tbuckley/cabot-search huggingface dataset:
Effects of formoterol or salmeterol on impulse oscillometry in patients with persistent asthma
Authors: Arvind Manoharan, Alexander von Wilamowitz-Moellendorff, Ashley Morrison, Brian J. Lipworth
Journal: Journal of Allergy and Clinical Immunology (2015)

Effects of small-particle long-acting β-agonists on the small airways have been poorly documented.We used impulse oscillometry (IOS) to compare single and repeated dosing effects of small- and large-particle long-acting β-agonists.After a 1- to 2-week run-in period, patients received either 12 μg of small-particle hydrofluoroalkane 134a-formoterol solution or 50 μg of large-particle salmeterol dry powder twice daily plus inhaled corticosteroid for 1 to 2 weeks with a 1- to 2-week washout period in between. Measurements were made over 60 minutes after the first and last doses.Sixteen patients completed the study as follows: mean age, 43 years; FEV1, 80%; forced midexpiratory flow between 25% and 75% of forced vital capacity (FEF(25-75)), 48%; total airway resistance at 5 Hz, 177%; peripheral airway resistance as the difference between 5 and 20 Hz, 0.18 kPa·L(-1)·s; Asthma Control Questionnaire score, 0.76; and inhaled corticosteroid dosage, 550 μg/d. There were significantly greater improvements with formoterol versus salmeterol in all IOS outcomes and FEF25-75, but not FEV1, at 5 minutes after the first dose, which were not sustained over 60 minutes. After the last dose, all IOS outcomes, but not FEV1 or FEF(25-75), were significantly better with formoterol over the entire 60 minutes: mean difference at 60 minutes between formoterol and salmeterol in total airway resistance at 5 Hz, 7.50% (95% CI, 1.56% to 13.43%, P = .02); central airway resistance at 20 Hz, 5.37% (95% CI, 0.13% to 10.62%, P = .045); peripheral airway resistance as the difference between 5 and 20 Hz, 12.76% (95% CI, 1.28% to 24.24%, P = .03); reactance area under the curve, 19.46% (95% CI, 7.56% to 31.36%, P = .003); reactance at 5 Hz, 11.19% (95% CI, 4.62% to 17.76%, P = .002); and resonant frequency, 9.34% (95% CI, 3.21% to 15.47%, P = .005). Peak expiratory flow significantly improved to a similar degree with both drugs.Significant improvements in IOS outcomes but not spirometry results occurred after chronic dosing with formoterol compared with salmeterol. This might reflect better deposition to the entire lung, including the small airways.
Abstract 3419: Positive Effect of Bone Marrow Progenitor Cell Transfer on Regional Post Infarction Ventricular Remodeling by Magnetic Resonance Imaging. Insights from the REPAIR AMI Trial.
Authors: Andreas Rolf, Susanne Mollmann, Johannes Rixe, Guido Conradi, Volker Schachinger, Stefanie Dimmeler, Andreas Zeiher, Christian Hamm, Thorsten Dill
Journal: Circulation (2007)

Objective : The acute loss of myocytes during infarction increases loading conditions, which in turn triggers adverse remodeling of infarcted, adjacent and remote regions. Late Gadolinium Enhancement (LGE) cardiac MRI (CMR) can distinguish these regions and thus determine the effect of bone marrow progenitor cell (BMC) therapy on regional remodeling and function. Methods : 47 patients from the REPAIR AMI trial who underwent CMR at baseline and 12 month were evaluated in a segment by segment fashion according to the AHAs 17 segment model, defining LGE positive segments as infarcted and LGE negative segments as adjacent or remote. We measured enddiastolic wall diameters (WD) and wall thickening (WT) at 0 and 12 month by serial MRI. Results : WD decreased in all patients and all segments with a tendency to smaller diameters in BMC treated patients. In the prespecified subgroup of patients with larger infarcts (EF below the median of 48.9%) we observed a positive effect on adverse remodeling in BMC patients not only in infarcted but also in the remote areas. Infarcted segments showed a decrease in WD of 21.9% ± 4.0 SE in the BMC group vs. 8.5% ± 3.4 in the Placebo Group p=0.02. In BMC patients WD decreased in remote segments by 8.1% ± 4.4 SE compared to 4.9% ± 3.3 SE in the Placebo group, p=0.03. This effect on remodeling translates into a functional benefit. In remote segments WT decreases in both gropus but significantly so only in Placebo patients (BMC-7.8% ± 5.4 p= 0.2 vs. Placebo −13.9% ± 4.4 p=0.002, p for interaction 0.4). The largest effect was observed in the infarcted segments where BMC therapy led to an increase in WT of 26.6% ± 5.1 SE compared to Placebo 0.7% ± 4.6 SE p= 0.0001. The positive effect is mediated by wall diameters, regression analysis shows a significant inverse relationship between WD and WT, p = 0.0001 Conclusion : BMC therapy effectively prevents adverse remodeling not only in the infarct zone but also in remote segments for patients with large infarcts resulting in increased contractility. This seems to be mediated by a positive effect on enddiastolic wall geometry yielding smaller wall diameters.
Abstract 9280: A Targeted Delivery of Adipocytokines into the Heart by Cell-Sheet Technique Induces Immune-Tolerance and Ameliorates Cardiac Performance in Autoimmune-Associated Fulminant Myocarditis in Rat
Authors: Sokichi Kamata, Shigeru Miyagawa, Satsuki Fukushima, Taichi Sakaguchi, Yukiko Imanishi, Atsuhiro Saito, Norikazu Maeda, Yoshiki Sawa
Journal: Circulation (2011)

