tbuckley/cabot-search huggingface dataset:
Abstract 218: Research On Myocardium Proteome Of Chinese mini-pigs With Myocardial Ischemia
Authors: Wenjing Chuo, Shuzhen Guo, Yong Wang, Chun Li, Hongjian Lian, Xuanchao Feng, Wei Wang
Journal: Circulation Research (2013)

Objective: To establish a stable myocardial ischemia animal model, and to find the characteristics of its myocardium proteome and also to seek the biomarkers for myocardial ischemia. Methods: Establishment and assessment of a stable model with myocardial ischemia Chinese experimental mini pigs (25±4 kg) were instrumented with a size-matched Ameroid constrictor on the anterior descending branch under general anesthesia in sterile conditions. The sham group didn’t place the Ameroid constrictor, the other were the same to the model group. After the operations, we dynamically observed the pathophysiology indicators from the two group animals for 12 weeks. Myocardium samples were obtained from the animals with myocardial ischemia and the sham operated animals after operation 12 weeks. Myocardium samples were separated by two-dimensional electrophoresis (2-DE) to identify differentially expressed proteins. A cluster of protein spots differentially expressed were selected and identified with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Results: Compared with the sham group, the differential expressed proteins in the model group 5 up-regulated protein spots and 3 down-regulated protein spots were detected in the 2-DE separation of pooled samples. Albumin, aldose reductase, troponin T, isocitrate dehydrogenase subunit alpha, myosin light chain 3 were significantly highly expressed in the myocardium samples, while NADH-ubiquinone oxidoreductase, ropomyosin alpha-1 chain, Hsp27 were decreased in the myocardium proteome. Conclusion: The detected differential expressed myocardium proteins of animals with myocardial ischemia were associated with the related proteins of energy metabolism obstruction, cytoskeleton proteins, cell damaged and apoptosis - related proteins. Thus, we supposed that energy metabolism obstruction may be the most important changes of physiological and biochemical process in myocardial ischemia, accompanied by cytoskeletal damage, apoptosis and a series of molecular level changes.
Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months
Authors: Nir Uriel, Paolo C. Colombo, Joseph C. Cleveland, James W. Long, Christopher Salerno, Daniel J. Goldstein, Chetan B. Patel, Gregory A. Ewald, Antone J. Tatooles, Scott C. Silvestry, Ranjit John, Christiano Caldeira, Valluvan Jeevanandam, Andrew J. Boyle, Kartik S. Sundareswaran, Poornima Sood, Mandeep R. Mehra
Journal: Circulation (2017)

The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS.We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient.In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065).In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months.URL: http://clinicaltrials.gov. Unique identifier: NCT02224755.
Heat-Not-Burn Tobacco Cigarettes
Authors: Reto Auer, Nicolas Concha-Lozano, Isabelle Jacot-Sadowski, Jacques Cornuz, Aurélie Berthet
Journal: JAMA Internal Medicine (2017)

This study analyzed the content of smoke from heat-not-burn tobacco cigarettes compared with that of conventional cigarettes to determine whether similar toxic compounds are released in heat-not-burn cigarette smoke.
Predictive role of MGMT status in recurrent glioblastoma (GBM) patients (PTS) treated with antiangiogenic drug (AD) plus temozolomide (TMZ) or CPT-11.
Authors: Giuseppe Lombardi, Fable Zustovich, Patrizia Farina, Roberta Bertorelle, Alessandro Della Puppa, Marina Paola Gardiman, Pasquale Fiduccia, Domenico D'Avella, Vittorina Zagonel
Journal: Journal of Clinical Oncology (2012)

