Performance measurement of nonhomogeneous Hong Kong hospitals using directional distance functions.

Cook et al. (Oper Res 61(3):666-676, 2013) propose a DEA-based model for the performance evaluation of non-homogeneous decision making units (DMUs) based on constant returns to scale (CRS), extended by Li et al. (Health Care Manag Sci 22(2):215-228, 2019) to variable returns to scale (VRS). This paper locates these models into more general DDF models to deal with nonhomogeneous DMUs and applies these to Hong Kong hospitals. The production process of each hospital is divided into subunits which have the same inputs and outputs and hospital performance is measured using the subunits. The paper provides CRS and VRS versions of DDF models and compares them with Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019). A kernel-based method is used to estimate the distributions as well as a DEA-based efficiency analysis adapted by Simar and Zelenyuk to test the distributions. Both DDF CRS and VRS versions produce results similar to Cook et al. (Oper Res 61(3):666-676, 2013) and Li et al. (Health Care Manag Sci 22(2):215-228, 2019) respectively. However, the statistical tests find differences for the different technologies assumed as would be expected. For hospital managers, the more generalised DDF models expand their range of options in terms of directional improvements and priorities as well as dealing with non-homogeneity.

ADRB3 induces mobilization and inhibits differentiation of both breast cancer cells and myeloid-derived suppressor cells.

Metastatic tumors are mainly composed of neoplastic cells escaping from the primary tumor and inflammatory cells egressing from bone marrow. Cancer cell and inflammatory cell are remained in the state of immaturity during migration to distant organs. Here, we show that ADRB3 is crucial in cell mobilization and differentiation. Immunohistochemistry revealed ADRB3 expression is significantly more frequent in breast cancer tissues than in adjacent noncancerous tissues (92.1% vs. 31.5%). Expression of ADRB3 correlated with malignant degree, TNM stage and poor prognosis. Moreover, ADRB3 expression was markedly high in activated disseminated tumor cells, myeloid-derived suppressor cells (MDSCs), lymphocytes and neutrophil extracellular traps of patients. Importantly, ADRB3 promoted the expansion of MDSC through stimulation of bone marrow mobilization and inhibiting of the differentiation of immature myeloid cells. Furthermore, ADRB3 promoted MCF-7 cells proliferation and inhibited transdifferentiation into adipocyte-like cell by activating mTOR pathway. Ultimately, the MDSC-deficient phenotype of ADRB3 -/- PyMT mice was associated with impairment of mammary tumorigenesis and reduction in pulmonary metastasis. Collectively, ADRB3 promotes metastasis by inducing mobilization and inhibiting differentiation of both breast cancer cells and MDSCs.

Measuring work complexity for acute care services.

Case weights capture the resource cost by diagnosis-related group (DRG) but may not fully reflect the complexity of the clinical services provided. This study describes the use of a work complexity index (WCI), for assessing acute care services focusing on those provided by physicians in healthcare systems. The services are classified using relative value units (RVUs) and their point value assigned using the resource-based relative value scale. 57,559 acute inpatients from a tertiary hospital were first classified into diagnosis-related groups, which together with the relative value units assigned to services were then used to calculate a work complexity index for 38 departments. A case mix index (CMI) was also compiled as a conventional measure of complexity which had a correlation of 0.676 (p < 0.001) with the WCI. The correlation between the WCI and the RVUs representing the weighted volume of physician activities was 0.342 (p = 0.036). The WCI represents a more output or activity focused measure of complexity whereas the CMI is more patient focused and thus provides better insights into Departments' productivity. Although this paper focuses on physicians, the WCI can be easily extended to include other clinical services.

Risk Prediction Model for Uncontrolled Hypertension in Chinese Community.

