Longitudinal Pilot Evaluation of the Gut Microbiota Comparing Patients With and Without Chronic Kidney Disease.

OBJECTIVE: The gut microbiota contributes to metabolic diseases, such as diabetes and hypertension, but is poorly characterized in chronic kidney disease (CKD). DESIGN AND METHODS: We enrolled 24 adults within household pairs, in which at least one member had self-reported kidney disease, diabetes, or hypertension. CKD was classified based on estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urine-albumin-to-creatinine ratio of ≥ 30 mg/g. Participants collected stool and dietary recalls seasonally over a year. Gut microbiota was characterized using 16s rRNA and metagenomic sequencing. RESULTS: Ten participants had CKD (42%) with a median (interquartile range) estimated glomerular filtration rate of 49 (44, 54) mL/min/1.73 m2. By 16s rRNA sequencing, there was moderate to high intraclass correlation (ICC = 0.63) for seasonal alpha diversity (Shannon index) within individuals and modest differences by season (P < .01). ICC was lower with metagenomics, which has resolution at the species level (ICC = 0.26). There were no differences in alpha or beta diversity by CKD with either method. Among 79 genera, Frisingicoccus, Tuzzerella, Faecalitalea, and Lachnoclostridium had lower abundance in CKD, while Collinsella, Lachnospiraceae_ND3007, Veillonella, and Erysipelotrichaceae_UCG_003 were more abundant in CKD (each nominal P < .05) using 16s rRNA sequencing. Higher Collinsella and Veillonella and lower Lachnoclostridium in CKD were also identified by metagenomics. By metagenomics, Coprococcus catus and Bacteroides stercoris were more and less abundant in CKD, respectively, at false discovery rate corrected P = .02. CONCLUSIONS: We identified candidate taxa in the gut microbiota associated with CKD. High ICC in individuals with modest seasonal impacts implies that follow-up studies may use less frequent sampling.

Effects of Lifestyle Modification on Psychosocial Function in Patients With Resistant Hypertension: SECONDARY OUTCOMES FROM THE TRIUMPH RANDOMIZED CLINICAL TRIAL.

PURPOSE: In a secondary analysis of the TRIUMPH clinical trial, psychological outcomes in patients with resistant hypertension (RH) receiving a diet and exercise intervention delivered in a cardiac rehabilitation setting were compared with those receiving a similar prescription of diet and exercise provided in a single counseling session by a health educator. METHODS: One hundred forty patients with RH were randomly assigned to a 4-mo program of dietary counseling, behavioral weight management, and exercise (C-LIFE) or a single counseling session providing standardized education and physician advice (SEPA). Participants completed a battery of questionnaires to assess psychological functioning before and after the intervention. A global measure of psychological functioning was derived from the General Health Questionnaire (GHQ), Perceived Stress Scale (PSS), Medical Outcomes Study 36-item Short Form Health Survey, Spielberger State-Trait Anxiety Inventory, Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory-II, and Patient-Reported Outcomes Measurement Information System (PROMIS) Anger scale. RESULTS: Participants in the C-LIFE intervention achieved greater improvements in psychological functioning compared with SEPA (C-LIFE: 58.9 [56.1, 61.8] vs SEPA: 66.5 [62.1, 70.9]; P = .024). Greater improvements were especially evident for the GHQ, PSS, and HADS. Examination of mediation revealed that greater weight loss ( B =-0.17, P = .004) and improved oxygen uptake ( B =-0.12, P = .044) were associated with improved psychological functioning. CONCLUSION: Compared with standard education and physician advice, a structured program of diet and exercise not only reduced blood pressure but also improved psychological functioning in patients with RH.

A Proposal for the Comprehensive Care of Men on Androgen Deprivation Therapy: Recommendations From the Multidisciplinary Prostate Cancer 360 Working Group.

