Survival of Patients with Colorectal Liver Metastases after Transarterial Chemoembolization Using Irinotecan-Eluting Microspheres: A Single-Center Retrospective Analysis Comparing RECIST 1.1 and Choi Criteria.

PURPOSE: To evaluate the factors that affected overall survival and hepatic progression-free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Choi criteria in patients with colorectal liver metastases treated with transarterial chemoembolization (TACE) using irinotecan-eluting microspheres (IEMs) who failed at least 1 line of systemic chemotherapy. MATERIALS AND METHODS: A single-institution retrospective analysis was performed including patients with unresectable liver metastases from a colorectal primary malignancy and treated with IEM-TACE. Radiologic hepatic progression-free survival was measured using the RECIST 1.1 and Choi criteria. RESULTS: The median patient age was 61.5 years, with 80 (67%) men. A total of 328 IEM-TACE procedures were performed during the study period. One hundred eighteen patients who failed at least 1 line of systemic chemotherapy before TACE demonstrated a median overall survival of 12.7 months. Overall survival was higher in patients who had previous primary resection (P < .05), prior ablation (P < .05), or completed the scheduled TACE treatments (P < .05) but was adversely affected by the presence of extrahepatic disease (P < .05) and larger preprocedural tumor burden (P < .01). Prior systemic chemotherapy lines (P = .98) and microsphere size (P = .34) did not affect survival. Partial radiologic response to treatment using the Choi criteria (n = 28, P < .01) correlated significantly with survival, a correlation not seen with the RECIST 1.1 measurements (n = 5, P = .13). CONCLUSIONS: A partial response to treatment of unresectable colorectal liver metastases treated by TACE with IEMs measured using the Choi criteria correlated significantly with improved survival, while RECIST 1.1 measurements did not.

A Meta-Analysis of 46 Studies Identified by the FDA Demonstrates that Soy Protein Decreases Circulating LDL and Total Cholesterol Concentrations in Adults.

BACKGROUND: Certain plant foods (nuts and soy protein) and food components (viscous fibers and plant sterols) have been permitted by the FDA to carry a heart health claim based on their cholesterol-lowering ability. The FDA is currently considering revoking the heart health claim for soy protein due to a perceived lack of consistent LDL cholesterol reduction in randomized controlled trials. OBJECTIVE: We performed a meta-analysis of the 46 controlled trials on which the FDA will base its decision to revoke the heart health claim for soy protein. METHODS: We included the 46 trials on adult men and women, with baseline circulating LDL cholesterol concentrations ranging from 110 to 201 mg/dL, as identified by the FDA, that studied the effects of soy protein on LDL cholesterol and total cholesterol (TC) compared with non-soy protein. Two independent reviewers extracted relevant data. Data were pooled by the generic inverse variance method with a random effects model and expressed as mean differences with 95% CI. Heterogeneity was assessed and quantified. RESULTS: Of the 46 trials identified by the FDA, 43 provided data for meta-analyses. Of these, 41 provided data for LDL cholesterol, and all 43 provided data for TC. Soy protein at a median dose of 25 g/d during a median follow-up of 6 wk decreased LDL cholesterol by 4.76 mg/dL (95% CI: -6.71, -2.80 mg/dL, P < 0.0001; I2 = 55%, P < 0.0001) and decreased TC by 6.41 mg/dL (95% CI: -9.30, -3.52 mg/dL, P < 0.0001; I2 = 74%, P < 0.0001) compared with non-soy protein controls. There was no dose-response effect or evidence of publication bias for either outcome. Inspection of the individual trial estimates indicated most trials (∼75%) showed a reduction in LDL cholesterol (range: -0.77 to -58.60 mg/dL), although only a minority of these were individually statistically significant. CONCLUSIONS: Soy protein significantly reduced LDL cholesterol by approximately 3-4% in adults. Our data support the advice given to the general public internationally to increase plant protein intake. This trial was registered at clinicaltrials.gov as NCT03468127.

