Comparing downstream consequences of normal exercise stress echocardiograms and cardiac computed tomography angiography scans in patients suspected of having of obstructive coronary artery disease: a retrospective cohort study of Tricare beneficiaries.

To compare overall number of downstream tests and total costs between negative exercise stress echocardiograms (ESE) or cardiac computed tomography angiography scans (CCTA) in symptomatic Tricare beneficiaries suspected of having coronary artery disease (CAD). This is a retrospective cohort study examining 651 propensity-matched patients who underwent ESE or CCTA with normal results between 2008 and 2014 at the United States' largest Department of Defense hospital. The total number of additional downstream tests over the next five years was determined. The total costs associated with each arm, inclusive of the initial test and all subsequent tests, were calculated using the 2018 Medicare Physician Fee Schedule. 18.5 percent of patients with a normal ESE result underwent some additional form of cardiac testing over the five years after initial testing compared to 12.8 percent of patients with a normal CCTA. The absolute difference in total number of downstream tests between both study groups was 5.7 percent (p = 0.03). When factoring the costs of the initial test as well as the downstream tests, the ESE group was associated with overall lower costs compared to the CCTA group, 351 United States Dollars (USD) versus 496 USD (p < 0.0001). This study demonstrates that, when compared to CCTA, ESE is associated with a higher total number of downstream tests, but overall lower total costs when chosen as initial testing strategy for suspected CAD.

Reporting the Presence of Coronary Artery Calcium in the Final Impression of Non-gated CT Chest Scans Increases the Appropriate Utilization of Statins.

Background Coronary artery calcium (CAC) scoring based on gated non-contrast cardiac computed tomography (CT) is a validated risk marker of major adverse cardiovascular events (MACE). Reporting of CAC on non-gated CT chest (NGCT) scans and the impact on medical therapy is not well studied. Methods A retrospective cohort of 5,043 NGCT scans was reviewed for the presence of CAC. The radiology report was reviewed to determine whether CAC was mentioned in either the body of the report or the final impression. Electronic medical records (EMR) were abstracted for baseline demographics, cardiovascular (CV) risk factors, lipid-lowering agents, and aspirin (ASA) prior to and after NGCT. Results CAC was present in 63.0% of NGCT scans. Of these scans, CAC was mentioned in the body of the report in 81.6% of studies. Conversely, CAC was mentioned in the final impressions in only 15.1% of these scans. Amongst patients with CAC, initiation of a statin in treatment-naive patients was more common when CAC was mentioned in the final impression versus the body only (12.3% vs. 4.9%, p=0.001) despite the fact that baseline utilization of statins in this cohort was higher (71.1% vs. 64.1%, p=0.005). Initiation of a statin in treatment-naive patients had a trend towards significance when CAC was mentioned in the body of the report versus not reported (4.9% vs. 2.62%, p=0.142). Reporting of CAC in the final impression significantly increased the initiation of ASA in treatment-naive patients (9.52% vs. 4.33%, p=0.033). Reporting of CAC in either the final impression or the body of the report did not affect the initiation of non-statin lipid-lowering therapies in patients with CAC. Conclusion The inclusion of CAC in the final impression of NGCT radiology reports positively impacts the appropriate initiation of statin and aspirin therapy in treatment-naive patients. Universal adherence to a standardized reporting system for the presence of CAC on NGCT should be considered to improve the initiation of guideline-directed medical therapy.

Incidence and Implication of Coronary Artery Calcium on Non-gated Chest Computed Tomography Scans: A Large Observational Cohort.

