Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced non-small cell lung cancer in a prospective study.

PURPOSE: Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC. METHODS: In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography. RESULTS: An impaired thyroid function was recorded in 23.4% of patients (n = 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p = 0.021) and multivariate analyses (p = 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p = 0.031). CONCLUSIONS: Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.

Impact of microscopic extrathyroidal extension on differentiated thyroid cancer post-surgical risk of recurrence: a retrospective analysis.

PURPOSE: In the last edition of the American Joint Committee on Cancer (AJCC) staging system, differentiated thyroid cancers (DTC) showing microscopic extrathyroidal extension (mETE) are considered comparable to intrathyroidal cancers for their clinical behavior and prognosis. The aim of the study is to evaluate the impact of this updated assessment of T, when applied to the postoperative recurrence risk stratification, according to the American Thyroid Association Guidelines (ATA-RR). METHODS: One-hundred DTC patients who underwent total thyroidectomy were retrospectively evaluated. The downstaging of mETE was introduced in the definition of T, and the updated classification defined as modified ATA-RR (ATAm-RR). For each patient, post-surgical basal and stimulated thyroglobulin (Tg) levels, neck ultrasound (US) and post-ablative 131-I whole body scan (WBS) reports were considered. The predictive performance (PP) of disease recurrence was calculated both for each single parameter, as well as for all of them. RESULTS: According to ATAm-RR classification, 19/100 patients (19%) were downstaged. ATA-RR proved a significant PP for disease recurrence (DR) (sensitivity 75.0%, specificity 63.0%, p = 0.023). However, ATAm-RR performed slightly better due to an increased specificity (sensitivity 75.0%, specificity 83.7%, p < 0.001). For both classifications, the PP was optimal when all the above-mentioned predictive parameters were considered. CONCLUSION: Our results suggest that the new assessment of T considering mETE resulted in a downgrading of ATA-RR class in a significant number of patients. This provides a better PP for disease recurrence, and the best PP was obtained when considering the whole predictive variables together.

Impact of pre-dialysis nephrology care engagement and decision-making on provider and patient action toward permanent vascular access.

BACKGROUND: While catheters are often thought the result of emergency hemodialysis (HD) initiation among patients with little or no pre-dialysis nephrology care, the role of patient level of engagement in care and modality decision-making have not been fully explored. METHODS: This is a retrospective medical record review of adults (age 18-89 years) who received care in academically affiliated private practice, public hospital, or Veterans Administration settings prior to initiating HD with a catheter between 10/1/2011 and 9/30/2012. Primary predictors were level of patient engagement in nephrology care within 6 months of HD initiation and timing of modality decision-making. Primary outcomes were provider action (referral) and any patient action (evaluation by a vascular surgeon, vein mapping or vascular surgery) toward [arteriovenous fistula or graft, (AVF/AVG)] creation. RESULTS: Among 92 incident HD patients, 66% (n = 61) initiated HD via catheter, of whom 34% (n = 21) had ideal engagement in care but 42% (n = 25) had no documented decision. Providers referred 48% (n = 29) of patients for AVF/AVG, of whom 72% (n = 21) took any action. Ideal engagement in care predicted provider action (adjusted OR 13.7 [95% CI 1.08, 175.1], p = 0.04), but no level of engagement in care predicted patient action (p > 0.3). Compared to patients with no documented decision, those with documented decisions within 3, 3-12, or more than 12 months before initiating dialysis were more likely to have provider action toward AVF/AVG (adjusted OR [95% CI]: 9.0 [1.4,55.6], p = 0.2, 37.6 [3.3423.4] p = 0.003, and 4.8 [0.8, 30.6], p = 0.1, respectively); and patient action (adjusted OR [95% CI]: 18.7 [2.3, 149.0], p = 0.006, 20.4 [2.6, 160.0], p = 0.004, and 6.2 [0.9, 44.0], p = 0.07, respectively). CONCLUSIONS: Timing of patient modality decision-making, but not level of engagement in pre-dialysis nephrology care, was predictive of patient and provider action toward AVF/AVG Interventions addressing patients' psychological preparation for dialysis are needed.

