Citations

OBJECTIVES: To evaluate the long-term impact of pediatric central line care practices in reducing PICU central line–associated bloodstream infection (CLA-BSI) rates and to evaluate the added impact of chlorhexidine scrub and chlorhexidine-impregnated sponges. METHODS: A 3-year, multi-institutional, interrupted time-series design (October 2006 to September 2009), with historical control data, was used. A nested, 18-month, nonrandomized, factorial design was used to evaluate 2 additional interventions. Twenty-nine PICUs were included. Two central line care bundles (insertion and maintenance bundles) and 2 additional interventions (chlorhexidine scrub and chlorhexidine-impregnated sponges) were used. CLA-BSI rates (January 2004 to September 2009), insertion and maintenance bundle compliance rates (October 2006 to September 2009), and chlorhexidine scrub and chlorhexidine-impregnated sponge compliance rates (January 2008 to June 2009) were assessed. RESULTS: The average aggregate baseline PICU CLA-BSI rate decreased 56% over 36 months from 5.2 CLA-BSIs per 1000 line-days (95% confidence interval [CI]: 4.4–6.2 CLA-BSIs per 1000 line-days) to 2.3 CLA-BSIs per 1000 line-days (95% CI: 1.9–2.9 CLA-BSIs per 1000 line-days) (rate ratio: 0.44 [95% CI: 0.37–0.53]; P < .0001). No statistically significant differences in CLA-BSI rate decreases between PICUs using or not using either of the 2 additional interventions were found. CONCLUSIONS: Focused attention on consistent adherence to the use of pediatrics-specific central line insertion and maintenance bundles produced sustained, continually decreasing PICU CLA-BSI rates. Additional use of either chlorhexidine for central line entry scrub or chlorhexidine-impregnated sponges did not produce any statistically significant additional reduction in PICU CLA-BSI rates.

Dialysis and transplantation are now standard treatments for end-stage renal failure. Often, neurologists are consulted regarding the neurological complications of these therapeutic procedures. In addition to previously reported complications, neurovascular disease is being recognized as a cause of mortality and morbidity in these patients. We report two cases of apparent thromboembolic stroke in young patients with renal failure -- one treated by dialysis and the other by renal transplantation. The risk factors of both dialysis and transplant are identified and data from the American College of Surgeons/National Institutes of Health Transplant Registry are reviewed.

BACKGROUND B-type natriuretic peptide (BNP), a key cardiac hormone in cardiorenal homeostasis, is produced as a 108 amino acid prohormone, proBNP1-108, which is converted to a biologically active peptide BNP1-32 and an inactive N-terminal (NT)-proBNP1-76. The widely accepted model is that the normal heart releases a proteolytically processed BNP1-32 and NT-proBNP, whereas the diseased heart secretes high amounts of unprocessed/glycosylated proBNP1-108 or inappropriately processed BNPs. In contrast, circulating proBNP1-108 has recently been identified in healthy individuals, indicating that the normal heart also secretes unprocessed proBNP1-108. However, the mechanism of proBNP1-108 secretion from the normal heart remains elusive. Our goal was to determine the molecular mechanisms underlying proBNP1-108 intracellular trafficking and secretion from the normal heart. METHODS We expressed preproBNP in cardiomyocytes, and determined the subcellular localization and dominant intracellular and extracellular forms of BNP. RESULTS Intracellular immunoreactive BNPs were first accumulated in the Golgi apparatus, and then distributed throughout the cytoplasm as secretory vesicles. The predominant intracellular form of BNP was nonglycosylated proBNP1-108, rather than BNP1-32. Glycosylated proBNP1-108, but not nonglycosylated proBNP1-108, was detected as the major extracellular form in the culture supernatants of preproBNP-expressing cell lines and primary human cardiomyocytes. Ablation of O-glycosylation of proBNP1-108 at T71 residue, near the convertase recognition site, reduced the extracellular proBNP1-108 and increased extracellular BNP1-32. CONCLUSIONS Intracellular proBNP trafficking occurs through a conventional Golgi–endoplasmic reticulum pathway. Glycosylation of proBNP1-108 controls the stability and processing of extracellular proBNP1-108. Our data establish a new BNP secretion model in which the normal cardiac cells secrete glycosylated proBNP1-108.