INTRODUCTION: To promote comprehensive care of patients throughout the androgen deprivation therapy (ADT) prescribing process, the Prostate Cancer 360 (PC360) Working Group developed monitoring and management recommendations intended to mitigate or prevent ADT-associated adverse events. METHODS: The PC360 Working Group included 14 interdisciplinary experts with a dedicated clinical interest in prostate cancer and ADT management. The working group defined challenges associated with ADT adverse event management and then collaboratively developed comprehensive care recommendations intended to be practical for ADT prescribers. RESULTS: The PC360 Working Group developed both overarching recommendations for ADT adverse event management and specific recommendations across 5 domains (cardiometabolic, bone, sexual, psychological, and lifestyle). The working group recommends an interdisciplinary, team-based approach wherein the ADT prescriber retains an oversight role for ADT management while empowering patients and their primary and specialty care providers to manage risk factors. The PC360 recommendations also emphasize the importance of proactive patient education that involves partners or other support providers. Recommended monitoring and assessment tools, risk factor management, and patient counseling points are also included for the 5 identified domains, with an emphasis on lifestyle and behavioral interventions that can improve quality of life and reduce the risk for ADT-associated complications. CONCLUSIONS: Comprehensive care of patients receiving ADT requires early and ongoing coordinated management of a variety of health domains, including cardiometabolic, bone, sexual, psychological health. Patient education and primary care provider involvement should begin prior to ADT initiation and continue throughout treatment to improve patient and partner quality of life.

Effects of Chinese heart-healthy diet on blood lipids, glucose, and estimated 10-y cardiovascular disease risk among Chinese adults: results on secondary outcomes of a randomized controlled trial.

BACKGROUND: Healthy diet is essential for cardiovascular disease risk management, but its effects among Chinese patients, whose diets differ from Western diets, remain largely unknown. METHODS: In this multicenter, patient- and outcome assessor-blind, randomized controlled feeding trial, 265 Chinese adults with baseline systolic blood pressure 130 to 159 mmHg were randomly assigned into Chinese heart-healthy (CHH) diet or usual diet for a 28-d intervention after a 7-d run-in period on usual diet. Blood lipids and glucose were measured from overnight fasting blood samples before and after the intervention. Ten-year cardiovascular disease risk was estimated using models previously developed and validated in Chinese. The changes in secondary outcomes of serum total cholesterol (TC), blood glucose, and 10-y cardiovascular disease risk over the intervention period were compared between intervention groups, adjusting for center, among participants with baseline and follow-up blood samples available. Sensitivity analyses were done with further adjustment for baseline values and covariables; missing data imputed; and among per-protocol population. RESULTS: Among 256 eligible participants (130 on CHH diet, 126 on control diet), 42% had hypercholesterolemia and 15% had diabetes at baseline. In the control group, TC and 10-y cardiovascular disease risk decreased after the intervention by 0.16 mmol/L and 0.91%, respectively, but blood glucose increased by 0.25 mmol/L. Compared with usual diet, the CHH diet lowered TC (-0.14 mmol/L, P = 0.017) and 10-y cardiovascular disease risk (-1.24%, P = 0.001) further. No effect on blood glucose was found. All sensitivity analyses confirmed the results on TC and 10-y cardiovascular disease risk, and analysis with multiple variables adjusted showed a borderline significant effect on blood glucose (-0.17 mmol/L, P = 0.051). The differences in intake of nutrients and food groups between intervention groups explained the results. CONCLUSIONS: The CHH diet reduced TC and 10-y cardiovascular disease risk and was likely to reduce blood glucose among Chinese adults with mild hypertension. Further studies with longer terms are warranted. This trial was registered at clinicaltrials.gov as NCT03882645.

Supplement use and gastric cancer risk in the Southern Community Cohort Study.

