Lowest Tertile Group Research Articles

Fasting serum free glycerol concentration is a potential surrogate marker of visceral obesity and insulin sensitivity in middle-aged Japanese men

Triglyceride (TG) is a tri-ester composed of a glycerol and 3 fatty acids. Degradation of TG in adipose tissue is increased in the fasting state but inhibited in the postprandial state. Although insulin suppresses adipose TG degradation, patients with insulin resistance have high concentrations of insulin and free glycerol (FG) in the fasting state. We examined whether the fasting FG concentration reflects visceral obesity and insulin sensitivity in middle-aged Japanese men. We measured the fasting serum FG concentration in 72 males aged 30 to 50years using a simple enzymatic method. The subjects were divided into tertiles according to their homeostasis model assessment of insulin resistance (HOMA-IR). Besides routine glucose- and lipid-related parameters, we determined insulin sensitivity as the rate of glucose disappearance in a 2-step hyperinsulinemic-euglycemic clamp and the abdominal visceral fat area (VFA) by magnetic resonance imaging. The highest HOMA-IR tertile group had a higher fasting FG concentration than the middle- and lowest-tertile groups (0.077±0.024 vs 0.063±0.017 and 0.061±0.016mmol/L, P<.05 and P<.01). The FG concentration was positively correlated with VFA (rs=0.36; P<.01) and the HOMA-IR score (rs=0.26, P<.05) but negatively correlated with insulin sensitivity (rs=-0.26, P<.05). Multivariate regression analysis revealed that the FG concentration is independently associated with VFA and insulin sensitivity. The fasting FG concentration reflects VFA and insulin sensitivity in middle-aged Japanese men. The fasting FG concentration may be a potential surrogate marker of visceral obesity and insulin resistance in outpatients.

P0673INVERSE ASSOCIATION OF TRANSFERRIN SATURATION WITH MORTALITY RISK IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Transferrin saturation (TSAT) is an indicator of iron deficiency or overload, but its relationship with mortality in patients with different stages of chronic kidney disease (CKD) is unclear. We investigated the association of TSAT with mortality in CKD patients. Method In 479 CKD patients (97 CKD3-4 patients, 298 CKD5 non-dialysis patients and 84 peritoneal dialysis patients; median age 58 years, 67% males, 33% cardiovascular disease, CVD, and 29% diabetes), biomarkers of iron status (plasma iron, TSAT, transferrin and ferritin), systemic inflammation (high sensitivity C-reactive protein, hsCRP, and interleukin-6, IL-6) and nutritional status were assessed. During median follow-up of 35.6 months, 139 (29%) patients died, and 176 (37%) patients underwent renal transplantation. Patients were stratified into low (n=157) and high (n=322) TSAT tertile groups. All-cause and CVD mortality risk were analyzed with competing risk regression with renal transplantation as competing risk. Results TSAT [median 23% (IQR 17-30%)] was negatively associated with presence of DM and CVD, body mass index, hsCRP, IL-6, Framingham´s CVD risk score (FRS), erythropoietin resistance index (ERI) and iron supplementation, and positively associated with hemoglobin, ferritin and s-albumin. In competing risk analysis, low tertile of TSAT was independently associated with increased all-cause mortality risk (sHR=1.50, 95%CI 1.05-2.14) after adjusting for CKD stages, 1-SD of FRS, 1-SD of hemoglobin, 1-SD of hsCRP, 1-SD of ESA dose and iron supplementation (Figure 1). Conclusion TSAT was inversely associated with mortality risk in CKD patients. When evaluating clinical outcomes of CKD patients, iron status using TSAT as a predictive marker, should be considered.