Background: Clinical prognosis is critically poor in fulminant myocarditis, whose initiation and progression are regulated in partby autoimmune disorders. Adiponectin (APN) and associated cytokines, which have anti-inflammatory/fibrotic effects, were shown to be immune-tolerance inducers, though effective delivery methods into target pathologies have not been established. We hypothesized cell sheet-based delivery system of adipocytokines, which we recently developed, might induce immune-tolerance and functional recovery in fulminant myocarditis. Methods and Results: Lewis rats were immunized against myosin for 7 days to develop experimental autoimmune myocarditis (EAM), which is an established fulminant myocarditis model. Scaffold-free induced adipocyte cell-sheet (iACS) was generated by inducing differentiation of syngeneic cultured adipose tissue-derived stem cells into the adipocytes on the temperature responsive dishes. Supernatants of iACS contained a high level of APN and hepatocyte growth factor (HGF), and reduced proliferation of CD4-positive T cells that were sorted from splenocytes of the EAM rats, in-vitro . EAM rats underwent iACS implantation onto the anterior surface of the heart (n=24) or sham operation (n=24). Immunohistolabelling showed that CD4-positive T cells significantly less migrated in the anterior myocardium at 21 days after the iACS implantation (73±35 /mm 2 ) than the sham (148±38 /mm 2 , P=0.03). This finding was consistent with reduced expression of Tnfα and Il2 , assessed by real-time PCR, and elevated level of APN (48±5 ng/ml vs. 5±2 ng/ml P=0.01) and HGF (37±4ng/ml vs. 8±5ng/ml P=0.01), assessed by ELISA, in the myocardium after the iACS implantation compared to the sham. Consequently, left ventricular ejection fraction was significantly greater at 42 days after the iACS implantation (52±3.8%) than the sham (43±4.7%, P=0.03) in association with less myocardial collagen accumulation. Conclusion: This tissue-engineered iACS treatment suppressed intramyocardial T cell activity and inflammation by persistently supplying adipocytokines to the heart, consequently inducing functional recovery in the EAM rat model. The findings support possible translation of this strategy into the clinical arena.
Abstract 8416: Clinical Predictors of Short- and Long-Term Mortality Among Patients with Cardiovascular Implantable Electronic Device Infection
Authors: Ammar Habib, Katherine Y Le, Christine M Lohse, Paul A Friedman, David L Hayes, Walter R Wilson, James M Steckelberg, Larry M Baddour, Muhammad R
Journal: Circulation (2011)

