Publications

BACKGROUND

Studies in persons without HIV infection have compared adipose tissue measured by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI), but no such study has been conducted in HIV-infected (HIV+) subjects, who have a high prevalence of regional fat loss.

OBJECTIVE

We compared DXA- with MRI-measured trunk, leg, arm, and total fat in HIV+ and control subjects.

DESIGN

A cross-sectional analysis was conducted in 877 HIV+ subjects and 260 control subjects in FRAM (Study of Fat Redistribution and Metabolic Change in HIV Infection), stratified by sex and HIV status.

RESULTS

Univariate associations of DXA with MRI were strongest for total and trunk fat (r > or = 0.92) and slightly weaker for leg (r > or = 0.87) and arm (r > or = 0.71) fat. The average estimated limb fat was substantially greater for DXA than for MRI for HIV+ and control men and women (all P < 0.0001). Less of a difference was observed in trunk fat measured by DXA and MRI, but the difference was still statistically significant (P < 0.0001). Bland-Altman plots showed increasing differences and variability. Greater average limb fat in control and HIV+ subjects (both P < 0.0001) was associated with greater differences between DXA and MRI measurements. Because the control subjects had more limb fat than did the HIV+ subjects, greater amounts of fat were measured by DXA than by MRI when control subjects were compared with HIV+ subjects. More HIV+ subjects had leg fat in the bottom decile of the control subjects by DXA than by MRI (P < 0.0001).

CONCLUSIONS

Although DXA- and MRI-measured adipose tissue depots correlate strongly in HIV+ and control subjects, differences increase as average fat increases, particularly for limb fat. DXA may estimate a higher prevalence of peripheral lipoatrophy than does MRI in HIV+ subjects.

BACKGROUND

Regenerative therapies, including myocardial tissue engineering, have been pursued as a new possibility to repair the damaged myocardium, and previously the transplantation of layered cardiomyocyte sheets has been shown to be able to improve cardiac function after myocardial infarction. We examined the effects of promoting neovascularization by controlling the densities of cocultured endothelial cells (ECs) within engineered myocardial tissues created using our cell sheet-based tissue engineering approach.

METHODS AND RESULTS

Neonatal rat cardiomyocytes were cocultured with GFP-positive rat-derived ECs on temperature-responsive culture dishes. Cocultured ECs formed cell networks within the cardiomyocyte sheets, which were preserved during cell harvest from the dishes using simple temperature reduction. We also observed significantly increased in vitro production of vessel-forming cytokines by the EC-positive cardiac cell sheets. After layering of 3 cardiac cell sheets to create 3-dimensional myocardial tissues, these patch-like tissue grafts were transplanted onto infarcted rat hearts. Four weeks after transplantation, recovery of cardiac function could be significantly improved by increasing the EC densities within the engineered myocardial tissues. Additionally, when the EC-positive cardiac tissues were transplanted to myocardial infarction models, we observed significantly greater numbers of capillaries in the grafts as compared with the EC-negative cell sheets. Finally, blood vessels originating from the engineered EC-positive cardiac tissues bridged into the infarcted myocardium to connect with capillaries of the host heart.

CONCLUSIONS

In vitro engineering of 3-dimensional cardiac tissues with preformed EC networks that can be easily connected to host vessels can contribute to the reconstruction of myocardial tissue grafts with a high potential for cardiac function repair. These results indicate that neovascularization can contribute to improved cardiac function after the transplantation of engineered cardiac tissues.

BACKGROUND

Individuals with end-stage renal disease (ESRD) manifest a chronic inflammatory state. Serum albumin, C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) have been associated with mortality in ESRD, although reports vary as to whether they are true independent markers of mortality. We undertook a prospective study to determine whether these markers could predict mortality in ESRD.

METHODS

A cohort of individuals on haemodialysis was followed prospectively for a mean of 2.1 years. Albumin, CRP, IL-6 and SAA were drawn at enrollment. Association between mortality and serum markers was assessed using Cox proportional hazards regression. A trend analysis was undertaken to establish the functional form of the association between serum markers and outcome.

RESULTS

After multivariable adjustment, IL-6 was most strongly associated with mortality, followed closely by albumin (P = 0.0002 and P = 0.0005, respectively). CRP was marginally associated with mortality (P = 0.046), and SAA was not independently associated with mortality. In the final model adjusting for the effects of both IL-6 and albumin simultaneously, both markers remained associated with mortality (P = 0.003 and P = 0.011).

CONCLUSION

IL-6 had the strongest independent association with mortality, followed closely by albumin. CRP and SAA were not associated with mortality when measured at single time points. Increasing levels of IL-6 and decreasing levels of albumin were associated with increased mortality. IL-6 and albumin may be capturing different aspects of the inflammatory burden observed in haemodialysis patients.

AIMS

Given the selectivity of clinical trial patients and meager representation of elderly in the major implantable cardioverter defibrillator (ICD) randomized trials (<25%), whether such data apply to elderly patients overall is unclear. The purpose of our study is to understand the influence of age on mortality after ICD implantation.

METHODS AND RESULTS

We performed a retrospective cohort study of 502 consecutive patients receiving ICDs from 1993 to 2003 at a single university hospital. The primary predictor was patient age, categorized as <65, 65-75, and >75 years at ICD implantation. The primary outcome was time to death. Mean follow-up was 4 years. Median survival after ICD implantation was 5.3 years among subjects >75 years, less than half that of the youngest group. After adjusting for potential confounders, compared with subjects <65 years of age, patients >75 years [hazard ratio (HR), 4.7; 95% confidence interval (CI), 2.8-7.9; P < 0.001] and those 65-75 years (HR, 2.8; 95% CI, 1.7-4.8; P < 0.001) were at greater risk of death. Increased age was associated with higher total, cardiac, and non-cardiac mortality (all P

CONCLUSION

Age at ICD implantation is strongly and independently associated with mortality. Age should be considered among potential co-morbidities in anticipating survival of the elderly patient prior to ICD implantation.