Sex Differences in the Association of Body Composition and Cardiovascular Mortality.

Background To determine whether differences in body composition contribute to sex differences in cardiovascular disease (CVD) mortality, we investigated the relationship between components of body composition and CVD mortality in healthy men and women. Methods and Results Dual energy x-ray absorptiometry body composition data from the National Health and Nutrition Examination Survey 1999-2004 and CVD mortality data from the National Health and Nutrition Examination Survey 1999-2014 were evaluated in 11 463 individuals 20 years of age and older. Individuals were divided into 4 body composition groups (low muscle mass-low fat mass-the referent; low muscle-high fat; high muscle-low fat, and high muscle-high fat), and adjusted competing risks analyses were performed for CVD versus non-CVD mortality. In women, high muscle/high fat mass was associated with a significantly lower adjusted CVD mortality rate (hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P=0.01), but high muscle/low fat mass was not. In men, both high muscle-high fat (HR, 0.74; 95% CI, 0.53-1.04; P=0.08) and high muscle-low fat mass (HR, 0.40; 95% CI, 0.21-0.77; P=0.01) were associated with lower CVD. Further, in adjusted competing risks analyses stratified by sex, the CVD rate in women tends to significantly decrease as normalized total fat increase (total fat fourth quartile: HR, 0.56; 95% CI, 0.34-0.94; P<0.03), whereas this is not noted in men. Conclusions Higher muscle mass is associated with lower CVD and mortality in men and women. However, in women, high fat, regardless of muscle mass level, appears to be associated with lower CVD mortality risk. This finding highlights the importance of muscle mass in healthy men and women for CVD risk prevention, while suggesting sexual dimorphism with respect to the CVD risk associated with fat mass.

Relation of Stress Hormones (Urinary Catecholamines/Cortisol) to Coronary Artery Calcium in Men Versus Women (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

The relation between high levels of psychosocial stress and the development of coronary artery disease (CAD) has been increasingly recognized, especially in women. We hypothesized that simple biomarkers of stress, urinary catecholamines/cortisol levels, are associated with more coronary artery calcium (CAC), an indicator of CAD, and that this relation is stronger in women compared with men. Using data from the Multi-Ethnic Study of Atherosclerosis Stress study, we examined the relation between urinary catecholamines/cortisol and CAC. The study cohort (n = 654) was 53% women, and 56.4% of the cohort had detectable CAC. Multivariable regression analyses assessed the relation between urinary catecholamines/cortisol and CAC (odds CAC >0 through logistic and ln CAC through Tobit model). There was an association between increased cortisol and increased CAC and an inverse association between dopamine and CAC. These relations were seen in men and women, with no difference between the genders. In conclusion, higher cortisol and lower dopamine levels are independently associated with higher CAC to a similar degree in men and women. These simple urinary biomarkers contribute to our understanding of the role of stress in the pathogenesis of CAD and may be incorporated into future strategies to prevent and treat CAD.

Reflection Magnitude, a Measure of Arterial Stiffness, Predicts Incident Heart Failure in Men But Not Women: Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Arterial stiffness is a risk factor for heart failure (HF) and is higher in women. Our objective was to investigate sex differences between arterial stiffness and incident HF in the Multi-Ethnic Study of Atherosclerosis (MESA) population. METHODS AND RESULTS: Applanation tonometry from 5959 participants (52.8% women) was used to calculate augmentation index (AIx), pulse pressure amplification (PPA), and reflection magnitude (RM). Sex-specific risk of HF was assessed with the use of a competing-risk regression model. Women had higher AIx (P < .00001), higher RM (P = .023), and lower PPA (P < .00001) indicating greater arterial stiffness in women. However, increasing RM quartile independently predicted HF in men (adjusted hazard ratios and 95% confidence intervals: Q2: 2.05 [1.06-3.96; P = .033]; Q3: 2.49 [1.30-4.73; P = .006]; Q4: 3.26 [1.75-6.08; P = .0002]) but not in women (Q2: 1.04 [0.54-1.98; P = .91]; Q3: 1.30 [0.71-2.37; P = .4]; Q4: 0.79 [0.4-1.55; P = .49]). CONCLUSION: Women demonstrate greater arterial stiffness than men. Despite this, arterial stiffness, as measured by RM, predicts incident HF in men but not in women. RM represents a novel risk factor for HF in men but not in women. Further investigation of risk factors for HF in women is warranted. CONCLUSION: Arterial stiffness, measured by RM, predicts incident HF in men but not in women in this MESA cohort.