Relation of total sugars, fructose and sucrose with incident type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Sugar-sweetened beverages are associated with type 2 diabetes. To assess whether this association holds for the fructose-containing sugars they contain, we conducted a systematic review and meta-analysis of prospective cohort studies. METHODS: We searched MEDLINE, Embase, CINAHL and the Cochrane Library (through June 2016). We included prospective cohort studies that assessed the relation of fructose-containing sugars with incident type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. We pooled risk ratios (RRs) using random effects meta-analyses. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: Fiffeen prospective cohort studies (251 261 unique participants, 16 416 cases) met the eligibility criteria, comparing the highest intake (median 137, 35.2 and 78 g/d) with the lowest intake (median 65, 9.7 and 25.8 g/d) of total sugars, fructose and sucrose, respectively. Although there was no association of total sugars (RR 0.91, 95% confidence interval [CI] 0.76-1.09) or fructose (RR 1.04, 95% CI 0.84-1.29) with type 2 diabetes, sucrose was associated with a decreased risk of type 2 diabetes (RR 0.89, 95% CI 0.80-0.98). Our confidence in the estimates was limited by evidence of serious inconsistency between studies for total sugars and fructose, and serious imprecision in the pooled estimates for all 3 sugar categories. INTERPRETATION: Current evidence does not allow us to conclude that fructose-containing sugars independent of food form are associated with increased risk of type 2 diabetes. Further research is likely to affect our estimates. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01608620.

Fructose vs. glucose and metabolism: do the metabolic differences matter?

PURPOSE OF REVIEW: Fructose is seen as uniquely contributing to the pandemics of obesity and its cardiometabolic complications. Much of the evidence for this view derives from the unique biochemical, metabolic, and endocrine responses that differentiate fructose from glucose. To understand whether these proposed mechanisms result in clinically meaningful modification of cardiovascular risk in humans, we update a series of systematic reviews and meta-analyses of controlled feeding trials to assess the cardiometabolic effects of fructose in isocaloric replacement for glucose. RECENT FINDINGS: A total of 20 controlled feeding trials (n = 344) have investigated the effect of fructose in/on cardiometabolic endpoints. Pooled analyses show that although fructose may increase total cholesterol, uric acid, and postprandial triglycerides in isocaloric replacement for glucose, it does not appear to be any worse than glucose in its effects on other aspects of the lipid profile, insulin, or markers of nonalcoholic fatty liver disease. It may also have important advantages over glucose for body weight, glycemic control, and blood pressure. SUMMARY: Depending on the cardiometabolic endpoint in question, fructose has variable effects when replacing glucose. In the absence of clear evidence of net harm, there is no justification to replace fructose with glucose in the diet.

The role of glycemic index and glycemic load in cardiovascular disease and its risk factors: a review of the recent literature.

A number of meta-analyses of cohort studies have assessed the impact of glycemic load (GL) and glycemic index (GI) on cardiovascular outcomes. The picture that emerges is that for women, a significant association appears to exist between the consumption of high GL/GI diets and increased cardiovascular disease (CVD) risk. This association appears to be stronger in those with greater adiposity and possibly in those with diabetes, although these findings are not uniform. There is also an indication that raised CRP levels may be reduced, which has special implications for women whose CRP levels, as an emerging CVD risk factor, may be higher than men. For men, the situation is not as clear-cut. Although some studies show association, the meta-analyses have not demonstrated a significant direct association with CVD, despite current evidence that risk factors, including LDL-C, may be reduced on low-GI diets. Moreover, in a recent meta-analysis, increases in dietary GL have been associated with increased risk of diabetes, another CVD risk factor, in both men and women. Studies in men expressing relative risk of CVD in relation to GL and GI, with corresponding confidence intervals, are needed to provide the necessary power for future meta-analyses on this topic.

Pancreas volume measurement in patients with Type 2 diabetes using magnetic resonance imaging-based planimetry.