Risk Factors Associated With Transition From Acute to Chronic Low Back Pain in US Patients Seeking Primary Care.

Importance: Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP. Objective: To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care. Design, Setting, and Participants: This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020. Exposures: SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral). Main Outcomes and Measures: Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records. Results: Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001). Conclusions and Relevance: In this cohort study, the transition rate to chronic LBP was substantial and increased correspondingly with SBT stratum and early exposure to guideline nonconcordant care.

Sociodemographic and Kidney Disease Correlates of Nutrient Intakes Among Urban African Americans With Uncontrolled Hypertension.

OBJECTIVE: The objective of this study was to determine the association between sociodemographic factors and intakes of 4 nutrients and associations between intakes and markers of kidney disease to identify opportunities to improve outcomes among clinically high-risk African Americans. DESIGN AND METHODS: We conducted a cross-sectional study of baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension in Baltimore MD. To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio >=30 mg/g. SETTING AND SUBJECTS: Baseline data from the Achieving Blood Pressure Control Together study, a randomized controlled trial of 159 African Americans (117 females) with uncontrolled hypertension, were obtained. METHODS: To determine the association between sociodemographic factors and nutrient intakes, we constructed linear and logistic regression models. Using logistic regression, we determined the association between below-median nutrient intakes and kidney disease. MAIN OUTCOME MEASURES: Our outcomes of interest were daily intakes of vitamin C, magnesium, dietary fiber, and potassium as estimated by the Block Fruit-Vegetable-Fiber Screener and kidney disease defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio ≥30 mg/g. RESULTS: Overall, compared to Institute of Medicine recommendations, participants had lower intakes of magnesium, fiber, and potassium but higher vitamin C intakes. For females, sociodemographic factors that significantly associated with lower intake of the 4 nutrients were older age, obesity, lower health numeracy, and lesser educational attainment. For males, none of the sociodemographic factors were significantly associated with nutrient intakes. Below-median intake was significantly associated with albumin-to-creatinine ratio ≥30 (adjusted odds ratio [95% confidence interval]: 3.4 [1.5, 7.8] for vitamin C; 3.6 [1.6, 8.4] for magnesium; 2.9 [1.3, 6.5] for fiber; 3.6 [1.6, 8.4] for potassium), but not with estimated glomerular filtration rate <60. CONCLUSION: African Americans with uncontrolled hypertension may have low intakes of important nutrients, which could increase their risk of chronic kidney disease. Tailored dietary interventions for African Americans at high risk for chronic kidney disease may be warranted.

Enantiomer-specific measurements of current-use pesticides in aquatic systems.

Some current-use pesticides are chiral and have nonsuperimposable mirror images called enantiomers that exhibit identical physical-chemical properties but can behave differently when in contact with other chiral molecules (e.g., regarding degradation and uptake). These differences can result in variations in enantiomer presence in the environment and potentially change the toxicity of pesticide residues. Several current-use chiral pesticides are applied in urban and agricultural areas, with increased potential to enter watersheds and adversely affect aquatic organisms. The present study describes a stereoselective analytical method for the current-use pesticides fipronil, cis-bifenthrin, cis-permethrin, cypermethrin, and cyfluthrin. We show use of the method by characterizing enantiomer fractions in environmental sample extracts (sediment and water), and laboratory-dosed fish and concrete extracts previously collected by California organizations. Enantiomer fractions for most environmental samples are the same as racemic standards (equal amounts of enantiomers, enantiomer fraction = 0.5) and therefore are not expected to differ in toxicity from racemic mixtures typically tested. In laboratory-derived samples, enantiomer fractions are more frequently nonracemic and favor the less toxic enantiomer; permethrin enantiomer fractions range from 0.094 to 0.391 in one type of concrete runoff and enantiomer fractions of bifenthrin in dosed fish range from 0.378 to 0.499. We use enantiomer fractions as a screening tool to understand environmental exposure and explore ways this uncommon measurement could be used to better understand toxicity and risk. Environ Toxicol Chem 2018;37:99-106. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Fructose intervention for 12 weeks does not impair glycemic control or incretin hormone responses during oral glucose or mixed meal tests in obese men.