Shining the light on abortion: Drivers of online abortion searches across the United States in 2018

ContextLegal abortion restrictions, stigma and fear can inhibit people’s voices in clinical and social settings posing barriers to decision-making and abortion care. The internet allows individuals to make informed decisions privately. We explored what state-level policy dimensions were associated with volume of Google searches on abortion and on the abortion pill in 2018.MethodsWe used Google Trends to quantify the relative search volume (RSV) for “abortion” and “abortion pill” (or “abortion pills” hereafter referred to as “abortion pill”) as a proportion of total search volume for all queries in each US state. We also identified the top search queries most related to “abortion” and “abortion pill” and considered these as indicators of population concern. Key exposures were healthcare cost, access and health outcomes, and number of legal restrictions and protections at the state level. In descriptive analyses, we first grouped the states into tertiles according to their RSV on “abortion” and “abortion pill”. To examine the association between each exposure (and other covariates) with the two outcomes, we used unadjusted and adjusted linear regression.ResultsThe average RSV for “abortion” in the low, moderate and high tertile groups was 48 (SD = 3.25), 55.5 (SD = 2.11) and 64 (SD = 4.72) (p-value <0.01) respectively; for “abortion pill” the average RSVs were 39.6 (SD = 16.68), 61.9 (SD = 5.82) and 81.7 (SD = 6.67) (p-value < 0.01) respectively. Concerns about contraceptive availability and access, and unplanned pregnancies independently predicted the relative search volumes for abortion and abortion pill. According to our baseline models, states with low contraceptive access had far higher abortion searches. Volume of abortion pill searches was additionally positively associated with poor health outcomes, poor access to abortion facilities and non-rurality.ConclusionSearch traffic analysis can help discern abortion-policy influences on population concerns and require close monitoring. State-policies can predict search volume for abortion and abortion pill. In 2018, concerns about contraceptives and unplanned pregnancies, predicted abortion searches. Current decreases in public contraceptive funding and the Title X Gag rule designed to block millions of people from getting care at Planned Parenthood, the largest provider of birth control and abortion care, may increase concerns about unintended pregnancies that can lead to increases in online relative volume of abortion searches.

A Digital Health Weight Loss Program in 250,000 Individuals.

Objective To evaluate whether individuals following a weight loss program based on a mobile application, wireless scale, and nutritional program but no face-to-face care can achieve clinically significant weight loss in a large cohort. Design Retrospective observational analysis. Setting. China from October 2016 to December 2017. Participants. Mobile application users with a minimum of 2 weights (baseline and ≥35 days). Intervention. A commercial (Weijian Technologies) weight loss program consisting of a dietary replacement, self-monitoring using a wireless home scale, and frequent guidance via mobile application. Main Outcome. Mean weight change around 42, 60, 90, and 120 days after program initiation with subgroup analysis by gender, age, and frequency of use. Results 251,718 individuals, with a mean age of 37.3 years (SD: 9.86) (79% female), were included with a mean weight loss of 4.3 kg (CI: ±0.02) and a mean follow-up of 120 days (SD: 76.8 days). Mean weight loss at 42, 60, 90, and 120 d was 4.1 kg (CI: ±0.02), 4.9 kg (CI: ±0.02), 5.6 kg (CI: ±0.03), and 5.4 kg (CI: ±0.04), respectively. At 120 d, 62.7% of participants had lost at least 5% of their initial weight. Both genders and all usage frequency tertiles showed statistically significant weight loss from baseline at each interval (P < 0.001), and this loss was greater in men than in women (120 d: 6.5 vs. 5.2 kg; P < 0.001). The frequency of recording (categorized as high-, medium-, or low-frequency users) was associated with greater weight loss when comparing high, medium, and low tertile use groups at all time intervals investigated (e.g., 120 d: −8.6, −5.6, and −2.2 kg, respectively; P < 0.001). Conclusions People following a commercially available hybrid weight loss program using a mobile application, wireless scale, and nutritional program without face-to-face interaction on average achieved clinically significant short- and midterm weight loss. These results support the implementation of comparable technologies for weight control in a large population.

Association Between Serum Bilirubin and the Progression of Carotid Atherosclerosis in Type 2 Diabetes.