2049 Background: Methylation and silencing of MGMT promoter is a favourable predictive factor in PTS with GBM treated with single alkylating agent such as TMZ. Yet, MGMT is an important resistance determinant to CPT-11 activity. AD can be administered in second line treatment as single agent or in combination to cytotoxic drugs. We analyzed the predictive role of MGMT status in PTS treated with AD plus TMZ or CPT-11 as second line treatment. Methods: Retrospectively, 55 PTS were analyzed: 36 (65%) with unmethlyated MGMT, 19 (35%) with methylated MGMT; 3 (5%) PTS with IDH1 mutations. 17 (31%) PTS performed a reoperation before the second line treatment and MGMT status was changed in 2 (18%) PTS, IDH1 status was unchanged in all PTS. 32 PTS were treated with sorafenib 800mg/die plus TMZ 40mg/m2/die, 23 with bevacizumab 10mg/Kg plus irinotecan every two weeks. Tumor response was evaluated by clinician assessment and by MRI according to RANO criteria every two months or when clinically indicated. Results: Among all PTS, median PFS was 2.7 months (95%CI 1.5-3.5), median OS from start of AD was 7.3 months (95%CI 6.02-8.5), 6-month PFS was 32%; no significant differences were observed and MGMT status was balanced between the two AD groups (p&gt;0.05). Analyzing MGMT status at first surgery, according to univariate analyses there were no significant differences in terms of PFS (3.5ms vs 2.1ms; p=0.2), OS (6.5ms vs 7.2ms; p=0.1) and 6-PFS (HR=0.2, CI95% 0.05-1.07) between PTS with unmethylated and methylated MGMT, respectively. On multivariate analysis, adjusted for performance status, age and cytotoxic drug, MGMT status was not statistically significant in terms of PFS (p=0.8) and OS (p=0.1). Yet, no significant differences emerged with MGMT status at second surgery as well as analyzing the two AD groups, separately. Conclusions: MGMT status might not be a predictive factor in recurrent GBM patients treated with AD plus TMZ or CPT-11 as second line treatment, although MGMT status may change in some PTS between first and second surgery. In conclusion, the outcome of patients with recurrent GBM receiving AD plus TMZ or CPT-11 is not significantly influenced by MGMT methylation status.
Use of the wii balance board to assess changes in postural balance across athletic season
Authors: Hilary M Cullen, Yao Sun, Brian R Christie, E Paul Zehr
Journal: British Journal of Sports Medicine (2017)

Objective The purpose of this study was to investigate potential utility of a customised Wii Balance Board (WBB) program to assess postural balance in an athletic population. Researchers hypothesised that WBB measures would be strongly correlated to the Balance Error Scoring System (BESS) used in concussion assessments. Design Cross-sectional time series. Static and dynamic balance was assessed using the WBB and BESS at three time points of an athletic season: 1) pre-season, 2) mid-season, and 3) post-season. Setting University research laboratory Subjects Intervention Outcome measures 1) BESS, 2) WBB dynamic recovery time, and 3) WBB static Centre of Pressure (COP). Results WBB COP data were found to be strongly correlated with BESS scores across all time points [pre-season (r=0.689, p&lt;0.05), mid-season (r=0.767, p&lt;0.01), and post-season (r=0.780, p&lt;0.01)]. There were significant differences in recovery time (p&lt;0.005) and COPx variance for the single-leg BESS condition across all time points (p&lt;0.005). No significant differences were observed in raw BESS scores across time points. Conclusions Study results support the use of a WBB as an objective tool in measuring variance in static and dynamic postural balance. This program has potential utility for clinicians when assessing balance deficits related to concussion. Planned work will examine the use of the WBB program in measuring variance in postural balance in individuals with sport-related concussion. Competing interests None.
Anti-FcRH5/CD3 T Cell Dependent Bispecific Antibody (TDB) for the Treatment of Multiple Myeloma
Authors: Ji Li, Nicola Stagg, Jennifer Johnston, Michael Harris, Sam Menzies, Danielle DiCara, Vanessa Clark, Ryan Cook, Dionysos Slaga, Rin Nakamura, McCarty Luke, Siddharth Sukumaran, Elizabeth Luis, Zhengmao Ye, Teiko Sumiyoshi, Dimitry Danilenko, Genee Lee, Klara Totpal, Diego Ellerman, Isidro Hötzel, John James, Teemu T Junttila
Journal: Blood (2016)
DIPG-23. PHASE I STUDY OF ADOPTIVE CELLULAR THERAPY (X-ALT) PLUS TOTAL TUMOR RNA-DENDRITIC CELL VACCINE (TTRNA-DC) + HEMATOPOIETIC STEM CELLS (HSC) DURING RECOVERY FROM IRRADIATION(RT) WITH (GROUP A) OR WITHOUT (GROUP B) DOSE-INTENSIFIED TEMOZOLOMIDE (DI-TMZ) IN PATIENT (PTS) WITH NEWLY DIAGNOSED DIFFUSE BRAIN STEM GLIOMAS (DIPG) (BRAVO TRIAL)
Authors: Sridharan Gururangan, Elias Sayour, Catherine Flores, Marcia Hodik, Duane Mitchell
Journal: Neuro-Oncology (2017)

