Associations between dietary fatty acid patterns and cognitive function in the Hispanic Community Health Study/Study of Latinos.

Our objective was to quantify the cross-sectional associations between dietary fatty acid (DFA) patterns and cognitive function among Hispanic/Latino adults. This study included data from 8,942 participants of the Hispanic Community Health Study/Study of Latinos, a population-based cohort study (weighted age 56.2 y and proportion female 55.2%). The NCI (National Cancer Institute) method was used to estimate dietary intake from two 24-hr recalls. We derived DFA patterns using principal components analysis with 26 fatty acid and total plant and animal monounsaturated fatty acid (MUFA) input variables. Global cognitive function was calculated as the average z-score of 4 neurocognitive tests. Survey linear regression models included multiple potential confounders such as age, sex, education, depressive symptoms, physical activity, energy intake, and cardiovascular disease. DFA patterns were characterized by consumption of long-chain saturated fatty acids (SFA), animal-based MUFA, and trans fatty acids (Factor 1); short to medium-chain SFA (Factor 2); very-long-chain omega-3 polyunsaturated fatty acids (PUFA) (Factor 3); very-long-chain SFA and plant-based MUFA and PUFA (Factor 4). Factor 2 was associated with greater scores for global cognitive function (ß=0.037 ± 0.012) and the Digit Symbol Substitution (DSS) (ß=0.56±0.17), Brief Spanish English Verbal Learning-Sum (B-SEVLT) (ß=0.23 ± 0.11), and B-SEVLT-Recall (ß=0.11 ± 0.05) tests (P<0.05 for all). Factors 1 (ß=0.04 ± 0.01) and 4 (ß=0.70 ± 0.18) were associated with the DSS test (P<0.05 for all). Consumption of short to medium-chain SFA may be associated with higher cognitive function among U.S.-residing Hispanic/Latino adults. Prospective studies are necessary to confirm these findings.

Circulating Plasma Metabolites and Cognitive Function in a Puerto Rican Cohort.

BACKGROUND: Minorities, including mainland Puerto Ricans, are impacted disproportionally by Alzheimer's disease (AD), dementia, and cognitive decline. Studying blood metabolomics in this population has the potential to probe the biological underpinnings of this health disparity. OBJECTIVE: We performed a comprehensive analysis of circulating plasma metabolites in relation to cognitive function in 736 participants from the Boston Puerto Rican Health Study (BPRHS) who underwent untargeted mass-spectrometry based metabolomics analysis and had undergone a battery of in-person cognitive testing at baseline. METHODS: After relevant exclusions, 621 metabolites were examined. We used multivariable regression, adjusted for age, sex, education, apolipoprotein E genotype, smoking, and Mediterranean dietary pattern, to identify metabolites related to global cognitive function in our cohort. LASSO machine learning was used in a complementary analysis to identify metabolites that could discriminate good from poor extremes of cognition. We also conducted sensitivity analyses: restricted to participants without diabetes, and to participants with good adherence to Mediterranean diet. RESULTS: Of 621 metabolites, FDR corrected (p < 0.05) multivariable linear regression identified 3 metabolites positively, and 10 negatively, associated with cognitive function in the BPRHS. In a combination of FDR-corrected linear regression, logistic regression regularized via LASSO, and sensitivity analyses restricted to participants without diabetes, and with good adherence to the Mediterranean diet, ß-cryptoxanthin plasma concentration was consistently associated with better cognitive function and N-acetylisoleucine and tyramine O-sulfate concentrations were consistently associated with worse cognitive function. CONCLUSION: This untargeted metabolomics study identified potential biomarkers for cognitive function in a cohort of Puerto Rican older adults.

Evaluation of Screening Tests for Cognitive Impairment in Patients Receiving Maintenance Hemodialysis.

