Neck Circumference, Brain Imaging Measures, and Neuropsychological Testing Measures.

BACKGROUND: Perivascular fat may have direct effects on local vascularity. Neck fat is associated with carotid intimal thickness, a predictor of brain aging outcomes. This study investigated whether neck circumference, an estimation of neck fat, has unique associations with brain aging outcomes. METHODS: The study sample (n = 2082, 53.5% women, mean age 60.9 years) was derived from Framingham Heart Study participants with brain magnetic resonance imaging (MRI) and neuropsychological (NP) test measures. Multivariable-adjusted regressions examined cross-sectional associations of neck circumference with brain MRI and NP test measures. Models were also constructed with waist circumference and body mass index (BMI) as exposures. RESULTS: A 1 standard deviation (2.8 cm [women]; 2.9 cm [men]) increment in neck circumference was associated with lower total cerebral brain volume (ß = -.22, P = .0006) and lower frontal brain volume (ß = -.55, P < .0001). However, a similar association was observed for both waist circumference and BMI. There were no associations between neck circumference and NP test measures after full covariate adjustment. CONCLUSIONS: There were no unique associations between neck circumference and brain MRI or NP measures. Consistent with prior observations, all adiposity measures showed associations with more adverse brain MRI and NP measures, suggesting a global association of generalized adiposity.

Intramuscular fat and associations with metabolic risk factors in the Framingham Heart Study.

OBJECTIVE: Intramuscular fat accumulates between muscle fibers or within muscle cells. We investigated the association of intramuscular fat with other ectopic fat deposits and metabolic risk factors. APPROACH AND RESULTS: Participants (n=2945; 50.2% women; mean age 50.8 years) from the Framingham Heart Study underwent multidetector computed tomography scanning of the abdomen. Regions of interest were placed on the left and right paraspinous muscle, and the muscle attenuation (MA) in Hounsfield units was averaged. We examined the association between MA and metabolic risk factors in multivariable models, and additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT) in separate models. MA was associated with dysglycemia, dyslipidemia, and hypertension in both sexes. In women, per standard deviation decrease in MA, there was a 1.34 (95% confidence interval, 1.10-1.64) increase in the odds of diabetes mellitus, a 1.40 (95% confidence interval, 1.22-1.61) increase in the odds of high triglycerides, and a 1.29 (95% confidence interval, 1.12-1.48) increase in the odds of hypertension. However, none of these associations persisted after adjustment for BMI or VAT. In men, we observed similar patterns for most risk factors. The exception was metabolic syndrome, which retained association in women even after adjustment for BMI and VAT, and low high density lipoprotein and high triglycerides in men, whose associations also persisted after adjustment for BMI and VAT. CONCLUSIONS: MA was associated with metabolic risk factors, but most of these associations were lost after adjustment for BMI or VAT. However, a unique association remained for metabolic syndrome in women and lipids in men.

Real-world risk of brain metastases in stage III non-small cell lung cancer in the era of PET and MRI staging.