BACKGROUND: Uncontrolled hypertension rate was still high across China. This study develops and validates an index to help quantify the combination of socio-behavioral aspects to screen high-risk patients in uncontrolled hypertension in Chinese primary care. METHODS: A cross-sectional study included 1,039 of patients with hypertension in the Chinese community. We assessed independent risk factors of uncontrolled blood pressure (defined as having a blood pressure ≥140/90 mmHg, even with antihypertensive therapy) and develop a risk prediction model. RESULTS: Among the 1,039 patients (53.9% male, the average age was 61 ± 13 years), 452 (43.5%) were uncontrolled hypertensive. Multivariable analysis showed that worker (odds ratio, OR: 1.98, 95% CI: 1.46-2.69), no health insurance (OR: 3.47, 95% CI: 2.08-5.80), non-marital status (OR: 2.01, 95% CI: 1.35-3.27), and other socio-behavioral aspects were independent risk factors of uncontrolled hypertension, which were included the final prediction model (C-static: 0.781). With internal validation by the bootstrap method, the risk score showed good discriminating ability and predicting ability for the incidence of uncontrolled hypertension (C-static: 0.771). CONCLUSIONS: This study showed that nearly half of the patients suffered from uncontrolled hypertension in the Chinese community. We established a prediction model with good predictability to help quantify the combination of socio-behavioral aspects and screen high-risk patients with uncontrolled hypertension.

ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma.

The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Genetic and pharmacologic inhibition of ADRB3 reverses tumor growth and inflammation in mouse. Furthermore, we demonstrate that M5D1, a novel anti-ADRB3 monoclonal antibody, inhibits human lung cancer cells proliferation and inflammation via affecting the intracellular mTOR pathway and activating p53. In NSCLC patients, we confirmed that upregulation of ADRB3 expression correlates with tumor progression and poor prognosis. Altogether, these results shed light on the role of ADRB3 in NSCLC and suggest that M5D1 could become powerful antitumor weapons.

MicroRNA­30a­5p promotes proliferation and inhibits apoptosis of human pulmonary artery endothelial cells under hypoxia by targeting YKL­40.

Pulmonary arterial hypertension (PAH) is a fatal and currently incurable cardiopulmonary disease. Numerous microRNAs (miRNAs) serve important roles in the development of PAH. While the expression of miR­30a­5p was downregulated in the lung tissue of rats in a pulmonary hypertension rat model, the expression pattern and function of miR­30a­5p in human PAH remain unclear. Reverse transcription quantitative polymerase chain reaction (RT­qPCR) was used to examine miR­30a­5p and chitinase­3­like protein 1 (YKL­40) mRNA expression levels. The expression levels of YKL­40 and apoptosis­associated proteins were measured by western blot analysis. Cell proliferation assays and flow cytometry analysis were performed to examine cell proliferation and apoptosis, respectively. The association between miR­30a­5p and YKL­40 was determined by a luciferase reporter assay, RT­qPCR and western blot analysis. The relative expression levels of miR­30a­5p in plasma were increased in patients with PAH [median=13.23 (25th percentile=6.388, 75th percentile=21.91)] compared with normal controls [median=2.25 (25th percentile=1.4, 75th percentile=3.7). The expression of miR­30a­5p was significantly downregulated while the protein expression of YKL­40 was significantly upregulated in hypoxia­induced human pulmonary artery endothelial cells (HPAECs) when compared with the hypoxia­induced group at 0 h. miR­30a­5p overexpression promoted HPAEC growth and inhibited apoptosis of HPAECs under hypoxia. A miR­30a­5p mimic decreased the luciferase activity of a luciferase reporter construct containing YKL­40 3'­untranslated region and also decreased YKL­40 protein expression. YKL­40 overexpression partly alleviated the effects of miR­30a­5p upregulation on proliferation and apoptosis of HPAECs under hypoxia. In conclusion, the data indicated that miR­30a­5p promoted cell growth and inhibited apoptosis of HPAECs under hypoxia by targeting YKL­40. Therefore, the miR­30a­5p/YKL­40 axis may provide a potential target for the development of novel PAH therapies.

