bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2583: Successful Use Of Immune Monitoring (Cylex) In Heart Trasnplantation For Rejection And Infection Risk
Authors: Kobashigawa Jon , Kiyosaki Krista , Kubak Bernard , Patel Jignesh , Kittleson Michelle , Ardehali Abbas 
Published: July 2021

Background: An unmet need in heart transplantation (HTx) has been the lack of a reliable immune monitoring test to indicate recipient immunoresponsiveness (IR). Trough immunosuppression blood levels do not reflect a recipient’s IR state. Recently, immune monitoring with Cylex (measure of ATP levels from activated lymphocytes) has been reported to predict risk of rejection or infection in kidney transplant patients. We now review our experience with immune monitoring and clinical course after HTx.
Methods: Between 2005 and 2007, 41 HTx patients had 82 immune monitoring assays obtained from 12 to 3034 days after HTx. ATP activity was graded as low IR (<225 ng/ml), moderate IR (225–525 ng/ml), or high IR (>525 ng/ml). Immune monitoring scores were correlated to infection and rejection episodes. All patients were treated with triple drug immunosuppression (tacrolimus, mycophenolate, and corticosteroids).
Results: For infectious episodes (n=34), immune monitoring scores <225 were found in 18/25 (72%) samples, compared to 16/57 (28%) samples >225, p < 0.001. The average immune monitoring score during infection compared to those samples without infection was 259 vs. 378, p <0.001. For rejection episodes (n=6), immune monitoring scores <225 were found in 0/24 (0%) samples compared to 6/58 (10%) samples >225, p = 0.101. The average immune monitoring score during rejection compared to those scores without rejection was 454 vs. 318, p = 0.041. There were 34 infections (1 parasitic, 8 viral, 13 bacterial, and 12 fungal infections).
Conclusion: Immune monitoring with Cylex for HTx patients appears to reflect the degree of recipient IR state and risk for rejection and infection.
Abstract 2602: Elevated Serum Neopterin Levels and Adverse Cardiac Events in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Kaski Juan Carlos , Consuegra-Sanchez Luciano , Fernandez-Berges Daniel J. , Cruz-Fernandez Jose M , Garcia-Moll Xavier , Marrugat Jaume , Mostaza José 
Published: July 2021

Objectives: We sought to assess whether plasma neopterin predicts adverse clinical outcomes in patients with NSTEACS. Background: Circulating C reactive protein (CRP), a marker of inflammation, correlates with events in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). High neopterin levels - a marker of macrophage activation - predict cardiovascular events in stable angina patients but their prognostic role in NSTEACS has not been systematically evaluated.
Methods: We prospectively assessed 397 patients (74 % men) admitted with NSTEACS: 169 (42.5%) had unstable angina and 228 (57.5%) non-ST-segment elevation myocardial infarction (NSTEMI). Blood samples for neopterin and CRP assessment were obtained at admission. TIMI risk score was also assessed among other clinical and biochemical variables. The study end point was the composite of cardiac death, acute myocardial infarction and recurrent angina at 180-days.

Results: Baseline neopterin concentrations (nmol/L) were similar in unstable angina and NSTEMI patients (8.3 [6.5–10.6] vs 8.0 [6.2–11.1], p = 0.54). Fifty-nine patients (14.9 %) had events during follow-up (highest third (%) 21.5 vs 1
st
and 2
nd
thirds 11.5, log rank 7.341, p = 0.007). On multivariable hazard Cox regression, only neopterin (highest vs 1
st
and 2
nd
thirds, HR 2.15, 95 % CI [1.21–3.81]) was independently associated with the combined endpoint.CRP levels, however, were not significantly different in patients with events compared to those without events (adjusted HR = 0.98, p = 0.89, 95% CI 0.80 –1.21).

Conclusion: Increased neopterin levels are an independent predictor of 180-day adverse cardiac events in patients with NSTEACS.
Abstract 2620: C1q Exacerbates Mitochondrial Dysfunction Without Activation Of The Terminal Complement In Neonatal Mice With Hypoxic-ischemic Brain Injury.
Authors: Ten Vadim S , Caspersen Casper , Baalasubramanian Sivasankar , Morgan Paul , Botto Marina , Starkov Anatoly , Polin Richard 
Published: July 2021

Deletion of C1q protects developing brain against hypoxia-ischemia (HI) (Ten V et al; 2005).
Hypothesis. C1q mediates HI-brain injury by:

Activation of terminal complement or/and

Exacerbation of mitochondrial dysfunction.