Device infection is associated with increased mortality in cardiovascular implantable electronic device (CIED) recipients. However, published data regarding clinical predictors of mortality in patients with CIED infection are limited. In current investigation, we sought to identify patient and device-related factors associated with mortality in CIED infection cases. We performed a retrospective review of all cases of CIED infection admitted to Mayo Clinic Rochester from 1991 to 2008. Survival data were obtained from hospital medical records and United Sates Social Security Index. Key data regarding patient demographics, device features, comorbid conditions, clinical presentation, echocardiographic findings and management strategies were abstracted. Potential risk factors for short (30-day) and long-term mortality were analyzed using univariate and multivariable logistic and Cox proportional hazards regression models, respectively. 415 cases of CIED infection were identified from the institutional database. The mean duration of follow-up for the 243 patients who were alive at last follow-up was 6.9 years. In multivariable model, congestive heart failure (CHF, Odds ratio 9.31, 95% CI 2.08-41.67), chronic corticosteroid use (OR 4.04, 1.40-11.60) and presentation with CIED-related infective endocarditis (CIED-IE), (OR 5.6, 2.25-13.92) were associated with increased odds of short-term mortality. Independent predictors of long-term mortality on multivariable model included patients' age (hazard ratio for 10-year increase 1.2, 95% CI 1.06-1.36), CHF (HR 2.01, 1.42-2.86), metastatic malignancy (HR 5.99, 1.67-21.53), corticosteroid use (HR 1.97, 1.22-3.18), renal failure (HR 1.94, 1.37-2.74) and CIED-IE (HR 1.68, 1.17-2.41). Our investigation provides some novel insights into predictors of short- and long-term mortality in CIED infection cases. While comorbid conditions and immunocompromised host status were primary determinants of both short- and long-term mortality, complicated device infection (CIED-IE) is the only predictor that presents an opportunity for intervention where mortality may be reduced by early diagnosis and expedited device removal.
Abstract 12241: Electroanatomic Substrate in Postoperative Patients with Congenital Heart Disease and Intra-Atrial Reentrant Tachycardia - Increased Scar Burden after Fontan Surgery Predicts Arrhythmia Recurrence following Catheter Ablation
Authors: Sing-Chien Yap, Louise Harris, Eugene Downar, Kumaraswamy Nanthakumar, Candice K Silversides, Vijay S Chauhan
Journal: Circulation (2010)

Introduction: There is an increased propensity to intra-atrial reentrant tachycardia (IART) recurrence after radiofrequency catheter ablation (RFCA) in Fontan patients when compared to other postop...
Abstract 12398: Adenylyl Cyclase 6 Improves Calcium Handling and LV Function in Aging Hearts
Authors: Tong Tang, H. Kirk Hammond, Amy Firth, Yuan Yang, Mei Hua Gao, Jason X Yuan, N. Chin Lai
Journal: Circulation (2010)

Background: Aging heart is characterized by impaired beta-adrenergic receptor signaling and reduced left ventricular (LV) function. We tested the hypothesis that activation of adenylyl cyclase 6 (AC6) expression in cardiac myocytes improves Ca2+ handling and LV function in aging mice. Methods & Results: Twenty-month-old mice with cardiac-directed and regulated AC6 expression were randomized into two groups, and AC6 expression was activated in one group (AC6-On) but not the other (AC6-Off). One month later, LV function and changes in cardiac myocyte Ca2+ handling were assessed. AC6 expression was associated with increased LV ejection fraction (AC6-Off: 59±3%; AC6-On: 70±4%; P=0.02), and increased systolic elastance (AC6-Off: 1.8±0.6 mmHg/uL; AC6-On: 4.6±1.0 mmHg/uL; P=0.04) (Figure shows representative mice). No changes in LV weight/tibial length ratio, LV fibrosis, expression of fetal genes (atrial natriuretic factor, alpha-skeletal muscle actin, and beta-myosin heavy chain), or expression of collagens we...
Abstract 244: The Detail of Individual Cardiovascular Disease on Inhospital Cardiopulmonary Arrest; From the Japanese Registry of CPR for Inhospital Cardiac Arrest (J-RCPR)
Authors: Taro Sasaoka, Naohiro Yonemoto, Hiroyuki Yokoyama, Hiroshi Nonogi, J-Rcpr Investigators
Journal: Circulation (2010)

Background:  In-hospital cardiopulmonary arrest (IHCPA) is still a serious problem for cardiologists; recent studies have shown almost one half of all the IHCPA patients are based on cardiovascular diseases. However, the detail of individual cardiovascular disease remains unknown.   Method:  A total of 491 consecutive adults with IHCPA were registered in J-RCPR as a multicenter trial. Among them, 222 (45%) patients were hospitalized with the treatment of cardiovascular diseases; acute coronary syndrome (ACS, Group A, n=78), heart failure (HF, Group B, n=56), and arrhythmia (Group C, n=77).   Result:  Baseline characteristics of sex, age, and consciousness before IHCPA did not show significant difference in each group. Compared with other groups, Group B showed lower rate of ECG monitoring (Group A: 90%, Group B: 70%, Group C: 95%, p   Conclusion:  ACS patients showed higher rate of IHCPA within 2days of hospitalization; thus, we need to pay special attention to those patients in acute phase of hospitalization. In addition, the fact that patients with HF showed poor prognosis implies ECG monitoring and possible intensive care may lead to better outcome.
Abstract 17562: Poorer Survival with Insulin Therapy at Discharge in Diabetic Patients with Acute Myocardial Infarction: The FAST-MI Registry
Authors: Etienne Puymirat, Geraldine Vedrenne, Maria Pia Donataccio, Nadia Aissaoui, Jacques Machecourt, Marianne Zeller, Didier Carrie, Jean Ferrìeres, Tabassome Simon, Nicolas Danchin
Journal: Circulation (2011)

