Citations

Background: Multivessel coronary artery disease carries significant mortality risk. Comprehensive data on inhospital outcomes following multivessel percutaneous coronary intervention (MVPCI) are sparse. Methods: We queried the Healthcare Cost and Utilization Project’s nationwide inpatient sample (NIS) between 2006 and 2011 using different International Classification of Diseases, 9th Revision, Clinical Modification procedure codes. The primary outcome was inhospital all-cause mortality, and the secondary outcome was a composite of inhospital mortality and periprocedural complications. Results: The overall mortality was low at 0.73% following MVPCI. Multivariate analysis revealed that (odds ratio, 95% confidence interval, P value) age (1.63, 1.48-1.79; <.001), female sex (1.19, 1.00-1.42; P = .05), acute myocardial infarction (AMI; 2.97, 2.35-3.74; <.001), shock (17.24, 13.61-21.85; <.001), a higher burden of comorbidities (2.09, 1.32-3.29; .002), and emergent/urgent procedure status (1.67, 1.30-2.16; <.001) are important predictors of primary and secondary outcomes. MVPCI was associated with higher mortality, length of stay (LOS), and cost of care as compared to single vessel single stent PCI. Conclusion: MVPCI is associated with higher inhospital mortality, LOS, and hospitalization costs compared to single vessel, single stent PCI. Higher volume hospitals had lower overall postprocedural mortality rate along with shorter LOS and lower hospitalization costs following MVPCI.

Abstract Objective Clinicians’ ability to use and interpret genetic information depends upon how those data are displayed in electronic health records (EHRs). There is a critical need to develop systems to effectively display genetic information in EHRs and augment clinical decision support (CDS). Materials and Methods The National Institutes of Health (NIH)-sponsored Clinical Sequencing Exploratory Research and Electronic Medical Records & Genomics EHR Working Groups conducted a multiphase, iterative process involving working group discussions and 2 surveys in order to determine how genetic and genomic information are currently displayed in EHRs, envision optimal uses for different types of genetic or genomic information, and prioritize areas for EHR improvement. Results There is substantial heterogeneity in how genetic information enters and is documented in EHR systems. Most institutions indicated that genetic information was displayed in multiple locations in their EHRs. Among surveyed institutions, genetic information enters the EHR through multiple laboratory sources and through clinician notes. For laboratory-based data, the source laboratory was the main determinant of the location of genetic information in the EHR. The highest priority recommendation was to address the need to implement CDS mechanisms and content for decision support for medically actionable genetic information. Conclusion Heterogeneity of genetic information flow and importance of source laboratory, rather than clinical content, as a determinant of information representation are major barriers to using genetic information optimally in patient care. Greater effort to develop interoperable systems to receive and consistently display genetic and/or genomic information and alert clinicians to genomic-dependent improvements to clinical care is recommended.

Dysfunction of the type 1 cholecystokinin (CCK) receptor (CCK1R) as a result of increased gallbladder muscularis membrane cholesterol has been implicated in the pathogenesis of cholesterol gallstones. Administration of ursodeoxycholic acid, which is structurally related to cholesterol, has been shown to have beneficial effects on gallstone formation. Our aims were to explore the possible direct effects and mechanism of action of bile acids on CCK receptor function. We studied the effects of structurally related hydrophobic chenodeoxycholic acid and hydrophilic ursodeoxycholic acid in vitro on CCK receptor function in the setting of normal and elevated membrane cholesterol. We also examined their effects on a cholesterol-insensitive CCK1R mutant (Y140A) disrupting a key site of cholesterol action. The results show that, similar to the impact of cholesterol on CCK receptors, bile acid effects were limited to CCK1R, with no effects on CCK2R. Chenodeoxycholic acid had a negative impact on CCK1R function, while ursodeoxycholic acid had no effect on CCK1R function in normal membranes but was protective against the negative impact of elevated cholesterol on this receptor. The cholesterol-insensitive CCK1R mutant Y140A was resistant to effects of both bile acids. These data suggest that bile acids compete with the action of cholesterol on CCK1R, probably by interacting at the same site, although the conformational impact of each bile acid appears to be different, with ursodeoxycholic acid capable of correcting the abnormal conformation of CCK1R in a high-cholesterol environment. This mechanism may contribute to the beneficial effect of ursodeoxycholic acid in reducing cholesterol gallstone formation.