N-terminal pro-brain natriuretic peptide improves the C-ACS risk score prediction of clinical outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: It remained unclear whether the combination of the Canada Acute Coronary Syndrome Risk Score (CACS-RS) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) could have a better performance in predicting clinical outcomes in acute ST-elevation myocardial infarction (STEMI) patients with primary percutaneous coronary intervention. METHODS: A total of 589 consecutive STEMI patients were enrolled. The potential additional predictive value of NT-pro-BNP with the CACS-RS was estimated. Primary endpoint was in-hospital mortality and long-term poor outcomes. RESULTS: The incidence of in-hospital death was 3.1%. Patients with higher NT-pro-BNP and CACS-RS had a greater incidence of in hospital death. After adjustment for the CACS-RS, elevated NT-pro-BNP (defined as the best cutoff point based on the Youden's index) was significantly associated with in hospital death (odd ratio = 4.55, 95%CI = 1.52-13.65, p = 0.007). Elevated NT-pro-BNP added to CACS-RS significantly improved the C-statistics for in-hospital death, as compared with the original score (0.762 vs. 0.683, p = 0.032). Furthermore, the addition of NT-pro-BNP to CACS-RS enhanced net reclassification improvement (0.901, p < 0.001) and integrated discrimination improvement (0.021, p = 0.033), suggesting effective discrimination and reclassification. In addition, the similar result was also demonstrated for in-hospital major adverse clinical events (C-statistics: 0.736 vs. 0.695, p = 0.017) or 3-year mortality (0.699 vs. 0.604, p = 0.004). CONCLUSIONS: Both NT-pro-BNP and CACS-RS are risk predictors for in hospital poor outcomes in patients with STEMI. A combination of them could derive a more accurate prediction for clinical outcome s in these patients.

Association between circulating levels of ACE2-Ang-(1-7)-MAS axis and ACE2 gene polymorphisms in hypertensive patients.

The angiotensin-converting enzyme 2-angiotensin-(1-7)-MAS axis (ACE2-Ang-[1-7]-MAS axis) plays an important role in the control of blood pressure. Some previous studies indicated that the genetic variants of ACE2 may have a potential to influence this axis. Therefore, the present study aimed at examining the association of ACE2 polymorphisms with circulating ACE2 and Ang-(1-7) levels in patients with essential hypertension.Hypertensive patients who met the inclusion criteria were enrolled in the present study. Three Tag single-nucleotide polymorphisms (rs2106809, rs4646155, and rs879922) in ACE2 gene were genotyped for all participants. Circulating ACE2 and Ang-(1-7) levels were detected by enzyme-linked immunosorbent assay.There were 96 (53.0%) females and 85 (47.0%) males participating in the present study. The circulating Ang-(1-7) levels were significantly greater in female patients carrying the rs2106809 CC or CT genotype compared with those carrying the TT genotype (1321.9 ±â€Š837.4 or 1077.5 ±â€Š804.4 pg/mL vs 751.9 ±â€Š612.4 pg/mL, respectively; P = 0.029, analysis of variance), whereas the circulating Ang-(1-7) levels were comparable among genotypes in male patients. In addition, there was no significant difference in the circulating ACE2 levels among rs2106809 CC, CT, and TT genotype groups in both female and male patients. The circulating ACE2 and Ang-(1-7) levels were related to neither rs4646155 nor rs879922 in female or male patients.In conclusion, the rs2106809 polymorphism of the ACE2 gene may be a determinant of the circulating Ang-(1-7) level in female patients with hypertension, suggesting a genetic association between circulating Ang-(1-7) levels and ACE2 gene polymorphisms in patients with hypertension.

Ischemic heart disease deaths, disability-adjusted life years and risk factors in Fujian, China during 1990-2013: Data from the Global Burden of Disease Study 2013.