Children with DIPG have a dismal prognosis and novel therapies are needed to improve survival. Based on lab studies demonstrating efficacy of x-ALT + ttRNA-DC vaccine +HSC following DI chemotherapy in DIPG models, we plan to conduct a study of this strategy in newly diagnosed pts with DIPG evaluating toxicity, preliminary evidence of efficacy, and usefulness of DI-TMZ in augmenting immune responses. Eligible pts (age 3- 21 years) will undergo tumor biopsy and a PBMC apheresis to obtain DCs for vaccine preparation. All pts will receive focal XRT (+/-TMZ). Four weeks following RT, group A pts will receive 3 bi-weekly tt-RNA DC (vaccines #1–3) followed by 2 monthly vaccines (vaccines # 4 and 5) during recovery from monthly DI-TMZ (85–100 mg/m2/day for 21 days) (cycles 1–3). Further apheresis (for lymphocytes and HSC) will be obtained following vaccine #3. Subsequently, pts will receive two additional monthly vaccines (# 6 and 7) with chemotherapy (cycle 4–5) followed by vaccine # 8 + x-ALT + HSC after cycle 6. Group B pts will receive a similar vaccine schedule (#1–7) and lymphocytes + HSC collection as Group A but without DI-TMZ and vaccine #8 +x-ALT + HSC following lymphodepletive conditioning with i.v cyclophosphamide +Fludarabine. Both groups will receive two additional vaccines (#9 and 10). Td boosts will be given to all pts at specific intervals. DC vaccine dose will be 1 x 107 cells. The starting dose of x-ALT will be 3 x 107/kg. Dose escalation of x-ALT will be based on phase I 3+3 design. Correlative studies include routine MRI imaging, profiling T-cell receptor repertoire and cytokines before and during treatment, and Gliosequencing plus immune transcriptome analysis of tumor tissue. The trial is expected to begin enrollment at our institution shortly following FDA and IRB approval with an accrual goal of 12–15 pts.
Клінічний випадок: діагностика тромбозу ворітної вени з успішним лікуванням та наступним трирічним спостереженням
Authors: Yu.M. Stepanov, S.V. Kosynska
Journal: GASTROENTEROLOGY (2017)

Стаття присвячена клінічному спостереженню позапечінкової портальної гіпертензії внаслідок тромбозу ворітної вени, що вперше проявилася кровотечею з варикозно розширених вен стравоходу та шлунка, у молодої пацієнтки. Особливості анамнезу, клінічної картини вказували на безсимптомний перебіг захворювання до моменту катастрофи. Складність ведення таких хворих пов’язана з недостатньою інформативністю рутинних методів дослідження, необхідністю застосування спеціальних методів дослі­дження для встановлення діагнозу та нестандартних методів лікування. Проаналізовано дані лабораторно-інструментальних методів дослідження в даної хворої, наведено сучасний діагностичний пошук причин захворювання печінки та синдрому портальної гіпертензії в реальних умовах. Виявлена відсутність ознак гепатиту, а оцінка стану печінки за допомогою еластометрії виключила наявність фіброзу в цієї хворої. Встановлений діагноз позапечінкової портальної гіпертензії, і хвора спрямована на оперативне лікування. В Інституті хірургії та трансплантології проведено успішну шунтуючу операцію. Далі встановлена позитивна динаміка клінічних даних, спленомегалії, що давала больовий синдром та явища гіперспленізму. Описано консервативне лікування синдрому портальної гіпертензії та симптоматичне лікування хворої, що застосовувалось. Обґрунтована необхідність індивідуального вибору рухового режиму та медикаментозного ведення, що включає урсодезоксихолеву кислоту. За 3 роки у хворої спостерігається значне зменшення портальної гіпертензії при збереженні паренхіми печінки, що дає надію на позитивні віддалені результати.
Tackle technique and body position of the tackler and ball carrier significantly influences head injury risk in rugby union
Authors: Ross Tucker, Ben Hester, Matthew Cross, Simon Kemp, Martin Raftery
Journal: British Journal of Sports Medicine (2017)