BACKGROUND: Neurocognitive testing shows that cognitive impairment is common among patients receiving maintenance hemodialysis. Identification of a well performing screening test for cognitive impairment might allow for broader assessment in dialysis facilities and thus optimal delivery of education and medical management. METHODS: From 2015 to 2018, in a cohort of 150 patients on hemodialysis, we performed a set of comprehensive neurocognitive tests that included the cognitive domains of memory, attention, and executive function to classify whether participants had normal cognitive function versus mild, moderate, or severe cognitive impairment. Using area-under-the-curve (AUC) analysis, we then examined the predictive ability of the Mini Mental State Examination, the Modified Mini Mental State Examination, the Montreal Cognitive Assessment, the Trail Making Test Part B, the Mini-Cog test, and the Digit Symbol Substitution Test, determining each test's performance for identifying severe cognitive impairment. RESULTS: Mean age was 64 years; 61% were men, 39% were black, and 94% had at least a high-school education. Of the 150 participants, 21% had normal cognitive function, 17% had mild cognitive impairment, 33% had moderate impairment, and 29% had severe impairment. The Montreal Cognitive Assessment had the highest overall predictive ability for severe cognitive impairment (AUC, 0.81); a score of ≤21 had a sensitivity of 86% and specificity of 55% for severe impairment, with a negative predictive value of 91%. The Trails B and Digit Symbol tests also performed reasonably well (AUCs, 0.73 and 0.78, respectively). The other tests had lower predictive performances. CONCLUSIONS: The Montreal Cognitive Assessment, a widely available and brief cognitive screening tool, showed high sensitivity and moderate specificity in detecting severe cognitive impairment in patients on maintenance hemodialysis.

Vitamin B-6 and depressive symptomatology, over time, in older Latino adults.

Background: Low vitamin B-6 status has been linked to depressive symptomatology. We examined the longitudinal association of vitamin B-6 status with depressive symptomatology across 3-time points over ∼5-7 years in a cohort of older Hispanic adults. Methods: We used two-level hierarchical linear regression models for continuous outcomes. Vitamin B-6 status was associated with depressive symptomatology across these time points. Results: Plasma pyridoxyl-5-phosphate (PLP) concentration, a time-varying predictor, was significantly associated with depressive symptomatology. Study participants with PLP deficiency, vs. optimal PLP, had higher baseline depressive symptoms (Center for Epidemiologic Studies-Depression Scale (CES-D) score of 22 ± 14, vs. 20 ± 13); this differential remained constant over time and persisted after controlling for age, sex, education, body mass index, smoking and alcohol use, other relevant nutritional factors, perceived stress, stressful life events, allostatic load, and use of antidepressant medication. However, PLP concentration was not associated with the rate of change in depressive symptomatology over time. Conclusions: Suboptimal plasma PLP is associated with higher depressive symptomatology in older Hispanic of Puerto Rican descent and this appears to persist over time. Our data suggest that identification and treatment of vitamin B-6 deficiency may be a useful preventive approach in this population.

Metabolic fate of strawberry polyphenols after chronic intake in healthy older adults.

Strawberries contain a wide array of nutrients and phytochemicals including polyphenols such as anthocyanins, proanthocyanidins and ellagitannins. These polyphenols are absorbed and metabolized to various phenolic metabolites/conjugates in the body, which may play a role in disease risk reduction. In the present study, we investigated the metabolic fate of strawberry polyphenols after chronic (90 days) supplementation of freeze-dried strawberry (24 g d-1, equivalent to 2 cups of fresh strawberries) vs. control powder in 19 healthy older adults. Blood samples were collected at two time-points i.e., fasting (t = 0 h) and 2 h after the breakfast meal. On days 45 and 90 breakfast also included a control or strawberry drink consistent with their treatment randomization. A total of 21 polyphenolic metabolites were quantified in plasma consisting of 3 anthocyanins/metabolites, 3 urolithin metabolites and 15 phenolic acid metabolites. Among anthocyanins/metabolite, pelargonidin glucuronide (85.7 ± 9.0 nmol L-1, t = 2 h, day 90) was present in the highest concentration. Persistent concentrations of anthocyanins/metabolites, urolithins and some phenolic acids were observed in fasting (t = 0 h) plasma samples on day 45 and 90 after strawberry drink consumption suggesting a role of enteric, enterohepatic recycling or upregulation of gut microbial and/or human metabolism of these compounds. Our results suggest that strawberry polyphenols are absorbed and extensively metabolized, and can persist in the circulation.

Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function.

Adult neurogenesis, a complex process by which stem cells in the hippocampal brain region differentiate and proliferate into new neurons and other resident brain cells, is known to be affected by many intrinsic and extrinsic factors, including diet. Neurogenesis plays a critical role in neural plasticity, brain homeostasis, and maintenance in the central nervous system and is a crucial factor in preserving the cognitive function and repair of damaged brain cells affected by aging and brain disorders. Intrinsic factors such as aging, neuroinflammation, oxidative stress, and brain injury, as well as lifestyle factors such as high-fat and high-sugar diets and alcohol and opioid addiction, negatively affect adult neurogenesis. Conversely, many dietary components such as curcumin, resveratrol, blueberry polyphenols, sulforaphane, salvionic acid, polyunsaturated fatty acids (PUFAs), and diets enriched with polyphenols and PUFAs, as well as caloric restriction, physical exercise, and learning, have been shown to induce neurogenesis in adult brains. Although many of the underlying mechanisms by which nutrients and dietary factors affect adult neurogenesis have yet to be determined, nutritional approaches provide promising prospects to stimulate adult neurogenesis and combat neurodegenerative diseases and cognitive decline. In this review, we summarize the evidence supporting the role of nutritional factors in modifying adult neurogenesis and their potential to preserve cognitive function during aging.

Avocado Consumption Increases Macular Pigment Density in Older Adults: A Randomized, Controlled Trial.

Lutein is selectively incorporated into the macula and brain. Lutein levels in the macula (macular pigment; MP) and the brain are related to better cognition. MP density (MPD) is a biomarker of brain lutein. Avocados are a bioavailable source of lutein. This study tests the effects of the intake of avocado on cognition. This was a six-month, randomized, controlled trial. Healthy subjects consumed one avocado (n = 20, 0.5 mg/day lutein, AV) vs. one potato or one cup of chickpeas (n = 20, 0 mg/day lutein, C). Serum lutein, MPD, and cognition were assessed at zero, three, and six months. Primary analyses were conducted according to intent-to-treat principles, with repeated-measures analysis. At six months, AV increased serum lutein levels by 25% from baseline (p = 0.001). C increased by 15% (p = 0.030). At six months, there was an increase in MPD from baseline in AV (p = 0.001) and no increase in C. For both groups, there was an improvement in memory and spatial working memory (p = 0.001; p = 0.032, respectively). For AV only there was improved sustained attention (p = 0.033), and the MPD increase was related to improved working memory and efficiency in approaching a problem (p = 0.036). Dietary recommendations including avocados may be an effective strategy for cognitive health.

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults.

Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism.Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology.Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean ± SD age: 73 ± 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilution-multiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small- and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology.Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower high-density lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile (higher LDL cholesterol and triglycerides).Conclusion: Choline and its metabolites have differential associations with cardiometabolic risk factors and subtypes of vascular disease, thereby suggesting differing roles in the pathogenesis of cardiovascular and cerebral large-vessel disease compared with that of small-vessel disease.

Food Insecurity Is Associated with Subsequent Cognitive Decline in the Boston Puerto Rican Health Study.

BACKGROUND: Living with hunger and fear of not having enough food is a growing worldwide concern. In our previous cross-sectional study, we found that food insecurity was associated with poor cognitive function, but the direction of this relation remains unclear. OBJECTIVE: We investigated whether food insecurity is associated with subsequent cognitive decline. METHODS: This was a longitudinal study of 597 participants aged 40-75 y from the Boston Puerto Rican Health Study cohort, with a Mini-Mental State Examination score of ≥24 at baseline. Food security was assessed at baseline with the US Household Food Security Scale. Participants completed cognitive batteries, which included 7 cognitive tests, twice-at baseline and again at a 2-y follow-up. The primary outcome was the change in global cognitive function over 2 y. Multiple linear regression was used to obtain adjusted mean differences and 95% CIs in cognitive decline across baseline food security status. RESULTS: Food insecurity at baseline was associated with a 2-y decline in global cognitive function (P-trend = 0.03) after adjusting for relevant potential confounders, including age, sex, baseline cognitive score, body mass index, education, poverty, acculturation score, depression score, smoking status, use of alcohol, physical activity score, presence of diabetes and hypertension, apolipoprotein E status, plasma homocysteine, healthy eating index, and time between baseline and follow-up measures. Compared with the food-secure group, the decline in the very low food security group was greater [mean difference: -0.26 (95% CI: -0.41, -0.10)]. Baseline food insecurity was significantly associated with a faster decline in executive function (P-trend = 0.02) but not memory function (P-trend = 0.66). CONCLUSIONS: Food insecurity was associated with faster cognitive decline in this cohort of Puerto Rican adults. Our study emphasizes the importance of developing interventions for food insecurity that take into account the impact of food insecurity on cognition.

