Kyle Porter

Depressive symptoms, omega-6:omega-3 fatty acids, and inflammation in older adults.

Objective: To address how interactions between polyunsaturated fatty acid (PUFA) levels and depressive symptoms were related to proinflammatory cytokine synthesis. Depression and stress promote proinflammatory cytokine production. Dietary intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs also influence inflammation; high n-6:n-3 ratios enhance proinflammatory cytokine production, although n-3 has anti-inflammatory properties. Methods: Blood samples from 43 older adults (mean age = 66.67 years, SD = 10.09) provided data on PUFAs and tumor necrosis factor (TNF)-&agr;, interleukin (IL)-6, and IL-6 soluble receptor (sIL-6r). Depressive symptoms were assessed by the Center for Epidemiological Studies Depression Scale. Results: Depressive symptoms and n-6:n-3 ratios worked together to enhance proinflammatory cytokines beyond the contribution provided by either variable alone, with substantial variance explained by their interaction: 13% for IL-6 and 31% for TNF-&agr;, whereas full models accounted for 18% and 40%, respectively. Although predicted cytokine levels were consistent across n-6:n-3 ratios with low depressive symptoms, higher n-6:n-3 ratios were associated with progressively elevated TNF-&agr; and IL-6 levels as depressive symptoms increased. Higher levels of sIL-6r were associated with higher n-6:n-3 ratios. Six individuals who met the criteria for major depressive disorder had higher n-6:n-3 ratios and TNF-&agr;, IL-6, and sIL-6r levels than those who did not meet the criteria; excluding these six individuals reduced the variance explained by the depressive symptoms and n-6:n-3 ratio interaction. Conclusions: Diets with high n-6:n-3 PUFA ratios may enhance the risk for both depression and inflammatory diseases. AA = arachidonic acid; BMI = body mass index; CES-D = Center for Epidemiological Studies Depression Scale; DHA = docosahexanoic acid; EPA = eicosapentaenoic acid; IL-6 = interleukin-6; sIL-6r = IL-6 soluble receptor; n-3 = omega-3; n-6 = omega-6; NF-&kgr;B = nuclear factor kappa B; PSQI = Pittsburgh Sleep Quality Index; PUFA = polyunsaturated fatty acid; TNF-&agr; = tumor necrosis factor-&agr;.

Poorer self-rated health is associated with elevated inflammatory markers among older adults

OBJECTIVE Self-rated health is a strong independent predictor of mortality after accounting for objective health status, behavioral risk factors, and sociodemographic characteristics. However, mechanisms underlying this association are largely unexplained. Inflammation has been associated with increased risk of morbidity and mortality in the elderly. The current study aimed to: (1) examine associations between self-rated health and serum inflammatory markers in older adults; (2) examine the relative strength of these associations for self-rated health versus self-rated change in recent health; (3) examine components of self-rated health that may underlie the association between inflammation and global self-rated health. METHODS Self-rated health, as measured by the RAND health survey, and serum interleukin (IL)-6 and C-reactive protein (CRP) were assessed among 250 generally healthy older adults (185 women, 65 men; average age=63.8±13.7 years). RESULTS A series of linear regression analyses demonstrated that poorer self-rated health was significantly associated with higher IL-6 and CRP. These relationships remained after controlling for age, body mass index, gender, and objective health conditions. These associations also remained after controlling for depressive symptoms, neuroticism, perceived change in health over the past year, and health behaviors (smoking, sleep quality, and physical activity). Analyses of RAND component measures demonstrated that poorer physical functioning was significantly associated with IL-6; the relationship between global self-rated health and both IL-6 and CRP remained after accounting for perceived physical functioning. CONCLUSIONS Poorer self-rated health is associated with elevated serum inflammatory markers among generally healthy older adults. The relationship of self-rated health with inflammatory markers is not secondary to depressive symptoms, neuroticism, or recent changes in perceived health. Subjective ratings of health provide important clinical information regarding inflammatory status, beyond traditional objective risk factors, even among generally healthy individuals.

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer

OBJECTIVE The objective of the study was to determine the outcome of surgical resection of metastatic papillary thyroid cancer (PTC) in cervical lymph nodes after failure of initial surgery and I(131) therapy. DESIGN This was a retrospective clinical study. SETTING The study was conducted at a university-based tertiary cancer hospital. PATIENTS A cohort of 95 consecutive patients with recurrent/persistent PTC in the neck underwent initial reoperation during 1999-2005. All had previous thyroidectomy (+/-nodal dissection) and I(131) therapy. Twenty-five patients with antithyroglobulin (Tg) antibodies were subsequently excluded. MAIN OUTCOME MEASURES Biochemical complete remission (BCR) was stringently defined as undetectable TSH-stimulated serum Tg. RESULTS A total of 107 lymphadenectomies were undertaken in these 70 patients through January 2010. BCR was initially achieved in 12 patients (17%). Of the 58 patients with detectable postoperative Tg, 28 had a second reoperation and BCR was achieved in five (18%), seven had a third reoperation, and none achieved BCR. No patient achieving BCR had a subsequent recurrence after a mean follow-up of 60 months (range 4-116 months). In addition, two more patients achieved BCR during long-term follow-up without further intervention. In total, 19 patients (27%) achieved BCR and 32 patients (46%) achieved a TSH-stimulated Tg less than 2.0 ng/ml. Patients who did not achieve BCR had significant reduction in Tg after the first (P < 0.001) and second (P = 0.008) operations. No patient developed detectable distant metastases or died from PTC. CONCLUSIONS Surgical resection of persistent PTC in cervical lymph nodes achieves BCR, when most stringently defined, in 27% of patients, sometimes requiring several surgeries. No biochemical or clinical recurrences occurred during follow-up. In patients who do not achieve BCR, Tg levels were significantly reduced. The long-term durability and impact of this intervention will require further investigation.

