FTY720, an analogue of sphingosine-1-phosphate, is cardioprotective during acute injury. Whether long-term FTY720 affords cardioprotection is unknown. Here, we report the effects of oral FTY720 on ischemia/reperfusion injury and in hypomorphic apoE mice deficient in SR-BI receptor expression (ApoeR61(h/h)/SRB1(-/- mice), a model of diet-induced coronary atherosclerosis and heart failure. We added FTY720 (0.3 mg·kg(-1)·d(-1)) to the drinking water of C57BL/6J mice. After ex vivo cardiac ischemia/reperfusion injury, these mice had significantly improved left ventricular (LV) developed pressure and reduced infarct size compared with controls. Subsequently, ApoeR61(h/h)/SRB1(-/-) mice fed a high-fat diet for 4 weeks were treated or not with oral FTY720 (0.05 mg·kg(-1)·d(-1)). This sharply reduced mortality (P < 0.02) and resulted in better LV function and less LV remodeling compared with controls without reducing hypercholesterolemia and atherosclerosis. Oral FTY720 reduced the number of blood lymphocytes and increased the percentage of CD4+Foxp3+ regulatory T cells (Tregs) in the circulation, spleen, and lymph nodes. FTY720-treated mice exhibited increased TGF-β and reduced IFN-γ expression in the heart. Also, CD4 expression was increased and strongly correlated with molecules involved in natural Treg activity, such as TGF-β and GITR. Our data suggest that long-term FTY720 treatment enhances LV function and increases longevity in mice with heart failure. These benefits resulted not from atheroprotection but from systemic immunosuppression and a moderate reduction of inflammation in the heart.

Many outpatient clinics where health professionals train will transition to a team-based medical home model over the next several years. Therefore, training programs need innovative approaches to prepare and incorporate trainees into team-based delivery systems. To address this need, educators at the San Francisco Veterans Affairs (VA) Medical Center included trainees in preclinic team "huddles," or briefing meetings to facilitate care coordination, and developed an interprofessional huddle-coaching program for nurse practitioner students and internal medicine residents who function as primary providers for patient panels in VA outpatient primary care clinics. The program aimed to support trainees' partnerships with staff and full participation in the VA's Patient Aligned Care Teams. The huddle-coaching program focuses on structuring the huddle process via scheduling, checklists, and designated huddle coaches; building relationships among team members through team-building activities; and teaching core skills to support collaborative practice. A multifaceted evaluation of the program showed positive results. Participants rated training sessions and team-building activities favorably. In interviews, trainees valued their team members and identified improvements in efficiency and quality of patient care as a result of the team-based approach. Huddle checklists and scores on the Team Development Measure indicated progress in team processes and relationships as the year progressed. These findings suggest that the huddle-coaching program was a worthwhile investment in trainee development that also supported the clinic's larger mission to deliver team-based, patient-aligned care. As more training sites shift to team-based care, the huddle-coaching program offers a strategy for successfully incorporating trainees.

Endoscopic mucosal resection (EMR) of early gastric cancer, which has been proved to be safe and effective and is the established standard of care in Japan, has become increasingly established worldwide in the past decade. Endoscopic submucosal dissection (ESD) is superior to EMR, as it is designed to provide precise pathologic staging and long-term curative therapy based on an en bloc R0 specimen irrespective of the size and/or location of the tumor. However, ESD requires highly skilled and experienced endoscopists. The introduction of ESD to the Western world necessitates collaborations between Eastern and Western endoscopists, pathologists, and surgeons.

OBJECTIVE

Diabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men.

DESIGN

Cross-sectional cohort using direct measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV-infected men and 241 HIV-uninfected men who were free of chronic kidney disease.

METHODS

Hyperfiltration was defined as glomerular filtration rate above 140-1 ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic, cardiovascular, HIV and cumulative antiretroviral exposure factors.

RESULTS

Among individuals without chronic kidney disease, the prevalence of hyperfiltration was higher for HIV-infected participants (25%) compared to uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61] and modified the association between diabetes and hyperfiltration, such that the association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were independent of known risk factors for hyperfiltration. Indicators of hyperglycemia and hypertension were also associated with hyperfiltration as was cumulative zidovudine exposure.

CONCLUSION

Hyperfiltration, a potential modifiable predictor of kidney disease progression, is significantly higher among antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the association of diabetes and hyperfiltration present in HIV-uninfected men.