Objective: The 2-year incidence of brain metastases (BrMs) in stage III non-small lung cell cancer (NSCLC) has been estimated to be around 30%. However, recent clinical trials have demonstrated considerably lower BrMs rates in this patient population. In this study, we aimed to review the real-world incidence, surveillance, and treatment patterns of BrMs in stage III NSCLC. Materials and methods: Using a retrospective single-center study design, we identified patients with stage III NSCLC who received radiation with curative intent over a 10-year period. Outcome variables included BrMs incidence, overall survival (OS), and survival from date of BrMs. Additionally, we assessed patterns of BrMs surveillance in stage III NSCLC and treatment. Results: We identified a total of 279 stage III NSCLC patients, of which 160 with adequate records were included in the final analyses [adenocarcinoma (n = 96), squamous cell carcinoma (n = 53), other histology subtype (n = 11)]. The median OS for the entire cohort was 41 months (95% CI, 28-53), while the median time from BrMs to death was 19 months (95% CI, 9-21). Twenty-three patients (14.4%) received planned surveillance brain MRIs at 6, 12, and 24 months after completion of treatment. The remaining 137 patients (85.6%) received brain MRIs at systemic recurrence (restaging) or when neurologically symptomatic. A total of 37 patients (23%) developed BrMs, with a 2-year cumulative BrMs incidence of 17% (95% CI, 11-23). A higher incidence of BrMs was identified in patients with adenocarcinoma relative to those with squamous cell carcinoma (p < 0.01). Similarly, a higher 2-year BrMs incidence was observed in patients who received planned surveillance brain MRI relative to those who did not, although statistical significance was not reached. Stereotactic radiosurgery (SRS) treated 29 of BrMs patients (78.4%) and was preferred over WBRT, which treated only 3 patients (8.1%). Conclusions: At our center, BrMs incidence in stage III NSCLC patients was lower than historically reported but notably higher than the incidence described in recent clinical trials. Routine BrMs surveillance potentially allows earlier detection of asymptomatic BrMs. However, asymptomatic BrMs were mostly detected on restaging MRI at the time of recurrence.

"But doctor, I googled it!": The "three Rs" of managing patients in the age of information overload.

Managing patient interactions in the age of the Internet can be particularly difficult due to the vast amount of information available. Dermatologists should be able to identify relevant patient concerns to adequately address them. We discuss the ethical issues involved in interacting with patients who use the Internet for medical knowledge, and we suggest a method, using the "three Rs" (reassure, redirect, refer), to conduct these interactions. Appropriate evaluation and categorization of patients with regard to their concerns and needs can help guide physicians on how to use the three Rs in managing patient care and expectations.

Upper Body Subcutaneous Fat Is Associated with Cardiometabolic Risk Factors.

BACKGROUND: Upper body subcutaneous fat is a distinct fat depot that may confer increased cardiometabolic risk. We examined the cross-sectional associations between upper body subcutaneous fat volume and cardiometabolic risk factors. METHODS: Participants were patients from the Framingham Heart Study who underwent multi-detector computed tomography between 2008 and 2011. Sex-specific multivariable-adjusted regression analyses were conducted. Covariates included age, ethnicity, smoking status, alcohol intake, physical activity, postmenopausal status, and hormone replacement therapy. Additional models included adjustment for body mass index (BMI), neck circumference, or abdominal visceral adipose tissue. RESULTS: There were 2306 participants (mean age 60 years, 54.4% women) included. Mean upper body subcutaneous fat was 309.9 cm3 in women and 345.6 cm3 in men. Higher upper body subcutaneous fat volume was associated with adverse cardiometabolic risk factors. In women and men, each additional 50-cm3 increment in upper body subcutaneous fat was associated with a 3.23 and 2.65 kg/m2 increase in BMI; 2.16 and 0.88 mm Hg increase in systolic blood pressure; 2.53 and 1.66 mg/dL increase in fasting plasma glucose; 0.12 and 0.11 mg/dL increase in log triglycerides; and 4.17 and 3.68 mg/dL decrease in high-density lipoprotein cholesterol, respectively (all P ≤.008). Similar patterns were observed with prevalent cardiometabolic risk factors. These associations remained significant after additional adjustment for BMI, neck circumference, or abdominal visceral adipose tissue. CONCLUSIONS: Higher upper body subcutaneous fat is cross-sectionally associated with adverse cardiometabolic risk factors. Our findings underscore the importance of subcutaneous adiposity in the upper body region that may provide a better understanding of the pathogenic properties of obesity in the development of cardiometabolic sequelae.

Intramuscular fat and physical performance at the Framingham Heart Study.

