Exploratory evaluation of the role of cardiac troponin on the clinical outcome of patients visiting emergency department with or without chronic kidney disease

Objective@#Elevated levels of cardiac troponin in chronic kidney disease (CKD) patients admitted to the emergency department (ED) is not well understood and is often ignored. This study aimed to investigate the impact of cardiac troponin I (TnI) levels on the clinical outcome of patients visiting the ED with or without CKD. @*Methods@#In this retrospective single-center cohort study, we enrolled patients visiting the ED without a diagnosis of coronary artery disease (CAD). Elevated cardiac TnI was defined as being ≥99th percentile of the normal population (Siemens ADVIA Centaur TnI-Ultra≥0.040 ng/mL). The clinical outcomes of patients with CKD stage≤2 and CKD stage ≥3 were compared. The primary endpoint was the 180-day all-cause death, including cardiovascular and non-cardiovascular deaths. @*Results@#Among a total of 30,472 patients (median age, 61 years; male sex, 54.3%), elevated TnI was found in 4,377 patients (14.4%). There were 3,634 deaths (11.9%) including 584 cardiovascular (1.9%) and 3,050 non-cardiovascular deaths (10.0%). The risk of all-cause death increased in patients with elevated TnI in both CKD stage≤2 (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.9-2.3) and CKD stage≥3 (HR, 1.5; 95% CI, 1.4-1.7), and so did the risks of cardiovascular and non-cardiovascular death (HR, 1.2-4.7) (P<0.05, all). The association of elevated TnI with death risk was consistent in multivariate analyses and in most clinical subgroup analyses. @*Conclusion@#Elevated TnI was associated with higher 180-day mortality irrespective of renal function among patients visiting the ED without documented CAD. CKD patients visiting the ED with elevated TnI may warrant additional evaluation or careful follow-up even without the presence of CAD.

Dynamic relocalization of NHERF1 mediates chemotactic migration of ovarian cancer cells toward lysophosphatidic acid stimulation

NHERF1/EBP50 (Na⁺/H⁺ exchanger regulating factor 1; Ezrin-binding phosphoprotein of 50 kDa) organizes stable protein complexes beneath the apical membrane of polar epithelial cells. By contrast, in cancer cells without any fixed polarity, NHERF1 often localizes in the cytoplasm. The regulation of cytoplasmic NHERF1 and its role in cancer progression remain unclear. In this study, we found that, upon lysophosphatidic acid (LPA) stimulation, cytoplasmic NHERF1 rapidly translocated to the plasma membrane, and subsequently to cortical protrusion structures, of ovarian cancer cells. This movement depended on direct binding of NHERF1 to C-terminally phosphorylated ERM proteins (cpERMs). Moreover, NHERF1 depletion downregulated cpERMs and further impaired cpERM-dependent remodeling of the cell cortex, suggesting reciprocal regulation between these proteins. The LPA-induced protein complex was highly enriched in migratory pseudopodia, whose formation was impaired by overexpression of NHERF1 truncation mutants. Consistent with this, NHERF1 depletion in various types of cancer cells abolished chemotactic cell migration toward a LPA gradient. Taken together, our findings suggest that the high dynamics of cytosolic NHERF1 provide cancer cells with a means of controlling chemotactic migration. This capacity is likely to be essential for ovarian cancer progression in tumor microenvironments containing LPA.

Conformance Analysis of Clinical Pathway Using Electronic Health Record Data / 대한의료정보학회지