PURPOSE: Gastric cancer remains a racial health disparity in the US, but few studies have examined supplements as a potential protective factor. We examined associations between regular supplement use and gastric cancer risk among the predominantly Black participants in the Southern Community Cohort Study (SCCS). METHODS: Of the 84,508 individuals recruited in the SCCS from 2002 to 2009, 81,884 responded to the baseline question: any vitamin or supplement taken at least once per month in the past year. Secondary analyses assessed specific supplement use. Associations with incident gastric cancer were examined using adjusted Cox proportional hazards models, stratified by histologic subtype and secondarily by healthy eating index (HEI). RESULTS: Approximately half of the participants (47%, n = 38,318) reported any regular supplement use. Among the 203 incident gastric cancers over the follow-up period (median, 7 years), 142 were non-cardia (NCGC), 31 cardia (CGC), and 30 unknown. Regular supplement use was associated with a 30% decreased risk of NCGC (hazards ratio (HR) 0.70; 95% confidence interval (CI) 0.49-0.99). Among participants below the HEI median, any regular supplement and multivitamin use were associated with a 52% and 70% decrease in risk of NCGC (HR 0.48; 95%CI 0.25-0.92 and HR 0.30; 95%CI 0.13-0.71), respectively. No associations were found for CGC. CONCLUSION: Regular supplement use, including multivitamins, was associated with a decreased risk of NCGC in the SCCS, particularly among participants with a lower quality diet. Inverse associations of supplement use and NCGC incidence provide support for clinical trials among high-risk populations in the US.

Diversity of plant DNA in stool is linked to dietary quality, age, and household income.

Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast trnL-P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.40 to 0.63). In adolescents unable to collect validated dietary survey data, trnL metabarcoding detected 111 plant taxa, with 86 consumed by more than one individual and four (wheat, chocolate, corn, and potato family) consumed by >70% of individuals. Adolescent pMR was associated with age and household income, replicating prior epidemiologic findings. Overall, trnL metabarcoding promises an objective and accurate measure of the number and types of plants consumed that is applicable to diverse human populations.

The Streaming Web-Based Exercise at Home Study for Breast and Prostate Cancer Survivors: A Feasibility Study Protocol.

BACKGROUND: Despite the known benefits of physical activity in cancer survivors, adherence to exercise guidelines remains low. Known barriers to adhering to guidelines include a lack of time and an unwillingness to return to treatment facilities. Virtual exercise programming could assist in mitigating these barriers. This protocol presents a single arm pilot study exploring the feasibility of personalized Zoom-delivered exercise training for breast and prostate cancer survivors. A secondary objective is to determine the preliminary efficacy of participation on body composition, estimated VO2max, hand grip, one repetition maximum leg press, resting heart rate, resting blood pressure, exercise self-efficacy, and intentions to remain active. METHODS: Breast (n = 10) and prostate (n = 10) cancer survivors will participate in a 24-week feasibility study, including (1) 12 weeks of one-on-one virtual personal training with an exercise physiologist (EP) via Zoom, and (2) individual exercise for a 12-week follow-up period using recordings of Zoom sessions for guidance. Physical assessments and surveys will be implemented at baseline, 12 weeks, and at the end of the study (24 weeks from baseline). CONCLUSIONS: While virtual exercise programming became popularized during the pandemic, evidence is still required to understand whether it can successfully address barriers and promote participation.

Identifying the behavior change techniques used in obesity interventions: An example from the EARLY trials.

Objective: The dissemination of effective obesity interventions requires the documentation of key elements of the intervention. But outcome papers and other published manuscripts often lack detail that allow the replication of the intervention. The Behavior Change Technique (BCT) Taxonomy (BCTTv1) is a widely used approach to identify key elements of an intervention study. This study compares the extent to which BCTs and domains identified in studies' intervention protocol are concordant with detail from corresponding intervention design and study outcome papers. Methods: Data come from four obesity interventions with complete intervention protocols as well as published intervention design and outcome papers. The number of domains and BCTs was calculated for each treatment arm and stratified by coding source. Emphasis of domains and BCTs was determined using an Analytical Hierarchy Process (AHP). Results: A review of each study's intervention protocol showed the mean number of domains and BCTs used in treatment arms as 11.8 and 26.7, respectively. Primary outcome papers had a mean loss of 34% of the reported domains and 43% of BCTS as compared with intervention protocl. Design papers showed a loss of 11% and 21% of domains and BCTs, respectively. Conclusions: The results confirm the limitations of using the BCTTv1 coding of outcome papers to describe obesity-related interventions. The results also highlight the need for mechanisms that allow for a full description of intervention content such as inclusion in a supplemental section of an online journal or the use of intervention-focused consort guidelines.

