Publications

Activated T cells may express FOXP3. It is thought that FOXP3 is not a specific marker to determine regulatory T cells (Treg) in humans. Here, we examined the functional phenotype and cytokine profile of the in vitro induced FOXP3(+) T cells, primary FOXP3(+) and FOXP3(-) T cells in patients with ulcerative colitis and tumors including colon carcinoma, melanoma, hepatic carcinoma, ovarian carcinoma, pancreatic cancer, and renal cell carcinoma. We observed similar levels of suppressive capacity of primary FOXP3(+) T cells in blood, tumors, and colitic tissues. Compared with primary FOXP3(-) T cells in the same microenvironment, these primary FOXP3(+) T cells expressed minimal levels of effector cytokines, negligible amount of cytotoxic molecule granzyme B, and levels of suppressive molecules interleukin-10 and PD-1. Although the in vitro activated T cells expressed FOXP3, these induced FOXP3(+) T cells expressed high levels of multiple effector cytokines and were not functionally suppressive. The data reinforce the fact that FOXP3 remains an accurate marker to define primary Tregs in patients with cancer and autoimmune disease. We suggest that the combination of FOXP3 and cytokine profile is useful for further functionally distinguishing primary Tregs from activated conventional T cells.

BACKGROUND

Patients with obstructive sleep apnea syndrome (OSAS) are known to have an increased risk for motor vehicle crashes. They suffer from sleep-related respiratory abnormality causing repetitive arousal leading to daytime sleepiness. In turn, it has been demonstrated that sleepiness can impair human psychomotor performance causing slowing of reaction times (RTs). Patients with OSAS present with RTs comparable to young adults under the influence of blood alcohol concentrations above the legally permitted level to drive a motor vehicle. Vigilance related risk levels in patients with upper airway resistance syndrome (UARS) and potential deficits in psychomotor performance are unknown.

METHODS

We designed a study to compare psychomotor performance in UARS and compared it to patients with OSAS. Forty-seven UARS patients were matched by gender and age with 47 OSAS patients. All subjects completed a standardized vigilant attention task utilizing reaction time before undergoing polygraphic sleep studies.

RESULTS

Patients with UARS presented worse psychomotor performance on most test metrics than patients with OSAS.

CONCLUSIONS

Our study results may suggest that patients with UARS may also present an increased risk for motor vehicle crashes as previously demonstrated in OSAS patients.

Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1beta (IL-1beta), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-gamma, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.

PURPOSE

Black patients have worse prognoses than whites with breast or colorectal cancer. Mechanisms underlying such disparities have not been fully explored. We examined the role of hospital factors in racial differences in late mortality after surgery for breast or colon cancer.

METHODS

Patients undergoing surgery after new diagnosis of breast or colon cancer were identified using the Surveillance Epidemiology and End Results-Medicare linked database (1995 to 2005). The main outcome measure was mortality at 5 years. Proportional hazards models were used to assess relationships between race and late mortality, accounting for patient factors, socioeconomic measures, and hospital factors. Fixed and random effects models were used to account for quality differences across hospitals.

RESULTS

Black patients, compared with white patients, had lower 5-year overall survival rates after surgery for breast (62.1% v 70.4%, respectively; P < .001) and colon cancer (41.3% v 45.4%, respectively; P < .001). After controlling for age, comorbidity, and stage, black race remained an independent predictor of mortality for breast (adjusted hazard ratio [HR] = 1.25; 95% CI, 1.16 to 1.34) and colon cancer (adjusted HR = 1.13; 95% CI, 1.07 to 1.19). After risk adjustment, hospital factors explained 36% and 54% of the excess mortality for black patients with breast cancer and colon cancer, respectively. Hospitals with large minority populations had higher late mortality rates independent of race.

CONCLUSION

Hospital factors, including quality, are important mediators of the association between race and mortality for breast and colon cancer. Hospital-level quality improvement should be a major component of efforts to reduce disparities in cancer outcomes.

OBJECTIVES

To determine the prevalence and factors associated with use of potentially inappropriate medications (PIMs) in older adults undergoing surgery.

DESIGN

Retrospective cohort study.

SETTING

Three hundred seventy-nine acute care hospitals participating in the nationally representative Perspective database (2006-2008).

PARTICIPANTS

Individuals aged 65 and older undergoing major inpatient gastrointestinal, gynecological, urological, and orthopedic surgery (N=272,351).

