A hypervirulent (hvKp) pathotype is undergoing global dissemination. In contrast to the usual health care-associated epidemiology of classical (cKp) infections, hvKp causes tissue-invasive infections in otherwise healthy individuals from the community, often involving multiple sites. An accurate test to identify hvKp strains is needed for improved patient care and epidemiologic studies. To fill this knowledge gap, clinical criteria or random blood isolates from North American and United Kingdom strain collections were used to assemble hvKp-rich ( = 85) and cKp-rich ( = 90) strain cohorts, respectively. The isolates were then assessed for multiple candidate biomarkers hypothesized to accurately differentiate the two cohorts. The genes ,, , plasmid-borne gene ( ), and all demonstrated >0.95 diagnostic accuracy for identifying strains in the hvKp-rich cohort. Next, to validate this epidemiological analysis, all strains were assessed experimentally in a murine sepsis model. ,, ,, and were all associated with a hazard ratio of>25 for severe illness or death, additionally supporting their utility for identifying hvKp strains. Quantitative siderophore production of ≥30 μg/ml also strongly predicted strains as members of the hvKp-rich cohort (accuracy, 0.96) and exhibited a hazard ratio of 31.7 for severe illness or death. The string test, a widely used marker for hvKp strains, performed less well, achieving an accuracy of only 0.90. Last, using the most accurate biomarkers to define hvKp, prevalence studies were performed on two Western strain collections. These data strongly support the utility of several laboratory markers for identifying hvKp strains with a high degree of accuracy.

The study offered some support for the importance of physician-nurse collaboration in ICU care delivery, a variable susceptible to intervention and further study.

Objectives The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA). Background Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD). Methods We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ≤35%) eligible for primary prevention ICDs. Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation (11C-meta-hydroxyephedrine [11C-HED]), perfusion (13N-ammonia) and viability (insulin-stimulated 18F-2-deoxyglucose). The primary endpoint was SCA defined as arrhythmic death or ICD discharge for ventricular fibrillation or ventricular tachycardia >240 beats/min. Results After 4.1 years follow-up, cause-specific SCA was 16.2%. Infarct volume (22 ± 7% vs. 19 ± 9% of left ventricle [LV]) and LVEF (24 ± 8% vs. 28 ± 9%) were not predictors of SCA. In contrast, patients developing SCA had greater amounts of sympathetic denervation (33 ± 10% vs. 26 ± 11% of LV; p = 0.001) reflecting viable, denervated myocardium. The lower tertiles of sympathetic denervation had SCA rates of 1.2%/year and 2.2%/year, whereas the highest tertile had a rate of 6.7%/year. Multivariate predictors of SCA were PET sympathetic denervation, left ventricular end-diastolic volume index, creatinine, and no angiotensin inhibition. With optimized cut-points, the absence of all 4 risk factors identified low risk (44% of cohort; SCA <1%/year); whereas ≥2 factors identified high risk (20% of cohort; SCA ~12%/year). Conclusions In ischemic cardiomyopathy, sympathetic denervation assessed using 11C-HED PET predicts cause-specific mortality from SCA independently of LVEF and infarct volume. This may provide an improved approach for the identification of patients most likely to benefit from an ICD. (Prediction of ARrhythmic Events With Positron Emission Tomography [PAREPET]; NCT01400334)

DNA methylation status may be used as a functional indicator of moderately depleted folate status. The slow response to the repletion diets observed suggests that normalization of DNA methylation after moderate folate depletion may be delayed in older women.

In this highly heterogeneous population of children with congenital lactic acidosis, oral DCA for 6 months was well tolerated and blunted the postprandial increase in circulating lactate. However, it did not improve neurologic or other measures of clinical outcome.

OBJECTIVE -To determine the effects of exercise, without weight loss, on insulin sensitivity (S I ), postheparin plasma lipase activity (PHPL), intravenous fat clearance rate (K 2 ), and fasting lipids in sedentary adults. RESEARCH DESIGN AND METHODS-At baseline and after 6 months of walk training (intensity 45-55 or 65-75% heart rate reserve, frequency 3-4 or 5-7 days/week, duration 30 min/session), anthropometric indexes, S I , PHPL, K 2 , and fasting lipids were measured in 18 sedentary adults (12 women, 6 men; 51.9 Ϯ 5.8 years of age, BMI 28.9 Ϯ 4.6 kg/m 2 ). ⅐ h Ϫ1 ) (both P Ͻ 0.001), without altering BMI, waist circumference, K 2 , or fasting lipids. Correlations between changes in LPL and the total:HDL cholesterol ratio (r ϭ Ϫ0.54) and changes in the LPL:HL ratio and waist circumference (r ϭ Ϫ0.50) were significant (P Ͻ 0.05). RESULTSCONCLUSIONS -Exercise, without weight loss, increases S I and PHPL activity in previously sedentary adults, without changing K 2 or fasting lipid levels. Furthermore, increased LPL is associated with a decreased total:HDL ratio, and an increased LPL:HL ratio is associated with a decreased waist circumference. Therefore, even modest amounts of exercise in the absence of weight loss positively affect markers of glucose and fat metabolism in previously sedentary, middle-aged adults. Diabetes Care 26:557-562, 2003I nsulin resistance (IR) is defined as an inappropriately high level of insulin required to maintain metabolic homeostasis (1) and is characterized by diminished peripheral insulin sensitivity (S I ). Obesity and central body fat distribution are strong predictors of IR (2). Previous research demonstrates that weight loss through caloric restriction is associated with improvement in visceral adiposity, S I , and lipid risk factors for coronary artery disease (3).Physical inactivity also results in markedly decreased S I (4). Several training studies (5-7) have demonstrated that regular aerobic exercise leads to enhanced S I in previously sedentary adults. Improvements in S I with training have been accompanied by significant reductions in body weight and body composition in some (5), but not all (6,7), of these studies.In addition to the profound effects of enhanced insulin action on glucose homeostasis, S I is an important independent determinant of the variation in free fatty acid (FFA) and triglyceride (TG) concentrations in adults (8). Exercise training is known to decrease TG concentrations (9,10) and has been shown to increase the intravenous fat clearance (K 2 ) of a TG emulsion (11,12). Enhanced K 2 (92% greater clearance rate) has also been reported for endurance athletes, compared with sedentary men, in a cross-sectional study (13).One potential mechanism by which exercise enhances lipid metabolism is alteration of plasma lipase activity (i.e., lipoprotein lipase [LPL] and hepatic lipase [HL]). The activity of LPL is a key determinant in the rate of catabolism of TG-rich lipoproteins (14), and impaired function of LPL has been found in individuals with IR (15,1...