Hypothesis (1) P7 WT (C57Bl/6j) pre-treated with vehicle or sCD59; progenies of C1q+/-, Factor B/C2-/-/-/- inter-mating were subjected to HI: ligation of right carotid artery + hypoxic exposure. At 24 hr of reperfusion the extent of damage, cerebral deposition of C1q, C3, iC3b and C9 were assessed. Hypothesis (2) In C1q-/-and WT mice cerebral ATP-content, mitochondrial O2-consumption rate, H2O2-production and membrane potential (î»m) were studied immediately after HI. At 12 hr electron microscopy for co-staining of C1q and gC1qR/p33 in neurons was performed. WT and C1q-/- cortical and granule neurons in culture were subjected to glutamate or energy failure stress (EFS), glucose deprivation and exposure to 5 mM Na azide. At 24 hr after stress cellular viability, C1q protein and C9 mRNA expression were examined.
Results. C1q-/- mice were significantly protected against HI compared to +/+ counterparts. This was associated with robust attenuation of deposition of C3, iC3b and C9 in brain. However, no protection was detected in FB/C2-/ -/ -/ - and sCD59-pretreated mice, although C9-deposition in the injured brain was significantly decreased compared to controls. C1q-/ - mice exhibited a stunning preservation of ATP in the ischemic brain immediately after HI. This was associated with higher O2-consumption rate in state 3 and significantly (two-folds) less production of H2O2 by C1q-/ - mitochondria compared to WT-counterparts without difference in the î»m. In WT-mice HI resulted in intraneuronal, and intramitochondrial accumulation of C1q and gC1qR/p33 only in the ischemic hemisphere. C1q-/ - vs WT cultured neurons were significantly protected against excitotoxic and EFS in the absence of C9-mRNA in cellular lysate.
Conclusion. C1q mediates HI-injury. Terminal complement activation has no role in C1q-mediated neuronal damage. The presence of C1q is associated with significantly increased mitochondrial ROS-production in HI-brain. This may represent a novel mechanism for HI-neurodegeneration.
Abstract 2672: Serial in vivo Non-invasive Imaging of Intramyocardially Injected Autologous Mesenchymal Stem Cells, Modified for Transgene Expression of Positron-Emission Tomography (PET) Reporter in Porcine Myocardial Infarction
Authors: Gyongyosi Mariann , Blanco Jeronimo , Marian Terez , Petnehazy Ors , Hemetsberger Rayyan , Pavo Imre , Font Gusztav , Toth Lajos , Huber Kurt , Glogar Dietmar 
Published: July 2021

Objective. The aim of our study was to elaborate an in vivo tracking method of the intramyocardially injected msenchymal stem cells (MSCs), modified for transgene expression of trifusion protein (lentiviral vector, expressing renilla luciferase /RL/, red fluoroscein protein /RFP/ and herpes simplex truncated thymidine kinase /tTK, positron emmission tomography PET-reporter gene/) using serial PET imaging in pig myocardial infarction (MI).
Methods. Bone marrow (100 ml) was harvested from pigs immediately before induction of MI by percutaneous balloon occlusion of the LAD followed by reperfusion. The MSCs were selected and cultivated. The lentiviral vector LV-RL-RFP-tTK was inoculated into the MSCs under control of CMV promoter. The cells with the highest fluorescence intensity (after achieving appr. 50% transfection efficacy) were sorted, and tracked in vitro by PET using 9-(4-[18F]fluoro-3-hydroxymethylbutyl)-guanine (18FHBG). The transfected MSCs (at least 3 mio MSCs/ pigs) were then injected direct intramyocardially using NOGA electromagnetic guidance in pigs in 10 locations of the infarct border zone (min. 0.3 million cells/injection), followed by PET imaging 30 hours and 7 days later, after intravenous injection of 5 mCi 18FHBG.
Results. The in vitro 18FHBG uptakes of the transgene modified MSCs by PET were 10 times larger than the control JY human B-lymphoblasts and T lymphocytes. The minimum number of the cells detectable with PET was 0.2 million. MRI of the pigs revealed a mean global EF of 47+/-3.5%. PET imaging displayed diffuse distribution of the injected MSCs with high activity of the PET tracer in the anterior wall and septum at 30h, and less tracer activity in the injections sites with diffuse distribution in the pericardium and pleura indicating the wandering of the living cells at 7 days. PET imaging did not show 18FHBG accumulation in the infarcted heart of the control animals. Myocardial histology with RL and RFP staining confirmed the distribution of the injected MSCs through an elongated track around the injected area, 9 days after delivery.
Conclusion. In vivo tracking of gene-modified porcine MSCs by PET imaging is feasible and allows serial noninvasive imaging of homing and propagation of MSCs in pigs after MI.
Abstract 2840: An Impedance Threshold Device Improves 24 Hour Survival in a Spontaneously Breathing Pediatric Porcine Model of Hemorrhagic Shock
Authors: Metzger Anja , Marino Brad , Matsuura Tim , Alexander Carly , Herman Margot , McKnite Scott , Srinivasan Vijay , Nadkarni Vinay , Lurie Keith 
Published: July 2021

