospital characteristic was associated with hospital rates of post-resuscitation survival including, academic status, total bed number, hospital ownership, use of intensivists; number and proportion of intensive care unit [ICU] beds, neurological services, and coronary angiography capability. Conclusions: Rates of post-resuscitation survival vary among U.S. hospitals. However, this variation is not explained by hospital structural characteristics, thus highlighting a pressing need to identify post-resuscitation best practices at top-performing hospitals in post-cardiac arrest care.
Abstract 1987: Expansion of pancreatic cancer stem-like cells through PGE2 accumulation in inflammatory environment
Authors: Takatsugu Ishimoto, Kota Arima, Luke Bu, Tomoyuki Uchihara, Keisuke Miyake, Tsugio Eto, Rumi Itoyama, Hideo Baba
Journal: Cancer Research (2018)

Abstract Chronic inflammation has a crucial role in cancer development and the progression of various tumors, including pancreatic ductal adenocarcinoma (PDAC). The arachidonate cascade is a major inflammatory pathway that produces several metabolites, such as prostaglandin E2 (PGE2). 15-hydroxyprostaglandin dehydrogenase (15-PGDH) participates in the degradation of PGE2 and has attracted attention in recent years. Although inhibition of 15-PGDH is reported to lead to PGE2 accumulation and expand tissue stem cell fraction, the role for pancreatic tumor progression is still unknown. The aim of this study is to elucidate the regulatory mechanism and functional role of 15-PGDH for cancer stem-like cell expansion during tumor progression in pancreas. We found that 15-PGDH expression is frequently down-regulated in PDAC cells and significantly correlated with the number of infiltrating macrophages in human PDAC tissues. Moreover, direct co-culture assay revealed that macrophage derived interleukin-1 beta down-regulates 15-PGDH expression in PDAC cells. Furthermore, pharmacological blockade of 15-PGDH led to PGE2 accumulation, and promoted growth and sphere formation through the expansion of ALDH1-positive cells. We also elucidated the molecular mechanism that PGE2 accumulation by 15-PGDH inhibition increases CYP26A1 expression and subsequently depletes all-trans retinoic acid, and results in ALDH1 up-regulation. Finally, genetic ablation of 15-Pgdh promoted tumorigenesis in KrasLSL-G12D; Ptf1aCre/+ mice through the expansion of ALDH1-positive cells. Our findings highlight the role and significance of PGE2 degradation pathway for PDAC tumor progression. Citation Format: Takatsugu Ishimoto, Kota Arima, Luke Bu, Tomoyuki Uchihara, Keisuke Miyake, Tsugio Eto, Rumi Itoyama, Hideo Baba. Expansion of pancreatic cancer stem-like cells through PGE2 accumulation in inflammatory environment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1987.
Disruption of Chromosomal Architecture of cox2 Locus Sensitizes Lung Cancer Cells to Radiotherapy
Authors: Yuxiang Sun, Hui Dai, Shaopeng Chen, Yajun Zhang, Tao Wu, Xianbin Cao, Guoping Zhao, An Xu, Jun Wang, Lijun Wu
Journal: Molecular Therapy (2018)

Despite treatment of lung cancer with radiotherapy and chemotherapy, the survival rate of lung cancer patients remains poor. Previous studies demonstrated the importance of upregulation of inflammatory factors, such as cyclooxygenase 2 (cox2), in tumor tolerance. In the present study, we investigated the role of cox2 in radiosensitivity of lung cancer. Our results showed that the combination treatment of radiation with aspirin, an anti-inflammatory drug, induced a synergistic reduction of cell survival in A549 and H1299 lung cancer cells. In comparison with normal human lung fibroblasts (NHLFs), the cell viability was significantly decreased and the level of apoptosis was remarkably enhanced in A549 cells. Mechanistic studies revealed that the reduction of cox2 by aspirin in A549 and H1299 was caused by disruption of the chromosomal architecture of the cox2 locus. Moreover, the disruption of chromatin looping was mediated by the inhibition of nuclear translocation of p65 and decreased enrichment of p65 at cox2-regulatory elements. Importantly, disorganization of the chromosomal architecture of cox2 triggered A549 cells sensitive to γ-radiation by the induction of apoptosis. In conclusion, we present evidence of an effective therapeutic treatment targeting the epigenetic regulation of lung cancer and a potential strategy to overcome radiation resistance in cancer cells.
Randomized trial of a pharmacy intervention for older adults with cancer.
Authors: Margaret Ruddy, Areej El-Jawahri, Daniel Lage, Mark Zangardi, Christine Chio, E. Bridget Kim, Barbara Kong Mui Li, Ying Long, Gayle C. Blouin, Jennifer S. Temel, Ryan David Nipp
Journal: Journal of Clinical Oncology (2018)