ObjectiveThis study investigated whether serum bilirubin levels can predict the progression of carotid atherosclerosis in individuals with type 2 diabetes mellitus (T2DM).MethodsThis observational study included 1,381 subjects with T2DM in whom serial measurements of carotid intima-media thickness (CIMT) were made at 1- to 2-year intervals for 6–8 years. The progression of carotid atherosclerosis was defined as newly detected plaque lesions on repeat ultrasonography. After dividing total serum bilirubin levels into tertiles, the association between total serum bilirubin at baseline and plaque progression status was analyzed.ResultsAmong 1,381 T2DM patients, 599 (43.4%) were categorized as having plaque progression in their carotid arteries. Those with plaque progression were significantly older; showed a higher prevalence of hypertension, abdominal obesity, and chronic kidney disease; and had a longer duration of T2DM, higher levels of total cholesterol (TC), triglycerides, and insulin resistance, and lower total bilirubin concentrations than those with no plaque progression. When total serum bilirubin levels were divided into tertiles, the highest tertile group was younger than the lowest tertile group, with higher levels of TC and high-density lipoprotein cholesterol. Multiple logistic regression analysis demonstrated that higher serum bilirubin levels were associated with a significantly lower risk of CIMT progression (odds ratio, 0.584; 95% confidence interval, 0.392–0.870; p=0.008). Age (p<0.001), body mass index (p=0.023), and TC (p=0.019) were also associated with the progression of carotid atherosclerosis in T2DM patients.ConclusionTotal serum bilirubin is independently associated with progression of atherosclerosis in the carotid arteries in T2DM patients.

Platelet-to-lymphocyte ratio is a predictor of long-term mortality in patients with acute coronary syndrome.

IntroductionAtherosclerosis is a chronic inflammatory process and inflammation is an important component of acute coronary syndrome (ACS). Platelet-to-lymphocyte ratio (PLR) is a useful parameter showing the degree of the inflammatory response.AimTo explore the association between PLR and long-term mortality in patients with ACS.Material and methodsA total of 538 patients who had a diagnosis of ACS between January 2012 and August 2013 were followed up to 60 months. On admission, blood sampling to calculate PLR and detailed clinical data were obtained.ResultsIn total, 538 patients with a mean age of 61.5 ±13.1 years (69% male) were enrolled in the study. Median follow-up was 79 months (IQR: 74–83 months). Patients were divided into 3 tertiles based on PLR levels. Five-year mortality of the patients was significantly higher among patients in the upper PLR tertile when compared with the lower and middle PLR tertile groups (55 (30.7%) vs. 27 (15.0%) and 34 (19.0%); p < 0.001, p = 0.010 respectively). In the Cox regression analysis, a high level of PLR was an independent predictor of 5-year mortality (OR = 1.005, 95% CI: 1.001–1.008, p = 0.004). Kaplan-Meier analysis according to the long-term mortality-free survival revealed the higher occurrence of mortality in the third PLR tertile group compared to the first (p < 0.001) and second tertiles (p = 0.009).ConclusionsPLR, which is an easily calculated and universally available marker, may be useful in long-term risk classification of patients presenting with ACS.

Clinical relevance of cell-free mitochondrial DNA during the early postoperative period in kidney transplant recipients

Recent studies indicate that urinary mitochondrial DNA (mtDNA) is predictive of ischemic AKI and is related to delayed graft function (DGF) in renal transplantation. Nevertheless, the clinical implications and prognostic value of urinary mtDNA in kidney transplantation remain undetermined. Here, we aimed to evaluate the associations between cell-free mtDNA and clinical parameters, including pathological findings in allograft biopsy and post-transplant renal function. A total of 85 renal transplant recipients were enrolled, and blood and urine samples were collected at a median of 17 days after transplantation. Cell-free nuclear and mtDNA levels were measured by quantitative polymerase chain reaction for LPL and ND1 genes. Urinary cell-free mtDNA levels were significantly higher in patients with DGF (P < 0.001) and cases of deceased donor transplantation (P < 0.001). The subjects with acute rejection showed higher urinary mtDNA levels than those without abnormalities (P = 0.043). In addition, allograft functions at 9- and 12-month post-transplantation were significantly different between tertile groups of mtDNA independent of the presence of DGF or acute rejection, showing significantly better graft outcome in the lowest tertile group. Urinary cell-free mtDNA levels during the early post-transplant period are significantly associated with DGF, acute rejection in graft biopsy, and short-term post-transplant renal function.