OBJECTIVES: Ischemic heart disease (IHD) is a large public health problem and is associated with a number of modifiable risk factors. The aim of this study was to estimate the IHD burden and attributable to risk factors in Fujian, China during 1990 to 2013. METHODS: IHD deaths, disability-adjusted life years (DALYs) and attributable to risk factors were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Statistical models were employed to produce comprehensive results of IHD deaths, DALYs and attributable to risk. Means and 95% uncertainty intervals (UIs) were calculated for mortality and DALYs. The median of the percent change and 95% UI were determined for the period between 1990 and 2013. RESULTS: The age-standardized IHD deaths rate increased by 15.3% from 1990 [74.7 (95% UI 62.9-99.1) per 100,000] to 2013 [82.7 (56.5-95.5) per 100,000]. The age-standardized IHD DALYs has slightly decreased 8.8% from 1990 to 2013[from 1356.2 (1134.3-1732.1) to 1202.7 (879.6-1404.6) per 100,000]. All risks combined account for 94.7% (92.9%- 96.0%) of IHD DALYs for all ages in 2013. The five leading risk factors for all ages IHD DALYs were high systolic blood pressure, high total cholesterol, smoking, diet high in sodium, and high fasting plasma glucose. CONCLUSION: Despite decreased age-standardized IHD deaths and DALY rate since 1990, population growth and aging led to a higher global burden of IHD in 2013. Behavioral, environmental, and metabolic risks can explain most of the IHD DALYs providing many opportunities for prevention.

Predictive factors associated with gefitinib response in patients with advanced non-small-cell lung cancer (NSCLC).

PURPOSE: A number of different clinical characteristics have been reported to singly correlate with therapeutic activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in advanced non-small-cell lung cancer (NSCLC). This study aimed to identify predictive factors associated with prognostic benefits of gefitinib. PATIENTS AND METHODS: EGFR gene typing in 33 advanced NSCLC patients received gefitinib (250 mg/day) were analyzed with mutant-enriched PCR assay. Gefitinib response was evaluated with potential predictive factors retrospectively. RESULTS: The overall objective response rate (ORR) and median progression-free survival (PFS) in the 33 patients treated by gefitinib were 45.5% and 3.0 (2.0-4.0) months. The ORR and median PFS in EGFR gene mutation patients were significantly higher/longer than those in EGFR gene wild-type patients (P<0.01). Similarly, the ORR and median PFS in non-smoker patients were significantly higher/longer than those in smoker patients (P<0.05, P<0.01, respectively). However, no difference for ORR and median PFS occurred between male and female patients. Logistic multivariate analysis showed that only EGFR mutated gene was significantly associated with the ORR (P<0.01). Both EGFR mutated gene and non-smoker were the major factors that contributed to PFS (P<0.05). CONCLUSIONS: EGFR mutated gene and non-smoker status are potential predictors for gefitinib response in NSCLC patients.

A core promoter variant of angiotensinogen gene and interindividual variation in response to angiotensin-converting enzyme inhibitors.

INTRODUCTION: The polymorphic angiotensinogen (AGT) gene is one of the most promising candidates for essential hypertension. The aim of this study was to examine the association between the A-6G variant of the AGT gene and the blood pressure response to angiotensin-converting enzyme (ACE) inhibitors in hypertensive subjects. METHODS: Five hundred and nine mildly to moderately hypertensive subjects received ACE inhibitors for six weeks after a two-week run-in period. AGT genotyping was performed by direct polymerase chain reaction amplification and deoxyribonucleic acid (DNA) nucleotide sequencing from peripheral blood. RESULTS: The AA genotype, AG genotype, and GG genotype were present in 301 (59.1%), 186 (36.6%), and 22 (4.3%) of patients, respectively. As compared with patients carrying the AA or AG genotype, those carrying the GG genotype had significantly greater reductions in systolic blood pressure, diastolic blood pressure, pulse pressure and mean arterial pressure (p=0.007, 0.014, 0.027 and 0.005, respectively). Moreover, stepwise multiple linear regression analysis showed that the A-6G genotype was a significant predictor of systolic blood pressure and pulse pressure reductions (p=0.040 and 0.019, respectively). CONCLUSION: Our study indicates that the A-6G variant of the AGT gene may be an important determinant of interindividual variation in the response to ACE inhibitors.

Hospital quality improvement initiative for patients with acute coronary syndromes in China: a cluster randomized, controlled trial.

Background- Substantial evidence-practice gaps exist in the management of acute coronary syndromes (ACS) in China. Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated. Methods and Results- Between October 2007 and August 2010, a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster randomized, controlled trial. Eligible hospitals were level 2 or level 3 centers routinely admitting >100 patients with ACS per year. Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later. Outcomes were several key performance indicators reflecting the management of ACS. The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals, using data collected from 50 consecutive patients in each hospital. Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy, with nonsignificant improvements or absence of effects on other key performance indicators. Conclusions- Among hospitals in China, the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments, but effectiveness was otherwise limited. An accompanying process evaluation identified several health system barriers to more successful implementation. Clinical Trial Registration- URL: http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.