Intramuscular fat may mediate associations between obesity and physical disability. We examined the associations between muscle attenuation, a proxy for intramuscular fat, and physical function. Paraspinous muscle computed tomography attenuation was obtained on a Framingham Heart Study subgroup (n = 1152, 56 % women, mean age 66 years). Regressions modeled cross-sectional associations between muscle attenuation and mobility disability, grip strength, and walking speed with standard covariates; models additionally adjusted for body mass index (BMI) and visceral adipose tissue (VAT). Separate models investigated associations between VAT and subcutaneous adipose tissue (SAT) and physical function. Per 1 standard deviation decrement in muscle attenuation (i.e., more muscle fat), we observed 1.29 (95 % CI = 1.11, 1.50; p = 0.0009) increased odds of walking speed ≤1 m/s in women and men. This persisted after separate BMI and VAT adjustments (p < 0.02). In men, there was a 1.29 kg (95 % CI = 0.57, 2.01; p = 0.0005) decrement in grip strength, which persisted after BMI and VAT adjustments (p ≤ 0.0004). For VAT and SAT, similar associations were not observed. Intramuscular fat is associated with increased odds of walking speed ≤1 m/s in both sexes and lower grip strength in men. There were no similar associations for VAT and SAT, highlighting the specificity of intramuscular fat in association with physical function.

Association Between Prolactin and Incidence of Cardiovascular Risk Factors in the Framingham Heart Study.

BACKGROUND: Prolactin is an anterior pituitary hormone that may modulate the adverse effects of obesity. Prolactin has been associated with cardiovascular disease mortality, but less is known about whether prolactin predicts incidence of cardiovascular disease risk factors. METHODS AND RESULTS: Our sample (n=3232, mean age 40.4 years, 52.1% women) was drawn from Framingham Heart Study participants who attended 2 examinations an average of 6.1 years apart. After excluding those with elevated prolactin (>30 mg/dL for women, >20 mg/dL for men), multivariable-adjusted regressions modeled the associations between baseline prolactin and changes in cardiovascular disease risk factors. Models were adjusted for age, sex, baseline value of the risk factor, smoking status, hormone replacement therapy, and menopausal status and additionally for body mass index. Mean prolactin levels were 11.9 mg/dL (SD 5.2) in women and 8.0 mg/dL (SD 2.9) in men. No associations were observed for change in weight, body composition, total cholesterol, triglycerides, or fasting glucose. In women, for example, for each 5-mg/dL increment in prolactin, odds of incident hypercholesterolemia were 1.06, which was not significant (95% CI 0.91-1.23, P=0.46). Some exceptions were of note. In women, for each 5-mg/dL increment in prolactin, we observed increased odds of low high-density lipoprotein cholesterol at follow-up (odds ratio 1.50, 95% CI 1.18-1.91, P=0.001) that persisted after adjustment for body mass index (P=0.001). In men, a 5-mg/dL increment in prolactin was associated with increased odds of incident hypertension (odds ratio 1.61, 95% CI 1.18-2.20 P=0.002) and incident diabetes (odds ratio 1.70, 95% CI 1.04-2.78, P=0.03). CONCLUSIONS: Prolactin is not associated with a comprehensive panel of incident cardiovascular disease risk factors. Measurement of circulating prolactin levels in the community likely does not provide substantial insight into cardiometabolic risk.

Adipose tissue attenuation as a marker of adipose tissue quality: Associations with six-year changes in body weight.

OBJECTIVE: Weight gain is associated with fat volume increases, but associations with fat quality are less well characterized The associations of weight change with visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume and attenuation were investigated. METHODS: Computed tomography abdominal scans were acquired on a Framingham Heart Study subset (N = 836; 40.2% women; mean age 45.7 years), a mean of 6.1 years apart. Fat attenuation estimated fat quality. RESULTS: Mean weight change was +2.0 (SD 6.8; IQR -0.7, 5.0) kg in women and +2.7 (SD 6.0; IQR -0.5, 5.4) kg in men. Per 2.5 kg weight increase in women, VAT volume increased 126 cm(3) (95% CI, 112-140, p < 0.0001), SAT volume increased 258 cm(3) (95% CI, 239-278, p < 0.0001), and fat attenuation decreased (i.e., fat quality worsened) in VAT and SAT (p < 0.0001). Increasing VAT volume was associated with decreasing fat attenuation even after accounting for weight change. Relative to weight-stable women (n = 129), women who lost >2.5 kg (n = 58) had smaller SAT attenuation decreases (p < 0.0001). Similar patterns were seen in men. CONCLUSIONS: Weight gain was associated with decreases in fat attenuation independent of VAT and SAT volume changes. These findings highlighted the associations of weight gain and worsening fat attenuation, suggesting fat attenuation may be dynamic.