BACKGROUND/OBJECTIVES: To compare pancreas volume (PV) measurement using MRI-based planimetry in patients with Type 2 diabetes mellitus (DM) to PV in normoglycemic individuals. METHODS: Our institutional review board granted approval of this retrospective study with waiver of informed consent. We searched 2296 consecutive abdominal MRI studies performed at our hospital on patients with no pancreas pathology between September 1, 2010 and February 28, 2013, for those who also had a fasting plasma glucose and/or hemoglobin A1C within six months of the MRI examination. For those patients who met biochemical criteria for DM, we used medication and clinical records to confirm that 32 of these patients had Type 2 DM. The pancreas contours of 32 Type 2 diabetics and 50 normoglycemic individuals were then traced on non-gadolinium T1-weighted 3D fat suppressed gradient echo images by a radiologist trained in abdominal MRI to calculate PV. PV index (PVI) was calculated as PV/weight to adjust PV for each patient's weight. PVs and PVIs in both cohorts were compared using t-tests and regression models correcting for weight, age and gender. RESULTS: Patients with Type 2 DM had significantly lower PVs than normoglycemic individuals (72.7 ± 20.7 cm(3) versus 89.6 ± 22.7 cm(3), p < 0.001), and significantly lower PVIs (1.0 ± 0.3 cm(3)/kg versus 1.3 ± 0.3 cm(3)/kg, p < 0.001). Using regression models, we found that given the same age, weight and gender, the PV in a patient with Type 2 DM was 17.9 mL (20%) lower compared to a normoglycemic individual (p < 0.001). CONCLUSION: PV is reduced in Type 2 DM compared to normoglycemic individuals and can be measured using MRI without contrast injection.

Total fructose intake and risk of hypertension: a systematic review and meta-analysis of prospective cohorts.

OBJECTIVES: Although most controlled feeding trials have failed to show an adverse effect of fructose on blood pressure, concerns continue to be raised regarding the role of fructose in hypertension. To quantify the association between fructose-containing sugar (high-fructose corn syrup, sucrose, and fructose) intake and incident hypertension, a systematic review and meta-analysis of prospective cohort studies was undertaken. METHODS: MEDLINE, EMBASE, CINAHL and the Cochrane Library (through February 5, 2014) were searched for relevant studies. Two independent reviewers reviewed and extracted relevant data. Risk estimates were aggregated comparing the lowest (reference) quintile with highest quintile of intake using inverse variance random effect models and expressed as risk ratios (RR) with 95% confidence intervals (CIs). Interstudy heterogeneity was assessed (Cochran Q statistic) and quantified (I(2) statistic). The Newcastle-Ottawa Scale assessed study quality. Clinicaltrials.gov NCT01608620. RESULTS: Eligibility criteria were met by 3 prospective cohorts (n = 37,375 men and 185,855 women) with 58,162 cases of hypertension observed over 2,502,357 person-years of follow-up. Median fructose intake was 5.7-6.0% total energy in the lowest quintile and 13.9-14.3% total energy in the highest quintile. Fructose intake was not associated with incident hypertension (RR = 1.02, 95% CI, 0.99-1.04), with no evidence of heterogeneity (I(2) = 0%, p = 0.59). Spline curve modeling showed a U-shaped relationship with a negative association at intakes ≤50th percentile (∼10% total energy) and a positive association at higher intakes. CONCLUSIONS: Total fructose intake was not associated with an increased risk of hypertension in 3 large prospective cohorts of U.S. men and women.

Effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Evidence from controlled trials encourages the intake of dietary pulses (beans, chickpeas, lentils and peas) as a method of improving dyslipidemia, but heart health guidelines have stopped short of ascribing specific benefits to this type of intervention or have graded the beneficial evidence as low. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the effect of dietary pulse intake on established therapeutic lipid targets for cardiovascular risk reduction. METHODS: We searched electronic databases and bibliographies of selected trials for relevant articles published through Feb. 5, 2014. We included RCTs of at least 3 weeks' duration that compared a diet emphasizing dietary pulse intake with an isocaloric diet that did not include dietary pulses. The lipid targets investigated were low-density lipoprotein (LDL) cholesterol, apolipoprotein B and non-high-density lipoprotein (non-HDL) cholesterol. We pooled data using a random-effects model. RESULTS: We identified 26 RCTs (n = 1037) that satisfied the inclusion criteria. Diets emphasizing dietary pulse intake at a median dose of 130 g/d (about 1 serving daily) significantly lowered LDL cholesterol levels compared with the control diets (mean difference -0.17 mmol/L, 95% confidence interval -0.25 to -0.09 mmol/L). Treatment effects on apolipoprotein B and non-HDL cholesterol were not observed. INTERPRETATION: Our findings suggest that dietary pulse intake significantly reduces LDL cholesterol levels. Trials of longer duration and higher quality are needed to verify these results. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01594567.

Fructose-containing sugars, blood pressure, and cardiometabolic risk: a critical review.

Excessive fructose intake from high-fructose corn syrup (HFCS) and sucrose has been implicated as a driving force behind the increasing prevalence of obesity and its downstream cardiometabolic complications including hypertension, gout, dyslidpidemia, metabolic syndrome, diabetes, and non-alcoholic fatty liver disease (NAFLD). Most of the evidence to support these relationships draws heavily on ecological studies, animal models, and select human trials of fructose overfeeding. There are a number of biological mechanisms derived from animal models to explain these relationships, including increases in de novo lipogenesis and uric acid-mediated hypertension. Differences between animal and human physiology, along with the supraphysiologic level at which fructose is fed in these models, limit their translation to humans. Although higher level evidence from large prospective cohorts studies has shown significant positive associations comparing the highest with the lowest levels of intake of sugar-sweetened beverages (SSBs), these associations do not hold true at moderate levels of intake or when modeling total sugars and are subject to collinearity effects from related dietary and lifestyle factors. The highest level of evidence from controlled feeding trials has shown a lack of cardiometabolic harm of fructose and SSBs under energy-matched conditions at moderate levels of intake. It is only when fructose-containing sugars or SSBs are consumed at high doses or supplement diets with excess energy that a consistent signal for harm is seen. The available evidence suggests that confounding by excess energy is an important consideration in assessing the role of fructose-containing sugars and SSBs in the epidemics of hypertension and other cardiometabolic diseases.

Effect of fructose on body weight in controlled feeding trials: a systematic review and meta-analysis.

BACKGROUND: The contribution of fructose consumption in Western diets to overweight and obesity in populations remains uncertain. PURPOSE: To review the effects of fructose on body weight in controlled feeding trials. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through 18 November 2011). STUDY SELECTION: At least 3 reviewers identified controlled feeding trials lasting 7 or more days that compared the effect on body weight of free fructose and nonfructose carbohydrate in diets providing similar calories (isocaloric trials) or of diets supplemented with free fructose to provide excess energy and usual or control diets (hypercaloric trials). Trials evaluating high-fructose corn syrup (42% to 55% free fructose) were excluded. DATA EXTRACTION: The reviewers independently reviewed and extracted relevant data; disagreements were reconciled by consensus. The Heyland Methodological Quality Score was used to assess study quality. DATA SYNTHESIS: Thirty-one isocaloric trials (637 participants) and 10 hypercaloric trials (119 participants) were included; studies tended to be small (<15 participants), short (<12 weeks), and of low quality. Fructose had no overall effect on body weight in isocaloric trials (mean difference, -0.14 kg [95% CI, -0.37 to 0.10 kg] for fructose compared with nonfructose carbohydrate). High doses of fructose in hypercaloric trials (+104 to 250 g/d, +18% to 97% of total daily energy intake) lead to significant increases in weight (mean difference, 0.53 kg [CI, 0.26 to 0.79 kg] with fructose). LIMITATIONS: Most trials had methodological limitations and were of poor quality. The weight-increasing effect of fructose in hypercaloric trials may have been attributable to excess energy rather than fructose itself. CONCLUSION: Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories. Free fructose at high doses that provided excess calories modestly increased body weight, an effect that may be due to the extra calories rather than the fructose. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research. (ClinicalTrials.gov registration number: NCT01363791).