[Association between sedentary life style and risks of metabolic syndrome and diabetes mellitus type 2].

OBJECTIVE: To explore the association of sedentary life style with risk of metabolic syndrome (MS) and diabetes mellitus type 2(T2DM). METHODS: A total of 6 016 local residents aged 18 years or older in Fujian province were recruited by multi-stage stratified cluster sampling method in 2010-2011. Data, including demographic information, physical activity and sedentary time were collected. Indices related to height, weight, waist circumference, blood pressure and blood lipid were determined while MS and T2DM were diagnosed by IDF (2005) and WHO (1999) criteria. Logistic regression was used to estimate the correlations between sedentary behavior and MS or T2DM. RESULTS: The prevalence rates of MS and T2DM were 19.0% and 8.0% respectively, in local residents aged 18 years or older, in Fujian province. The overall rate of sedentary behavior was 18.1%, with the mean sedentary time as 4.3 hours. Both data showed significantly differences (P < 0.001) among control group,MS without T2DM group,MS with T2DM group and T2DM without MS group. Compared with the group of sedentary time <2.0 h/d, 1) the group with 2.0-3.5 h/d was significantly correlated with MT group (OR = 1.44, 95% CI:1.03-2.03, P < 0.05), 2) groups of 3.5-6.0 h/d and ≥6.0 h/d were significantly correlated with M, T, MT group, respectively (OR:1.49-1.76 and 1.28-1.58 respectively, 95% CI:1.19-2.45 and 1.02-2.23 respectively, P < 0.05), and 3) sedentary behavior was independently associated with an increased risk of MT group (OR = 1.82, 95% CI: 1.33-2.48, P < 0.01) and M group (OR = 1.43, 95%CI:1.14-1.78, P < 0.01), after the adjustment for factors as age, sex, cigarette smoking, alcohol drinking,BMI, education, occupation, sedentary behavior/sedentary time. CONCLUSION: MS and T2DM were associated with sedentary lifestyle, but these findings should be confirmed through further longitudinal studies.

Serum pepsinogens, gastrin-17 and Helicobacter pylori antibody in the residents of two cities in china with distinct mortality rates of gastric cancer.

Gastric cancer is one of the most common malignant tumors causing death in Fujian Province, China. However, the mortality of gastric cancer is greatly varied in different areas in Fujian; for example, the mortality in Changle City is 7.4 times higher than that in Fuan City. In this study, we compared the differences in serological parameters, pepsinogen (PG) I, PG II, gastrin-17 (G-17), and Helicobacter pylori (H. pylori) antibody, between the two cities. It has been reported that low serum PG I is correlated with atrophic gastritis, a high-risk condition for developing gastric cancer, while high serum G-17 has been used for serological detection of atrophic corpus gastritis. We recruited 224 healthy subjects in Changle and 229 healthy subjects in Fuan, matched in age and sex. The serum levels of PG II and G-17 were significantly higher in Changle than those in Fuan. Importantly, the frequency of the subjects with low serum PG I (< 25 µg/L) was significantly higher in Changle than in Fuan, although the serum PG I levels were similar between the two cities. Moreover, the percentage of the subjects with high serum G-17 (≥ 2 pmol/L) and the positive rate of serum IgG antibody against H. pylori were significantly higher in Changle than those in Fuan. The detected differences in these serological parameters are consistent with the notion that the prevalence of atrophic gastritis may be higher in Changle than in Fuan, which results in a higher risk condition for developing gastric cancer in Changle.

MicroRNA 16 enhances differentiation of human bone marrow mesenchymal stem cells in a cardiac niche toward myogenic phenotypes in vitro.