Development and reproducibility of a computed tomography-based measurement for upper body subcutaneous neck fat.

BACKGROUND: Upper body subcutaneous neck fat (UBSF) is a unique fat depot anatomically separate from visceral abdominal fat that appears to be associated with cardiometabolic risk above and beyond generalized adiposity. We sought to develop a protocol to quantify UBSF using multidetector computed tomography measurements. METHODS AND RESULTS: Protocol development was performed in participants from the Framingham Heart Study who had participated in the multidetector computed tomography scanning substudy, consisting of chest scans. Volumetric assessment of UBSF was defined by 40 contiguous 0.625­mm slices superior to the body of the sternum. The reader manually traced the chest to identify total neck fat. Breast tissue exterior to the chest wall was excluded. Subcutaneous and visceral fat volumes were obtained using standard protocols. Age­ and sex­adjusted Pearson correlation coefficients were used to assess the association among UBSF, traditional adiposity measures, and cardiometabolic risk factors. Inter­ and intrareader reproducibility was assessed using intraclass correlation coefficients. Volumetric assessments were obtained in 92 participants because 8 scans were not readable (51% women; mean age: 59 years [women], 58 years [men]). The mean volume of UBSF was 310 cm3 for women and 345 cm3 for men. Intra­ and interreader class correlation coefficients were 0.99 and 0.99, respectively. UBSF was correlated with waist circumference (r=0.90), neck circumference (r=0.75), body mass index (r=0.89), subcutaneous adipose tissue (r=0.87), and visceral adipose tissue (r=0.86). CONCLUSIONS: UBSF can be quantified reproducibly using computed tomography in a community­dwelling sample from the Framingham Heart Study.

Visceral and subcutaneous fat quality and cardiometabolic risk.

OBJECTIVES: The aim of this study was to evaluate whether computed tomography (CT) attenuation, as a measure of fat quality, is associated with cardiometabolic risk factors above and beyond fat quantity. BACKGROUND: Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are pathogenic fat depots associated with cardiometabolic risk. Adipose tissue attenuation in CT images is variable, similar to adipose tissue volume. However, whether the quality of abdominal fat attenuation is associated with cardiometabolic risk independent of the quantity is uncertain. METHODS: Participants were drawn from the Framingham Heart Study CT substudy. The VAT and SAT volumes were acquired by semiquantitative assessment. Fat quality was measured by CT attenuation and recorded as mean Hounsfield unit (HU) within each fat depot. Sex-specific linear and logistic multivariable regression models were used to assess the association between standard deviation (SD) decrease in HU and each risk factor. RESULTS: Lower CT attenuation of VAT and SAT was correlated with higher body mass index levels in both sexes. Risk factors were generally more adverse with decreasing HU values. For example, in women, per 1 SD decrease in VAT HU, the odds ratio (OR) was increased for hypertension (OR: 1.80), impaired fasting glucose (OR: 2.10), metabolic syndrome (OR: 3.65), and insulin resistance (OR: 3.36; all p < 0.0001). In models that further adjusted for VAT volume, impaired fasting glucose, metabolic syndrome, and insulin resistance remained significant. Trends were similar but less pronounced for SAT and for men. There was evidence of an interaction between HU and fat volume among both women and men. CONCLUSIONS: Lower CT attenuation of VAT and SAT is associated with adverse cardiometabolic risk above and beyond total adipose tissue volume. Qualitative indices of abdominal fat depots may provide insight regarding cardiometabolic risk independent of fat quantity.