Omega-3 polyunsaturated fatty acids status and cognitive function in young women

BackgroundResearch indicates that low omega-3 polyunsaturated fatty acid (n-3 PUFA) may be associated with decreased cognitive function. This study examined the association between n-3 PUFA status and cognitive function in young Australian women.MethodsThis was a secondary outcome analysis of a cross-sectional study that recruited 300 healthy women (18–35 y) of normal weight (NW: BMI 18.5–24.9 kg/m2) or obese weight (OB: BMI ≥30.0 kg/m2). Participants completed a computer-based cognition testing battery (IntegNeuro™) evaluating the domains of impulsivity, attention, information processing, memory and executive function. The Omega-3 Index (O3I) was used to determine n-3 PUFA status (percentage of EPA (20:5n-3) plus DHA (22:6n3) in the red cell membrane) and the participants were divided into O3I tertile groups: T1 < 5.47%, T2 = 5.47–6.75%, T3 > 6.75%. Potential confounding factors of BMI, inflammatory status (C-reactive Protein), physical activity (total MET-min/wk), alpha1-acid glycoprotein, serum ferritin and hemoglobin, were assessed. Data reported as z-scores (mean ± SD), analyses via ANOVA and ANCOVA.ResultsTwo hundred ninety-nine women (26.9 ± 5.4 y) completed the study (O3I data, n = 288). The ANOVA showed no overall group differences but a significant group × cognition domain interaction (p < 0.01). Post hoc tests showed that participants in the low O3I tertile group scored significantly lower on attention than the middle group (p = 0.01; ES = 0.45 [0.15–0.74]), while the difference with the high group was borderline significant (p = 0.052; ES = 0.38 [0.09–0.68]). After confounder adjustments, the low group had lower attention scores than both the middle (p = 0.01) and high (p = 0.048) groups. These findings were supported by univariate analyses which found significant group differences for the attention domain only (p = 0.004).ConclusionsCognitive function in the attention domain was lower in women with lower O3I, but still within normal range. This reduced but normal level of cognition potentially provides a lower baseline from which cognition would decline with age. Further investigation of individuals with low n-3 PUFA status is warranted.

Homocysteine as a potential predictive factor for high major adverse cardiovascular events risk in female patients with premature acute coronary syndrome.

We aimed to investigate the correlation of homocysteine (Hcy) level with clinical characteristics, and explore its predictive value for major adverse cardiovascular events (MACE) risk in female patients with premature acute coronary syndrome (ACS).The serum Hcy level was detected from 1299 female patients with premature ACS. According to the tertile of Hcy level, patients were divided into 3 groups: lowest tertile group (≤9.1 μmol/L), middle tertile group (9.2–11.6 μmol/L) and highest tertile group (>11.6 μmol/L). MACE incidence was recorded and MACE-free survival was caculated with the median follow-up duration of 28.3 months.Increased Hcy correlated with older age (P < .001), higher creatinine level (P < .001), and enhanced uric acid level (P = .001), while reduced fasting glucose concentration (P < .001). MACE incidence was 10.7% and it was highest in highest tertile group (22.1%), followed by middle tertile group (7.7%) and lowest tertile group (2.4%) (P < .001). Receiver operating characteristic curve showed that Hcy distinguished MACE patients from non-MACE patients with the area under the curve of 0.789 (95% CI: 0.742–0.835). Kaplan–Meier curves revealed that MACE-free survival was shortest in Hcy highest tertile group, followed by middle tertile group and lowest tertile group (P < .001). Multivariate Cox analyses further showed that higher Hcy level was an independent predictive factor for poor MACE-free survival (middle tertile vs lowest tertile (P = .001, HR: 3.615, 95% CI: 1.661–7.864); highest tertile vs lowest tertile (P < .001, HR: 11.023, 95% CI: 5.356-22.684)).Hcy serves as a potential predictive factor for increased MACE risk in female patients with premature ACS.