AIM: Upregulation of microRNA 16 (miR-16) contributed to the differentiation of human bone marrow mesenchymal stem cells (hMSCs) toward myogenic phenotypes in a cardiac niche, the present study aimed to determine the role of miR-16 in this process. MAIN METHODS: hMSCs and neonatal rat ventricular myocytes were co-cultured indirectly in two chambers to set up a cardiac microenvironment (niche). miRNA expression profile in cardiac-niche-induced hMSCs was detected by miRNA microarray. Cardiac marker expression and cell cycle analysis were determined in different treatment hMSCs. Quantitative real-time PCR and Western blot were used to identify the expression of mRNA, mature miRNA and protein of interest. KEY FINDINGS: miRNA dysregulation was shown in hMSCs after cardiac niche induction. miR-16 was upregulated in cardiac-niche-induced hMSCs. Overexpression of miR-16 significantly increased G1-phase arrest of the cell cycle in hMSCs and enhanced the expression of cardiac marker genes, including GATA4, NK2-5, MEF2C and TNNI3. Differentiation-inducing factor 3 (DIF-3), a G0/G1 cell cycle arrest compound, was used to induce G1 phase arrest in cardiac-niche-induced hMSCs, and the expression of cardiac marker genes was up-regulated in DIF-3-treated hMSCs. The expression of CCND1, CCND2 and CDK6 was suppressed by miR-16 in hMSCs. CDK6, CCND1 or CCND2 knockdown resulted in G1 phase arrest in hMSCs and upregulation of cardiac marker gene expression in hMSCs in a cardiac niche. SIGNIFICANCE: miR-16 enhances G1 phase arrest in hMSCs, contributing to the differentiation of hMSCs toward myogenic phenotypes when in a cardiac niche. This mechanism provides a novel strategy for pre-modification of hMSCs before hMSC-based transplantation therapy for severe heart diseases.

High levels of glucose induce "metabolic memory" in cardiomyocyte via epigenetic histone H3 lysine 9 methylation.

Diabetic patients continue to develop inflammation and cardiovascular complication even after achieving glycemic control, suggesting a "metabolic memory". Metabolic memory is a major challenge in the treatment of diabetic complication, and the mechanisms underlying metabolic memory are not clear. Recent studies suggest a link between chromatin histone methylation and metabolic memory. In this study, we tested whether histone 3 lysine-9 tri-methylation (H3K9me3), a key epigenetic chromatin marker, was involved in high glucose (HG)-induced inflammation and metabolic memory. Incubating cardiomyocyte cells in HG resulted in increased levels of inflammatory cytokine IL-6 mRNA when compared with myocytes incubated in normal culture media, whereas mannitol (osmotic control) has no effect. Chromatin immunoprecipitation (ChIP) assays showed that H3K9me3 levels were significantly decreased at the promoters of IL-6. Immunoblotting demonstrated that protein levels of the H3K9me3 methyltransferase, Suv39h1, were also reduced after HG treatment. HG-induced apoptosis, mitochondrial dysfunction and cytochrome-c release were reversible. However, the effects of HG on the expression of IL-6 and the levels of H3K9me3 were irreversible after the removal of HG from the culture. These results suggest that HG-induced sustained inflammatory phenotype and epigenetic histone modification, rather than HG-induced mitochondrial dysfunction and apoptosis, are main mechanisms responsible for metabolic memory. In conclusion, our data demonstrate that HG increases expression of inflammatory cytokine and decreases the levels of histone-3 methylation at the cytokine promoter, and suggest that modulating histone 3 methylation and inflammatory cytokine expression may be a useful strategy to prevent metabolic memory and cardiomyopathy in diabetic patients.

Role of procalcitonin in the diagnosis of severe infection in pediatric patients with fever and Neutropenia--a systemic review and meta-analysis.