Sleep disordered breathing and post-discharge mortality in patients with acute heart failure

BACKGROUND Hospitalizations for heart failure are associated with a high post-discharge risk for mortality. Identification of modifiable predictors of post-discharge mortality during hospitalization may improve outcome. Sleep disordered breathing (SDB) is the most common co-morbidity in heart failure patients. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of patients hospitalized with acute heart failure (AHF) in a single academic heart hospital. Between January 2007 and December 2010, all patients hospitalized with AHF who have left ventricular ejection fraction (LVEF) ≤ 45% and were not already diagnosed with SDB were the target population. MAIN OUTCOMES AND MEASURES Patients underwent in-hospital attended polygraphy testing for SDB and were followed for a median of 3 years post-discharge. Mortality was recorded using national and state vital statistics databases. RESULTS During the study period, 1117 hospitalized AHF patients underwent successful sleep testing. Three hundred and forty-four patients (31%) had central sleep apnoea (CSA), 525(47%) patients had obstructive sleep apnoea (OSA), and 248 had no or minimal SDB (nmSDB). Of those, 1096 patients survived to discharge and were included in the mortality analysis. Central sleep apnoea was independently associated with mortality. The multivariable hazard ratio (HR) for time to death for CSA vs. nmSDB was 1.61 (95% CI: 1.1, 2.4, P = 0.02). Obstructive sleep apnoea was also independently associated with mortality with a multivariable HR vs. nmSDB of 1.53 (CI: 1.1, 2.2, P = 0.02). The Cox proportional hazards model adjusted for the following covariates: LVEF, age, BMI, sex, race, creatinine, diabetes, type of cardiomyopathy, coronary artery disease, chronic kidney disease, discharge systolic blood pressure <110, hypertension, discharge medications, initial length of stay, admission sodium, haemoglobin, and BUN. CONCLUSIONS This is the largest study to date to evaluate the effect of SDB on post-discharge mortality in patients with AHF. Newly diagnosed CSA and OSA during AHF hospitalization are independently associated with post-discharge mortality.

Clostridium difficile Infection in Ohio Hospitals and Nursing Homes During 2006

CONTEXT Healthcare data suggest that the incidence and severity of Clostridium difficile infection (CDI) in hospitals are increasing. However, the overall burden of disease and the mortality rate associated with CDI, including the contribution from cases of infection that occur in nursing homes, are poorly understood. OBJECTIVE To describe the epidemiology, disease burden, and mortality rate of healthcare-onset CDI. METHODS In 2006, active public reporting of healthcare-onset CDI, using standardized case definitions, was mandated for all Ohio hospitals and nursing homes. Incidence rates were determined and stratified according to healthcare facility characteristics. Death certificates that listed CDI were analyzed for trends. RESULTS There were 14,329 CDI cases reported, including 6,376 cases at 210 hospitals (5,217 initial cases [ie, cases identified more than 48 hours after admission to a healthcare facility in patients who had not had CDI during the previous 6 months] and 1,159 recurrent cases [ie, cases involving patients who had had CDI during the previous 6 months]) and 7,953 cases at 955 nursing homes (4,880 initial and 3,073 recurrent cases) . After adjusting for missing data, the estimated total was 18,200 cases of CDI, which included 7,000 hospital cases (5,700 initial and 1,300 recurrent cases) and 11,200 nursing homes cases (6,900 initial and 4,300 recurrent cases). The rate for initial cases was 6.4-7.9 cases/10,000 patient-days for hospitals and 1.7-2.9 cases/10,000 patient-days for nursing homes. The rate for initial cases in nursing homes decreased during the study (P < .001). Nonpediatric hospital status (P = .011), a smaller number of beds (P = .003), and location in the eastern or northeastern region of the state (P = .011) were each independently associated with a higher rate of initial cases in hospitals. Death certificates for 2006 listed CDI among the causes of death for 893 Ohio residents; between 2000 and 2006, this number increased more than 4-fold. CONCLUSION Healthcare-onset CDI represents a major public health threat that, when considered in the context of an increasing mortality rate, should justify a major focus on prevention efforts.