Orthostatic change in systolic blood pressure associated with cold pressor reflection and heart rate variability in the elderly

ABSTRACTBackground: Impaired orthostatic blood pressure (BP) response is a frequent finding in the elderly. The goal of the study was to investigate the association of variability of supine-to-orthostatic BP with cold pressor reflection and heart rate variability in the elderly.Methods: From June 2010 to September 2013, 287 elderly aged ≥ 60 years were enrolled in Jinan area, China. The elderly were classified into lower (n = 96), intermediate (n = 95), and higher (n = 96) tertile groups according to the tertile of the percentage change of supine-to-orthostatic systolic BP.Results: There were significant increasing trends in systolic BP response to the CPT at 0 and 60 sec; the plasma levels of epinephrine, norepinephrine, and angiotensin II; and decreasing trends in DNN, SDNN index, and SDANN from the lower to the higher tertile group, and differences between any two groups were significant (P < .05). The percentage change of supine-to-orthostatic systolic BP was positively correlated with systolic BP response to CPT at 0 and 60 sec, VLF, epinephrine, norepinephrine, and angiotensin II (P < .001) and negatively correlated with SDNN, SDNN index, SDANN, rMSSD, pNN50, LF, and ratio of LF/HF (P < .001). The BP response to CPT, parameters of HRV, and the plasma levels of norepinephrine and angiotensin II were independently associated with the percentage change of supine-to-orthostatic systolic BP after adjustment for confounders.Conclusion: Aggressive variability of supine-to-orthostatic systolic BP might be significantly associated with the imbalance of sympathetic and parasympathetic activity, especially high sensitivity sympathetic response in the elderly.Abbreviations: BP: blood pressure; BMI: body mass index; CPT: cold pressor test; HRV: heart rate variability; SDNN: standard deviation of all normal-to-normal R-R intervals; SDNN index: mean of the standard deviations of all 5-min normal-to-normal R-R intervals of the entire recording; SDANN: standard deviation of the averages of normal-to-normal R-R intervals during all 5-min periods of the entire recording; rMSSD: square root of the mean squared differences between successive normal R-R intervals; pNN50: number of adjacent normal R-R intervals differing by more than 50 ms; VLF: very low frequency; LF: low frequency; HF: high frequency; TCHO: total cholesterol; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; SD: standard deviation.

High high-sensitivity C-reactive protein/BMI ratio predicts future adverse outcomes in patients with acute coronary syndrome.

The prognostic value of high-sensitivity C-reactive protein (hsCRP) and obesity in patients with coronary artery disease is controversial. In previous studies, hsCRP was significantly associated with BMI. Thus, we integrated hsCRP and BMI to assess the predictive value in patients with acute coronary syndrome (ACS). In this observational cohort study, 478 patients with ACS were enrolled in Fuwai Hospital from 2010 to 2011,with a mean follow-up of 4.2 years. The endpoint of major adverse cardiovascular events (MACE) was the composite of cardiovascular death, myocardial infarction, revascularization again, heart failure, or stroke. Compared with patients without MACE, we found that patients with MACE had higher hsCRP (3.86 ± 3.66 vs. 3.00 ± 3.17, P = 0.033). Furthermore, we identified that hsCRP was significantly correlated with BMI (r = 0.134, P = 0.005). Thus, hsCRP level was adjusted by BMI to further clarify its role in the prognosis of patients with ACS. According to the tertiles of hsCRP/BMI ratio, the rates of MACE in the lowest tertile group, the median tertile group, and the highest tertile group were 14.0% (21/150), 14.0% (21/150), and 26% (39/150) (P = 0.008), respectively. In multivariate analysis, hsCRP/BMI was independently and positively related to MACE. Similarly, according to risk category of hsCRP (low hsCRP group < 3.0 mg/l, high hsCRP group ≥ 3.0 mg/l) and BMI (< 24 and ≥ 24.0 kg/m), patients in the high hsCRP but normal or low weight group had the lowest MACE-free survival (log-rank P = 0.003) compared with other groups. We confirmed that C-reactive protein level should be adjusted by BMI to reflect the prognosis of patients with ACS. High hsCRP/BMI ratio was associated with adverse outcomes. Patients with ACS with high hsCRP plus overweight had the same risk for MACE as those with lower hsCRP but normal weight.

Soluble Neprilysin in the General Population: Clinical Determinants and Its Relationship to Cardiovascular Disease.