A 2-Year Randomized Controlled Trial of Human Caloric Restriction: Feasibility and Effects on Predictors of Health Span and Longevity.

BACKGROUND: Caloric restriction (CR), energy intake reduced below ad libitum (AL) intake, increases life span in many species. The implications for humans can be clarified by randomized controlled trials of CR. METHODS: To determine CR's feasibility, safety, and effects on predictors of longevity, disease risk factors, and quality of life in nonobese humans aged 21-51 years, 218 persons were randomized to a 2-year intervention designed to achieve 25% CR or to AL diet. Outcomes were change from baseline resting metabolic rate adjusted for weight change ("RMR residual") and core temperature (primary); plasma triiodothyronine (T3) and tumor necrosis factor-α (secondary); and exploratory physiological and psychological measures. RESULTS: Body mass index averaged 25.1 (range: 21.9-28.0 kg/m(2)). Eighty-two percent of CR and 95% of AL participants completed the protocol. The CR group achieved 11.7±0.7 %CR (mean ± standard error) and maintained 10.4±0.4% weight loss. Weight change in AL was negligible. RMR residual decreased significantly more in CR than AL at 12 months (p = .04) but not 24 months (M24). Core temperature change differed little between groups. T3 decreased more in CR at M12 and M24 (p < .001), while tumor necrosis factor-α decreased significantly more only at M24 (p = .02). CR had larger decreases in cardiometabolic risk factors and in daily energy expenditure adjusted for weight change, without adverse effects on quality of life. CONCLUSIONS: Sustained CR is feasible in nonobese humans. The effects of the achieved CR on correlates of human survival and disease risk factors suggest potential benefits for aging-related outcomes that could be elucidated by further human studies.

A novel comparative effectiveness study of Tai Chi versus aerobic exercise for fibromyalgia: study protocol for a randomized controlled trial.

BACKGROUND: Fibromyalgia is a chronic musculoskeletal pain syndrome that causes substantial physical and psychological impairment and costs the US healthcare system over $25 billion annually. Current pharmacological therapies may cause serious adverse effects, are expensive, and fail to effectively improve pain and function. Finding new and effective non-pharmacological treatments for fibromyalgia patients is urgently needed. We are currently conducting the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise (a recommended component of the current standard of care) in a large fibromyalgia population. This article describes the design and conduct of this trial. METHODS/DESIGN: A single-center, 52-week, randomized controlled trial of Tai Chi versus aerobic exercise is being conducted at an urban tertiary medical center in Boston, Massachusetts. We plan to recruit 216 patients with fibromyalgia. The study population consists of adults ≥21 years of age with fibromyalgia who meet American College of Rheumatology 1990 and 2010 diagnostic criteria. Participants are randomized to one of four Tai Chi intervention groups: 12 or 24 weeks of supervised Tai Chi held once or twice per week, or a supervised aerobic exercise control held twice per week for 24 weeks. The primary outcome is the change in Revised Fibromyalgia Impact Questionnaire total score from baseline to 24 weeks. Secondary outcomes include measures of widespread pain, symptom severity, functional performance, balance, muscle strength and power, psychological functioning, sleep quality, self-efficacy, durability effects, and health-related quality of life at 12, 24, and 52 week follow-up. DISCUSSION: This study is the first comparative effectiveness randomized trial of Tai Chi versus aerobic exercise in a large fibromyalgia population with long-term follow up. We present here a robust and well-designed trial to determine the optimal frequency and duration of a supervised Tai Chi intervention with regard to short- and long-term effectiveness. The trial also explores multiple outcomes to elucidate the potential mechanisms of Tai Chi and aerobic exercise and the generalizability of these interventions across instructors. Results of this study are expected to have important public health implications for patients with a major disabling disease that incurs substantial health burdens and economic costs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01420640 , registered 18 August 2011.