Objective Interventions to reduce head injury range from law changes to technique training and education. The effective targeting of such interventions requires that the mechanism of injury be well understood. This study describes the events contributing to head injuries in Rugby Union. Design An observational study with a cohort comprised of six professional Rugby Union competitions. Every Head Injury Assessment (HIA) reported during a three-year period was documented and described according to 15 descriptive criteria. Outcome measures Descriptive criteria, and combinations thereof, including preceding and inciting event, tackle type, speed, direction and technique-related variables. The incidence of head injury was calculated per 1,000 events for each variable Main results 611 HIAs were performed in 1,516 matches. 464 HIAs occurred after tackles (1.94 HIAs/1000 tackles). Active shoulder tackles, front-on tackles and high speed tackles have the greatest incidence of head injuries. For any tackle type and tackler position, the lowest incidence of HIAs occurs when the ball carrier is bent at the waist (1.2 HIAs/1000 tackles vs 2.4 and 9.8 HIAs/1000 tackles for upright and falling positions, respectively). For any ball carrier position, the greatest risk of head injury exists when the tackler is upright (2.7 HIAs/1000 tackles vs 1.9 and 1.2 HIAs/1000 tackles for bent at waist and diving, respectively). Conclusions Technique components of the tackle, related primarily to the body position adopted by the tackler and ball carrier, significantly influence head injury risk. Interventions may be targeted at improving these variables to reduce head injury incidence in the sport. Competing interests The primary author is employed in a scientific and research role by World Rugby (Pty) Ltd, who also funded the research study.
Intraoperative radiotherapy combined with kyphoplasty (Kypho-IORT) for spinal metastases: Phase II dose escalation study and update of clinical results from a pilot phase.
Authors: Tina Reis, Frederic Bludau, Grit Welzel, Frank Schneider, Elena Sperk, Udo Obertacke, Frederik K. Wenz
Journal: Journal of Clinical Oncology (2015)

e20563 Background: Kyphoplasty combined with intraoperative radiotherapy (Kypho-IORT) is a technically feasible new treatment approach without severe side effects for patients with spinal metastases in the palliative treatment setting. We conducted a dose escalation study to determine the maximum tolerable dose (MTD) and updated the clinical data from a pilot phase. Methods: For Kypho-IORT a 50 kV X-ray source with a specially designed applicator was used. Three radiation dose levels were tested in the phase II study (NCT 01280032): 8 Gy in 8 mm, 8 Gy in 10 mm and 8 Gy in 13 mm depth from the isocenter of the radiation source. Eligible patients were ≥ 50 years with a Karnofsky-Index of ≥ 60% and had histologically or radiologically documented spinal metastases ( ≤ 2cm) caudal the 3rd thoracic vertebra. Off-study patients were treated with 8 Gy in 8 mm (n = 49) and 8 Gy in 13 mm (n = 3) depth from isocenter of the radiation source. Results: Overall Kypho-IORT was performed in 61 patients. 9 of these patients were included in the dose escalation study. In the whole group the 3, 6 and 12 months overall survival was 76.9%, 64.0% and 48.4%; The 3, 6 and 12 months local progression free survival (PFS) was 97.5%, 93.8% and 93.8%. The median pain score using the visual analogue scale (VAS) significantly improved from VAS 5/10 before the procedure to VAS 2/10 at the first postoperative day (p < 0.001). The 3, 6 and 12 months local PFS was 100%, 83.3% and 83.3% for the on study patients. The median pain score improved from VAS 4/10 preoperatively to VAS 1/10 at the first postoperative day (p = 0.018). In the off-study group the 3, 6 and 12 months local PFS was 96.9%, respectively. There was pain reduction from VAS 5/10 before to VAS 2/10 after Kypho-IORT (p < 0.001). No dose-limiting toxicities were seen in the three dose escalation levels in all on study patients. Conclusions: Kypho-IORT results in immediate and permanent pain relief with good local control. The dose of 8 Gy in 13 mm depth from the isocenter of the radiation source was determined as the maximally tolerated dose and will be tested in a phase III study. Clinical trial information: NCT 01280032.
Cardiovascular toxicity following anti-angiogenic therapy in persons over age 65 with advanced renal cell carcinoma.
Authors: Sekwon Jang, Chaoyi Zheng, Huei-Ting Tsai, Alex z Fu, Ana Barac, Michael B. Atkins, Andrew N Freeman, Lori M. Minasian, Arnold L. Potosky
Journal: Journal of Clinical Oncology (2015)

