Dose-dependent effect of statins on the incidence of acute kidney injury after cardiac surgery.

Abstract:
BACKGROUND Acute kidney injury (AKI) after cardiac surgery is associated with increased morbidity and mortality.
 METHODS We assessed whether statin treatment is associated with a lower incidence of postoperative AKI in 2,104 consecutive patients who underwent coronary artery bypass graft or valve surgery at the Minneapolis Veterans Administration Medical Center. Acute kidney injury was defined as absolute increase greater than 0.3 mg/dL or relative increase greater than 50% in serum creatinine from baseline, within 48 hours after surgery or requiring postoperative hemodialysis per AKI network. Propensity scores were utilized to adjust for the differences between the statin and the no-statin treatment groups. All statins were converted to equivalent-dose simvastatin and divided at the median to construct high-dose (≥40 mg) and low-dose (<40 mg) statin groups.
 RESULTS Of the 2,104 patients, 1,435 (68%) were taking statins (638 high-dose) and 495 (24%) developed AKI (25% high-dose vs 40% low-dose vs 35% no-statin; p = 0.014). Estimated preoperative glomerular filtration rate (p = 0.003), diabetes mellitus (p=0.02), valve surgery with or without coronary artery bypass graft (p = 0.024), cardiopulmonary bypass time (p = 0.001), and intraaortic balloon pump (p = 0.055) were independent predictors of AKI. After propensity adjustment statin treatment was not associated with postoperative AKI (odds ratio 0.79; 95% confidence interval 0.59 to 1.06; p = 0.11 for high-dose v. no-statin). After full adjustment for all independent predictors of AKI, the results did not change. Statins also had no effect on the incidence of postoperative hemodialysis (0.8% high-dose vs 1.9% low-dose vs 1% no-statin; p = 0.15).
 CONCLUSIONS Statin treatment is not associated with a lower incidence of AKI after cardiac surgery.


Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover.

Abstract: Several growth factors are expressed in distinct temporal and spatial patterns during fracture repair. Of these, vascular endothelial growth factor, VEGF, is of particular interest because of its ability to induce neovascularization (angiogenesis). To determine whether VEGF is required for bone repair, we inhibited VEGF activity during secondary bone healing via a cartilage intermediate (endochondral ossification) and during direct bone repair (intramembranous ossification) in a novel mouse model. Treatment of mice with a soluble, neutralizing VEGF receptor decreased angiogenesis, bone formation, and callus mineralization in femoral fractures. Inhibition of VEGF also dramatically inhibited healing of a tibial cortical bone defect, consistent with our discovery of a direct autocrine role for VEGF in osteoblast differentiation. In separate experiments, exogenous VEGF enhanced blood vessel formation, ossification, and new bone (callus) maturation in mouse femur fractures, and promoted bony bridging of a rabbit radius segmental gap defect. Our results at specific time points during the course of healing underscore the role of VEGF in endochondral vs. intramembranous ossification, as well as skeletal development vs. bone repair. The responses to exogenous VEGF observed in two distinct model systems and species indicate that a slow-release formulation of VEGF, applied locally at the site of bone damage, may prove to be an effective therapy to promote human bone repair.


Nicotinic receptor-mediated neuroprotection in neurodegenerative disease models.

Abstract: Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathology of Alzheimer's disease (AD) and Parkinson's disease (PD). This review article presents evidence for nicotinic acetylcholine receptor (nAChR)-mediated protection and the signal transduction involved in this mechanism. The data is based mainly on our studies using rat-cultured primary neurons. Nicotine-induced protection was blocked by an alpha7 nAChR antagonist, a phosphatidylinositol 3-kinase (PI3K) inhibitor, and an Src inhibitor. Levels of phosphorylated Akt, an effector of PI3K, Bcl-2 and Bcl-x were increased by nicotine administration. From these experimental data, our hypothesis for the mechanism of nAChR-mediated survival signal transduction is that the alpha7 nAChR stimulates the Src family, which activates PI3K to phosphorylate Akt, which subsequently transmits the signal to up-regulate Bcl-2 and Bcl-x. Up-regulation of Bcl-2 and Bcl-x could prevent cells from neuronal death induced by beta-amyloid (Abeta), glutamate and rotenone. These findings suggest that protective therapy with nAChR stimulation could delay the progress of neurodegenerative diseases such as AD and PD.


Skeletal muscle interleukin‐6 regulates metabolic factors in iWAT during HFD and exercise training

Abstract:
OBJECTIVE To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism.
 METHODS Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD in combination with exercise training (HFD ExTr) for 16 weeks.
 RESULTS Total fat mass increased (P < 0.05) in both genotypes with HFD. However, HFD IL-6 MKO mice had lower (P < 0.05) inguinal adipose tissue (iWAT) mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP activated protein kinase (AMPK)(Thr172) phosphorylation, and fatty acid synthase (FAS) mRNA content were lower (P < 0.05) in IL-6 MKO than Floxed mice on Chow. In addition, iWAT AMPK(Thr172) and hormone-sensitive lipase (HSL)(Ser565) phosphorylation as well as perilipin protein content was higher (P < 0.05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P < 0.05) in HFD ExTr IL-6 MKO than HFD ExTr Floxed mice.
 CONCLUSIONS These findings indicate that SkM IL-6 affects iWAT mass through regulation of glucose uptake capacity as well as lipogenic and lipolytic factors.