Inflammation moderates the effects of lifestyle modification on neurocognition among individuals with resistant hypertension.

Individuals with resistant hypertension (RH) have the greatest risk of cerebrovascular disease and cognitive impairment among individuals with hypertension. Elevated levels of pro-inflammatory cytokines may represent a critical yet unexamined factor influencing the impact of healthy lifestyle changes on cognitive function. We explored the influence of inflammation on changes in cognition following lifestyle modification among individuals with RH participating in the TRIUMPH clinical trial. One hundred forty participants with RH completed a battery of neurocognitive tests along with the inflammatory marker C-reactive protein (hsCRP) and were subsequently randomized to an intensive 4-month lifestyle modification intervention or to education and physician advice control. Results indicated that the effects of lifestyle modification on Executive Function and Learning were moderated by pre-intervention hsCRP levels (P = .049), with treatment efficacy increasing across levels of baseline inflammation levels (low: d = 0.12; mild: d = 0.43; moderate: d = 0.81). We conclude that inflammatory profiles may help identify individuals more likely to improve executive functioning resulting from lifestyle modification.

Self-Perceived Barriers and Facilitators to Dietary Approaches to Stop Hypertension Diet Adherence Among Black Americans With Chronic Kidney Disease: A Qualitative Study.

OBJECTIVE: The Dietary Approaches to Stop Hypertension (DASH) eating plan improves hypertension in Black individuals and is associated with favorable chronic kidney disease (CKD) outcomes. Yet, adherence to DASH is low among US adults in general, particularly among Black Americans. We assessed perceptions about DASH, its cultural compatibility, and barriers and facilitators to DASH adherence in Black adults with CKD. DESIGN AND METHODS: We conducted focus groups and semistructured individual interviews involving 22 Black men and women with CKD Stages 3-4 from outpatient clinics at a US academic medical center. Transcripts of audio-recorded interviews were analyzed using thematic analysis. RESULTS: Among participants (2 focus groups [N = 8 and 5] and 9 individual interviews), 13 (59%) had CKD Stage 3, 13 (59%) were female, the median age was 61 years, and 19 (90%) had hypertension. After receiving information about DASH, participants perceived it as culturally compatible based on 3 emergent themes: (1) Black individuals already eat DASH-recommended foods ("Blacks eat pretty much like this"), (2) traditional recipes (e.g., southern or soul food) can be modified into healthy versions ("you can come up with decent substitutes to make it just as good"), and ( 3) diet is not uniform among Black individuals ("I can't say that I eat traditional"). Perceived barriers to DASH adherence included unfamiliarity with serving sizes, poor cooking skills, unsupportive household members, and high cost of healthy food. Eleven (52%) reported after paying monthly bills that they "rarely" or "never" had leftover money to purchase healthy food. Perceived facilitators included having local access to healthy food, living alone or with supportive household members, and having willpower and internal/external motivation for change. CONCLUSIONS: Black adults with CKD viewed DASH as a healthy, culturally compatible diet. Recognizing that diet in Black adults is not uniform, interventions should emphasize person-centered, rather than stereotypically culture-centered, approaches to DASH adherence.

Microbiota responses to different prebiotics are conserved within individuals and associated with habitual fiber intake.