Depression and all-cause mortality in hemodialysis patients.

BACKGROUND: There are limited data regarding the relationship between depression and mortality in hemodialysis (HD) patients. METHODS: Among 323 patients receiving maintenance HD, depression symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale, with a score of ≥16 consistent with depression. Adjusted Cox proportional-hazards models with additional analyses incorporating antidepressant medication use were used to evaluate the association between depression and mortality. Baseline CES-D scores were used for the primary analyses, while secondary time-dependent analyses incorporated subsequent CES-D results. RESULTS: The mean age was 62.9 ± 16.5 years, 46% of the subjects were women and 22% were African-American. The mean baseline CES-D score was 10.7± 8.3, and 83 (26%) participants had CES-D scores ≥16. During a median (25th, 75th) follow-up of 25 (13, 43) months, 154 participants died. After adjusting for age, sex, race, primary cause of kidney failure, dialysis vintage and access, baseline depression was associated with an increased risk of all-cause mortality (HR 1.51 and 95% CI 1.06-2.17). This attenuated with further adjustment for cardiovascular disease, smoking, Kt/V, serum albumin, log C-reactive protein and use of antidepressants (HR 1.21 and 95% CI 0.82-1.80). When evaluating time-dependent CES-D, depression remained associated with increased mortality risk in the fully adjusted model (HR 1.44 and 95% CI 1.00-2.06). CONCLUSIONS: Greater symptoms of depression are associated with an increased risk of mortality in HD patients, particularly when accounting for the most proximate assessment. This relationship was attenuated with adjustment for comorbid conditions, suggesting a complex relationship between clinical characteristics and depression symptoms. Future studies should evaluate whether treatment for depression impacts mortality among HD patients.

Dietary modulators of statin efficacy in cardiovascular disease and cognition.

Cardiovascular disease remains the leading cause of morbidity and mortality in the United States and other developed countries, and is fast growing in developing countries, particularly as life expectancy in all parts of the world increases. Current recommendations for the prevention of cardiovascular disease issued jointly from the American Academy of Cardiology and American Heart Association emphasize that lifestyle modification should be incorporated into any treatment plan, including those on statin drugs. However, there is a dearth of data on the interaction between diet and statins with respect to additive, complementary or antagonistic effects. This review collates the available data on the interaction of statins and dietary patterns, cognition, genetics and individual nutrients, including vitamin D, niacin, omega-3 fatty acids, fiber, phytochemicals (polyphenols and stanols) and alcohol. Of note, although the available data is summarized, the scope is limited, conflicting and disparate. In some cases it is likely there is unrecognized synergism. Virtually no data are available describing the interactions of statins with dietary components or dietary pattern in subgroups of the population, particularly those who may benefit most were positive effects identified. Hence, it is virtually impossible to draw any firm conclusions at this time. Nevertheless, this area is important because were the effects of statins and diet additive or synergistic harnessing the effect could potentially lead to the use of a lower intensity statin or dose.

Phase I dose-escalation trial of clofarabine followed by escalating doses of fractionated cyclophosphamide in children with relapsed or refractory acute leukemias.