The effects of fructose intake on serum uric acid vary among controlled dietary trials.

Hyperuricemia is linked to gout and features of metabolic syndrome. There is concern that dietary fructose may increase uric acid concentrations. To assess the effects of fructose on serum uric acid concentrations in people with and without diabetes, we conducted a systematic review and meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials (through August 19, 2011). Analyses included all controlled feeding trials ≥ 7 d investigating the effect of fructose feeding on uric acid under isocaloric conditions, where fructose was isocalorically exchanged with other carbohydrate, or hypercaloric conditions, and where a control diet was supplemented with excess energy from fructose. Data were aggregated by the generic inverse variance method using random effects models and expressed as mean difference (MD) with 95% CI. Heterogeneity was assessed by the Q statistic and quantified by I(2). A total of 21 trials in 425 participants met the eligibility criteria. Isocaloric exchange of fructose for other carbohydrate did not affect serum uric acid in diabetic and nondiabetic participants [MD = 0.56 µmol/L (95% CI: -6.62, 7.74)], with no evidence of inter-study heterogeneity. Hypercaloric supplementation of control diets with fructose (+35% excess energy) at extreme doses (213-219 g/d) significantly increased serum uric acid compared with the control diets alone in nondiabetic participants [MD = 31.0 mmol/L (95% CI: 15.4, 46.5)] with no evidence of heterogeneity. Confounding from excess energy cannot be ruled out in the hypercaloric trials. These analyses do not support a uric acid-increasing effect of isocaloric fructose intake in nondiabetic and diabetic participants. Hypercaloric fructose intake may, however, increase uric acid concentrations. The effect of the interaction of energy and fructose remains unclear. Larger, well-designed trials of fructose feeding at "real world" doses are needed.

'Catalytic' doses of fructose may benefit glycaemic control without harming cardiometabolic risk factors: a small meta-analysis of randomised controlled feeding trials.

Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, 'catalytic' doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of 'catalytic' doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring 'catalytic' fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I 2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. 'Catalytic' doses of fructose significantly reduced HbA1c (MD - 0·40, 95 % CI - 0·72, - 0·08) and fasting glucose (MD - 0·25, 95 % CI - 0·44, - 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that 'catalytic' fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using 'catalytic' fructose to confirm these results.

Gut microbiota, diet, and heart disease.

Modulation of the gut microbiota is an area of growing interest, particularly for its link to improving and maintaining the systemic health of the host. It has been suggested to have potential to reduce risk factors associated with chronic diseases, such as elevated cholesterol levels in coronary heart disease (CHD). Diets of our evolutionary ancestors were largely based on plant foods, high in dietary fiber and fermentable substrate, and our gut microbiota has evolved against a background of such diets. Therapeutic diets that mimic plant-based diets from the early phases of human evolution may result in drug-like cholesterol reductions. In contrast, typical Western diets low in dietary fiber and fermentable substrate, and high in saturated and trans fatty acids, are likely contributors to the increased need for pharmacological agents for cholesterol reduction. The gut microbiota of those consuming a Western diet are likely underutilized and depleted of metabolic fuels, resulting in a less than optimal gut microbial profile. As a result, this diet is mismatched to our archaic gut microbiota and, therefore, to our genome, which has changed relatively little since humans first appeared. While the exact mechanism by which the gut microbiota may modulate cholesterol levels still remains uncertain, end products of bacterial fermentation, particularly the short chain fatty acids (i.e., propionate), have been suggested as potential candidates. While more research is required to clarify the potential link between gut microbiota and CHD risk reduction, consuming a therapeutic diet rich in plant foods, dietary fiber, and fermentable substrate would be a useful strategy for improving systemic health, possibly by altering the gut microbiota.