BACKGROUND: Short-chain fatty acids (SCFAs) derived from gut bacteria are associated with protective roles in diseases ranging from obesity to colorectal cancers. Intake of microbially accessible dietary fibers (prebiotics) lead to varying effects on SCFA production in human studies, and gut microbial responses to nutritional interventions vary by individual. It is therefore possible that prebiotic therapies will require customizing to individuals. RESULTS: Here, we explored prebiotic personalization by conducting a three-way crossover study of three prebiotic treatments in healthy adults. We found that within individuals, metabolic responses were correlated across the three prebiotics. Individual identity, rather than prebiotic choice, was also the major determinant of SCFA response. Across individuals, prebiotic response was inversely related to basal fecal SCFA concentration, which, in turn, was associated with habitual fiber intake. Experimental measures of gut microbial SCFA production for each participant also negatively correlated with fiber consumption, supporting a model in which individuals' gut microbiota are limited in their overall capacity to produce fecal SCFAs from fiber. CONCLUSIONS: Our findings support developing personalized prebiotic regimens that focus on selecting individuals who stand to benefit, and that such individuals are likely to be deficient in fiber intake. Video Abstract.

Effects of Cuisine-Based Chinese Heart-Healthy Diet in Lowering Blood Pressure Among Adults in China: Multicenter, Single-Blind, Randomized, Parallel Controlled Feeding Trial.

BACKGROUND: More than one-fifth of the world's population consumes Chinese cuisines regularly, but no evidence-based healthy diets fitting the Chinese food culture are available for implementation. METHODS: A multicenter, patient- and outcome assessor-blind, randomized feeding trial was conducted among 265 participants with 130 to 159 mm Hg baseline systolic blood pressure (SBP) for 4 major Chinese cuisines (Shangdong, Huaiyang, Cantonese, Szechuan). After a 7-day run-in period on a control diet matching the usual local diets, participants were randomized to continue with the control diet or the cuisine-based Chinese heart-healthy diet for another 28 days. The primary outcome was SBP, and secondary outcomes included diastolic blood pressure and food preference score. Linear regression models were used to estimate the intervention effects and adjustments for the center. The incremental cost per 1 mm Hg reduction in SBP was also calculated. RESULTS: A total of 265 participants were randomized (135 on the Chinese heart-healthy diet and 130 on the control diet), with 52% women, mean age of 56.5±9.8 years, and mean SBP and diastolic blood pressure of 139.4±8.3 and 88.1±8.0 mm Hg, respectively, at baseline. The change in SBP and diastolic blood pressure from baseline to the end of the study in the control group was -5.0 (95% CI, -6.5 to -3.5) mm Hg and -2.8 (95% CI, -3.7 to -1.9) mm Hg, respectively. The net difference of change between the 2 groups in SBP and diastolic blood pressure were -10.0 (95% CI, -12.1 to -7.9) mm Hg and -3.8 (95% CI, -5.0 to -2.5) mm Hg, respectively. The effect size did not differ among cuisines (P for interaction=0.173). The mean food preference score was 9.5 (with 10 the best preferred) at baseline, and the net change during intervention was 0.1 (95% CI, -0.1 to 0.2; P=0.558). The incremental cost-effectiveness ratio per 1 mm Hg SBP reduction was CNY 0.4 (USD 0.06) per day. No difference in the number of adverse events was found between the 2 groups (P=0.259), and none of the adverse events was associated with the intervention. CONCLUSIONS: The Chinese heart-healthy diet is effective, palatable, and cost-effective in reducing blood pressure in Chinese adults with high blood pressure, with a clinically significant effect applicable across major Chinese cuisine cultures. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03882645.

Lifestyle modification and cognitive function among individuals with resistant hypertension: cognitive outcomes from the TRIUMPH trial.