Local Variability of Macular Thickness Measurements With SD-OCT and Influencing Factors.

PURPOSE: To compare the intrasession variability of spectral-domain optical coherence tomography (SD-OCT)-derived local macular thickness measures and explore influencing factors. METHODS: One hundred two glaucomatous eyes (102 patients) and 21 healthy eyes (21 subjects) with three good quality macular images during the same session were enrolled. Thickness measurements were calculated for 3° superpixels for the inner plexiform (IPL), ganglion cell (GCL), or retinal nerve fiber layers (mRNFL), GC/IPL, ganglion cell complex, and full macular thickness. Spatial distribution and magnitude of measurement errors (ME; differences between the 3 individual superpixel values and their mean) and association between MEs and thickness, age, axial length, and image quality were explored. RESULTS: MEs had a normal distribution with mostly random noise along with a small fraction of outliers (1.2%-6.6%; highest variability in mRNFL and on the nasal border) based on M-estimation. Boundaries of 95% prediction intervals for variability reached a maximum of 3 µm for all layers and diagnostic groups after exclusion of outliers. Correlation between proportion of outliers and thickness measures varied among various parameters. Age, axial length, or image quality did not influence MEs (P > 0.05 for both groups). CONCLUSIONS: Local variability of macular SD-OCT measurements is low and uniform across the macula. The relationship between superpixel thickness and outlier proportion varied as a function of the parameter of interest. TRANSLATIONAL RELEVANCE: Given the low and uniform variability within and across eyes, definition of an individualized 'variability space' seems unnecessary. The variability measurements from this study could be used for designing algorithms for detection of glaucoma progression.

Are red blood cell transfusions associated with nosocomial infections in pediatric intensive care units?

OBJECTIVES: To determine whether red blood cell transfusion is similarly associated with nosocomial infections in pediatric intensive care unit patients and whether reduced lymphocyte numbers is a possible mechanism. In adult studies, red blood cell transfusions are associated with nosocomial infections. DESIGN: Historical cohort study. SETTING: Single-center, mixed medical-surgical, closed pediatric intensive care unit of a tertiary university-affiliated children's hospital. PATIENTS: All patients < or = 18 yrs old admitted to the pediatric intensive care unit during a 6-month period from January 1 to July 3, 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nosocomial infections (respiratory, urinary tract, and bloodstream infections) were the primary outcome measure and were defined as post transfusion if occurring within 14 days after red blood cell transfusion. Of the 209 subjects enrolled, 32 (15%) acquired nosocomial infections and 45 (22%) received red blood cell transfusions. Patients with versus without nosocomial infections had received red blood cell transfusions significantly more often (odds ratio, 18.0; 95% confidence interval, 7.6-45.9; p < .001). In a dose-dependence analysis, we found that patients receiving > or = 3 red blood cell transfusions had a similar prevalence of nosocomial infections compared with those receiving one to two red blood cell transfusions (61% vs. 44%, p = .365), but greater mortality (22% vs. 0%, p = .04). In a multiple logistic regression analysis controlling for gender, age, pediatric intensive care unit length of stay, presence of an invasive catheter, mechanical ventilation, and surgery, red blood cell transfusion remained independently associated with risk of nosocomial infection (odds ratio, 3.73; 95% confidence interval, 1.19-11.85, p = .023). Transfused subjects had lower absolute lymphocyte counts compared with nontransfused subjects (1605 vs. 2054/microL, p = .041), but similar total white blood cell counts (10.4 vs. 11.4 x 10/microL, p = .52). CONCLUSION: Red blood cell transfusion in pediatric intensive care unit patients is associated with an increased risk of nosocomial infections.

Accuracy of clinical evaluation of locally advanced breast cancer in patients receiving neoadjuvant chemotherapy.