4544 Background: Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of patients with renal cell carcinoma (RCC) in 2005-2006. We conducted a population-based observational cohort study on the cardiovascular effects of VEGFR TKI therapy in elderly RCC patients. Methods: We analyzed patients with RCC diagnosed from 2000-2009 ages 66 and older using data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We examined the incidence of cardiovascular adverse events through December 2010 including congestive heart failure and cardiomyopathy (CHF/CM), acute myocardial infarction (AMI), stroke, and cardiovascular deaths. We performed Cox-proportional hazard model to estimate the risk of these events associated with sunitinib or sorafenib adjusting for age, sex, comorbidity, and use of other systemic therapy. Results: A total of 171 out of 670 patients who received either sunitinib or sorafenib had cardiovascular events. The incidence rates for CHF/CM, AMI, stroke, and cardiovascular death in those who received one of the two drugs were 0.87, 0.14, 0.14, and 0.05 per 1000 person-days, respectively. Sunitinib or sorafenib use was associated with an increased risk of stroke (adjusted HR = 2.72, 95% CI: 1.49 -4.97) compared with 788 patients diagnosed with advanced RCC from 2007-2009 eligible for Part D but did not receive either agent. There were no statistically significant increased risks of CHF/CM, AMI, or cardiovascular deaths. Conclusions: Sunitinib or sorafenib are significantly associated with an increased risk of stroke, and clinicians should be aware of these rare adverse events.
FIB‐4 stage of liver fibrosis predicts incident heart failure among HIV‐infected and uninfected patients
Authors: Kaku A. So‐Armah, Joseph K. Lim, Vincent Lo Re, Janet P. Tate, Chung‐Chou H. Chang, Adeel A. Butt, Cynthia L. Gibert, David Rimland, Vincent C. Marconi, Matthew B. Goetz, Maria C. Rodriguez‐Barradas, Matthew J. Budoff, Hilary A. Tindle, Jeffrey H. Samet, Amy C. Justice, Matthew S. Freiberg
Journal: Hepatology (2017)

Liver fibrosis is common, particularly in individuals who are infected with human immunodeficiency virus (HIV). HIV-infected individuals have excess congestive heart failure (CHF) risk compared with uninfected people. It remains unknown whether liver fibrosis stage influences the CHF risk or if HIV or hepatitis C virus (HCV) infection modifies this association. Our objectives were to assess whether 1) stage of liver fibrosis is independently associated with incident CHF and 2) the association between stage of liver fibrosis and incident CHF is modified by HIV/HCV status. Participants alive on or after April 1, 2003, in the Veterans Aging Cohort Study were included. Those without prevalent cardiovascular disease were followed until their first CHF event, death, last follow-up date, or December 31, 2011. Liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. Cox proportional hazards regression models were adjusted for cardiovascular disease risk factors. Among 96,373 participants over 6.9 years, 3844 incident CHF events occurred. FIB-4 between 1.45 and 3.25 (moderate fibrosis) and FIB-4 > 3.25 (advanced fibrosis/cirrhosis) were associated with CHF (hazard ratio [95% confidence interval], 1.17 [1.07-1.27] and 1.65 [1.43-1.92], respectively). The association of advanced fibrosis/cirrhosis and incident CHF persisted regardless of HIV/HCV status.Moderate and advanced liver fibrosis/cirrhosis are associated with an increased risk of CHF. The association for advanced fibrosis/cirrhosis persists even among participants without hepatitis C and/or HIV infection. Assessing liver health may be important for reducing the risk of future CHF events, particularly among HIV and hepatitis C infected people among whom cardiovascular disease risk is elevated and liver disease is common. (Hepatology 2017;66:1286-1295).