BackgroundNeprilysin is a metalloprotease involved in proteolysis of numerous peptides, including natriuretic peptides, and is of prognostic and therapeutic importance in heart failure with reduced ejection fraction. No studies have investigated circulating neprilysin in the community, its clinical correlates, or its relationship to cardiovascular disease in the general population.Methods and ResultsPlasma neprilysin was measured in 1536 participants from Olmsted County, Minnesota, using a commercially available sandwich ELISA assay. Clinical and echocardiographic correlates and subsequent outcomes were determined. Soluble neprilysin is non‐normally distributed in the community (median: 3.9 ng/mL; interquartile range: 1.0–43.0 ng/mL). There was no relationship between plasma neprilysin and age (Spearman correlation: −0.04, P=0.16); body mass index (Spearman correlation: −0.04, P=0.16); glomerular filtration rate (Spearman correlation: −0.007, P=0.8); or A‐, B‐, or C‐type natriuretic peptides (Spearman correlation: 0.03, P=0.22; −0.001, P=0.96; 0.01, P=0.67, respectively). Among tertiles of neprilysin, the lowest tertile group had the highest prevalence of smokers (P<0.001), hypertension (P=0.04), dyslipidemia (P=0.03), and diastolic dysfunction (P=0.02). Soluble neprilysin was not prospectively associated with death or heart failure over a median of 10.7 years.ConclusionsIn a large community‐based cohort, for the first time, we described the distribution of circulating neprilysin in the general community. We observed that neprilysin does not correlate with natriuretic peptide levels and is not independently associated with adverse outcomes. The novel associations observed between low soluble neprilysin levels and an adverse cardiometabolic and smoking profile requires further investigation.

Association between a High-Potassium Diet and Hearing Thresholds in the Korean Adult Population

The aim of this study was to determine and evaluate the association between potassium intake and hearing thresholds in the Korean adult population. Data from the Korean National Health and Nutrition Examination Survey were analyzed. Participants were divided into tertiles on the basis of their potassium intake as follows: low, middle, and high. Pure-tone audiometry was performed using an automated audiometer. We calculated as the average threshold at the low-frequency pure-tone average (0.5 and 1 kHz), mid-frequency pure-tone average (2 and 3 kHz), and high-frequency pure-tone average (4 and 6 kHz). The average hearing threshold (AHT) was calculated as the pure-tone average of the thresholds at 0.5~3 kHz. Hearing loss (HL) was defined as an AHT of >40 dB in the better ear. There were 1975 participants each in the low, middle, and high tertile groups. The four different average hearing thresholds significantly decreased with an increase in the potassium intake tertile. Multivariate analysis revealed that the four different average hearing thresholds were significantly lower in the high tertile group than in the other two groups. In addition, univariate and multivariate linear regression analyses showed that the potassium intake level was inversely associated with each of the four different average hearing thresholds. Analyses of participants matched based on propensity scores and participants not matched based on propensity scores yielded similar results. The results of this study suggest that high potassium intake levels were associated with a lower prevalence of HL and lower hearing thresholds in the Korean adult population.

Daytime light exposure in daily life and depressive symptoms in bipolar disorder: A cross-sectional analysis in the APPLE cohort

ObjectivesControlled artificial daylight exposure, such as light therapy, is effective in bipolar depression, but the association between uncontrolled daytime light and depressive symptoms in bipolar disorder (BD) is unclear. This study investigated the association between daytime light exposure under real-life situations and depressive symptom in patients with BD. MethodsThis cross-sectional study enrolled 181 outpatients with BD. The average daytime light intensity and the total duration of light intensity of ≥1000 lux were recorded over 7 consecutive days using an actigraph that measured ambient light. Depressive symptoms were assessed using Montgomery–Åsberg Depression Rating Scale, and scores of ≥8 points were treated as depressed state. ResultsNinety-seven (53.6%) subjects were depressed state. At higher average daytime light intensity tertiles, the proportion of depressed state was significantly lower (P for trend, 0.003). In multivariable analysis adjusted for age, employment status, age at onset of BD, Young Mania Rating Scale score, bedtime, and physical activity, the highest tertile group in average daytime light intensity suggested a significantly lower odds ratio (OR) for depressed state than the lowest tertile group (OR, 0.33; 95% confidence interval [CI], 0.14–0.75; P = 0.009). Similarly, the longest tertile group in light intensity ≥1000 lux duration was significantly associated with lower OR for depressed state than lowest tertile group (OR, 0.42; 95% CI, 0.18–0.93; P = 0.033). ConclusionsThe findings suggest that greater daytime light exposure in daily life is associated with decreased depressive symptoms in BD.