BACKGROUND AND AIMS: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. METHODS AND RESULTS: As many as 66 obese (BMI 26-40 kg/m2) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). CONCLUSION: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge.

Intravenous iron administration strategies and anemia management in hemodialysis patients.

Background: The effect of maintenance intravenous (IV) iron administration on subsequent achievement of anemia management goals and mortality among patients recently initiating hemodialysis is unclear. Methods: We performed an observational cohort study, in adult incident dialysis patients starting on hemodialysis. We defined IV administration strategies over a 12-week period following a patient's initiation of hemodialysis; all those receiving IV iron at regular intervals were considered maintenance, and all others were considered non-maintenance. We used multivariable models adjusting for demographics, clinical and treatment parameters, iron dose, measures of iron stores and pro-infectious and pro-inflammatory parameters to compare these strategies. The outcomes under study were patients' (i) achievement of hemoglobin (Hb) of 10-12 g/dL, (ii) more than 25% reduction in mean weekly erythropoietin stimulating agent (ESA) dose and (iii) mortality, ascertained over a period of 4 weeks following the iron administration period. Results: Maintenance IV iron was administered to 4511 patients and non-maintenance iron to 8458 patients. Maintenance IV iron administration was not associated with a higher likelihood of achieving an Hb between 10 and 12 g/dL {adjusted odds ratio (OR) 1.01 [95% confidence interval (CI) 0.93-1.09]} compared with non-maintenance, but was associated with a higher odds of achieving a reduced ESA dose of 25% or more [OR 1.33 (95% CI 1.18-1.49)] and lower mortality [hazard ratio (HR) 0.73 (95% CI 0.62-0.86)]. Conclusions: Maintenance IV iron strategies were associated with reduced ESA utilization and improved early survival but not with the achievement of Hb targets.

Risk Factors, Methods, and Timing of Suicide Attempts Among US Army Soldiers.

IMPORTANCE: Suicide attempts in the US Army have risen in the past decade. Understanding the association between suicide attempts and deployment, as well as method and timing of suicide attempts, can assist in developing interventions. OBJECTIVE: To examine suicide attempt risk factors, methods, and timing among soldiers currently deployed, previously deployed, and never deployed at the time this study was conducted. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal, retrospective cohort study of Regular Army-enlisted soldiers on active duty from 2004 through 2009 used individual-level person-month records to examine risk factors (sociodemographic, service related, and mental health), method, and time of suicide attempt by deployment status (never, currently, and previously deployed). Administrative data for the month before each of 9650 incident suicide attempts and an equal-probability sample of 153 528 control person-months for other soldiers were analyzed using a discrete-time survival framework. MAIN OUTCOMES AND MEASURES: Suicide attempts and career, mental health, and demographic predictors were obtained from administrative and medical records. RESULTS: Of the 9650 enlisted soldiers who attempted suicide, 86.3% were male, 68.4% were younger than 30 years, 59.8% were non-Hispanic white, 76.5% were high school educated, and 54.7% were currently married. The 40.4% of enlisted soldiers who had never been deployed (n = 12 421 294 person-months) accounted for 61.1% of enlisted soldiers who attempted suicide (n = 5894 cases). Risk among those never deployed was highest in the second month of service (103 per 100 000 person-months). Risk among soldiers on their first deployment was highest in the sixth month of deployment (25 per 100 000 person-months). For those previously deployed, risk was highest at 5 months after return (40 per 100 000 person-months). Currently and previously deployed soldiers were more likely to attempt suicide with a firearm than those never deployed (currently deployed: OR, 4.0; 95% CI, 2.9-5.6; previously deployed: OR, 2.7; 95% CI, 1.8-3.9). Across deployment status, suicide attempts were more likely among soldiers who were women (currently deployed: OR, 3.4; 95% CI, 3.0-4.0; previously deployed: OR, 1.5; 95% CI, 1.4-1.7; and never deployed: OR, 2.4; 95% CI, 2.3-2.6), in their first 2 years of service (currently deployed: OR, 1.9; 95% CI, 1.5-2.3; previously deployed: OR, 2.2; 95% CI, 1.9-2.7; and never deployed: OR, 3.1; 95% CI, 2.7-3.6), and had a recently received a mental health diagnosis in the previous month (currently deployed: OR, 29.8; 95% CI, 25.0-35.5; previously deployed: OR, 22.2; 95% CI, 20.1-24.4; and never deployed: OR, 15.0; 95% CI, 14.2-16.0). Among soldiers with 1 previous deployment, odds of a suicide attempt were higher for those who screened positive for depression or posttraumatic stress disorder after return from deployment and particularly at follow-up screening, about 4 to 6 months after deployment (depression: OR, 1.4; 95% CI, 1.1-1.9; posttraumatic stress disorder: OR, 2.4; 95% CI, 2.1-2.8). CONCLUSIONS AND RELEVANCE: Identifying the timing and risk factors for suicide attempt in soldiers requires consideration of environmental context, individual characteristics, and mental health. These factors can inform prevention efforts.

