Virtually Supervised Exercise Programs for People With Cancer: A Scoping Review.

BACKGROUND: Exercise has been shown to improve physical function and quality of life for individuals with cancer. However, low rates of exercise adoption and commonly reported barriers to accessing exercise programming have demonstrated a need for virtual exercise programming in lieu of traditional in-person formats. OBJECTIVE: The aim of this study was to summarize the existing research on supervised exercise interventions delivered virtually for individuals living with and beyond cancer. METHODS: We conducted a scoping review of randomized controlled trials, pilot studies, or feasibility studies investigating virtually supervised exercise interventions for adults either during or after treatment of cancer. The search included EMBASE, MEDLINE, CINAHL, SPORTDiscus, Cochrane Library, and conference abstracts. RESULTS: Fifteen studies were included. The interventions were delivered mostly over Zoom in a group format, with various combinations of aerobic and resistance exercises. Attendance ranged from 78% to 100%, attrition ranged from 0% to 29%, and satisfaction ranged from 94% to 100%. No major adverse events were reported, and only 3 studies reported minor adverse events. Significant improvements were seen in upper and lower body strength, endurance, pain, fatigue, and emotional well-being. CONCLUSION: Supervised exercise interventions delivered virtually are feasible and may improve physical function for individuals with cancer. The supervision included in these virtual programs promoted similar safety as seen with in-person programming. More randomized controlled trials with large cohorts are needed to validate these findings. IMPLICATIONS FOR PRACTICE: Individuals living with and beyond cancer can be encouraged to join virtually supervised exercise programs because they are safe, well enjoyed, and may improve physical function and quality of life.

Outpatient Embedded Palliative Care for Patients with Advanced Thoracic Malignancy: A Retrospective Cohort Study.

Although cancer care is often contextualized in terms of survival, there are other important cancer care outcomes, such as quality of life and cost of care. The ASCO Value Framework assesses the value of cancer therapies not only in terms of survival but also with consideration of quality of life and financial cost. Early palliative care for patients with advanced cancer is associated with improved quality of life, mood, symptoms, and overall survival for patients, as well as cost savings. While palliative care has been shown to have numerous benefits, the impact of real-world implementation of outpatient embedded palliative care on value-based metrics is not fully understood. We sought to describe the association between outpatient embedded palliative care in a multidisciplinary thoracic oncology clinic and inpatient value-based metrics. We performed a retrospective cohort study of 215 patients being treated for advanced thoracic malignancies with non-curative intent. We evaluated the association between outpatient embedded palliative care and inpatient clinical outcomes including emergency room visits, hospitalizations, intensive care unit admissions, hospital charges, as well as hospital quality metrics including 30-day readmissions, admissions within 30 days of death, inpatient mortality, and inpatient hospital charges. Outpatient embedded palliative care was associated with lower hospital charges per day (USD 3807 vs. USD 4695, p = 0.024). Furthermore, patients who received outpatient embedded palliative care had lower hospital admissions within 30 days of death (O.R. 0.45; 95% CI 0.29, 0.68; p < 0.001) and a lower inpatient mortality rate (IRR 0.67; 95% CI 0.48, 0.95; p = 0.024). Our study further supports that outpatient palliative care is a high-value intervention and alternative models of palliative care, including one embedded into a multidisciplinary thoracic oncology clinic, is associated with improved value-based metrics.

Brief Report: Outcomes of Individuals Using HIV Postexposure Prophylaxis-In-Pocket ("PIP") for Low-Frequency, High-Risk Exposures in Toronto, Canada.

BACKGROUND: HIV postexposure prophylaxis-in-pocket ("PIP") is a self-initiated, event-driven HIV prevention modality for individuals with a low frequency of HIV exposures. METHODS: A cohort of 111 patients using PIP as their primary HIV prevention modality was longitudinally evaluated for PIP self-initiation, HIV and sexual transmitted infections, and switching to other HIV prevention modalities between February 2016 and December 2022. RESULTS: A total of 111 patients had 178.7 cumulative patient-years of PIP use. PIP was self-initiated 69 times by 35 (31.5%) individuals, with 0 HIV seroconversions identified. Thirty four individuals (30.6%) transitioned from PIP to pre-exposure prophylaxis and 33 individuals (29.7%) switched from pre-exposure prophylaxis to PIP. CONCLUSIONS: PIP is a useful addition to other pharmacologic HIV prevention tools, and may help prevent infection in those with a lower frequency of unanticipated HIV exposures.