Glycemic Index Versus Wheat Fiber on Arterial Wall Damage in Diabetes: A Randomized Controlled Trial.

OBJECTIVE: High cereal fiber and low-glycemic index (GI) diets are associated with reduced cardiovascular disease (CVD) risk in cohort studies. Clinical trial evidence on event incidence is lacking. Therefore, to make trial outcomes more directly relevant to CVD, we compared the effect on carotid plaque development in diabetes of a low-GI diet versus a whole-grain wheat-fiber diet. RESEARCH DESIGN AND METHODS: The study randomized 169 men and women with well-controlled type 2 diabetes to counseling on a low GI-diet or whole-grain wheat-fiber diet for 3 years. Change in carotid vessel wall volume (VWV) (prespecified primary end point) was assessed by MRI as an indication of arterial damage. RESULTS: Of 169 randomized participants, 134 completed the study. No treatment differences were seen in VWV. However, on the whole-grain wheat-fiber diet, VWV increased significantly from baseline, 23 mm3 (95% CI 4, 41; P = 0.016), but not on the low-GI diet, 8 mm3 (95% CI -10, 26; P = 0.381). The low-GI diet resulted in preservation of renal function, as estimated glomerular filtration rate, compared with the reduction following the wheat-fiber diet. HbA1c was modestly reduced over the first 9 months in the intention-to-treat analysis and extended with greater compliance to 15 months in the per-protocol analysis. CONCLUSIONS: Since the low-GI diet was similar to the whole-grain wheat-fiber diet recommended for cardiovascular risk reduction, the low-GI diet may also be effective for CVD risk reduction.

The application of the glycemic index and glycemic load in weight loss: A review of the clinical evidence.

Obesity is rapidly becoming a global epidemic. As it is a significant risk factor for several chronic diseases, including type 2 diabetes and cardiovascular disease, it is imperative to study dietary and lifestyle approaches that help reduce its prevalence. Recently, due to its possible link to appetite control and metabolism, several clinical studies have assessed the effect of low glycemic index (GI) and glycemic load (GL) diets on weight loss. To determine the application of GI/GL in the prevention and treatment of obesity, we searched several databases and identified 23 clinical trials that examined low GI/GL diets and weight loss as the primary outcome measure. In general, these studies showed much inconsistency in their findings. While a few studies found significantly greater weight loss on the low GI/GL diets, most of the other studies showed a non-significant trend that favored low GI/GL diets; suggesting that factors other than GI/GL may play a role. It would be helpful if a pooled analysis were undertaken to clarify the current findings and outline the limitations of these studies. There is also a need for more long-term randomized, controlled trials that not only focus on weight loss but also on weight maintenance and body composition.

Health effects of mixed fruit and vegetable concentrates: a systematic review of the clinical interventions.

Diets rich in fruits and vegetables (FV) have been associated with a reduced risk of chronic disease, including cardiovascular disease. Unfortunately, public health campaigns to increase FV intake have had limited success. A number of mixed concentrated FV products have been studied, which may help certain individuals improve nutrient status. However, the possible health benefits of FV supplements have not been systematically reviewed. We, therefore, undertook a systematic search of MEDLINE and EMBASE to identify clinical interventions that examined the effect of commercially available concentrated mixed FV supplements on cardiovascular disease risk factors. Twenty-two reports, which used commercially available products, were identified. None of the studies reported any serious adverse effects. Overall, daily consumption of FV supplements significantly increased serum concentrations of the major antioxidant provitamins and vitamins found in plant foods (ß-carotene, vitamins C and E) and folate. Functional changes, such as reduced serum homocysteine and markers of protein, lipid, and DNA oxidation, were also reported; in addition, the health advantages on markers of inflammation, immunity, and endothelial function are promising. Limitations of the available studies were related to the diversity of studies conducted with respect to design and study population and the variability in the measured outcomes and assays utilized. While mixed FV supplements may serve as an efficacious complement for individuals who have difficulty achieving their daily FV intake requirement, further research on additional retail preparations is warranted. Key teaching points: Mixed fruit and vegetable supplements produced from plant foods may serve as an efficacious complement to the habitual diet in individuals who have suboptimal intake or variety of nutrient-dense fruits and vegetables. Current research indicates that fruit and vegetable concentrates significantly increase serum levels of antioxidant provitamins and vitamins (ß-carotene, vitamins C and E) and folate and reduce homocysteine and markers of oxidative stress. Mechanistic studies and larger, randomized, placebo-controlled double-blind trials in both healthy and high-risk populations are necessary to better understand the health effects of these supplements.