Mental health difficulties across childhood and mental health service use: findings from a longitudinal population-based study.

Abstract:
BACKGROUND Over the past 20 years the prevalence of child and adolescent mental disorders in high-income countries has not changed despite increased investment in mental health services. Insufficient contact with mental health services may be a contributing factor; however, it is not known what proportion of children have sufficient contact with health professionals to allow delivery of treatment meeting minimal clinical practice guidelines, or how long children experience symptoms prior to receiving treatment. AimsTo investigate the level of mental healthcare received by Australian children from age 4 years to 14 years.
 METHOD Trajectories of mental health symptoms were mapped using the Strengths and Difficulties Questionnaire. Health professional attendances and psychotropic medications dispensed were identified from linked national Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme records.
 RESULTS Four trajectories of mental health symptoms were identified (low, high-decreasing, moderate-increasing and high-increasing). Most children with mental health symptoms had few MBS mental health attendances, and only a minority received care meeting study criteria for minimally adequate treatment. Children in the high-increasing and moderate-increasing trajectories were more likely to access care, yet there was no evidence of improvement in symptoms.
 CONCLUSIONS It is important that children and adolescents with mental health problems receive treatment that meets minimal practice guidelines. Further research is needed to identify the quality of care currently provided to children with mental health difficulties and how clinicians can be best funded and supported to provide care meeting minimal practice guidelines. Declaration of interestsNone.


Prevalence of the Metabolic Syndrome Among Us Adults: Findings From the Third National Health and Nutrition Examination Survey

Abstract: Metabolic syndrome is diagnosed when three or more of the following criteria are met: abdominal obesity (waist circumference more than 102 cm in men and 88 cm in women); hypertriglyceridemia of 150 mg/dl or above; a high-density lipoprotein (HDL) cholesterol level less than 40 mg/dl in men or 50 mg/dl in women; blood pressure of 130/85 mm Hg or higher; or fasting glucose of at least 110 mg/dl. Individuals with metabolic syndrome are likelier than others to develop diabetes and cardiovascular disease and have increased mortality from all causes (and from cardiovascular disease in particular). The investigators attempted to determine the prevalence of the syndrome in the United States by analyzing data on 8814 men and women 20 years of age or older who took part in the Third National Health and Nutrition Examination Survey in the years 1988 to 1994. This is a cross-sectional health survey of a sample of the noninstitutionalized civilian American population. The overall age-adjusted prevalence of metabolic syndrome was 23.7%. The prevalence rose from 6.7% in persons 20 to 29 years of age to 42% in those aged 70 years and more. There was virtually no gender-related difference in prevalence rates for the combined racial groups. Metabolic syndrome was most prevalent in Mexican Americans and least prevalent in whites, African Americans, and "others. " Among both African Americans and Mexican Americans, women had higher prevalence rates than men. Extrapolating from age-specific prevalence rates and US census counts from the year 2000, 47 million US residents have metabolic syndrome. Considering its prevalence, it seems important to estimate the direct medical costs of metabolic syndrome. In the great majority of cases the critical causes are improper nutrition and insufficient physical activity, emphasizing the importance of controlling obesity and encouraging physical activity in the United States.


Role of Computerized Physician Order Entry Systems in Facilitating Medication Errors

Abstract:
as compared with 103 (8.2 percent) in the control group; the Kaplan-Meier estimates of the likelihood of freedom from deep-vein thrombosis or pulmonary embolism at 90 days were 94.1 percent (95 percent confidence interval, 92.5 to 95.4 percent) and 90.6 percent (95 percent confidence interval, 88.7 to 92.2 percent), respectively (P 0.001). The computer alert reduced the risk of deep-vein thrombosis or pulmonary embolism at 90 days by 41 percent (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81; P 0.001).
 CONCLUSIONS The institution of a computer-alert program increased physicians’ use of prophylaxis and markedly reduced the rates of deep-vein thrombosis and pulmonary embolism among hospitalized patients at risk. Editorial Comment: Most hospitals have adopted electronic systems to alert physicians of drug interactions or possible substitutions, as well as other measures designed to improve the quality of care and decrease expenses. This approach was taken one step further by these authors, who evaluated whether notifying physicians that their patients were at increased risk for venous thromboembolism would decrease the incidence of deep vein thrombosis or pulmonary embolism. The premise was that simply notifying the physician would increase the use of appropriate prophylactic measures. Major surgery (defined as anything requiring general anesthesia), cancer and age greater than 75 years were included among the risk factors, each of which frequently applies to a urology population. In fact, more than 13% of the patients in the intervention group had a known diagnosis of a genitourinary cancer. The computer alert decreased the risk of deep vein thrombosis or pulmonary embolism by 41%. There are 2 lessons urologists can learn from this study. First, many urology patients are at increased risk for venous thromboembolism and appropriate prophylaxis should be used. In addition, although computer alert systems may seem intrusive at times, clinicians can expect to see more and more of them if there is further documentation that they improve the quality of care.