Graphene Field Effect Biosensor for Concurrent and Specific Detection of SARS-CoV-2 and Influenza.

The SARS-CoV-2 pandemic has highlighted the need for devices capable of carrying out rapid differential detection of viruses that may manifest similar physiological symptoms yet demand tailored treatment plans. Seasonal influenza may be exacerbated by COVID-19 infections, increasing the burden on healthcare systems. In this work, we demonstrate a technology based on liquid-gated graphene field-effect transistors (GFETs), for rapid and ultraprecise sensing and differentiation of influenza and SARS-CoV-2 surface protein. Most distinctively, the device consists of 4 onboard GFETs arranged in a quadruple architecture, where each quarter is functionalized individually (with either antibodies or chemically passivated control) but measured jointly. The sensor platform was tested against a range of concentrations of viral surface proteins from both viruses with the lowest tested and detected concentration at ∼50 ag/mL, or 88 zM for COVID-19 and 227 zM for Flu, which is 5-fold lower than the values reported previously on a similar platform. Unlike the classic real-time polymerase chain reaction test, which has a turnaround time of a few hours, the graphene technology presents an ultrafast response time of ∼10 s even in complex and clinically relevant media such as saliva. Thus, we have developed a multianalyte, highly sensitive, and fault-tolerant technology for rapid diagnostic of contemporary, emerging, and future pandemics.

A digital health intervention to improve nutrition and physical activity in breast cancer survivors: Rationale and design of the Cook and Move for Your Life pilot and feasibility randomized controlled trial.

BACKGROUND: The design of a randomized pilot trial evaluating the feasibility of two doses of a digital health intervention promoting changes in nutrition and physical activity in breast cancer (BC) survivors is described. METHODS: Eligible women were adults with history of early-stage breast cancer and > 60 days post-treatment, consumed <5 servings/day of fruits/vegetables and/or engaged in <150 min/week of aerobic moderate-to-vigorous physical activity, and had internet access. Participants were randomized to 6 months of either a "low" (1 session) or "high" (12 sessions) dose digital health intervention. Zoom-delivered sessions focused on improving diet and physical activity through didactic and experiential classes delivered by a registered dietitian, chef, exercise physiologist, and culinary educator. All study participants received weekly motivational texts, a Fitbit, and study website access. Diet, accelerometry, anthropometric, psychosocial, and biospecimen data were collected remotely at baseline and six months. Primary outcome was feasibility measured via accrual rate, adherence, retention, and acceptability. RESULTS: Recruitment began in December 2019, was suspended in March 2020 due to the COVID-19 pandemic, resumed September 2020, and concluded in January 2021. Women were identified from the local BC registry and flyers posted in the oncology clinic. Of 929 women recruited, 321 completed the screening assessment, and of these, 138 were eligible. A total of 74 women were enrolled and randomized to the study. CONCLUSION: BC survivors were successfully enrolled in a digital health nutrition and physical activity intervention. If feasible, this intervention will be tested in larger and more diverse populations of cancer survivors. TRIAL REGISTRATION: ClinicalTrials.govNCT04200482.

An Oncology Urgent Care Clinic for the Management of Immune-Related Adverse Events: A Descriptive Analysis.

Introduction: With the increasing use of immune checkpoint inhibitors (ICI) for cancer, there is a growing burden on the healthcare system to provide care for the toxicities associated with these agents. Herein, we aim to identify and describe the distribution of encounters seen in an urgent care setting for immune-related adverse events (irAEs) and the clinical outcomes from irAE management. Methods: Patient demographics, disease characteristics, and treatment data were collected retrospectively from encounters at an oncology Urgent Care Clinic (UCC) from a single tertiary center for upper aerodigestive malignancies from 1 July 2018 to 30 June 2019. Data were summarized using descriptive statistics with odds ratios for associations between patient features and hospitalization after UCC evaluation. Results: We identified 494 encounters from 289 individual patients over the study period. A history of ICI therapy was noted in 34% (n = 170/494) of encounters and 29 encounters (29/170, 17%) were confirmed and treated as irAEs. For those treated for irAEs, the majority (n = 19/29; 66%) were discharged home. Having an irAE was associated with an increased risk of hospitalization compared to non-irAEs (OR 5.66; 95% CI 2.15−14.89; p < 0.001). Conclusion: In this single institution experience, the majority of UCC encounters for confirmed irAEs were safely managed within the UCC. In ICI-treated patients, having an irAE was associated with an increased risk of hospitalization versus non-irAEs.