The first objectives of this article are to review the structure, chemistry, and physiology of bile acids and the types of bile acid malabsorption observed in clinical practice. The second major theme addresses the classical or known properties of bile acids, such as the role of bile acid sequestration in the treatment of hyperlipidemia; the use of ursodeoxycholic acid in therapeutics, from traditional oriental medicine to being, until recently, the drug of choice in cholestatic liver diseases; and the potential for normalizing diverse bowel dysfunctions in irritable bowel syndrome, either by sequestering intraluminal bile acids for diarrhea or by delivering more bile acids to the colon to relieve constipation. The final objective addresses novel concepts and therapeutic opportunities such as the interaction of bile acids and the microbiome to control colonic infections, as in Clostridium difficile-associated colitis, and bile acid targeting of the farnesoid X receptor and G protein-coupled bile acid receptor 1 with consequent effects on energy expenditure, fat metabolism, and glycemic control.

AbstractRationale, aims and objectivesAlthough the condition of low haemoglobin (Hb) levels has been established as a risk factor in the development of coronary artery disease (CAD), it is still a debate particularly in patients with angiographically documented disease. In the present study, we sought to identify the relationship between Hb levels and the presence of CAD.MethodsThe study consisted of 356 consecutive patients referred for elective coronary angiography (CAG). Exclusion criteria included a history of prior MI within last 3 months, presence of neoplastic disorders or any inflammatory diseases or overt diabetes mellitus. Blood samples for haematologic and biochemical measurements were collected on admission following at least 12 hours of overnight fasting. Patients were divided into four groups based on the quartiles of Hb (quartile I < 13.50 g/dL, quartile II 13.50–14.70 g/dL, quartile III 14.71–15.74 g/dL, quartile IV > 15.74 g/dL). Additionally, patients filled out a questionnaire of asking their brief medical histories and baseline characteristics.ResultsLower Hb quartiles were independently related to the presence of CAD in subjects who were referred to elective CAG. The patients with older age [P = 0.008, odds ratio (OR) = 1.042], male gender (P = 0.007, OR = 3.408), in quartile I (P = 0.003, OR = 5.697), in quartile II (P < 0.001, OR = 8.767), in quartile III (P = 0.011, P = 3.076), higher white blood cells count (P = 0.037, OR = 1.208), lower platelet count (P = 0.049, OR = 0.995), condition of current smoker (P = 0.030, OR = 2.548), higher value of fasting glucose (P = 0.014, OR = 1.038), estimated glomerular filtration rate < 60 (mL/min/1.73 m2; P = 0.004, OR = 3.269) were more likely associated with the risk of the presence of CAD.ConclusionsThe present study revealed that lower quartiles of Hb levels were independently related to the presence of CAD in subjects who were referred to elective CAG. Hb levels, which can be measured easily in almost all medical centres, may be considered as a potential predictor for the presence of CAD in patients at high risk for CAD.

Lower body negative pressure (LBNP) is often used to simulate blood loss in humans. It is unknown if cerebral blood flow responses to actual blood loss are analogous to simulated blood loss during LBNP. Nine healthy men were studied at baseline, during three levels of LBNP (5 min at −15, −30, and −45 mmHg), and during three levels of blood loss (333, 667, and 1,000 ml). LBNP and blood loss conditions were randomized. Intra-arterial mean arterial pressure (MAP) during LBNP was similar to that during blood loss ( P ≥ 0.42). Central venous pressure (2.8 ± 0.7 vs. 4.0 ± 0.8, 1.2 ± 0.6 vs. 3.5 ± 0.8, and 0.2 ± 0.9 vs. 2.1 ± 0.9 mmHg for levels 1, 2, and 3, respectively, P ≤ 0.003) and stroke volume (71 ± 4 vs. 80 ± 3, 60 ± 3 vs. 74 ± 3, and 51 ± 2 vs. 68 ± 4 ml for levels 1, 2, and 3, respectively, P ≤ 0.002) were lower during LBNP than blood loss. Despite differences in central venous pressure, middle cerebral artery velocity (MCAv) and cerebrovascular conductance were similar between LBNP and blood loss at each level (MCAv at level 3: 62 ± 6 vs. 66 ± 5 cm/s, P = 0.37; cerebrovascular conductance at level 3: 0.72 ± 0.05 vs. 0.73 ± 0.05 cm·s−1·mmHg−1, P = 0.53). While the slope of the MAP-MCAv relationship was slightly different between LBNP and blood loss (0.41 ± 0.03 and 0.66 ± 0.04 cm·s−1·mmHg−1, respectively, P = 0.05), time domain gain between MAP and MCAv at maximal LBNP/blood loss ( P = 0.23) and low-frequency MAP-mean MCAv transfer function coherence, gain, and phase were similar ( P ≥ 0.10). Our results suggest that cerebral hemodynamic responses to LBNP to −45 mmHg and blood loss up to 1,000 ml follow a similar trajectory, and the arterial pressure-cerebral blood velocity relationship is not altered from baseline under these conditions.