Association of Net Ultrafiltration Rate With Mortality Among Critically Ill Adults With Acute Kidney Injury Receiving Continuous Venovenous Hemodiafiltration

Net ultrafiltration (NUF) is frequently used to treat fluid overload among critically ill patients, but whether the rate of NUF affects outcomes is unclear. To examine the association of NUF with survival among critically ill patients with acute kidney injury being treated with continuous venovenous hemodiafiltration. The Randomized Evaluation of Normal vs Augmented Level (RENAL) of Renal Replacement Therapy trial was conducted between December 30, 2005, and November 28, 2008, at 35 intensive care units in Australia and New Zealand among critically ill adults with acute kidney injury who were being treated with continuous venovenous hemodiafiltration. This secondary analysis began in May 2018 and concluded in January 2019. Net ultrafiltration rate, defined as the volume of fluid removed per hour adjusted for patient body weight. Risk-adjusted 90-day survival. Of 1434 patients, the median (interquartile range) age was 67.3 (56.9-76.3) years; 924 participants (64.4%) were male; median (interquartile range) Acute Physiology and Chronic Health Evaluation III score was 100 (84-118); and 634 patients (44.2%) died. Using tertiles, 3 groups were defined: high, NUF rate greater than 1.75 mL/kg/h; middle, NUF rate from 1.01 to 1.75 mL/kg/h; and low, NUF rate less than 1.01 mL/kg/h. The high-tertile group compared with the low-tertile group was not associated with death from day 0 to 6. However, death occurred in 51 patients (14.7%) in the high-tertile group vs 30 patients (8.6%) in the low-tertile group from day 7 to 12 (adjusted hazard ratio [aHR], 1.51; 95% CI, 1.13-2.02); 45 patients (15.3%) in the high-tertile group vs 25 patients (7.9%) in the low-tertile group from day 13 to 26 (aHR, 1.52; 95% CI, 1.11-2.07); and 48 patients (19.2%) in the high-tertile group vs 29 patients (9.9%) in the low-tertile group from day 27 to 90 (aHR, 1.66; 95% CI, 1.16-2.39). Every 0.5-mL/kg/h increase in NUF rate was associated with increased mortality (3-6 days: aHR, 1.05; 95% CI, 1.00-1.11; 7-12 days: aHR, 1.08; 95% CI, 1.02-1.15; 13-26 days: aHR, 1.11; 95% CI, 1.04-1.18; 27-90 days: aHR, 1.13; 95% CI, 1.05-1.22). Using longitudinal analyses, increase in NUF rate was associated with lower survival (β = .056; P < .001). Hypophosphatemia was more frequent among patients in the high-tertile group compared with patients in the middle-tertile group and patients in the low-tertile group (high: 308 of 477 patients at risk [64.6%]; middle: 293 of 472 patients at risk [62.1%]; low: 247 of 466 patients at risk [53.0%]; P < .001). Cardiac arrhythmias requiring treatment occurred among all groups: high, 176 patients (36.8%); middle: 175 patients (36.5%); and low: 147 patients (30.8%) (P = .08). Among critically ill patients, NUF rates greater than 1.75 mL/kg/h compared with NUF rates less than 1.01 mL/kg/h were associated with lower survival. Residual confounding may be present from unmeasured risk factors, and randomized clinical trials are required to confirm these findings. ClinicalTrials.gov identifier: NCT00221013.

The association of dietary animal and plant protein with putative risk markers of colorectal cancer in overweight pre-diabetic individuals during a weight-reducing programme: a PREVIEW sub-study.