Introduction  Coronary artery calcification (CAC) scoring is typically performed utilizing non-contrast, electrocardiogram- (ECG) gated CT and offers an estimation of cardiovascular (CV) prognosis and risk stratification beyond previously established cardiac risk factors. Coronary calcification can also be assessed during non-gated chest CT, which is significant given the recent recommendations for lung cancer screening by low-dose CT. Methods We retrospectively reviewed 4,953 non-contrast chest CT scans in a single, closed referral tertiary military treatment facility over an 18-month period. Baseline CV outcomes to include myocardial infarction (MI), cerebral vascular accidents (CVA), revascularization with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), death, or a composite of all major adverse cardiac events (MACE), and baseline CV risk factors were abstracted from an electronic medical record (EMR) review. Results CAC was seen in 3,119 (63%) patients while 1,834 (27%) were without CAC. All traditional CV risk factors were more commonly observed in patients with CAC. Unadjusted odds of composite MACE, death, MI, coronary revascularization, and CVA between presence and absence of CAC were as follows: 3.55 [95% confidence interval (CI): 2.60-4.86, p: <0.0001]; 2.98 (95% CI: 2.02-4.40, p: <0.0001); 24.42 (95% CI: 3.36-177.6, p: <0.0001); 5.64 (95% CI: 2.58-12.32, p: <0.0001); and 2.32 (95% CI: 1.19-4.50, p: 0.0104), respectively. However, after adjusting for baseline risk factors, CAC on non-gated CT was associated only with an increased observed rate of MI (aOR: 38.1, 95% CI: 4.57-318.2, p: <0.0001) and revascularization (aOR: 5.58, 95% CI: 2.22-14.0, p; 0.0003). Conclusions Findings of CAC on non-gated chest CT may help to recognize patients who are at increased risk of MI and revascularization. Given the expected increase in chest CT utilization among former smokers for lung cancer screening, observed CAC should be reported to ordering providers in order to identify patients at increased risk of these important outcomes.

Split-Night Polysomnography Overestimates Apnea-Hypopnea Index in High-Risk Professions.

INTRODUCTION: According to the American Academy of Sleep Medicine (AASM) guidelines, split-night polysomnography (SN-PSG) is an acceptable alternative to full-night PSG (FN-PSG) and may be considered in patients with an apnea-hypopnea index (AHI) ≥20/hr within the first 2 hours of the study. While SN-PSGs are an accurate approximation of moderate-to-severe obstructive sleep apnea (OSA), there remains the potential to misclassify the severity of sleep disordered breathing. Risks associated with the misclassification of OSA severity may be significant in high-risk professions such as active duty service members (ADSMs). The purpose of our study was to determine the accuracy of split-night polysomnography (SN-PSG) in a cohort of ADSMs. MATERIALS AND METHODS: We conducted a retrospective review of ADSMs undergoing FN-PSG with approval by our institution's Department of Clinical Investigation. FN-PSG data were processed using t-test, ANOVA, Chi-Squared, and logistical regression using JMP v12.0 to obtain partial-night data for the first 2 and 3 hours of recording. Significance was established with p-value less than 0.05. OSA severity was determined by calculating the AHI of each subject's FN-PSG and SN-PSG. RESULTS: Three-hundred patients were included in the study. Overall 79% were male with a mean age of 37.6 ± 8.4 years and mean BMI of 28.5 ± 3.3 kg/m2. Of our cohort, 112 patients (37%) would have qualified for a SN-PSG, of which 94 (84%) were appropriately classified and 18 patients (16%) were misclassified. CONCLUSIONS: In the relatively young, non-obese ADSM population, the majority did not qualify for a SN-PSG. The 3-hour SN-PSG accurately determined OSA severity in those with moderate-severe OSA; however, some patients with mild OSA would have been misclassified which can result in unnecessary duty limitations. A SN-PSG may not be ideal for this population.

Controlling dimensionality in templated layer, chain and framework structures by combining metal fluorides with oxotetrahedra.

The use of metal fluorides in hydrothermal reactions with linking phosphate and arsenate groups leads to the synthesis of numerous, frequently non-centrosymmetric, structures of controlled dimensionality.

Cerium(IV) fluoride and fluoride-arsenate frameworks.

Five new cerium (IV) fluoride and fluoride-arsenate framework structures have been synthesised hydrothermally using CeF(4) as a fluoride source. Cs[Ce(2)F(8)[F.H(2)O]] (I) consists of layers, formed from linked Ce(F,O)(n) polyhedra cross-linked by hydrogen bonding that defines large channels containing the caesium ions. [(NH(4))(5)(H(2)O)(2)][Ce(4)(AsO(4))(6)(H(2)O)F(3)] (II), has an open framework structure with large channels filled with NH(4)(+) cations and H(2)O molecules. Ce[AsO(4)]F (III) and Ce[AsO(4)]F[H(2)O] (IV) exhibit two types of bridging (Ce-O-Ce and Ce-F-Ce) bonds between Ce(O,F)(n) polyhedra, and (NH(4))[CeF(2)(AsO(4))] (V), is isostructural with the previously reported fluoride-phosphate (NH(4))[Ce(IV)F(2)(PO(4))] (R. B. Yu, D. Wang, T. Takei, N. Kumada, H. Koizumi and N. Kinomura, J. Solid State Chem., 2001, 157, 180).