Randomized Controlled Trial of Percutaneous Radiologic Gastrostomy Performed With and Without Gastropexy: Technical Success, Patient-Reported Outcomes and Safety.

PURPOSE: The aim of this study is to compare balloon-retention percutaneous radiologic gastrostomy (PRG) tube insertion performed with and without gastropexy, primarily focusing on pain and patient-reported outcomes. MATERIALS AND METHODS: Research ethics board approved a dual-arm, single-centre, randomized trial of 60 patients undergoing primary 14-French PRG tube insertion (NCT04107974). Patients were randomized to receive either PRG with gastropexy or without gastropexy. Data were collected for technical outcomes, patient-reported outcomes pre-procedure, post-procedure and at 1-month, as well as quality of life parameters at 1-month post-procedure (EQ5D-5L, Visual Analogue Scale and Functional Assessment of Cancer Therapy-Enteral Feeding questionnaires). Complications occurring up to 6-months post-procedure were recorded. RESULTS: Sixty patients were randomized to the gastropexy group (n = 30) or non-gastropexy (n = 30) group. One non-gastropexy patient was withdrawn from the study due to failed insertion. PRG procedural time was significantly longer when using gastropexy (mean 11.4 ± 7.19 min) compared with non-gastropexy (mean 6.79 ± 4.63 min; p < 0.05). Pain scores did not differ between the two groups pre-procedure, post-procedure and at 1-month follow-up, nor did 1-month quality of life parameters. Six (20%) minor complications occurred in the gastropexy group and nine (31%) minor complications in the non-gastropexy group (p = 0.330). Two (6.9%) major complications occurred in the non-gastropexy group (p = 0.458). CONCLUSION: There is comparable patient tolerability when balloon-retention PRG insertion is performed with or without gastropexy sutures. This study also demonstrated a trend towards fewer complications when gastropexy is utilized. However, further larger trials are required to compare complications of the two approaches for PRG insertion. LEVEL OF EVIDENCE: Level 2, randomized trial.