Longitudinal changes in serum proinflammatory markers across pregnancy and postpartum: Effects of maternal body mass index

BACKGROUND The maternal immune system undergoes substantial changes to support healthy pregnancy. Although obesity is a primary driver of inflammation and predictive of perinatal complications, additive effects of pregnancy and obesity on changes in inflammatory processes are not well delineated. METHODS This study examined serum proinflammatory markers interleukin(IL)-6, IL-8, tumor necrosis factor (TNF)-α, IL-1β, and C-reactive protein (CRP) during each trimester of pregnancy and 4-6 weeks postpartum among 57 women. RESULTS Overall, IL-6 showed an increasing trend across pregnancy and significant increase at postpartum. Similarly, TNF-α increased significantly across gestation, with a further increase at postpartum. Both IL-8 and IL-1β showed a U-shaped curve, decreasing from early to later pregnancy, and increasing at postpartum. Finally, serum CRP decreased significantly across pregnancy, with further decreases at postpartum. Maternal obesity predicted higher IL-6 at each study visit. Obese women showed a trend toward elevated serum CRP during pregnancy, and significantly higher levels at postpartum. DISCUSSION The course of pregnancy and postpartum is characterized by significant changes in serum proinflammatory mediators. Obese women show elevations in serum proinflammatory markers relative to normal weight women during pregnancy and postpartum. Further research is needed to determine the extent to which obesity-induced inflammation affects maternal and fetal health.

Ultra‐early predictive assay for treatment failure using functional magnetic resonance imaging and clinical prognostic parameters in cervical cancer

The authors prospectively evaluated magnetic resonance imaging (MRI) parameters quantifying heterogeneous perfusion pattern and residual tumor volume early during treatment in cervical cancer, and compared their predictive power for primary tumor recurrence and cancer death with the standard clinical prognostic factors. A novel approach of augmenting the predictive power of clinical prognostic factors with MRI parameters was assessed.

Stress-Induced Inflammatory Responses in Women: Effects of Race and Pregnancy

Objective African Americans experience preterm birth at nearly twice the rate of whites. Chronic stress associated with minority status is implicated in this disparity. Inflammation is a key biological pathway by which stress may affect birth outcomes. This study examined the effects of race and pregnancy on stress-induced inflammatory responses. Methods Thirty-nine women in the second trimester of pregnancy (19 African American, 20 white) and 39 demographically similar nonpregnant women completed an acute stressor (Trier Social Stress Test). Psychosocial characteristics, health behaviors, and affective responses were assessed. Serum interleukin (IL)-6 was measured at baseline, 45 minutes, and 120 minutes poststressor. Results IL-6 responses at 120 minutes poststressor were 46% higher in African Americans versus whites (95% confidence interval = 8%–81%, t(72) = 3.51, p = .001). This effect was present in pregnancy and nonpregnancy. IL-6 responses at 120 minutes poststressor tended to be lower (15%) in pregnant versus nonpregnant women (95% confidence interval = −5%–32%, p = .14). Racial differences in inflammatory responses were not accounted for by demographics, psychological characteristics, health behaviors, or differences in salivary cortisol. Pregnant whites showed lower negative affective responses than did nonpregnant women of either race (p values ⩽ .007). Conclusions This study provides novel evidence that stress-induced inflammatory responses are more robust among African American women versus whites during pregnancy and nonpregnancy. The ultimate impact of stress on health is a function of stressor exposure and physiological responses. Individual differences in stress-induced inflammatory responses represent a clear target for continued research efforts in racial disparities in health during pregnancy and nonpregnancy.

How stress and anxiety can alter immediate and late phase skin test responses in allergic rhinitis.

Allergic rhinitis (AR) is the fifth most common chronic disease, and the association between allergic disorders and anxiety is well-documented. To investigate how anxiety and stressors modulate skin prick test (SPT) responses and associated inflammatory responses, 28 men and women with AR were selected by clinical history and skin test responses. The participants were admitted twice to a hospital research unit for 4h in a crossover trial. Changes in SPT wheals were assessed before and after a standardized laboratory speech stressor, as well as again the following morning; skin responses assessed twice during a lab session without a stressor and again the following morning served as the contrast condition. Anxiety heightened the magnitude of allergen-induced wheals following the stressor. As anxiety increased, SPT wheal diameters increased after the stressor, compared to a slight decrease following the control task. Anxiety also substantially enhanced the effects of stress on late phase responses: even skin tests performed the day after the stressor reflected the continuing impact of the speech stressor among the more anxious participants. Greater anxiety was associated with more IL-6 production by Con A-stimulated leukocytes following the stressor compared to the control visit. The data suggest that stress and anxiety can enhance and prolong AR symptoms.

Semi‐automated imaging system to quantitate Her‐2/neu membrane receptor immunoreactivity in human breast cancer

Immunocytochemical methods for quantitating Her‐2/neu immunoreactivity rest on subjective semi‐quantitative interpretations with resulting interobserver, intraobserver, and fatigue variability.