Mucoepidermoid carcinoma of the palate in adolescence.

Although relatively rare, minor salivary gland tumors are more likely to be malignant in pediatric patients than in adults. Mucoepidermoid carcinoma (MEC) represents the most common malignant tumor of the salivary glands. It is critical to differentiate such tumors from common benign salivary gland lesions. The purposes of this report are to present the case of a 15-year-old female with MEC of the palate, and to discuss the importance of a thorough intraoral examination on all patients regardless of age, as well as the need for timely referral for appropriate diagnosis and treatment.

Effect of intravenous iron use on hospitalizations in patients undergoing hemodialysis: a comparative effectiveness analysis from the DEcIDE-ESRD study.

BACKGROUND: Intravenous iron use in hemodialysis patients has greatly increased over the last decade, despite limited studies on the safety of iron. METHODS: We studied the association of receipt of intravenous iron with hospitalizations in an incident cohort of hemodialysis patients. We examined 9544 patients from Dialysis Clinic, Inc. (DCI). We ascertained intravenous iron use from DCI electronic medical record and USRDS data files, and hospitalizations through Medicare claims. We examined the association between iron exposure accumulated over 1-, 3- or 6-month time windows and incident hospitalizations in the follow-up period using marginal structural models accounting for time-dependent confounders. We performed sensitivity analyses including recurrent events models for multiple hospitalizations and models for combined outcome of hospitalization and death. RESULTS: There were 22 347 hospitalizations during a median follow-up of 23 months. Higher cumulative dose of intravenous iron was not associated with all-cause, cardiovascular or infectious hospitalizations [HR 0.97 (95% CI: 0.77-1.22) for all-cause hospitalizations comparing >2100 mg versus 0-900 mg of iron over 6 months]. Findings were similar in models examining the risk of hospitalizations in 1- and 3-month windows [HR 0.88 (95% CI: 0.79-0.99) and HR 0.88 (95% CI: 0.74-1.03), respectively] or the risk of combined outcome of hospitalization and death in the 6-month window [HR 0.98 (95% CI: 0.78-1.23)]. CONCLUSIONS: Higher cumulative dose of intravenous iron may not be associated with increased risk of hospitalizations in hemodialysis patients. While clinical trials are needed, employing higher iron doses to reduce erythropoiesis-stimulating agents does not appear to increase morbidity in routine clinical care.

Intravenous iron exposure and mortality in patients on hemodialysis.