OBJECTIVES: The objective of this study was to confirm the conformance rate of the actual usage of the clinical pathway (CP) using Electronic Health Record (EHR) log data in a tertiary general university hospital to improve the CP by reflecting real-world care processes. METHODS: We analyzed the application and matching rates of clinicians' orders with predefined CP order sets based on data from 164 inpatients who received appendectomies out of all patients who were hospitalized from August 2013 to June 2014. We collected EHR log data on patient information, medication orders, operation performed, diagnosis, transfer, and CP order sets. The data were statistically analyzed. RESULTS: The average value of the actual application rate of the prescribed CP order ranged from 0.75 to 0.89. The application rate decreased when the order date was factored in along with the order code and type. Among CP pre-operation, intra-operation, post-operation, routine, and discharge orders, orders pertaining to operations had higher application rates than other types of orders. Routine orders and discharge orders had lower application rates. CONCLUSIONS: This analysis of the application and matching rates of CP orders suggests that it is possible to improve these rates by updating the existing CP order sets for routine discharge orders to reflect data-driven evidence. This study shows that it is possible to improve the application and matching rates of the CP using EHR log data. However, further research should be performed to analyze the effects of these rates on care outcomes.

Discovery of Outpatient Care Process of a Tertiary University Hospital Using Process Mining / 대한의료정보학회지

OBJECTIVES: There is a need for effective processes in healthcare clinics, especially in tertiary hospitals, that consist of a set of complex steps for outpatient care, in order to provide high quality care and reduce the time cost. This study aimed to discover the potential of a process mining technique to determine an outpatient care process that can be utilized for further improvements. METHODS: The outpatient event log was defined, and the log data for a month was extracted from the hospital information system of a tertiary university hospital. That data was used in process mining to discover an outpatient care process model, and then the machine-driven model was compared with a domain expert-driven process model in terms of the accuracy of the matching rate. RESULTS: From a total of 698,158 event logs, the most frequent pattern was found to be "Consultation registration > Consultation > Consultation scheduling > Payment > Outside-hospital prescription printing" (11.05% from a total cases). The matching rate between the expert-driven process model and the machine-driven model was found to be approximately 89.01%, and most of the processes occurred with relative accuracy in accordance with the expert-driven process model. CONCLUSIONS: Knowledge regarding the process that occurs most frequently in the pattern is expected to be useful for hospital resource assignments. Through this research, we confirmed that process mining techniques can be applied in the healthcare area, and through detailed and customized analysis in the future, it can be expected to be used to improve actual outpatient care processes.

Inositol 5'-phosphatase, SHIP1 interacts with phospholipase C-gamma1 and modulates EGF-induced PLC activity

Phospholipase C-gamma1, containing two SH2 and one SH3 domains which participate in the interaction between signaling molecules, plays a significant role in the growth factor-induced signal transduction. However, the role of the SH domains in the growth factor-induced PLC-gamma1 regulation is unclear. By peptide-mass fingerprinting analysis, we have identified SHIP1 as the binding protein for the SH3 domain of PLC-gamma1. SHIP1 was co-immunoprecipitated with PLC-gamma1 and potentiated EGF-induced PLC-gamma1 activation. However, inositol 5'-phosphatase activity of SHIP1 was not required for the potentiation of EGF-induced PLC-gamma1 activation. Taken together, these results suggest that SHIP1 may function as an adaptor protein which can potentiate EGF-induced PLC-gamma1 activation without regards to its inositol 5'-phosphatase activity.

Dexamethasone differentiates NG108-15 cells through cyclooxygenase1 induction

Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid into prostanoids which participate in various cellular functions including apoptosis, mitogenesis, inflammation, immune modulation and differentiation. Moreover, the synthetic glucocorticoid, dexamethasone has immune modulating and anti-inflammatory effects in vivo. Recently, dexamethasone was found to enhance retinoic acid-induced neuronal differentiation. In this study, we investigated the mechanisms of dexamethasone-mediated neuronal differentiation. Immunoblotting and morphological analysis demonstrated that dexamethasone induced neuronal differentiation through COX 1 induction. This phenomenon was inhibited by indomethacin, a COX inhibitor. In addition, the addition of exogenous prostaglandin E2 (PGE2), a substance produced by the COX-mediated pathway, triggered neurite outgrowth of cells treated with COX inhibitor. Taken together, COX 1 appears to play an important role in dexamethasone-mediated neuronal differentiation.