Dual-species origin of an adaptive chemical defense polymorphism.

Allopolyploid speciation and chemical defense diversification are two of the most characteristic features of plant evolution; although the former has likely shaped the latter, this has rarely been documented. Here we document allopolyploidy-mediated chemical defense evolution in the origin of cyanogenesis (HCN release upon tissue damage) in white clover (Trifolium repens). We combined linkage mapping of the loci that control cyanogenesis (Ac, controlling production of cyanogenic glucosides; and Li, controlling production of their hydrolyzing enzyme linamarase) with genome sequence comparisons between white clover, a recently evolved allotetraploid, and its diploid progenitors (Trifolium pallescens, Trifolium occidentale). The Ac locus (a three-gene cluster comprising the cyanogenic glucoside pathway) is derived from T. occidentale; it maps to linkage group 2O (occidentale subgenome) and is orthologous to a highly similar cluster in the T. occidentale reference genome. By contrast, Li maps to linkage group 4P (pallescens subgenome), indicating an origin in the other progenitor species. These results indicate that cyanogenesis evolved in white clover as a product of the interspecific hybridization that created the species. This allopolyploidization-derived chemical defense, together with subsequent selection on intraspecific cyanogenesis variation, appears to have contributed to white clover's ecological success as a globally distributed weed species.

Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact.

BACKGROUND: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized. METHODS: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified. In addition to patient, tumor, and treatment related characteristics, specific baseline frailty markers (Charlson comorbidity index, ECOG, patient reported weight loss, BMI, hemoglobin, creatinine, albumin) were recorded. All cancer-related hospitalizations during or within 30 days of completing radiation were identified. Associations between baseline variables and any hospitalization, number of hospitalizations, and overall survival were identified using multivariable linear regression and multivariable Cox proportional-hazards models, respectively. RESULTS: Of 270 patients included: median age was 66.6 years (31-88), 50.4% of patients were male (n = 136), 62% were Caucasian (n = 168). Cancer-related hospitalization incidence was 17% (n = 47), of which 21% of patients hospitalized (n = 10/47) had > 1 hospitalization. On multivariable analysis, each 1 g/dL baseline drop in albumin was associated with a 2.4 times higher risk of any hospitalization (95% confidence interval (CI) 1.2-5.0, P = 0.01), and baseline hemoglobin ≤10 was associated with, on average, 2.7 more hospitalizations than having pre-treatment hemoglobin > 10 (95% CI 1.3-5.4, P = 0.01). After controlling for baseline variables, cancer-related hospitalization was associated with 1.8 times increased risk of all-cause death (95% CI: 1.02-3.1, P = 0.04). CONCLUSIONS: Our data show baseline factors can predict those who may be at increased risk for hospitalization, which was independently associated with increased mortality. Taken together, these data support the need for developing further studies aimed at early and aggressive interventions to decrease hospitalizations during treatment.

Fertility preservation for transgender adolescents and young adults: a systematic review.