BACKGROUND AND OBJECTIVES: Clinical trials assessing effects of larger cumulative iron exposure with outcomes are lacking, and observational studies have been limited by assessment of short-term exposure only and/or failure to assess cause-specific mortality. The associations between short- and long-term iron exposure on all-cause and cause-specific mortality were examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 14,078 United States patients on dialysis initiating dialysis between 2003 and 2008. Intravenous iron dose accumulations over 1-, 3-, and 6-month rolling windows were related to all-cause, cardiovascular, and infection-related mortality in Cox proportional hazards models that used marginal structural modeling to control for time-dependent confounding. RESULTS: Patients in the 1-month model cohort (n=14,078) were followed a median of 19 months, during which there were 27.6% all-cause deaths, 13.5% cardiovascular deaths, and 3% infection-related deaths. A reduced risk of all-cause mortality with receipt of >150-350 (hazard ratio, 0.78; 95% confidence interval, 0.64 to 0.95) or >350 mg (hazard ratio, 0.79; 95% confidence interval, 0.62 to 0.99) intravenous iron compared with >0-150 mg over 1 month was observed. There was no relation of 1-month intravenous iron dose with cardiovascular or infection-related mortality and no relation of 3- or 6-month cumulative intravenous iron dose with all-cause or cardiovascular mortality. There was a nonstatistically significant increase in infection-related mortality with receipt of >1050 mg intravenous iron in 3 months (hazard ratio, 1.69; 95% confidence interval, 0.87 to 3.28) and >2100 mg in 6 months (hazard ratio, 1.59; 95% confidence interval, 0.73 to 3.46). CONCLUSIONS: Among patients on incident dialysis, receipt of ≤ 1050 mg intravenous iron in 3 months or 2100 mg in 6 months was not associated with all-cause, cardiovascular, or infection-related mortality. However, nonstatistically significant findings suggested the possibility of infection-related mortality with receipt of >1050 mg in 3 months or >2100 mg in 6 months. Randomized clinical trials are needed to assess the safety of exposure to greater cumulative intravenous iron doses.

Test meals rich in marine long-chain n-3 polyunsaturated fatty acids increase postprandial chylomicron response.

Postprandial lipid abnormalities are considered an independent cardiovascular risk factor. Hence, it is important to find nutritional strategies that are able to positively influence these abnormalities. Since the effect of n-3 polyunsaturated fatty acids (PUFA) and polyphenols on postprandial lipids in humans is still under debate, we evaluated the acute response of triglyceride-rich lipoproteins to test meals that are naturally rich in polyphenols and/or marine long-chain (LC) n-3 PUFAs. We hypothesized that LC n-3 PUFA would have a different effect on chylomicron and very low density lipoproteins when compared with polyphenols or their combination. We randomly assigned 78 individuals who were at high cardiometabolic risk to 4 isoenergetic diets. These diets only differed in amount of LC n-3 PUFA and/or polyphenols. Prior to starting the intervention, each subject underwent a test meal similar to the type of diet assigned: low in LC n-3 PUFA and polyphenols (control), rich in LC n-3 PUFA and low in polyphenols, rich in polyphenols and low in LC n-3 PUFA, or rich in both. Blood samples were taken before and up to 6 hours after the test meal in order to evaluate cholesterol and triglycerides (plasma and triglyceride-rich lipoprotein), apolipoprotein B-48 (large very low density lipoprotein), glucagon-like peptide-1, and free fatty acid plasma levels. The levels of chylomicron cholesterol and triglyceride in response to the test meal rich in LC n-3 PUFA were significantly higher than after the control meal (P = .037 and P = .018); there was no difference in the other variables. In conclusion, this study indicates that acute administration of marine LC n-3 PUFA increases postprandial chylomicron response in contrast with their lowering chronic effects. These differences underline the importance of understanding the acute and chronic effects of nutritional, as well as of other types of, interventions.

A CHO/fibre diet reduces and a MUFA diet increases postprandial lipaemia in type 2 diabetes: no supplementary effects of low-volume physical training.