The role of insulin therapy after AMI is debated. We assessed 3-year survival in survivors of AMI with diabetes, according to the prescription of insulin at discharge. All patients were included in the FAST-MI registry, a French nationwide registry of patients with AMI hospitalized in 2005 in 223 institutions. Of the 1228 diabetic patients, 467 (38%) had insulin at discharge. These were older (70±12 vs 69±12 years, p=0.004), had a higher GRACE risk score (156 ± 33 vs 147 ± 35, p&lt;0.001), higher admission glycemia (232 ± 110 vs 190 ± 85 mg/dL, p&lt;0.001), higher HbA1c (8.1 ± 1.6 vs 7.2 ± 1.4, p&lt;0.001) and longer duration of diabetes (diabetes Hx &gt;10 years: 35% vs 16.5%, p&lt;0.001). Type of MI did not differ (STEMI: 39% vs 44%, p=0.11). Fewer patients in the insulin group had coronary angiography (78% vs 88%, p&lt;0.001) or PCI (53% vs 67%, p&lt;0.001) during the hospital stay. Optimal medical therapy at discharge was prescribed in 51% vs 47% of the patients, respectively (P=0.12). Finally, other antidiabetic medications at discharge were less frequent in the insulin group (metformin: 8% vs 25%, p&lt;0.001; sulfonylureas: 9% vs 36%, p&lt;0.001; glitazones: 0.2% vs 3.4%, p&lt;0.001). Three-year survival was 66% in insulin-treated versus 80% in patients without insulin (p&lt;0.001). Subgroup analyses confirmed higher mortality in patients with insulin at discharge in both STEMI and NSTEMI patients, in those aged 75 years or less, or in those with or without PCI. Using Cox multivariate analysis (covariates: age, sex, risk factors, comorbidities, type of AMI, CAD extent, use of PCI, use of CABG, HbA1c and admission glycemia levels, duration of diabetes, in-hospital complications, and other discharge medications), the adjusted HR for 3-year death was 1.56 (1.15-2.10), p=0.004, for patients with insulin at discharge; when treatment with insulin within 48 hours of admission was added to the model, the HR was 1.40 (1.06-1.84), p&lt;0.02. Finally, in propensity score matched cohorts (n=240 in each group), HR for death at 3 years was 1.41 (1.01-1.98), p=0.04 for patients receiving insulin. Conclusion: in this real-world nationwide registry, the prescription of insulin at discharge in diabetic patients was associated with poorer long-term survival, even after extensive multivariate adjustment for confounders.
Abstract 14132: Importance of Confirmation of Mitral Isthmus Block During Ablation of Persistent Atrial Fibrillation
Authors: Michael L Bernard, Frank Cuoco, Peter Netzler, Christopher Rowley, J Lacy Sturdivant, Robert Leman, Michael R Gold, J Marcus Wharton
Journal: Circulation (2011)

Introduction: Linear lesions across the posterior mitral isthmus (PMI) have been shown to increase the success rate of catheter ablation (CA) of persistent AF. However, PMI ablation often requires ...
Genomic landscape of cutaneous T cell lymphoma
Authors: Jaehyuk Choi, Gerald Goh, Trent Walradt, Bok S Hong, Christopher G Bunick, Kan Chen, Robert D Bjornson, Yaakov Maman, Tiffany Wang, Jesse Tordoff, Kacie Carlson, John D Overton, Kristina J Liu, Julia M Lewis, Lesley Devine, Lisa Barbarotta, Francine M Foss, Antonio Subtil, Eric C Vonderheid, Richard L Edelson, David G Schatz, Titus J Boggon, Michael Girardi, Richard P Lifton
Journal: Nature Genetics (2015)
Abstract 15957: Prospective Assessment of the Relationship Between Use of Evidence-Based Secondary Prevention Therapies and Long-Term (4-Year) Clinical Outcomes in Stable Outpatients With Established Atherothrombotic Disease: Insights from the International REduction of Atherothrombosis for Continued Health (REACH) Registry
Authors: Dharam J Kumbhani, Ph. Gabriel Steg, Christopher P Cannon, Kim A Eagle, Sidney C Smith, Kevin Crowley, Shinya Goto, E M Ohman, Deepak L Bhatt
Journal: Circulation (2011)

Objectives: Significant variations exist in the use of long-term evidence-based secondary prevention therapies such as antiplatelet agents, statins, and anti-hypertensive medications in patients wi...
Delayed discharge and hospital congestion
Authors: D. R J Jarrett
Journal: BMJ (2003)

Editor—Black and Pearson identified the complex factors driving up length of stay and causing palpable tensions in every hospital in the United Kingdom.1 The NHS is unique among health services in having no effective lever to discharge patients who no longer require hospital care. Black and Pearson say that patients can elect to remain in hospital until a final placement is found. In reality it is not so much patients seeking placements at rest homes and nursing homes but their families, who have the power to adopt an approach of masterful inactivity to discharge.