OBJECTIVE: The aim of this study was to determine the accuracy of the procalcitonin (PCT) test for diagnosis of bacterial sepsis in pediatric cancer patients with febrile neutropenia. METHODS: Three major databases, MEDLINE, EMBASE and the Cochrane Library were searched for studies that evaluated the diagnostic value of PCT alone or compared with other laboratory markers such as C-reactive protein (CRP) to identify bacterial sepsis in children with fever and neutropenia. A bivariate model was used to derive summary sensitivity and specificity of the diagnostic tests. RESULTS: A total of 10 studies looking into PCT tests and 8 studies looking into CRP tests were included in the final analysis. The prevalence of bacterial sepsis was 304 of 1031 (29.5%) in PCT studies and 741 of 1316 (56.3%) in CRP studies. In terms of area under the receiver operating characteristic curve, PCT had comparable discrimination to CRP (area under the curve: 0.75 versus 0.74). PCT was not as sensitive as the CRP test. The pooled sensitivity of PCT was 0.59 (95% confidence interval [CI]: 0.42-0.74) as compared with 0.75 (95% CI: 0.61-0.85) for CRP. PCT was more specific than sensitive whereas CRP was more sensitive than specific in this population. The pooled specificity was 0.76 (95% CI: 0.64-0.85) for PCT and 0.62 (95% CI: 0.49-0.73) for CRP. PCT had greater likelihood ratio positive (2.50; 95% CI: 1.64-3.81), making it the better rule-in test. CONCLUSIONS: Of three markers potentially useful for diagnosing bacterial sepsis in children with fever and neutropenia, PCT had comparable diagnostic accuracy to CRP.

Effect of ranolazine on rat intrarenal arteries in vitro.

Ranolazine is mainly used to treat patients with chronic stable angina in clinical practice. However, ranolazine does not lower significantly systemic blood pressure. The direct effect of ranolazine on vascular tone remains unknown. In the present study, we investigated the vascular effects and mechanisms of action of ranolazine in isolated rat intrarenal arteries. Rings of intrarenal arteries were mounted in a small vessel myography using two stainless steel wires for the measurement of isometric tension. L-type Ca²âº currents were recorded in isolated single renal arterial smooth muscle cells using patch clamp techniques in whole-cell mode. Ranolazine induced concentration-dependent relaxations in rings contracted with phenylephrine, but ranolazine failed to cause any relaxation in rings pre-contracted by U46619, 5-HT or endothelin-1. Ranolazine also induced relaxations in norepinephrine pre-contracted rings. Yohimbine failed to induce relaxation in rings pre-contracted by norepinephrine. Propranolol did not affect ranolazine-induced relaxation but the relaxant effect of ranolazine was much less than that of prazosin. Ranolazine-induced relaxations were slight but significantly attenuated by endothelial denudation. Partial inhibition was observed in endothelium-intact arteries exposed to a combination of iberiotoxin and apamin. Ranolazine at higher concentration (>30 µM) inhibited Ca²âº-induced contraction in a noncompetitive manner. Ranolazine reduced L-type Ca²âº currents at potentials between -30 and 50 mV in isolated renal artery myocytes. Therefore it can be said that ranolazine has significant α1-adrenergic receptor and weak calcium channel antagonistic effects in rat intrarenal arteries.

Association between polymorphisms of the renin-angiotensin system and coronary artery disease in Chinese patients with type 2 diabetes.

BACKGROUND: The renin-angiotensin system (RAS) is regarded as one of the most important regulatory systems for cardiovascular homeostasis. In this study, we investigated associations of the five genetic polymorphisms in the RAS and presence of coronary artery disease (CAD) in type 2 diabetes. METHODS: Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. We used the generalised multifactor dimensionality reduction (GMDR) method to identify gene-gene interactions. RESULTS: The D allele in the ACE gene was significantly more frequent in type 2 diabetic patients with CAD (p = 0.04). In multivariate logistic regression analysis, the DD genotype was associated with a significantly increased risk of CAD (p = 0.044). 1675G/A variant in the AT2R gene was found to be associated with CAD in female subjects with type 2 diabetes (p = 0.025). The three other polymorphisms of the RAS do not seem to influence the development of CAD in type 2 diabetes. No significant gene-gene interaction for any combinations of genotypes was found in the GMDR method. CONCLUSION: The DD variant of the ACE gene polymorphism is associated with increased risk of developing CAD in Chinese patients with type 2 diabetes. A slight impact of AT2R 1675G/A polymorphism on CAD was found only in female diabetic patients.