BACKGROUND: By inhibiting DNA repair, clofarabine (CLO) may augment cyclophosphamide (CY)-induced DNA damage and apoptosis. We performed a Phase I study for refractory and/or relapsed (R/R) leukemia in children to determine maximum-tolerated dose (MTD) of time-sequential CLO followed by CY. PROCEDURE: Thirteen patients with (R/R) ALL (n = 8) and AML (N = 5), median age 9 years (range: 2-12 years), were treated with escalating doses of CLO on days 1, 2, 3 and 8, 9, 10 and CY 200 mg/m(2) /day on days 0 and 1 then 400 mg/m(2) /day on days 2, 3, 8, 9, and 10. Ten patients were treated at dose level 1 (DL1) (CLO 20 mg/m(2) /day) and three patients at DL2 (CLO 30 mg/m(2) /day). The average number of prior chemotherapies was 8.9. DNA damage testing was performed before treatment on day 0, and 2 hours after CY on day 0, before sequential CLO, CY treatment on day 1, and 2 hours after CLO followed by CY on day 1. RESULTS: Two patients at DL2 had dose-limiting toxicities (DLTs) that included hypotension with cardio-respiratory failure (1) and hepato-renal failure (1). Complete remission (CR) was achieved in 2/11 (18.2%) and partial remission (PR) in 2/11 (18.2%) for an overall response (OR) of 36.4%. The use of CLO before CY augmented CY-induced DNA damage in leukemic blasts compared to CY alone. CONCLUSION: In pediatric patients with R/R leukemia, 20 mg/m(2) /day is the MTD for CLO in timed sequential combination with CY. Increased DNA damage with the use of this combination suggests a mechanism for the sequential timing of these two chemotherapeutic agents.

Tandem dosing of samarium-153 ethylenediamine tetramethylene phosphoric acid with stem cell support for patients with high-risk osteosarcoma.

BACKGROUND: Samarium-153 ethylenediamine tetramethylene phosphoric acid (153Sm-EDTMP) is a radiopharmaceutical that has been used to treat osteosarcoma. The authors conducted a phase 2 study to test safety and response of high-risk osteosarcoma to tandem doses of 153Sm-EDTMP and to determine correlation between radiation delivered by low and high administered activities. METHODS: Patients with recurrent, refractory osteosarcoma detectable on standard 99mTc bone scan received a low dose of 153Sm-EDTMP (37.0-51.8 MBq/kg), followed upon count recovery by a second, higher dose (222 MBq/kg). Fourteen days later, patients were rescued with autologous hematopoietic stem cells. The authors assessed response to therapy, performed dosimetry to determine the relationship between administered activity and tumor absorbed dose, and investigated whether changes in 2-(fluorine-18) fluoro-2-deoxy-d-glucose (18F-FDG) tumor uptake upon hematologic recovery reflected disease response. RESULTS: Nine patients were given tandem doses of 153Sm-EDTMP; 2 received only the initial dose because of disease progression. Six patients experienced radiographic disease stabilization, but this was not considered a response, so the study was terminated early. There was a linear relationship between administered activity and tumor absorbed dose, but there was no correlation between change in 18F-FDG positron emission tomography tumor uptake and tumor absorbed dose or time to progression. The median time to progression for the entire group was 79 days. CONCLUSIONS: Tandem doses of 153Sm-EDTMP were safe for this cohort of heavily pretreated patients with very high-risk disease. The strong correlation between absorbed dose and administered activity within each evaluable patient provides a methodology to individually tailor tandem doses of this agent.

Dose-finding study of 153Sm-EDTMP in patients with poor-prognosis osteosarcoma.

BACKGROUND: Samarium-153 ethylenediaminetetramethylene phosphonic acid ((153)Sm-EDTMP) has been used to treat patients with high-risk osteosarcoma. The purpose of the current study was to determine the maximally tolerated dose of (153)Sm-EDTMP that permits hematopoietic recovery within 6 weeks. METHODS: Patients with recurrent or refractory osteosarcoma with bone metastases were enrolled in this study. Subjects were treated with increasing doses of (153)Sm-EDTMP, beginning with 1.0 millicuries (mCi)/kg and followed initially with 40% increment dose level escalations, using a continual reassessment method for dose escalation and de-escalation with a target dose-limiting toxicity (DLT) rate of 30%. Complete blood counts were monitored weekly, and the primary DLT was defined as failure to achieve an absolute neutrophil count >750/mm(3) and a platelet count >75,000/mm(3) within 6 weeks of treatment. In addition to assessing toxicity, dosimetry measurements were made to estimate the radiation dose delivered to target lesions. RESULTS: The maximally tolerated dose of (153)Sm-EDTMP was 44.8 megabecquerel (MBq)/kg (1.21 mCi/kg). DLTs were confined to hematologic toxicities, particularly delayed platelet recovery in 2 patients treated at a dose of 51.8 MBq/kg (1.4 mCi/kg). Grade 2 and 3 pulmonary toxicity (graded according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) as reported in 2 patients (at administered activities of 44.8 MBq/kg and 51.8 MBq/kg) was attributable to progressive pulmonary disease. No other significant nonhematologic toxicities were observed. CONCLUSIONS: Patients with osteosarcoma who have previously been heavily treated with chemotherapy can be safely administered (153)Sm-EDTMP with rapid hematologic recovery. The data from the current study support the development of a future trial to assess the efficacy of combining targeted radiotherapy with cytotoxic chemotherapy as a treatment option for patients with high-risk osteosarcoma.

