Comparison Between Anatomical and Functional Imaging Modalities for Evaluation of Chest Pain in the Emergency Department.

Evaluation of chest pain in the emergency department (ED) frequently employs a noninvasive strategy, including coronary computed tomography angiography (CCTA), stress echocardiography (SE), or myocardial perfusion imaging (MPI). We sought to report the real-world experience of utilizing CCTA compared with SE and MPI at an urban hospital ED. We conducted a retrospective cohort study of consecutively enrolled patients presenting with chest pain who had normal or nondiagnostic electrocardiogram (ECG), negative initial troponin-T, at least intermediate risk based on modified Diamond-Forrester criteria, and who underwent CCTA, SE, or MPI based on their individual test eligibility criteria. The primary outcome was ED discharge time. Secondary outcomes included test utilization and 30-days rehospitalization rates. The 2,143 patients who were included (mean age was 56 ± 12 years; 55% women) utilization rate (test performed/eligible) was lower for CCTA (n = 354/1,329) and MPI (n = 530/1,435) compared with SE (n = 1,259/1,650), p <0.001. Mean ED discharge times for both CCTA and SE were 12.5 ± 7.4 versus 16 ± 7.3 hours for MPI (p <0.0001). Patients with SE and CCTA were less likely to undergo coronary angiography (29%, 25%, vs 52% for MPI). There was a 1% cardiac-related 30-days rehospitalization rate in the CCTA group versus 1% in SE and 3% in the MPI group (p <0.01). In conclusion, CCTA and SE were associated with faster ED discharge and lower frequency of diagnostic coronary angiography. Notwithstanding its clinical utility, CCTA was underutilized at our large urban ED setting.

Coronary Computed Tomography Angiography Versus Stress Echocardiography in Acute Chest Pain: A Randomized Controlled Trial.

OBJECTIVES: This study sought to compare early emergency department (ED) use of coronary computed tomography angiography (CTA) and stress echocardiography (SE) head-to-head. BACKGROUND: Coronary CTA has been promoted as the early ED chest pain triage imaging method of choice, whereas SE is often overlooked in this setting and involves no ionizing radiation. METHODS: The authors randomized 400 consecutive low- to intermediate-risk ED acute chest pain patients without known coronary artery disease and a negative initial serum troponin level to immediate coronary CTA (n = 201) or SE (n = 199). The primary endpoint was hospitalization rate. Secondary endpoints were ED and hospital length of stay. Safety endpoints included cardiovascular events and radiation exposure. RESULTS: Mean patient age was 55 years, with 43% women and predominantly ethnic minorities (46% Hispanics, 32% African Americans). Thirty-nine coronary CTA patients (19%) and 22 SE patients (11%) were hospitalized at presentation (difference 8%; 95% confidence interval: 1% to 15%; p = 0.026). Median ED length of stay for discharged patients was 5.4 h (interquartile range [IQR]: 4.2 to 6.4 h) for coronary CTA and 4.7 h (IQR: 3.5 to 6.0 h) for SE (p < 0.001). Median hospital length of stay was 58 h (IQR: 50 to 102 h) for coronary CTA and 34 h (IQR: 31 to 54 h) for SE (p = 0.002). There were 11 and 7 major adverse cardiovascular events for coronary CTA and SE, respectively (p = 0.47), over a median 24 months of follow-up. Median/mean complete initial work-up radiation exposure was 6.5/7.7 mSv for coronary CTA and 0/0.96 mSv for SE (p < 0.001). CONCLUSIONS: The use of SE resulted in the hospitalization of a smaller proportion of patients with a shorter length of stay than coronary CTA and was safe. SE should be considered an appropriate option for ED chest pain triage (Stress Echocardiography and Heart Computed Tomography [CT] Scan in Emergency Department Patients With Chest Pain; NCT01384448).

A plant-derived recombinant human glucocerebrosidase enzyme--a preclinical and phase I investigation.

UNLABELLED: Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase leading to the dysfunction in multiple organ systems. Intravenous enzyme replacement is the accepted standard of treatment. In the current report, we evaluate the safety and pharmacokinetics of a novel human recombinant glucocerebrosidase enzyme expressed in transformed plant cells (prGCD), administered to primates and human subjects. Short term (28 days) and long term (9 months) repeated injections with a standard dose of 60 Units/kg and a high dose of 300 Units/kg were administered to monkeys (n = 4/sex/dose). Neither clinical drug-related adverse effects nor neutralizing antibodies were detected in the animals. In a phase I clinical trial, six healthy volunteers were treated by intravenous infusions with escalating single doses of prGCD. Doses of up to 60 Units/kg were administered at weekly intervals. prGCD infusions were very well tolerated. Anti-prGCD antibodies were not detected. The pharmacokinetic profile of the prGCD revealed a prolonged half-life compared to imiglucerase, the commercial enzyme that is manufactured in a costly mammalian cell system. These studies demonstrate the safety and lack of immunogenicity of prGCD. Following these encouraging results, a pivotal phase III clinical trial for prGCD was FDA approved and is currently ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT00258778.

Human erythropoietin gene therapy for patients with chronic renal failure.

Gene therapy holds a major promise. However, until now, this promise was fulfilled only in few cases, in rare genetic diseases. One very common clinical condition is anemia. Patients with anemia of chronic renal failure are treated with erythropoietin. The objective of this study was to develop a therapeutic platform for serum-secreted proteins like erythropoietin. We developed a tissue protein factory based on dermal cores (Biopump) harvested and implanted autologously. In this study, an adenovector was designed to express the human erythropoietin under the control of the cytomegalovirus (CMV) promoter. This vector transduced the harvested dermal cores ex vivo. The transduced cores were implanted, and erythropoietin and reticulocyte counts were measured. Dermal cores were harvested from 13 patients with chronic renal failure, and implantation was performed in 10. There were no significant drug-related side effects to this procedure. Erythropoietin serum levels increased significantly to therapeutic levels from day 1 after implantation reaching a peak during the first week of follow-up. The expression period was transient for up to 14 days. The rise of erythropoietin was followed by a transient significant increase in reticulocyte counts. The decrease of erythropoietin expression coincided with a significant dermal infiltrate of CD8 cytotoxic T cells. Antierythropoietin antibodies were not detected until day 90 following implantation. Implantation of dermal cores ex vivo transduced with human genes could eventually be used in the clinical setting to express therapeutic serum proteins. However, nonimmunogenic delivery system should be tested as gene vehicles.