BACKGROUND: Physical examination (PE), mammography (MG), breast magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (PET), and pathologic evaluation are used to assess primary breast cancer. To the authors' knowledge, their accuracy has not been well studied in patients receiving neoadjuvant chemotherapy. Accuracies of each modality in tumor and lymph node assessment in patients with T3/T4 tumors receiving neoadjuvant chemotherapy were compared. METHODS: Forty-five patients of a prospective clinical trial studying T3-T4M0 tumors were included. Patients received neoadjuvant chemotherapy: docetaxel/carboplatin with or without trastuzumab before and/or after surgery (depending on HER-2/neu status and randomization). Tumor measurements by PE, MG, and MRI and lymph node status by PE and PET were obtained before and after neoadjuvant chemotherapy. Concordance among different clinical measurements was assessed and compared with the tumor and lymph node staging by pathology. Spearman correlation (r) and root mean square error (RMSE) were used to measure the accuracy of measurements among all modalities and between modalities and pathologic tumor size. RESULTS: Compared with the tumor size measured by PE, MRI was more accurate than MG at baseline (r=0.559, RMSE=35.4% vs r=0.046, RMSE=66.1%). After neoadjuvant chemotherapy, PE correlated better with pathology than MG or MRI (r=0.655, RMSE=88.6% vs r=0.146, RMSE=147.1% and r=0.364, RMSE=92.6%). Axillary lymph node assessment after neoadjuvant chemotherapy demonstrated high specificity but low sensitivity by PET and PE. CONCLUSIONS: Findings suggested that MRI was a more accurate imaging study at baseline for T3/T4 tumor, and PE correlated best with pathology finding. PET and PE both correctly predicted positive axillary lymph nodes but not negative lymph nodes.

Randomized controlled study of extracorporeal albumin dialysis for hepatic encephalopathy in advanced cirrhosis.

UNLABELLED: Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11-50) and CPT 13 (10-15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD + SMT (n = 39) or SMT alone (n = 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (P = 0.044) and was reached faster and more frequently than in the SMT group (P = 0.045). Subjects receiving ECAD tolerated treatment well with no unexpected adverse events. CONCLUSION: The use of ECAD may be associated with an earlier and more frequent improvement of HE (grade 3/4). Because this 5-day study was not designed to examine the impact of MARS on survival, a full assessment of the role of albumin dialysis awaits the results of additional controlled trials.

Randomized trial of medical or endoscopic therapy to prevent recurrent ulcer hemorrhage in patients with adherent clots.

BACKGROUND & AIMS: Treatment of high-risk patients with nonbleeding adherent clots on ulcers is controversial. In a previous randomized trial, there was no benefit to endoscopic therapies compared with medical therapy for prevention of ulcer rebleeding. Our purpose was to test the hypothesis that patients treated with combination endoscopic therapy would have significantly lower rebleeding rates than those treated with medical therapy. METHODS: In this randomized, controlled trial, 32 high-risk patients with severe ulcer hemorrhage and nonbleeding adherent clots resistant to target irrigation were randomized to medical therapy or to combination endoscopic therapy (with epinephrine injection, shaving down the clot with cold guillotining, and bipolar coagulation on the underlying stigmata). Physicians blinded to the endoscopic therapy managed all patients. RESULTS: Patients were similar at study entry, except for older age in the medical group and lower platelet count in the endoscopic group. By hospital discharge, significantly more medically treated patients (6/17; 35.3%) than endoscopically treated patients (0/15; 0%) rebled (P = 0.011). There were no complications of endoscopic treatment. CONCLUSIONS: Combination endoscopic therapy of nonbleeding adherent clots significantly reduced early ulcer rebleeding rates in high-risk patients compared with medical therapy alone. This endoscopic treatment was safe.

Utilization of health care resources for low-risk patients with acute, nonvariceal upper GI hemorrhage: an historical cohort study.

BACKGROUND: Adults hospitalized with acute, nonvariceal upper GI hemorrhage can be accurately stratified according to their risk of subsequent adverse outcomes by using the Rockall score. Low-risk patients (Rockall score less-than-or-equal 2) may be candidates for early discharge. METHODS: Cases were identified with ICD-9-CM codes for calendar years 1997 and 1998. Medical record data to determine patient Rockall risk score, health care resource utilization, and adverse outcomes were abstracted with standardized forms. RESULTS: Fifty-three of 175 (30%) cases had Rockall scores < or =2. As predicted, those patients with Rockall scores < or =2 had a low risk of adverse outcomes with only 2 of 53 (4%) meeting criteria for recurrent bleeding as defined by the "Rebleed" variable, and no mortality. These low-risk patients had a mean hospital stay of 2.6 plus minus 2.1 days; 49% were admitted to an intermediate or intensive care unit bed and 57% were given H2 receptor antagonists intravenously. CONCLUSIONS: The proportion of patients admitted with acute, nonvariceal, upper GI hemorrhage with Rockall Scores < or =2 was substantial. Adverse outcomes were rare. In contrast, the level of health care resource utilization appeared high. The Rockall score has potential as a clinically based concurrent decision rule to improve the quality of care by finding those patients less likely to require intensive health care services.