Food insecurity and cognitive function in Puerto Rican adults.

BACKGROUND: Food insecurity is associated with nutrient inadequacy and a variety of unfavorable health outcomes. However, little is known about whether food security is associated with lower cognitive function in the elderly. OBJECTIVE: We investigated the prevalence of food insecurity in a representative sample of 1358 Puerto Ricans aged 45-75 y living in Massachusetts in relation to cognitive function performances. DESIGN: Food security was assessed with the US Household Food Security Scale. Cognitive function was measured to capture general cognition with a battery of 7 tests: Mini-Mental State Examination (MMSE), word list learning (verbal memory), digit span (attention), clock drawing and figure copying (visual-spatial ability), and Stroop and verbal fluency tests (fluency executive functioning). RESULTS: The overall prevalence of food insecurity during the past 12 mo was 12.1%; 6.1% of the subjects reported very low food security. Food insecurity was inversely associated with global cognitive performance, as assessed by the MMSE score. The adjusted difference in the MMSE score was -0.90 (95% CI: -1.6, -0.19; P for trend = 0.003) for a comparison of participants with very low food security with those who were food secure, after adjustment for age, smoking, education, poverty status, income, acculturation, plasma homocysteine, alcohol, diabetes, and hypertension. Food insecurity was significantly associated with lower scores for word-list learning, percentage retention, letter fluency, and digit span backward tests. CONCLUSIONS: Very low food security was prevalent among the study subjects and was associated with lower cognitive performance. Further studies, both observational and experimental, are warranted to clarify the direction of causality in this association.

Decreased levels of plasma vitamin C and increased concentrations of inflammatory and oxidative stress markers after stroke.

BACKGROUND AND PURPOSE: Inflammatory response is a critical component of the complex pathophysiological response to stroke. Vitamin C has been shown to have important roles in cell performance and vascular function. In this study, we compared the nutritional status and levels of inflammatory markers between stroke cases and controls and assessed which antioxidant was associated with levels of inflammatory markers and oxidative stress among cases and controls. METHODS: We evaluated the nutritional status and measured plasma levels of vitamins C and E, uric acid, serum levels of C-reactive protein (CRP), the cytokines tumor necrosis factor-alpha and interleukin-1beta, intercellular adhesion molecule-1 (ICAM-1) and chemokine monocyte chemoattractant protein-1 (MCP-1), prostaglandins PGE2 and PGI2, and 8-isoprostanes (8-epiPGF2alpha) for 15 patients with ischemic stroke within 2 to 5 days after stroke onset and for 24 control subjects. RESULTS: Stroke patients had significantly lower plasma levels of vitamin C than did controls. Among stroke patients, CRP was significantly elevated, as were the ICAM-1, MCP-1, and 8-epiPGF2alpha, but the prostaglandins PGE2 and PGI2 were significantly reduced. Interestingly, vitamin C concentration was significantly inversely correlated with the levels of CRP and 8-epiPGF2alpha among stroke patients, and 8-epiPGF2alpha was significantly associated with the levels of CRP. Uric acid was also elevated among stroke patients. CONCLUSIONS: Lower vitamin C concentration, higher serum levels of inflammatory (CRP, ICAM-1, MCP-1) and oxidative stress (8-epiPGF2alpha) markers, and lower PGI2 and PGE2 concentrations among stroke patients indicate the presence of an inflammatory response associated with stroke.