BACKGROUND: Many transgender individuals choose to undergo gender-affirming hormone treatment (GAHT) and/or sex reassignment surgery (SRS) to alleviate the distress that is associated with gender dysphoria. Although these treatment options often succeed in alleviating such symptoms, they can also negatively impact future reproductive potential. OBJECTIVE AND RATIONALE: The purpose of this systematic review was to synthesize the available psychosocial and medical literature on fertility preservation (FP) for transgender adolescents and young adults (TAYAs), to identify gaps in the current research and provide suggestions for future research directions. SEARCH METHODS: A systematic review of English peer-reviewed papers published from 2001 onwards, using the preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines, was conducted. Four journal databases (Ovid MEDLINE, PubMed Medline, Ovid Embase and Ovid PsychINFO) were used to identify all relevant studies exploring psychosocial or medical aspects of FP in TAYAs. The search strategy used a combination of subject headings and generic terms related to the study topic and population. Bibliographies of the selected articles were also hand searched and cross-checked to ensure comprehensive coverage. All selected papers were independently reviewed by the co-authors. Characteristics of the studies, objectives and key findings were extracted, and a systematic review was conducted. OUTCOMES: Included in the study were 19 psychosocial-based research papers and 21 medical-based research papers that explore fertility-related aspects specific for this population. Key psychosocial themes included the desire to have children for TAYAs; FP discussions, counselling and referrals provided by healthcare providers (HCPs); FP utilization; the attitudes, knowledge and beliefs of TAYAs, HCPs and the parents/guardians of TAYAs; and barriers to accessing FP. Key medical themes included fertility-related effects of GAHT, FP options and outcomes. From a synthesis of the literature, we conclude that there are many barriers preventing TAYAs from pursuing FP, including a lack of awareness of FP options, high costs, invasiveness of the available procedures and the potential psychological impact of the FP process. The available medical data on the reproductive effects of GAHT are diverse, and while detrimental effects are anticipated, the extent to which these effects are reversible is unknown. WIDER IMPLICATIONS: FP counselling should begin as early as possible as a standard of care before GAHT to allow time for informed decisions. The current lack of high-quality medical data specific to FP counselling practice for this population means there is a reliance on expert opinion and extrapolation from studies in the cisgender population. Future research should include large-scale cohort studies (preferably multi-centered), longitudinal studies of TAYAs across the FP process, qualitative studies of the parents/guardians of TAYAs and studies evaluating the effectiveness of different strategies to improve the attitudes, knowledge and beliefs of HCPs.

Moving towards Universal Coverage of Direct-Acting Antiviral Therapies for Hepatitis C Infection in Canada: An Environmental Scan of Canadian Provinces and International Jurisdictions.

BACKGROUND: Direct-acting antivirals (DAAs) have become the standard treatment for patients with chronic hepatitis C infections because of their high cure rates and favourable side effect profiles; however, access to this new class of agents has been limited because of its high cost.  Public payers across Canada have implemented strict criteria for drug coverage in order to contain expenditures. Efforts have been made to improve access to medication for this high-burden condition. Recent coverage criteria across national and international jurisdictions have been compared. METHODS: Coverage criteria for several DAAs were reviewed by accessing Canadian provincial drug formularies. International coverage (e.g., Europe, Australia, United States, Egypt, India) was reviewed by searching available literature. RESULTS: Coverage criteria vary across Canada. By April 2018, most Canadian jurisdictions had removed the stage 2 liver fibrosis requirement for patients to be eligible for coverage. Internationally, patients' access to DAAs differs significantly. Many jurisdictions restrict DAA prescribing authority to specialists and request documentation of chronic hepatitis C. In the US, considerable gaps of coverage are identifiable and patients might face significant financial burden to receive treatment. CONCLUSION: DAAs appear to be generally accessible through public drug plans in Canada compared to other countries.

The Relative Impact of Sleep and Circadian Drive on Motor Skill Acquisition and Memory Consolidation.

Study Objectives: Sleep during the biological night facilitates memory consolidation. Here we determined the impact of sleep and wake on motor skill learning (acquisition) and subsequent off-line skill improvement (memory consolidation), independent of circadian phase, and compared this to the impact of the endogenous circadian system, independent of whether sleep occurred during the biological night or day. Methods: Participants completed two 8-day sleep laboratory visits, adhering on one visit to a circadian aligned ("normal") sleep schedule for the full duration of the protocol, and on the other to a circadian misaligned (12-hour inverted) schedule, with alignment during the first 3 days, a 12-hour 'slam shift' on Day 4, followed by circadian misalignment during the last 4 days of the protocol. Participants were repeatedly trained and tested on different versions of the finger-tapping motor sequence task across each visit. Results: Sleep facilitated offline memory consolidation regardless of whether it occurred during the biological day or night, while circadian phase had no significant impact. These sleep-related benefits remained after accounting for general motor speed, measured in the absence of learning. In addition, motor skill acquisition was facilitated when the training session followed shortly after sleep, without significant impact of circadian phase (biological morning vs. evening). This effect was largely driven by heightened acquisition in participants who slept during the day and were trained shortly thereafter, that is, when acquisition occurred during the biological evening. These benefits were also retained after controlling for general motor speed. Conclusions: Sleep benefits both the acquisition and consolidation of motor skill regardless of whether they occur during the biological day or night. After controlling for general motor speed, a critical adjustment that few studies perform, these sleep benefits remain intact. Our findings have clear implications for night shift workers who obtain their sleep during the day.

Successful Point-Of-Care Ultrasound-Guided Treatment of Submassive Pulmonary Embolism.