Effect of low glycaemic index or load dietary patterns on glycaemic control and cardiometabolic risk factors in diabetes: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To inform the update of the European Association for the Study of Diabetes clinical practice guidelines for nutrition therapy. DESIGN: Systematic review and meta-analysis of randomised controlled trials. DATA SOURCES: Medline, Embase, and the Cochrane Library searched up to 13 May 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials of three or more weeks investigating the effect of diets with low glycaemic index (GI)/glycaemic load (GL) in diabetes. OUTCOME AND MEASURES: The primary outcome was glycated haemoglobin (HbA1c). Secondary outcomes included other markers of glycaemic control (fasting glucose, fasting insulin); blood lipids (low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), non-HDL-C, apo B, triglycerides); adiposity (body weight, BMI (body mass index), waist circumference), blood pressure (systolic blood pressure (SBP) and diastolic blood pressure (DBP)), and inflammation (C reactive protein (CRP)). DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. Data were pooled by random effects models. GRADE (grading of recommendations assessment, development, and evaluation) was used to assess the certainty of evidence. RESULTS: 29 trial comparisons were identified in 1617 participants with type 1 and 2 diabetes who were predominantly middle aged, overweight, or obese with moderately controlled type 2 diabetes treated by hyperglycaemia drugs or insulin. Low GI/GL dietary patterns reduced HbA1c in comparison with higher GI/GL control diets (mean difference −0.31% (95% confidence interval −0.42 to −0.19%), P<0.001; substantial heterogeneity, I2=75%, P<0.001). Reductions occurred also in fasting glucose, LDL-C, non-HDL-C, apo B, triglycerides, body weight, BMI, systolic blood pressure (dose-response), and CRP (P<0.05), but not blood insulin, HDL-C, waist circumference, or diastolic blood pressure. A positive dose-response gradient was seen for the difference in GL and HbA1c and for absolute dietary GI and SBP (P<0.05). The certainty of evidence was high for the reduction in HbA1c and moderate for most secondary outcomes, with downgrades due mainly to imprecision. CONCLUSIONS: This synthesis suggests that low GI/GL dietary patterns result in small important improvements in established targets of glycaemic control, blood lipids, adiposity, blood pressure, and inflammation beyond concurrent treatment with hyperglycaemia drugs or insulin, predominantly in adults with moderately controlled type 1 and type 2 diabetes. The available evidence provides a good indication of the likely benefit in this population. STUDY REGISTRATION: ClinicalTrials.gov NCT04045938.

Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms.

The apparently smaller LDL cholesterol (LDL-C)-lowering effect of soy in recent studies has prompted the U.S. FDA to reexamine the heart health claim previously allowed for soy products. We therefore attempted to estimate the intrinsic and extrinsic (displacement) potential of soy in reducing LDL-C to determine whether the heart health claim for soy continues to be justified. The intrinsic effect of soy was derived from a meta-analysis using soy studies (20-133 g/d soy protein) included in the recent AHA Soy Advisory. The extrinsic effect of soy in displacing foods higher in saturated fat and cholesterol was estimated using predictive equations for LDL-C and NHANES III population survey data with the substitution of 13-58 g/d soy protein for animal protein foods. The meta-analysis of the AHA Soy Advisory data gave a mean LDL-C reduction of 0.17 mmol/L (n = 22; P < 0.0001) or 4.3% for soy, which was confirmed in 11 studies reporting balanced macronutrient profiles. The estimated displacement value of soy (13-58 g/d) using NHANES III population survey data was a 3.6-6.0% reduction in LDL-C due to displacement of saturated fats and cholesterol from animal foods. The LDL-C reduction attributable to the combined intrinsic and extrinsic effects of soy protein foods ranged from 7.9 to 10.3%. Thus, soy remains one of a few food components that reduces serum cholesterol (>4%) when added to the diet.

Intersection between sleep and neurovascular coupling as the driving pathophysiology of Alzheimer's disease.

Alzheimer's disease (AD) is the commonest cause of dementia. There are tremendous personal and systemic costs associated with the disease. Although there has been significant progress in understanding the disease process, the precise pathophysiologic mechanism remains elusive. The amyloid hypothesis is the leading theory with impaired clearance of the amyloid beta (Aß) believed to be the underpinning disease process. However, what triggers and propagates the accumulation of Aß remains unclear. We propose that the impairment of neurovascular coupling triggers a cascade that ultimately leads to impaired Aß clearance. With aging there is a generalized decline in cerebral blood flow and impairment of cerebrovascular reactivity. With impairment of this neurovascular coupling, the normal bulk clearance of cerebrospinal fluid and interstitial fluid (ISF) becomes hindered. We postulate that this clearance process occurs during non-rapid eye movement slow wave sleep, driven by the tight neurovascular coupling, via a pump-like action. The impairment of ISF clearance results in change in the interstitial microenvironment from accumulation of metabolites, reactive oxygen species, metal ions and results in decreased pH. The changes in the microenvironment promotes the accumulation and aggregation of Aß, heralding the disease process.