Background— Diastolic dysfunction associated with high blood pressure (BP) leads to cardiac remodeling and fibrosis and progression to congestive heart failure. B-type natriuretic peptide (BNP) has BP-lowering, antifibrotic, and antihypertrophic properties, which makes BNP an attractive agent for attenuating the adverse cardiac remodeling associated with hypertension. In the current study, we tested the effects of sustained cardiac proBNP gene delivery on BP, cardiac function, and remodeling in spontaneously hypertensive rats (SHR). Methods and Results— We used the myocardium-tropic adeno-associated virus serotype 9 (AAV9) vector to achieve continuously enhanced cardiac rat proBNP expression. In SHR, a single systemic administration of AAV9 vector allowed long-term cardiac BNP overexpression, resulting in reductions in systolic and diastolic BP for 9 months after injection. Left ventricular (LV) thickness, LV end-systolic dimensions, and LV mass were reduced, whereas ejection fraction was significantly increased, in BNP-treated compared with untreated SHR. Circumferential systolic strain and strain rate of the early phase of diastole were improved in BNP-treated compared with untreated SHR. Noncardiac overexpression of BNP via AAV2 vector was not associated with changes in BP and plasma BNP in SHR. Furthermore, normal Wistar rats injected with AAV9 proBNP vector showed significantly reduced heart weights 4 weeks after injection without BP reduction. Conclusions— AAV9 vector facilitates sustained cardiac proBNP overexpression and improves LV function in hypertensive heart disease. Long-term proBNP delivery improved both systolic and diastolic function. The effects on cardiac structure and function occurred independently of BP-lowering effects in normal Wistar rats.

AbstractObesity is a controversial risk factor for colorectal cancer (CRC) in older women. We evaluated associations between multiple body size parameters and incident CRC in the prospective, population-based Iowa Women's Health Study (IWHS). IWHS participants, ages 55 to 69 years, provided data regarding height; weight; weight at ages 50, 40, 30, 18 years; hip circumference; and waist circumference at baseline (1986). Derived variables included body mass index (BMI), waist-to-hip ratio (WHR), and “overweight years” (OWY; conceptually similar to cigarette pack-years). Incident CRC cases (n = 1,464) were ascertained from the State Health Registry of Iowa, through 2005. Multivariable Cox regression models were fit to estimate body size–associated CRC risks. Among 36,941 women (619,961 person-years), baseline height, weight, BMI, hip circumference, waist circumference, and WHR were all positively associated with incident CRC (Ptrend ≤ 0.003 for each). Baseline BMI yielded the highest CRC risk estimates (obese III versus normal, RR = 1.56; 95% CI = 1.10–2.22; Ptrend < 0.001) and was more closely associated with distal than proximal tumors (Ptrend < 0.001 versus 0.06). Conversely, height was more closely associated with proximal than distal tumors (Ptrend < 0.001 versus 0.04). Other body size parameters were less predictive of incident CRC. These data strongly support a positive association between increased body size and CRC risk among older women. Further investigation of when increased body size has the greatest effect on CRC risk (i.e., early adulthood versus later adulthood) might also be informative, particularly with respect to defining subsite-specific pathways of colorectal carcinogenesis. Cancer Prev Res; 3(12); 1608–20. ©2010 AACR.

AbstractBackground: Supplement use among cancer patients is high, and folic acid intake in particular may adversely affect the progression of colorectal cancer. Few studies have evaluated the use of folic acid–containing supplements (FAS) and its predictors in colorectal cancer patients.Objective: To assess the use of FAS, change in use, and its predictors after colorectal cancer diagnosis.Design: We used logistic regression models to investigate predictors of FAS use and its initiation after colorectal cancer diagnosis in 1,092 patients recruited through the Colon Cancer Family Registry.Results: The prevalence of FAS use was 35.4% before and 55.1% after colorectal cancer diagnosis (P = 0.004). Women were more likely than men to use FAS after diagnosis [odds ratio (OR), 1.47; 95% confidence interval (95% CI), 1.14-1.89], as were those consuming more fruit (Ptrend < 0.0001) or vegetables (Ptrend = 0.001), and U.S. residents (P < 0.0001). Less likely to use FAS after diagnosis were nonwhite patients (OR, 0.66; 95% CI, 0.45-0.97), current smokers (OR, 0.67; 95% CI, 0.46-0.96), and those with higher meat intake (Ptrend = 0.03). Predictors of FAS initiation after diagnosis were generally similar to those of FAS use after diagnosis, although associations with race and vegetable intake were weaker and those with exercise stronger.Conclusions: Our analysis showed substantial increases in the use of FAS after diagnosis with colorectal cancer, with use or initiation more likely among women, Caucasians, U.S. residents, and those with a health-promoting life-style.Impact: Studies of cancer prognosis that rely on prediagnostic exposure information may result in substantial misclassification. Cancer Epidemiol Biomarkers Prev; 19(8); 2023–34. ©2010 AACR.

This study compares results of endoscopic carpal tunnel release using the two-portal technique in two groups of patients based on whether or not they were receiving workers' compensation. There were 50 patients in the worker's compensation group and 63 in the nonworker's compensation group. Mean follow-up was 40.8 months and 44.8 months, respectively. Duration of symptoms before surgery was statistically different in the two groups, 13.6 months in the worker's compensation groups compared to 26.2 months in the nonworker's compensation group. Worker's compensation patients tended to be younger, have shorter duration of symptoms before surgery, report lower postoperative activity levels, have more subsequent surgeries, and have mediocre results when compared to nonworker's compensation patients. There was no statistically significant difference in the rate or timing of return to work. Our series of 113 patients who had endoscopic carpal tunnel release indicates that careful patient selection is necessary to achieve satisfactory outcomes in worker's compensation patients.