Pulmonary embolism is associated with significant mortality and impaired long-term functional outcomes. Timely identification and treatment is crucial for successful management. Unfortunately, prompt diagnosis can be challenging in patients without overt signs of cardiovascular compromise. Point-of-care cardiac ultrasound (POCCUS) can be used to identify signs of acute pulmonary embolism, risk stratify patients for adverse outcomes and assess response to therapy. This report describes a patient with submassive pulmonary embolism and evidence of acute right ventricular strain on POCCUS successfully treated with thrombolytic therapy. The dynamic changes observed on point-of-care ultrasound are presented.

Effect of Bariatric Weight Loss on the Adipose Lipolytic Transcriptome in Obese Humans.

BACKGROUND: Dysregulated lipolysis has been implicated in mechanisms of cardiometabolic disease and inflammation in obesity. PURPOSE: We sought to examine the effect of bariatric weight loss on adipose tissue lipolytic gene expression and their relationship to systemic metabolic parameters in obese subjects. METHODS/RESULTS: We biopsied subcutaneous adipose tissue in 19 obese individuals (BMI 42 ± 5 kg/m(2), 79% female) at baseline and after a mean period of 8 ± 5 months (range 3-15 months) following bariatric surgery. We performed adipose tissue mRNA expression of proteins involved in triglyceride hydrolysis and correlated their weight loss induced alterations with systemic parameters associated with cardiovascular disease risk. mRNA transcripts of adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and lipid droplet proteins comparative gene identification 58 (CGI-58) and perilipin increased significantly after weight loss (p < 0.05 for all). ATGL expression correlated inversely with plasma triglyceride (TG), hemoglobin A1C (HbA1C), and glucose, and HSL expression correlated negatively with glucose, while CGI-58 was inversely associated with HbA1C. CONCLUSION: We observed increased expression of adipose tissue lipolytic genes following bariatric weight loss which correlated inversely with systemic markers of lipid and glucose metabolism. Functional alterations in lipolysis in human adipose tissue may play a role in shaping cardiometabolic phenotypes in human obesity.

The Human Circadian System Has a Dominating Role in Causing the Morning/Evening Difference in Diet-Induced Thermogenesis.

OBJECTIVE: Diet-induced thermogenesis (DIT) is lower in the evening and at night than in the morning. This may help explain why meal timing affects body weight regulation and why shift work is a risk factor for obesity. The separate effects of the endogenous circadian system--independent of behavioral cycles--and of circadian misalignment on DIT are unknown. METHODS: Thirteen healthy adults undertook a randomized crossover study with two 8-day laboratory visits: three baseline days followed either by repeated simulated night shifts including 12-h inverted behavioral cycles (circadian misalignment) or by recurring simulated day shifts (circadian alignment). DIT was determined for up to 114 min (hereafter referred to as "early DIT") following identical meals given at 8AM and 8PM in both protocols. RESULTS: During baseline days, early DIT was 44% lower in the evening than morning. This was primarily explained by a circadian influence rather than any behavioral cycle effect; early DIT was 50% lower in the biological evening than biological morning, independent of behavioral cycle influences. Circadian misalignment had no overall effect on early DIT. CONCLUSIONS: The circadian system plays a dominating role in the morning/evening difference in early DIT and may contribute to the effects of meal timing on body weight regulation.

Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans.

Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic ß-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.

Forkhead box O-1 modulation improves endothelial insulin resistance in human obesity.

OBJECTIVE: Increased visceral adiposity has been closely linked to insulin resistance, endothelial dysfunction, and cardiometabolic disease in obesity, but pathophysiological mechanisms are poorly understood. We sought to investigate mechanisms of vascular insulin resistance by characterizing depot-specific insulin responses and gain evidence that altered functionality of transcription factor forkhead box O-1 (FOXO-1) may play an important role in obesity-related endothelial dysfunction. APPROACH AND RESULTS: We intraoperatively collected paired subcutaneous and visceral adipose tissue samples from 56 severely obese (body mass index, 43 ± 7 kg/m(2)) and 14 nonobese subjects during planned surgical operations, and characterized depot-specific insulin-mediated responses using Western blot and quantitative immunofluorescence techniques. Insulin signaling via phosphorylation of FOXO-1 and consequent endothelial nitric oxide synthase stimulation was selectively impaired in the visceral compared with subcutaneous adipose tissue and endothelial cells of obese subjects. In contrast, tissue actions of insulin were preserved in nonobese individuals. Pharmacological antagonism with AS1842856 and biological silencing using small interfering RNA-mediated FOXO-1 knockdown reversed insulin resistance and restored endothelial nitric oxide synthase activation in the obese. CONCLUSIONS: We observed profound endothelial insulin resistance in the visceral adipose tissue of obese humans which improved with FOXO-1 inhibition. FOXO-1 modulation may represent a novel therapeutic target to diminish vascular insulin resistance. In addition, characterization of endothelial insulin resistance in the adipose microenvironment may provide clues to mechanisms of systemic disease in human obesity.