BACKGROUND: Resistant hypertension is associated with increased risk of cognitive decline, stroke, and dementia. Lifestyle modification has been suggested to improve cognitive function through its salutary effects on vascular function. METHODS: Participants included 140 patients with resistant hypertension participating in the TRIUMPH trial. Participants were randomized to a cardiac rehabilitation-based lifestyle program (C-LIFE) or a standardized education and physician advice condition (SEPA). Participants completed a 45-min cognitive test battery consisting of tests of Executive Functioning and Learning, Memory, and Processing Speed. Biomarkers of vascular [flow mediated dilation of the brachial artery (FMD)], microvascular, and cerebrovascular function were also collected, in addition to weight, fitness, and ambulatory blood pressure. RESULTS: Participants averaged 63 years of age, 48% women, 59% black, and obese [mean BMI = 36 kg/m 2 (SD = 4)]. Cognitive performance improved across the entire cohort during the 4-month trial [ t -scores pretreatment = 48.9 (48, 50) vs. posttreatment = 50.0 (49, 51), P  < 0.001]. Postintervention Executive Function/Learning composite performance was higher for participants in C-LIFE compared to SEPA ( d  = 0.37, P  = 0.039). C-LIFE intervention effects on Memory and Processing Speed were moderated by sex and baseline stroke risk, respectively ( P  = 0.026 and P  = 0.043 for interactions), such that males and participants with greater stroke risk showed the greatest cognitive changes. FMD [C-LIFE: +0.3% (-0.3, 1.0) vs. SEPA: -1.4% (-2.5, -0.3), P  = 0.022], and microvascular function [C-LIFE: 97 (65, 130) vs. SEPA: 025 (-75, 23), P  < 0.001] were improved in C-LIFE compared with SEPA, whereas cerebrovascular reactivity was not [C-LIFE: -0.2 (-0.4, 0) vs. SEPA: 0.1 (-0.2, 0.4), P  = 0.197). Mediation analyses suggested that increased executive function/learning was associated with reduced ambulatory SBP levels secondary to weight loss [indirect effect: B  = 0.25 (0.03, 0.71)]. CONCLUSION: Lifestyle modification individuals with resistant hypertension improves cognition, which appeared to be associated with reduced ambulatory SBP changes through weight loss. Cognitive improvements were accompanied by parallel improvements in endothelial and microvascular function.

Bioavailability of phosphorus and kidney function in the Jackson Heart Study.

BACKGROUND: High phosphorus (P) exposure may have negative effects on kidney function. Nutrient databases provide total P, but bioavailability varies by source. OBJECTIVES: We aimed to assess natural, added, and bioavailable P intake, and to relate these to estimated glomerular filtration rate (eGFR) in the Jackson Heart Study (JHS). METHODS: A total of 3962 African-American participants of the JHS, aged 21-84 y, with urine albumin:creatinine ratio < 30 mg/g, and eGFR ≥ 60 mL · min-1 · 1.73 m-2, and without self-reported kidney disease, were included. Diet was assessed by FFQ. We assigned P in foods as naturally occurring or added, and weighted intake by P bioavailability, based on published literature. Relations between P variables and eGFR were assessed using multivariable regression. RESULTS: Mean ± SE intakes were 1178 ± 6.7 mg and 1168 ± 5.0 mg for total P, 296 ± 2.8 mg and 291 ± 2.1 mg for bioavailable added P, and 444 ± 2.9 mg and 443 ± 2.2 mg for bioavailable natural P, in participants with eGFR = 60-89 and ≥90 mL · min-1 · 1.73 m-2, respectively. Major sources of total P included fish, milk, beef, eggs, cheese, and poultry; and of added P, fish, beef, processed meat, soft drinks, and poultry. After adjustment for confounders, P intakes, including total (ß ± SE: -0.32 ± 0.15; P = 0.03), added (ß ± SE: -0.73 ± 0.27; P = 0.01), bioavailable total (ß ± SE: -0.62 ± 0.23; P = 0.01), and bioavailable added (ß ± SE: -0.77 ± 0.29; P = 0.01), were significantly associated with lower eGFR. However, neither total nor bioavailable P from natural sources were associated with eGFR. CONCLUSIONS: Added, but not natural, P was negatively associated with kidney function, raising concern about P additives in the food supply. Further studies are needed to improve estimation of dietary P exposure and to clarify the role of added P as a risk factor for kidney disease.