Introduction: Traumatic injury and hypovolemic shock are leading causes of death in children worldwide. We previously demonstrated that augmentation of negative intrathoracic pressure generated by spontaneously breathing through an impedance threshold device (ITD) improves blood pressure and cardiac output in a pediatric porcine model of hemorrhagic shock. However, the optimal method to restore intravascular volume, prevent secondary organ damage, and prevent progression of reversible shock to irreversible circulatory collapse after severe blood loss in children is not known.
Hypothesis: Breathing through an ITD for 90 min prior to fluid resuscitation will safely increase short and long-term survival rates.
Methods: Seventeen spontaneously breathing female piglets (12.4 ± 0.1 kg), anesthetized with propofol, were subjected to a 40% bleed and randomized in a prospective, blinded manner to either a sham or active ITD (cracking pressure of -7 cmH2O, Advanced Circulatory Systems, Minneapolis, MN) for 90 min. Shed blood was then reinfused. Work of breathing (WOB), 90 minute and 24 hour survival were evaluated. Survival analysis was performed using the Wilcoxon Rank Sum Test, Fischer’s Exact Test, and Kaplan-Meier Methods.
Results: Baseline and post-bleed heart rate, blood pressure, lactate levels, and arterial blood gas parameters were similar between groups. Piglets treated with the active ITD had significantly improved survival compared to the piglets treated with the sham ITD at 90 min (8/9 vs. 3/8, p=0.04). At 24 hours, Kaplan-Meier curve analysis revealed improved survival with the active ITD (6/9 vs. 2/8, p=0.04). The 3 animals in the active ITD group that did not survive died at a median time of 280 minutes (82–580), and the 6 animals in the sham group that did not survive, died at a median time of 69 minutes (24 –101) after bleed (p=0.11). The WOB at 45 min (J/L) was 73% higher in the active ITD group than the sham group (1.18 ± 0.07 vs. 0.68 ± 0.07, p= 0.001). The piglets safely tolerated the active ITD therapy.
Conclusion: In this spontaneously breathing, anesthetized piglet model of hemorrhagic shock, treatment with an active ITD for 90 min without supplemental fluid resuscitation significantly improved short and long-term survival rates.
Abstract 2919: Medical And Economic Long-term Effects Of B-type Natriuretic Peptide Testing In Patients With Acute Dyspnea
Authors: Mueller Christian , Breidthardt Tobias , Strohmeyer Anne-Henny , Schindler Christian , Meier Sophie , Fischer Michael , Scholer Andre , Noveanu Markus , Christ Michael , Perruchoud André P 
Published: July 2021

Background: The objective of this prospective study was to assess the medical and economic long-term effects of using B-type natriuretic peptide (BNP) levels in the management of patients with acute dyspnea.
Methods: We performed follow-up analysis of BASEL, a randomized study including 452 patients who presented to the emergency department with acute dyspnea. Participants were randomly assigned to a diagnostic strategy involving the rapid measurement of BNP levels (n=225) or assessment in a standard manner (n=227). Mortality was assessed at 720 days, morbidity and economic data at 360 days.
Results: BNP testing induced several important changes in initial patient management including a reduction in the initial hospital admission rate, the use of intensive care, as well as initial time to discharge. At 720 days, 172 deaths had occurred. Cumulative all-cause 720-day mortality was not different between the BNP group (37%) and the control group (36%, P =0.6). Morbidity as reflected by days spent in-hospital at 360 days was significantly lower in the BNP group (median 12 days [IQR 2–28]) as compared to the control group (median 16 days [IQR 7–32], P =0.025). Functional status was similar in both groups. Economic outcome as quantified by total treatment cost at 360 days was significantly improved in the BNP group (mean $10,144 versus $12,748 in the control group, P =0.008).
Conclusions: Rapid BNP testing in patients with acute dyspnea has no effect on long-term mortality. However, morbidity as quantified by days spent in-hospital and economic outcome are still improved at 360 days.
Abstract 2983: Sex Differences in Quality of Life and Health Status in the COURAGE Trial
Authors: Kolm Paul , Boden William E , Spertus John A , Maron David J , O’Rourke Robert , Dada Marcin , Zhang Wei , Hartigan Pamela M , Weintraub William S 
Published: July 2021