MEASUREMENTS

Medications were classified as PIMs using previously published criteria defining 33 medications deemed potentially inappropriate in people aged 65 and older. Information about participant and provider characteristics and administration of PIMs was obtained from hospital discharge file data. Logistic regression techniques were used to examine factors associated with use of PIMs in the perioperative period.

RESULTS

One-quarter of participants received at least one PIM during their surgical admission. Meperidine was the most frequently prescribed PIM (37,855, 14% of participants). In adjusted analysis, PIM use was less likely as age advanced (adjusted odds ratio (AOR)=0.98 per year of age, 95% confidence interval (CI)=0.97-0.98) and in men (AOR=0.83, 95% CI=0.81-0.85). PIMs were more likely to be prescribed to participants cared for by orthopedic surgeons than for those cared for by general surgeons (AOR=1.22, 95% CI=1.08-1.40). Participants undergoing surgery in the West (AOR=1.79, 95% CI=1.02-3.16) and South (AOR=2.24, 95% CI=1.38-3.64) were more likely to receive a PIM than those in the Northeast.

CONCLUSION

Receipt of PIMs in older adults undergoing surgery is common and varies widely between providers and geographic regions and according to participant characteristics. Interventions aimed at reducing the use of PIMs in the perioperative period should be considered in quality improvement efforts.

OBJECTIVE

To determine surgical risk in nursing home residents undergoing major abdominal surgery.

BACKGROUND

Recent studies suggest that surgery can be performed safely in the very old. Surgical risk in nursing home residents is poorly understood.

METHODS

We used national Medicare claims and the nursing home Minimum Data Set (1999-2006) to identify nursing home residents undergoing surgery (surgery for bleeding duodenal ulcer, cholecystectomy, appendectomy, and colectomy, n = 70,719). We compared operative mortality and use of invasive interventions (mechanical ventilation, intravascular hemodynamic monitoring, feeding tube placement, tracheostomy, and vena cava filters) among nursing home residents to rates among noninstitutionalized Medicare enrollees age 65 and older undergoing the same procedures. (n = 1,060,389). We adjusted for patient characteristics using logistic regression.

RESULTS

Operative mortality among nursing home residents was substantially higher than among noninstitutionalized Medicare enrollees for all procedures (surgery for bleeding duodenal ulcer, 42% versus 26%, adjusted odds ratio (AOR) 1.79; colectomy, 32% versus 13%, AOR 2.06; appendectomy, 12% versus 2%, AOR 3.27; cholecystectomy, 11% versus 3%, AOR 2.65; P < 0.001 for all comparisons). Overall, invasive interventions were more common among nursing home residents than controls (ranging from 18% and 5%, respectively, for cholecystectomy to 55% and 43%, respectively, for surgery for bleeding duodenal ulcer, P < 0.0001 for all comparisons).

CONCLUSIONS

Nursing home residents experience substantially higher rates of mortality and invasive interventions after major surgery than other Medicare beneficiaries that are independent of age and measured comorbidities. Our data suggest that the risks of major surgery are substantially higher in nursing home residents and this information should inform decisions of physicians and patients and their families.

OBJECTIVES

To determine functional status and mortality rates after colon cancer surgery in older nursing home residents.

DESIGN

Retrospective cohort study.

SETTING

Nursing homes in the United States.

PARTICIPANTS

Six thousand eight hundred twenty-two nursing home residents aged 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005.

MEASUREMENTS

Changes in functional status were assessed before and after surgery using the Minimum Data Set Activity of Daily Living (MDS-ADL) summary scale, a 28-point scale in which score increases as functional dependence increases. Regression techniques were used to identify patient characteristics associated with mortality and functional decline 1 year after surgery.

RESULTS

On average, residents who underwent colectomy had a 3.9-point worsening in MDS-ADL score at 1 year. One year after surgery, rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (≥ 80 vs 65-69, adjusted relative risk (ARR) = 1.53, 95% confidence interval (CI) = 1.15-2.04, P < .001), readmission after surgical hospitalization (ARR = 1.15, 95% CI = 1.03-1.29, P = .02), surgical complications (ARR = 1.11, 95% CI = 1.02-1.21, P = .01), and functional decline before surgery (ARR = 1.21, 95% CI = 1.11-1.32, P < .001) were associated with functional decline at 1 year.

CONCLUSION

Mortality and sustained functional decline are common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population.