Geriatric Assessment Reveals Actionable Impairments in Hematopoietic Stem Cell Transplantation Candidates Age 18 to 80 Years.

Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for both malignant and nonmalignant hematologic diseases; however, reported rates of treatment-related mortality approach 30%. Outcomes are worse in patients who begin HCT with functional impairments. To detect such impairments, a geriatric assessment (GA) is recommended in adults age ≥65 years. Younger HCT candidates also may be impaired because of chemotherapy regimens pre-HCT. Therefore, we hypothesized that GA can be beneficial for adult patients of all ages and subsequently created a clinical pretransplantation optimization program to assess all HCT candidates using a modified GA. One-hundred fifty-seven patients were evaluated in 4 functional domains- physical, cognitive, nutritional, and psychological-at 2 time points prior to HCT-new patient evaluation (NPE) and sign-off (SO)-between October 2017 and January 2020. At NPE, 80.9% of the patients had at least 1 domain with a functional impairment, and physical (P = .006), cognitive (P = .04), and psychological (P = .04) impairments were associated with an increased likelihood of not proceeding to HCT. In addition, patients age 18 to 39 years were more likely than older patients to have a physical function impairment (P = .001). Between NPE and SO, 51.9% of the patients had resolution of 1 or more impairments, and nutritional impairment at SO was predictive of worse overall survival (P = .01). Our study shows that GA can identify functional impairments in patients of all ages. Early identification of impairments could facilitate referrals to supportive care and resolution of impairments prior to HCT, suggesting that GA could be recommended for HCT candidates of all ages.

Weight loss via a low-carbohydrate diet improved the intestinal permeability marker, zonulin, in prostate cancer patients.

BACKGROUND: Accumulating evidence suggest that gut microbiota may impact urologic health including prostate cancer (PC), potentially via affecting intestinal permeability (IP). Studies have indicated that disrupted IP may be improved by healthy diets and weight loss. In the Carbohydrate and Prostate Study 2 (CAPS2) clinical trial, which showed that a low-carbohydrate diet (LCD) reduced weight significantly in men with PC and suggestively slowed PC disease progression, we explored the impact of LCD on an IP marker, zonulin and an inflammation marker, high sensitivity C-reactive protein (hsCRP). METHODS: CAPS2 was a 6-month randomized controlled trial testing a LCD intervention vs. control on PC progression using prostate-specific antigen doubling time (PSADT) as the marker. All 45 participants had prior primary PC treatment, PSADT >3 and <36 months, and body mass index (BMI) ≥24 kg/m2. RESULTS: At 6-month, zonulin decreased in the LCD arm (median -8.3%, IQR -16.6, 0.3%) while the control increased slightly (median 1.4%, IQR -3.0, 13.3%; p = .014). No changes were observed in hsCRP. Linear regression models showed that weight change was significantly associated with log(PSADT) such that the greater the weight loss, the longer the PSADT(p = .003). There was a similar inverse trend between change in zonulin and log(PSADT) (p = .050). Nevertheless, the mediation analysis showed that zonulin was not a significant intermediary mechanism of the effect of weight change on PSADT (p = .3). CONCLUSION: Future studies are merited to examine further the potential association of IP with inflammation and to clarify if improvement in IP is associated with decreased PC progression. Trial registration: NCT01763944. KEY MESSAGESGut microbiota may impact urologic health including prostate cancer, potentially via affecting intestinal permeability.Weight loss significantly improved intestinal permeability in prostate cancer patients.Improvement in intestinal permeability was associated with slowed prostate cancer progression as indicated by the PSA doubling time.