Purpose: The Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial randomized 2,287 patients to percutaneous coronary intervention (PCI) plus optimal medical treatment (OMT) or OMT alone. The purpose of this study was to assess sex differences in quality of life (QOL) and health status between randomized initial management strategies over the trial follow-up period.
Methods: Of the 2,287 patients, 979 males and 169 females were randomized to PCI, and 968 males and 169 females were randomized to OMT. Quality of life was assessed with the Seattle Angina Questionnaire (SAQ) and health status with the RAND-36 at baseline, 1, 3, 6, 12 months and annually thereafter. SAQ and RAND-36 scores were assessed by analysis of variance (ANOVA), and linear mixed effects models.

Results: There were no significant sex by treatment group interactions indicating PCI vs. OMT differences were similar for the 1,947 men (85%) and 338 women (15%). Men had significantly higher SAQ Physical Functioning scores at baseline and 1 month post-treatment (p < 0.004) and a trend of higher means thereafter (Figure 1A

) and significantly higher RAND-36 Physical Functioning scores over 3 years of follow-up (p < 0.001, Figure 1B

). Men also had significantly higher RAND-36 Energy/Fatigue means scores (p < 0.05, Figure 1C

). RAND-36 scores for the other domains were similar fbetween the two groups (Figure 1D

).

Conclusions: Men and women in both arms experienced improvement in quality of life and health status over time. Men had significantly higher physical functioning as well as energy/fatigue scores, but were similar to women in other quality of life and health status domains.
Abstract 3003: Programmed Ventricular Stimulation Does Not Predict the Outcome of Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (from DARVIN study)
Authors: Corrado Domenico , Leoni Loira , Link Mark S , Calkins Hugh , Wichter Thomas , Bevilacqua Michela , Basso Cristina , McKenna William J , Estes Mark N , Favale Stefano , Santini Massimo , Buja Gianfranco , Thiene Gaetano , Iliceto Sabino 
Published: July 2021

Background: The Defibrillator in Arrhythmogenic Right Ventricular Cardiomyopathy International (DARVIN) study was a multicenter investigation that enrolled patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) who received an implantable defibrillator (ICD) for either secondary or primary prevention of sudden death.
Methods: In this DARVIN substudy, we examined whether programmed ventricular stimulation (PVS) is able to predict the arrhythmic risk in a large cohort of 201 ARVC patients (133 males, 68 females, aged 36 ± 12 years) who received an ICD. Implant indications were a history of cardiac arrest in 13 (6%) patients; sustained ventricular tachycardia (VT) in 82 (41%); syncope in 42 (21%); asymptomatic nonsustained VT in 40 (20%); and a family history of sudden death in 24 (12%). PVS prior to ICD implantation was carried out in 143 of 201 patients (71%). All antiarrhythmic drugs were discontinued ≥ 5 half-lives (≥ 6 weeks for amiodarone) before the study. PVS included a minimum of 2 drive cycles length and up to 3 ventricular extrastimuli while pacing from two right ventricular sites.
Results: One hundred-nine patients (76%) were inducible to either sustained VT (patients 70; 64%), with a mean cycle length of 287 ± 66ms (range 220 to 410 ms), or ventricular fibrillation/flutter (VF) (patients 39; 36%). Of 109 patients who were inducible at PVS, 56 (52%) did not experience ICD therapy during a mean follow-up of 47 ± 22 months, whereas 11 of 34 (33%) noninducible patients had appropriate ICD interventions. Overall, the positive predictive value of PVS was 48%, the negative predictive value 67%, and the test accuracy 53%. The incidence of ICD discharges on VF, which in all likelihood would have been fatal in the absence of ICD therapy, did not differ between patients who were and were not inducible at PVS (26 of 109, 24% vs 7 of 34, 21%; p=0.87), regardless of clinical presentation. The type of ventricular arrhythmia inducible at PVS did not predict VF during the follow-up.
Conclusions: The presence (or absence) of an inducible arrhythmia on PVS did not correlate with subsequent appropriate ICD interventions, suggesting a limited role for PVS in arrhythmic risk stratification of ARVC patient population. A negative PVS may not indicate better prognosis.
Abstract 3021: Fatigue as a symptom of Acute Myocardial Infarction
Authors: Eckhardt Ann , Fennessy Michelle , Fink Anne , Jones Jessica , Szigetvari Kathryn , Kruse Donna , Tucco Laura , Ryan Cathy , Zerwic Julie J 
Published: July 2021