Currently available serum biomarkers are insufficiently reliable to distinguish patients with epithelial ovarian cancer (EOC) from healthy individuals. Metabonomics, the study of metabolic processes in biologic systems, is based on the use of 1 H-NMR spectroscopy and multivariate statistics for biochemical data generation and interpretation and may provide a characteristic fingerprint in disease. In an effort to examine the utility of the metabonomic approach for discriminating sera from women with EOC from healthy controls, we performed 1 H-NMR spectroscopic analysis on preoperative serum specimens obtained from 38 patients with EOC, 12 patients with benign ovarian cysts and 53 healthy women. After data reduction, we applied both unsupervised Principal Component Analysis (PCA) and supervised Soft Independent Modeling of Class Analogy (SIMCA) for pattern recognition. The sensitivity and specificity tradeoffs were summarized for each variable using the area under the receiver-operating characteristic (ROC) curve. In addition, we analyzed the regions of NMR spectra that most strongly influence separation of sera of EOC patients from healthy controls. PCA analysis allowed correct separation of all serum specimens from 38 patients with EOC (100%) from all of the 21 premenopausal normal samples (100%) and from all the sera from patients with benign ovarian disease (100%). In addition, it was possible to correctly separate 37 of 38 (97.4%) cancer specimens from 31 of 32 (97%) postmenopausal control sera. SIMCA analysis using the Cooman's plot demonstrated that sera classes from patients with EOC, benign ovarian cysts and the postmenopausal healthy controls did not share multivariate space, providing validation for the class separation. ROC analysis indicated that the sera from patients with and without disease could be identified with 100% sensitivity and specificity at the 1 H-NMR regions 2.77 parts per million (ppm) and 2.04 ppm from the origin (AUC of ROC curve ‫؍‬ 1.0). In addition, the regression coefficients most influential for the EOC samples compared to postmenopausal controls lie around ␦3.7 ppm (due mainly to sugar hydrogens). Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancies. There are more than 23,000 cases annually in the United States, and 14,000 women can be expected to die from the disease in 2003. 1 Despite important advances in surgery and chemotherapy that have been made over the past 20 years, the overall survival for patients with EOC has not changed significantly. The high mortality rate of EOC occurs primarily because most women are diagnosed with advanced disease (stage III/IV), which has a 5-year survival rate of 15-20%. 1 In contrast, the small proportion of patients with accurately diagnosed stage I disease have 5-year survival rates in excess of 90%. 2 Current candidate strategies for the detection of EOC are based on biochemical tumor markers, such as CA125, and biophysical markers assessed by ultrasound and/or Doppler imaging of the ovaries. Unf...

Introduction Tobacco use is associated with poor outcomes in cancer patients, but there is little information on the practice patterns or perceptions of tobacco use and smoking cessation by oncology providers. Methods An online survey of practices, perceptions, and barriers to tobacco assessment and cessation in cancer patients was conducted in members of the International Association for the Study of Lung Cancer (IASLC). Responses of physician level respondents were analyzed and reported. Results Responses from 1,507 IASLC members who completed the survey are reported representing 40.5% of IASLC members. Over 90% of physician respondents believe current smoking affects outcome and that cessation should be a standard part of clinical care. At the initial patient visit, 90% ask patients about tobacco use, 79% ask patients if they will quit, 81% advise patients to stop tobacco use, but only 40% discuss medication options, 39% actively provide cessation assistance, and fewer yet address tobacco at follow-up. Dominant barriers to physician cessation effort are pessimism regarding their ability to help patients stop using tobacco (58%) and concerns about patient resistance to treatment (67%). Only 33% report themselves adequately trained to provide cessation interventions. Discussion Physicians who care for lung cancer patients recognize the importance of tobacco cessation as a necessary part of clinical care, but many still do not routinely provide assistance to their patients. Increasing tobacco cessation will require increased assessment and cessation at diagnosis and during follow-up, increased clinician education, and improved tobacco cessation methods.