In North America and most of Europe powerful financial incentives mitigate unnecessary delays to discharge from hospital. We have the ludicrous situation whereby many frail acutely ill elderly people are being discharged home too early in an attempt to reduce their length of stay by one or two days, with all the concomitant risks of failed discharge and readmission. At the other end of the spectrum many discharges grind to a halt, with inordinately long length of stay far outweighing the occupied bed days saved by risky premature discharge. We are compromising the care of acutely ill elderly people at the expense of neglecting the delayed discharges of a relatively small number of patients with very long length of stay.

In our own unit a spot survey in October last year showed that out of 398 beds in the department, 152 were occupied by patients whose discharge had been delayed. Of the 172 patients in continuing care, four were deemed to have had their discharge delayed owing to patient or family choice. These patients had an average delay of about 210 days from the time they were deemed fit for discharge—the equivalent of lopping two days off the length of stay of 100 acute patients.

We need to tackle the politically sensitive issue of discharging patients from hospital against patients', or more realistically patients' families', wishes rather than invest huge effort in trying to prevent admission of acutely ill patients with a variety of ill conceived and untested initiatives for intermediate care. We suspect that this will not happen so long as politicians and policy makers fear the adverse publicity from a few individual cases more than the less dramatic media coverage of delayed discharges and cancelled operations.
Abstract P6-03-09: Targeting the c-myc/E2F1 pathway in TNBC promotes a DNA damage dependent synthetic lethality
Authors: Jason P Carey, Khandan Keyomarsi
Journal: Cancer Research (2015)

Abstract The c-myc/E2F1 pathway is highly upregulated in TNBC and dictates increased genomic instability, a higher frequency of relapse and poor overall survival. C-myc is a potent oncogene with overexpression activity that influences several pathways including metabolism, DNA replication, DNA damage, cell cycle and apoptosis. The essential role of c-myc in normal cells has made therapeutic intervention elusive. However the role of c-myc influencing cell cycle progression has demonstrated that CDK inhibition downregulates c-myc expression in TNBC breast cancer cells. We hypothesize that CDK inhibition downregulates c-myc expression resulting in an accumulation of DNA damage thus increasing the susceptibility of TNBC cells to PARP inhibition. A panel of TNBC cell lines was assessed for c-myc/E2F1 pathway expression and downregulation in the presence of CDK inhibitor Dinaciclib. An MTT-based High Throughput Survival Assay (HTSA) was utilized to assess growth inhibition response to drug treatment in TNBC cells. FACS analysis was performed on Dinaciclib treated TNBC cell lines to asses cell cycle response to CDK inhibition. DNA damage and Homologous Recombination DNA repair was assessed by γH2AX, BRCA1, RAD51 foci formation by immunofluorescence. Lentiviral knockdown of c-myc, E2F1, BRCA1 and RAD51 were performed to assess susceptibility to PARP inhibition. Combination treatment of Dinaciclib + PARP inhibitor MK4827 was assessed via combination index values calculated by Calcusyn. CDK inhibition resulted in downregulation of both c-myc and E2F1 in all TNBC cells. The pan-CDK inhibitor Dinaciclib universally inhibited proliferation in all TNBC cell lines in the presence of the drug however drug removal allowed TNBC cells to recover a normal proliferative profile. Dinaciclib induction increased γH2AX foci formation while decreasing BRCA1 and RAD51 foci formation resulting in an increase in DNA damage induced cell death that correlated with c-myc downregulation. CDK inhibition correlated with downregulation of c-myc/E2F1 target genes. Lentiviral knockdown of c-myc and not E2F1 induced susceptibility to PARP inhibitor MK4827. Combination CDK + PARP inhibitor resulted in a dose dependent synthetic lethal increase in PARP inhibitor efficacy in both BRCA1 mutant and wild-type cells. Together these results suggest that c-myc downregulation via CDK inhibition in combination with PARP inhibition may pose a novel combination therapy for TNBC patients. Citation Format: Jason P Carey, Khandan Keyomarsi. Targeting the c-myc/E2F1 pathway in TNBC promotes a DNA damage dependent synthetic lethality [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-03-09.