The aim of the study was to evaluate the effects of a supervised physical training added to a healthy diet-rich in either carbohydrate and fibre (CHO/fibre) or monounsaturated fatty acids (MUFA)-on postprandial dyslipidaemia, an independent cardiovascular risk factor particularly relevant in type 2 diabetes (T2D). Participants were forty-five overweight/obese subjects with T2D, of both genders, in good blood glucose control with diet or diet+metformin, with normal fasting plasma lipids. According to a parallel groups 2 × 2 factorial design, participants were randomized to an 8-week isoenergetic intervention with a CHO/fibre or a MUFA diet, with or without a supervised low-volume aerobic training programme. The main outcome of the study was the incremental area under the curve (iAUC) of lipid concentrations in the plasma chylomicron+VLDL lipoprotein fraction, isolated by preparative ultracentrifugation (NCT01025856). Body weight remained stable during the trial in all groups. Physical fitness slightly improved with training (VO2 peak, 16 ± 4 vs. 15 ± 3 ml/kg/min, M ± SD, p < 0.05). Postprandial triglyceride and cholesterol iAUCs in plasma and chylomicron+VLDL fraction decreased after the CHO/fibre diet, but increased after the MUFA diet with a significant effect for diet by two-way ANOVA (p < 0.05). The addition of exercise training to either dietary intervention did not significantly influence postprandial lipid response. A diet rich in carbohydrates and fibre reduced postprandial triglyceride-rich lipoproteins compared with a diet rich in MUFA in patients with T2D. A supervised low-volume physical training did not significantly influence these dietary effects.

Protein expression pattern of human MIER1 alpha, a novel estrogen receptor binding protein.

MIER1 is a transcriptional regulator that exists as several isoforms. Of particular interest is the MIER1α isoform, which contains in its unique C-terminus an LXXLL motif for interaction with nuclear hormone receptors. Indeed, MIER1α has been shown to interact with ERα and inhibit estrogen-stimulated growth of breast carcinoma cells. Moreover, the subcellular localization of MIER1α changes dramatically, from nuclear to cytoplasmic, during progression to invasive breast carcinoma. While human MIER1 RNA and protein expression pattern data have been posted on several websites, none of these studies use probes or antibodies that distinguish between the α and ß isoforms. We report here the first immunohistochemical study of the MIER1α protein expression pattern in human tissues. Our analysis revealed intense staining of specific cell types within virtually every endocrine and reproductive tissue except for the thyroid gland. In particular, we detected intense staining of ovarian follicles and germinal epithelium, ductal epithelial cells of the breast, pancreatic islet cells, all areas of the anterior pituitary and all zones of the adrenal cortex; moderate staining of germ cells and Leydig cells within the testis, patches of chromaffin cells in the adrenal medulla and weak staining of the fibromuscular stroma within the prostate. Immunoreactivity was limited to the cytoplasm in all positive cells except for oocytes and germinal epithelial cells in which the nucleus was also stained and in ductal epithelial cells of the breast in which staining was exclusively nuclear. In general, non-endocrine tissues were negative, however a few exceptions were noted. These included hepatocytes, myocardial fibers and neurons in all regions of the brain examined, with the exception of the thalamus. Neuronal staining was restricted to the cell bodies and dendrites, as most axons were negative. These data suggest that human MIER1α functions specifically in endocrine tissues and in a limited number of non-endocrine organs.

Fasting APO B48 levels are associated with microalbuminuria in patients with type 2 diabetes.

In view of the high incidence of macrovascular diseases in patients with type 2 diabetes mellitus and microalbuminuria, the study evaluates the association of microalbuminuria with fasting plasma Apo B48 levels, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic. We studied 50 patients with type 2 diabetes aged 35-75 years. Exclusion criteria were overt macrovascular disease, overt nephropathy (Glomerular filtration rate (GFR) <45 ml/min/1.73 m(2)), or use of hypolipidemic agents. Anthropometry, fasting plasma lipids, plasma creatinine, and HbA1c were measured. Urinary albumin excretion was measured on a morning urine sample with the ELISA and expressed as albumin/creatinine ratio. GFR was estimated using the MDRD formula. The plasma fasting Apo B48 was measured by ELISA. Age, gender distribution, fasting plasma lipids, HbA1c, smoking status, plasma creatinine, estimate GFR, and the proportion of patients treated with insulin or antihypertensive drugs were similar for patients with or without microalbuminuria. People with microalbuminuria had longer diabetes duration (borderline significance) and significantly higher Apo B48 (1.765 ± 1.379 µg/ml vs. 1.022 ± 0.692 µg/ml, p = 0.01) than those without microalbuminuria. Multivariate logistic regression analysis confirmed that fasting Apo B48 levels were significantly associated with microalbuminuria independent of major confounders measured in the study. In patients with type 2 diabetes, microalbuminuria is associated with elevated Apo B48 levels, independent of major confounders; this may partly explain the excess cardiovascular risk of these patients.

Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people.

BACKGROUND AND AIM: The intake of wholemeal foods is consistently associated with reduced risk of type 2 diabetes and cardiovascular diseases in epidemiological studies, although the mechanisms of this association are unclear. Here we aim to compare in healthy subjects the metabolic effects of a diet rich in wholemeal wheat foods versus one based on the same products in refined form. METHODS AND RESULTS: Fifteen healthy individuals (12 M/3 F), mean age 54.5+/-7.6 years, BMI 27.4+/-3.0 kg/m(2) (mean+/-SD), participated in a randomized sequential crossover study. After 2 weeks run-in, participants were randomly assigned to two isoenergetic diets with similar macronutrient composition, one rich in wholemeal wheat foods and the other with the same foods but in refined form (cereal fibre 23.1 vs. 9.8 g/day). After the two treatment periods (each lasting 3 weeks) plasma glucose and lipid metabolism, antioxidant activity, acetic acid, magnesium, adipokines, incretins and high-sensitivity C-reactive protein (hs-CRP) were measured at fasting and for 4h after a standard test meal (kcal 1103, protein 12%, CHO 53%, fat 35%) based on wholemeal or refined wheat foods, respectively. After the two diets there were no differences in fasting nor in postprandial plasma parameter responses; only glucose was slightly but significantly lower at 240 min after the refined wheat food meal compared to the wholemeal wheat food meal. Conversely, after the wholemeal diet both total (-4.3%; p<0.03) and LDL (-4.9%; p<0.04) cholesterol levels were lower than after the refined wheat diet at fasting. CONCLUSIONS: Consumption of wholemeal wheat foods for 3 weeks reduces significantly fasting plasma cholesterol as well as LDL cholesterol levels in healthy individuals without major effects on glucose and insulin metabolism, antioxidant status and sub-clinical inflammation markers.

Potential aluminum exposure from parenteral nutrition in patients with acute kidney injury.

BACKGROUND: Patients' exposure to and potential toxicity from aluminum in parenteral nutrition (PN) formulations is an important concern of healthcare providers. OBJECTIVE: To determine the potential for aluminum toxicity caused by PN in hospitalized adults who have risk factors of both acute kidney injury and PN. METHODS: Adults who required PN and had a serum creatinine (SCr) level at least 1.5 times greater than the admission SCr on the first day of PN were studied in a retrospective fashion. Protein was administered based on whether hemodialysis was being used (0.6-1 g/kg/day without hemodialysis; 1.2-1.5 g/kg/day with hemodialysis). Aluminum exposure was determined for each patient by multiplying the volume of each PN component by its concentration of aluminum. Unpaired t-tests, Fisher's exact test, and analysis of variance were used for statistical analysis. Data are presented as mean +/- SD. RESULTS: Thirty-six patients (aged 50.4 +/- 20.4 y; weight 90.2 +/- 32.8 kg) were studied. Initial serum urea nitrogen and SCr were 47 +/- 23 and 3.3 +/- 1.4 mg/dL, respectively. Twelve patients received hemodialysis. The mean aluminum exposure was 3.8 +/- 2 microg/kg/day in the 36 patients. Of these, 29 had safe calculated aluminum exposure (<5 microg/kg/day) and 7 had high calculated aluminum exposure (>5 microg/kg/day). Patients with safe aluminum exposure had significantly higher SCr levels than did those with high aluminum exposure (3.5 +/- 1.5 vs 2.2 +/- 0.7 mg/dL; p < 0.04). Patients with high aluminum exposure received significantly more aluminum from calcium gluconate compared with those who had safe aluminum exposure (357 +/- 182 vs 250 +/- 56 microg/day; p < 0.02). Limitations of the study include its retrospective design, which resulted in calculated versus direct measurement of aluminum. CONCLUSIONS: Using our calculations, we believe that most patients with acute kidney injury who require PN do not receive excessive exposure to aluminum from the PN formulation, despite having 2 risk factors (acute kidney injury, PN) for aluminum toxicity.