10012 Background: Oncology clinicians often struggle with managing medications and vaccinations in older adults with cancer. We sought to demonstrate the feasibility and preliminary efficacy of integrating pharmacists into the care of older adults with cancer to enhance medication management and administration of appropriate vaccinations. Methods: We enrolled patients age ≥65 years with breast, gastrointestinal (GI), or lung cancer receiving first-line chemotherapy and randomly assigned them to the pharmacy intervention or usual care. Patients assigned to the intervention met with a pharmacist during their second or third chemotherapy infusion. The pharmacist performed medication reconciliation, obtained vaccination history and made recommendations to the care team. We obtained information about patients’ medications and vaccinations via patient-report and from the electronic health record (EHR) at baseline and week 4. We determined the number of discrepant medications, defined as the difference between patient-report and the EHR; and categorized medications as potentially inappropriate, based on Beers Criteria as determined by non-intervention pharmacists blinded to group assignment. We defined the intervention as feasible if > 75% of patients enrolled in the study and attended the visit with the pharmacist. Results: From 1/17/17-10/27/17, we randomized 60 patients (median age = 71.5 years [range 65.1-91.5]; 32 [53.3%] female; 39 [65.0%] retired; cancer types: 27 [45.0%] GI, 21 [35.0%] lung, and 12 [20.0%] breast). We enrolled 80.1% of patients approached, and 96.6% of patients assigned to the intervention attended the pharmacist visit. At week 4, patients assigned to the intervention had higher vaccination rates for pneumonia (67.9% vs 40.0%, P = .040) and influenza (67.9% vs 23.3%, P = .001). Compared with usual care, intervention patients had fewer discrepant (5.8 vs 8.3, P = .081) and potentially inappropriate (3.5 vs 4.8, P = .069) medications at week 4, although the differences were not statistically significant. Conclusions: Integrating pharmacists into the care of older adults with cancer is feasible with encouraging preliminary efficacy for enhancing medication management and improving patients’ vaccination rates. Clinical trial information: NCT02871115.
Beating Atrial Septal Defect Closure Monitored by Epicardial Real-Time Three-Dimensional Echocardiography Without Cardiopulmonary Bypass
Authors: YoshihiroSuematsu, ShinichiTakamoto, YukihiroKaneko, ToshiyaOhtsuka, HirooTakayama, YutakaKotsuka, ArataMurakami
Journal: Circulation (2003)

Background— We assessed the feasibility of beating atrial septal defect (ASD) closure monitored by real-time 3D echocardiography (RT3DE). Methods and Results— RT3DE was developed with prototype ultrasound equipment consisting of a high-speed 3D rendering unit with a frame rate of 5 to 10 frames/s. We also developed a prototype semiautomatic suture device and suture cutting system. In the experiment, 12 mongrel dogs were anesthetized, and after median sternotomy, the echo probe was applied directly to the surface of the right atrium. Three surgical maneuvers (balloon atrial septectomy, enlargement of the ASD, and ASD closure) were performed through the atrial port inserted into the right atrial appendage. The heart was then excised, and the area of the ASD measured by RT3DE was compared with its area measured directly. The ASD was successfully closed in all experimental animals except the first 2. Examination of the excised heart showed that none of the sutures were loose. The mean area of the ASD was 82.5...