Modifiers of mammary tumor progression and metastasis on mouse chromosomes 7, 9, and 17.

Tumor progression, the growth and dissemination of primary tumor to secondary sites, is of critical clinical importance since the vast majority of patients succumb to metastatic disease rather than to the primary tumor. Many factors are likely to influence this process, including the primary oncogenic events, environmental exposures and stress and progressive stochastic mutations. Previously, our laboratory demonstrated that an additional factor, the genetic background on which tumors arose, had a significant effect on metastatic efficiency. Using a highly metastatic transgene-induced mammary tumor model, a locus modulating metastatic efficiency, Mtes1, was localized on proximal mouse Chromosome 19. In addition, a number of additional suggestive loci were observed on several other chromosomes. To confirm the presence of these additional loci before initiating cloning strategies, chromosomal substitution strains have been constructed and assayed for modification of the cancer phenotypes. Using the chromosomal substitution strains, an additional modifier modulating tumor latency was confirmed, as well as three new modifier genes that alter the kinetics of tumor progression. Identification and analysis of these loci will likely present interesting and novel information about cancer heterogeneity in the human population.

Caffeine suppresses metastasis in a transgenic mouse model: a prototype molecule for prophylaxis of metastasis.

A significant fraction of cancer patients have occult disseminated tumors at the time of primary diagnosis, which usually progress to become clinically relevant lesions. Since the majority of cancer mortality is associated with metastatic disease, the ability to inhibit the growth of the secondary tumors would significantly reduce cancer-related morbidity and mortality. We have investigated whether caffeine, which has been shown to suppress tumor cell invasiveness and experimental metastasis, can suppress metastasis in a spontaneous transgene-induced mammary tumor model. Chronic exposure to caffeine prior to the appearance of palpable mammary tumors significantly reduced both tumor burden and metastatic colonization. However, when caffeine exposure began after the appearance of frank tumors, caffeine suppressed metastasis without changing primary tumor burden. The means by which caffeine suppressed metastatic activity may be associated with inhibition of malignant transformation of mammary epithelial cells, inhibition of conversion of dormant tumor cells to micrometastases, micrometastases to macrometastases, or inhibition of tumor cell adhesion and motility. Gene and protein expression patterns resulting from caffeine treatment showed that metastasis suppression may be associated with up-regulation the mRNA expression of multiple extracellular matrix genes, including Fbln1, Bgn, Sparc, Fbn1, Loxl1, Colla1, Col3a1, Col5a1, ColS5a2, ColSa3, Col6a1, Col6a2, and Col6a3. These data suggested that caffeine or other methyl xanthine derivatives may improve the clinical outcome in patients prior to and following the diagnosis of metastatic disease, and could potentially reduce the morbidity and mortality associated with disseminated tumors.

A bioinformatics-based strategy identifies c-Myc and Cdc25A as candidates for the Apmt mammary tumor latency modifiers.

The epistatically interacting modifier loci (Apmt1 and Apmt2) accelerate the polyoma Middle-T (PyVT)-induced mammary tumor. To identify potential candidate genes loci, a combined bioinformatics and genomics strategy was used. On the basis of the assumption that the loci were functioning in the same or intersecting pathways, a search of the literature databases was performed to identify molecular pathways containing genes from both candidate intervals. Among the genes identified by this method were the cell cycle-associated genes Cdc25A and c-Myc, both of which have been implicated in breast cancer. Genomic sequencing revealed noncoding polymorphism in both genes, in the promoter region of Cdc25A, and in the 3' UTR of c-Myc. Molecular and in vitro analysis showed that the polymorphisms were functionally significant. In vivo analysis was performed by generating compound PyVT/Myc double-transgenic animals to mimic the hypothetical model, and was found to recapitulate the age-of-onset phenotype. These data suggest that c-Myc and Cdc25A are Apmt1 and Apmt2, and suggest that, at least in certain instances, bioinformatics can be utilized to bypass congenic construction and subsequent mapping in conventional QTL studies.