Cerebrovascular Function, Vascular Risk, and Lifestyle Patterns in Resistant Hypertension.

BACKGROUND: Impaired cerebrovascular reactivity (CVR) and blunted cerebral hemodynamic recruitment are thought to be important mechanisms linking hypertension to cerebrovascular and cognitive outcomes. Few studies have examined cardiovascular or dietary correlates of CVR among hypertensives. OBJECTIVE: To delineate associations between cardiometabolic risk, diet, and cerebrovascular functioning among individuals with resistant hypertension from the TRIUMPH trial (n = 140). METHODS: CVR was assessed by examining changes in tissue oxygenation (tissue oxygenation index [TOI] and oxygenated hemoglobin [HBO2]) using functional near-infrared spectroscopy (fNIRS) during a breath holding test, a standardized CVR assessment to elicit a hypercapnic response. Participants also underwent fNIRS during three cognitive challenge tasks. Vascular function was assessed by measurement of brachial artery flow-mediated dilation and hyperemic flow response. Cardiometabolic fitness was assessed from peak VO2 on an exercise treadmill test and body mass index. Dietary patterns were quantified using the DASH eating score. Cognitive function was assessed using a 45-minute test battery assessing Executive Function, Processing Speed, and Memory. RESULTS: Greater levels fitness (B = 0.30, p = 0.011), DASH compliance (B = 0.19, p = 0.045), and lower obesity (B = -0.30, p = 0.004), associated with greater changes in TOI, whereas greater flow-mediated dilation (B = 0.19, p = 0.031) and lower stroke risk (B = -0.19, p = 0.049) associated with greater HBO2. Similar associations were found for cerebral hemodynamic recruitment, and associations between CVR and cognition were moderated by duration of hypertension. CONCLUSION: Impaired CVR elevated cardiometabolic risk, obesity, vascular function, and fitness among hypertensives.

Serum metabolomic analysis of men on a low-carbohydrate diet for biochemically recurrent prostate cancer reveals the potential role of ketogenesis to slow tumor growth: a secondary analysis of the CAPS2 diet trial.

BACKGROUND: Systemic treatments for prostate cancer (PC) have significant side effects. Thus, newer alternatives with fewer side effects are urgently needed. Animal and human studies suggest the therapeutic potential of low carbohydrate diet (LCD) for PC. To test this possibility, Carbohydrate and Prostate Study 2 (CAPS2) trial was conducted in PC patients with biochemical recurrence (BCR) after local treatment to determine the effect of a 6-month LCD intervention vs. usual care control on PC growth as measured by PSA doubling time (PSADT). We previously reported the LCD intervention led to significant weight loss, higher HDL, and lower triglycerides and HbA1c with a suggested longer PSADT. However, the metabolic basis of these effects are unknown. METHODS: To identify the potential metabolic basis of effects of LCD on PSADT, serum metabolomic analysis was performed using baseline, month 3, and month 6 banked sera to identify the metabolites significantly altered by LCD and that correlated with varying PSADT. RESULTS: LCD increased the serum levels of ketone bodies, glycine and hydroxyisocaproic acid. Reciprocally, LCD reduced the serum levels of alanine, cytidine, asymmetric dimethylarginine (ADMA) and 2-oxobutanoate. As high ADMA level is shown to inhibit nitric oxide (NO) signaling and contribute to various cardiovascular diseases, the ADMA repression under LCD may contribute to the LCD-associated health benefit. Regression analysis of the PSADT revealed a correlation between longer PSADT with higher level of 2-hydroxybutyric acids, ketone bodies, citrate and malate. Longer PSADT was also associated with LCD reduced nicotinamide, fructose-1, 6-biphosphate (FBP) and 2-oxobutanoate. CONCLUSION: These results suggest a potential association of ketogenesis and TCA metabolites with slower PC growth and conversely glycolysis with faster PC growth. The link of high ketone bodies with longer PSADT supports future studies of ketogenic diets to slow PC growth.