Purpose: Fatigue may be a commonly experienced symptom of acute myocardial infarction (AMI); however, there is a disturbing lack of data about the fatigue that occurs among men and women at the time of AMI. The purpose of this study was to characterize the fatigue experienced among men and women during AMI using three validated fatigue questionnaires.
Method: Ninety AMI patients were recruited from six Midwestern hospitals. The Profile of Mood States (POMS), Fatigue Severity Index (FSI), and the Short Form 36 Health Survey (SF-36) were completed by each hemodynamically stable subject.
Results: The sample included 76% men (mean age = 61, SD = 10), 24% women (mean age = 59, SD = 13); 78% non-Hispanic white. Subjects scored 1.7 on the POMS fatigue subscale (0 = none, 4 = extremely), 47.3 on the SF-36 vitality subscale (0 = most, 100 = least), and 6.4 on the “most fatigued” item of the FSI (0 = not fatigued at all, 10 = as fatigued as I could be). Scores from AMI subjects were compared to published scores in other populations. Compared to older adult male subjects, AMI subjects had higher levels of fatigue on the POMS fatigue subscale (M = 0.71, t = 7.2, p < 0.001) and the SF-36 vitality subscale (M = 51.0, t = 2.85, p < 0.01). In addition, AMI patients were more fatigued on the “most fatigued” item of the FSI compared to cancer patients in active treatment (M = 5.5, t = 2.28, p = 0.05). Men and women reported similar levels of fatigue across all three measures; however, women reported that fatigue caused more disruption of activities of daily living (p < 0.001), more difficulty with physical activities (p < 0.01), poorer rating of general health (p < 0.05), and more interference with social activities (p < 0.05).
Conclusion: To date, fatigue as a symptom of AMI has focused on using qualitative methods in women. This study used three well-established measures of fatigue to demonstrate that fatigue is commonly experienced by both men and women and at levels that are higher than a healthy older adult sample and cancer patients. Interestingly, fatigue had a greater negative impact on women’s lives.
Abstract 433: HDAC7 is Essential for Stem Cell Differentiation into Smooth Muscle Cells
Authors: Margariti Andriana , Xiao Qingzhong , Zampetaki Anna , Hu Yanhua , Zeng Lingfang , Xu Qingbo 
Published: July 2021

Background: Embryonic stem cells (ESCs) possess the potential to differentiate into specific cell lineages, such as vascular smooth muscle cells (SMCs). The homeostasis of histone acetylation and deacetylation mediated by histone deacetylase (HDAC) is known to play a central role in the regulation of gene expression, through co-operation with other transcription factors. However, it is unknown whether HDAC plays a role in mediating stem cell differentiation into SMCs.
Methods and results: Mouse ESCs were seeded on collagen IV-coated flasks and cultured in the absence of Leukemia Inhibitory Factor (LIF) in differentiation medium for 3 to 9 days in order to induce SMCs differentiation. Western blots and double-immunofluorescence staining demonstrated that HDAC7 expressed in parallel with SMC marker genes. Upregulation of HDAC7 expression resulted in increase in SMC marker expression, while downregulation of HDAC7 by siRNA caused decrease of SMC marker expression. In ex vivo culture of embryonic cells from SM22-LacZ transgenic mice, over-expression of HDAC7 significantly increased beta-gal positive cells, indicating a crucial role of HDAC7 in SMC differentiation during embryonic development. An important observation of this study is that HDAC7 undergoes alternative splicing during ESC differentiation, resulting in alternative translation from second ATG codon, giving rise to a short HDAC7 missing the N-terminal 22 amino acids. We also found that PDGF induced SMCs differentiation through the regulation of HDAC7 transcription and splicing, in which siHDAC7 knockdown ablated PDGF-induced SMC marker expression. Spliced HDAC7 increased SMC differentiation, while the short HDAC7 had no effect or even downregulated SMC differentiation. Further experiments revealed that the short HDAC7 isoform bound to MEF2C, while the full length HDAC7 did not, indicating that HDAC7 splicing can induce SMCs differentiation through the modulation of MEF2C-mediated gene expression.
Conclusions: Our findings provide novel information on the mechanism involved in SMC differentiation, and identify HDAC7 as a new target in therapeutic intervention on vascular disease, where inhibition of vascular progenitor cell differentiation into SMCs would be beneficial.