Insights into elastic fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in fibrillin 1 (FBN1) gene. These mutations result in defects in the skeletal, ocular, and cardiovascular systems. Aortic aneurysm is the leading cause of premature mortality in untreated MFS patients. Elastic fiber fragmentation in the aortic vessel wall is a hallmark of MFS-associated aortic aneurysms. FBN1 mutations result in FBN1 fragments that also contribute to elastic fiber fragmentation. Although recent research has advanced our understanding of MFS, the contribution of elastic fiber fragmentation to the pathogenesis of aneurysm formation remains poorly understood. This review provides a comprehensive overview of the molecular mechanisms of elastic fiber fragmentation and its role in the pathogenesis of aortic aneurysm progression. Increased comprehension of elastic fragmentation has significant clinical implications for developing targeted interventions to block aneurysm progression, which would benefit not only individuals with Marfan syndrome but also other patients with aneurysms. Moreover, this review highlights an overlooked connection between inhibiting aneurysm and the restoration of elastic fibers in the vessel wall with various aneurysm inhibitors, including drugs and chemicals. Investigating the underlying molecular mechanisms could uncover innovative therapeutic strategies to inhibit elastin fragmentation and prevent the progression of aneurysms.

Measuring Epidemiologic Effects of Enterococcal Bacteremia and Outcomes From a Nationwide Inpatient Sample Database.

Introduction Enterococcus is a gram-positive, non-sporing, facultative anaerobe. It is a common cause of nosocomial infections in the United States. Enterococcal bacteremia is primarily a nosocomial infection in the medical intensive care unit (ICU), with a preference for elderly patients with multiple comorbidities.  Material and methods This is a retrospective cohort study using the publicly accessible National (Nationwide) Inpatient Sample (NIS) database from October 2015 to December 2017. We examined data from 75,430 patients aged 18 years and older in the NIS who developed enterococcal bacteremia, as identified from the ICD-10 CM codes (B95), to discuss the epidemiologic effects and outcomes of enterococcal bacteremia. Patients were classified based on demographics, and comorbidities were identified. Three primary outcomes were studied: in-hospital mortality, length of stay, and healthcare cost. The secondary outcome was identifying any comorbidities associated with enterococcal bacteremia. Length of stay was defined as days from admission to discharge or death. Healthcare costs were estimated from the hospital perspective from hospital-level ratios of costs-to-charges. SAS 9.4 (2013; SAS Institute Inc., Cary, North Carolina, United States) was used for univariate and multivariate analyses. For data analysis, mortality was modeled using logistic regression. Length of stay and costs were modeled using linear regression, controlling for patient and hospital characteristics. Statistical analyses were performed using SAS. Statistical significance was defined as P<0.05. Results A total of 75,430 patients with enterococcal bacteremia were included in the study. Of this, 44,270 were males and 31,160 females. A total of 50,270 (68.67%) were Caucasians, 11,210 (15.31%) were African Americans, 6,445 (8.80%) were Hispanic and 2,025 (2.77%) were native Americans. Important comorbidities were congestive heart failure (25.91%), valvular disease (8.08%), neurological complications (11.87%), diabetes mellitus with complications (18.89%), renal failure (28.52%), and obesity (11.61%). In-hospital mortality was 11.07%, length of stay was 13.8 days, and a healthcare cost of 41,232.6 USD.  Conclusions Enterococcal bacteremia is a nosocomial infection with a preference for the elderly with renal failure, cardiac failure, cardiac valvular diseases, stroke, obesity, and diabetes with complications. Further studies are needed to see whether the mortality caused by enterococcal bacteremia is attributable to comorbidities or to the bacteremia. It is associated with a more extended hospital stay and higher healthcare expenditure. Implementing contact precautions to contain the spread of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus(VRE) has also checked the spread of enterococci. Further prospective studies can be planned using chart-based data.

Comparison of left ventricular mechanical dyssynchrony parameters between exercise and adenosine triphosphate stress tests using gated single-photon emission computed tomography myocardial perfusion imaging.

BACKGROUND: Left ventricular mechanical dyssynchrony (LVMD) can be induced after stress test. However, no studies have compared the influence of different stress­inducing methods on LVMD parameters. AIMS: The aim of the study was to determine whether there is a difference between exercise and adenosine triphosphate (ATP) stress tests in terms of changes in LVMD parameters assessed using gated single­photon emission computed tomography myocardial perfusion imaging (GSPECT MPI). METHODS: A total of190 patients who underwent 99mTc ­sestamibi GSPECT MPI were consecutively enrolled. Treadmill exercise and ATP stress tests were performed in 95 patients each. Normal myocardial perfusion was defined as the summed stress score (SSS) ≤3 and summed rest score (SRS) ≤3, myocardial ischemia as SSS >3 and SRS ≤3, and myocardial infarction as SSS >3 and SRS >3. Parameters of LVMD, including phase standard deviation (PSD), phase bandwidth (PBW), skewness, and kurtosis were compared. Subtraction was made between values during stress and rest phases to acquire ∆PSD, ∆PBW, ∆skewness, and ∆kurtosis Results: There were no differences in LVMD parameters between the exercise and ATP groups. The same results were obtained in the normal perfusion, ischemia, and infarction subgroups. Furthermore, no differences were observed in ∆PSD (median [interquartile range, IQR], 0.25 [-2.3 to 3.1] vs 0.42 (-1.7 to 3.1]; P = 0.73), ∆PBW (median [IQR], 1 [-7 to 11] vs 1 [-6 to 11]; P = 0.95), ∆skewness (mean [SD], -0.06 [0.63] vs 0 [0.81]; P = 0.53), and ∆kurtosis (median [IQR], -0.47 [-4.2 to 4.3] vs -0.42 [-4.8 to 5.2]; P = 0.73) between the exercise and ATP stress­inducing methods. CONCLUSIONS: There are no differences between the exercise and ATP stress tests in terms of changes in LVMD parameters. Thus, the 2 methods can be used alternatively.