The 'taking place' of health and wellbeing: towards non-representational theory.

For the last two decades health geography has focused on the dynamics between health and place. Although the social constructivist perspective of much research has provided many insights into the meanings of health and health care arguably, mirroring progress in the parent discipline of human geography, there could be a far more serious engagement with non-representational theory and the 'taking place' of health and health care. To showcase the importance and potential of this broadly, the idea of wellbeing is re-approached. The paper reflects on the ways wellbeing has been treated in research primarily as a meaningful and relatively prescribed state of life, to the neglect of process. Based on this critique, a qualitative study then illustrates the most immediate and everyday ways wellbeing might arise through 'affect'; the pre-personal mobile energies and intensities that result from physical encounters within assemblages of bodies and objects. Indeed, theoretically the findings support the proposition that, at one level, wellbeing might not be taken from environment but instead might emerge as the affective environment. They certainly raise awareness of how much in health might originate at the surface, prior to meaning, within life's infinite spatial doings, and thus they launch some final thoughts on the wider challenges and opportunities for non-representational health geographies.

Blunted nocturnal cortisol rise is associated with higher carotid artery intima-media thickness (CIMT) in overweight African American and Latino youth.

BACKGROUND: Blunted diurnal cortisol variation has been associated with overt cardiovascular disease in adults. The relationship between the diurnal cortisol variation and subclinical atherosclerosis in youth has yet to be investigated. The objectives of this study were to (1) determine the relationship between overnight cortisol measures and CIMT in overweight and obese, African-American and Latino children; (2) assess ethnic differences in these relationships; and (3) explore whether overnight cortisol and CIMT relationships were independent of inflammatory markers, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-∝ (TNF-∝). METHODS: One hundred fifty-six overweight and obese African-American and Latino children (ages 8-17, 86 M/70 F, 55 African-American/101 Latino) underwent measures of CIMT by B-mode ultrasound, nocturnal cortisol rise (NCR = salivary cortisol rise from 2200 h to awakening at 0530 h), cortisol awakening response (CAR = salivary cortisol from time of awakening to 30 min later), fasting serum cortisol and overnight urinary free cortisol. RESULTS: Using linear regression, salivary cortisol(0530 h) and NCR were negatively associated with CIMT (ß(standardized) = -0.215 and -0.220, p < 0.01) independent of age, height, percent body fat, ethnicity and systolic blood pressure. Nocturnal salivary cortisol(2200 h), morning serum cortisol, and overnight urinary free cortisol were not associated with CIMT. Using ANCOVA, participants with LOW NCR (NCR < 0.44 µg/dL, n = 52) had significantly greater CIMT than those with HIGH NCR (NCR ≥ 0.91 µg/dL, n = 52; 0.632 ± 0.008 vs. 0.603 ± 0.008 mm, p=0.01) after controlling for covariates. Ethnicity was independently associated with CIMT, whereby African-American children had greater CIMT than Latino children (-0.028 ± 0.009, p=0.006). The relationships between cortisol measures and CIMT did not differ between the two ethnic groups (all p(interaction) = 0.28-0.97). CRP, IL-6 and TNF-∝ were not associated with CIMT (p > 0.05). IL-6 was inversely related to NCR (r = -0.186, p = 0.03), but it did not explain the relationship between NCR and CIMT. CONCLUSIONS: Salivary cortisol(0530 h) and NCR, but not CAR, nocturnal salivary cortisol(2200 h), morning serum cortisol or overnight urinary free cortisol were associated with CIMT, independent of relevant covariates, including inflammatory factors. A low awakening salivary cortisol or a blunted NCR may be related to increased atherosclerosis risk in overweight and obese minority youth. These findings support adult studies suggesting flattened daytime diurnal cortisol variation impacts cardiovascular disease risk.