Diets with increased protein content are popular strategies for body weight regulation, but the effect of such diets for the colonic luminal environment is unclear. We aimed to investigate the associations between putative colorectal cancer-related markers and total protein intake, plant and animal proteins, and protein from red and processed meat in pre-diabetic adults (> 25years). Analyses were based on clinical and dietary assessments at baseline and after 1year of intervention. Protein intake was assessed from 4-day dietary records. Putative colorectal cancer-related markers identified from 24-h faecal samples collected over three consecutive days were: concentration of short-chain fatty acids, phenols, ammonia, and pH. In total, 79 participants were included in the analyses. We found a positive association between change in total protein intake (slope: 74.72 ± 28.84µmol per g faeces/E%, p = 0.01), including animal protein intake (slope: 87.63 ± 32.04µmol per g faeces/E%, p = 0.009), and change in faecal ammonia concentration. For change in ammonia, there was a dose-response trend from the most negative (lowest tertile) to the most positive (highest tertile) association (p = 0.01): in the high tertile, a change in intake of red meat was positively associated with an increase in ammonia excretion (slope: 2.0 ± 0.5µmol per g faeces/g/day, p < 0.001), whereas no such association was found in the low and medium tertile groups. Increases in total and animal protein intakes were associated with higher excretion of ammonia in faeces after 1year in overweight pre-diabetic adults undertaking a weight-loss intervention. An increase in total or relative protein intake, or in the ratio of animal to plant protein, was not associated with an increase in faeces of any of the other putative colorectal cancer risk markers. ClinicalTrials.gov Identifier: NCT01777893.

Predictive value of serum myostatin for the severity and clinical outcome of heart failure

BackgroundThe exact relationship between serum myostatin and the severity and prognosis of chronic heart failure (CHF) is unclear. In this study, we investigated the association between serum myostatin and the severity and prognosis in patients with CHF. MethodsTwo hundred and eighty-eight CHF patients and 62 healthy controls were studied. Cardiac ultrasound and serum myostatin, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and other parameters were detected. CHF patients were divided into 3 groups according to tertiles of NT-proBNP or myostatin levels respectively. ResultsSerum myostatin levels were higher in CHF patients than in controls. New York Heart Association (NYHA) class IV patients had the highest levels of serum myostatin among the four NYHA classes. Compared with the low tertile NT-proBNP group, serum myostatin levels were significantly higher in the moderate and high tertile groups (15.47 ± 4.25 vs. 14.18 ± 3.69 ng/mL, p = .026; 16.28 ± 5.34 vs. 14.18 ± 3.69 ng/mL, p = .002). During 51-months follow-up, of 173 patients there were 36 deaths. Compared to survivors, nonsurvivors had significantly higher serum myostatin (18.11 ± 4.52 vs. 14.85 ± 5.11 ng/mL, p < .01). Patients in the high tertile myostatin group had lower survival rate (73.95% vs. 93.75%; p < .05) and larger number of CHF rehospitalization than those in the low tertile group. Cox regression analysis showed that serum myostatin was an independent predictor of mortality. ConclusionsSerum myostatin levels can reflect the severity of CHF and be a predictor of adverse prognosis in CHF patients.

Genetic Determinants of Weight Loss After Bariatric Surgery.

The weight loss after bariatric surgery shows considerable individual variation. Twin studies of response to dietary interventions and studies of bariatric surgery patients suggest that genetic differences may play a role. This study aimed to examine the effect of three genetic risk scores on the inter-individual variation in excess body mass index loss (EBMIL) after Roux-en-Y gastric bypass. Furthermore, we searched among known adiposity-related single nucleotide polymorphisms (SNPs) for genetic determinants of the inter-individual variation in EBMIL. Patients with morbid obesity underwent Roux-en-Y gastric bypass and were genotyped (n = 577). Two genetic risk scores for weight loss after bariatric surgery and a genetic risk score for body mass index were calculated. Associations between the genetic risk scores and EBMIL were evaluated. Lasso regression was performed on 126 SNPs known to be associated with adiposity. The average EBMIL was 76.9% (range 21.7-149.2%). EBMIL was 81.1% (SD 20.6) and 73.9% (SD 21.7) in the high and low tertile groups of a genetic risk score for weight loss. Patients with a low genetic risk score for body mass index (in the lowest 5% percentile) had an EBMIL of 68.8% (SD 20.6, p = 0.018). Thirteen adiposity-related SNPs were identified to associate with EBMIL through lasso regression. A genetic risk score was associated with EBMIL after bariatric surgery, but may not yet be applicable to clinical practice. Patients genetically predisposed to low body mass index had lower weight loss after bariatric surgery.

Correlation and Prediction of Living-Donor Remaining Function by Using Predonation Computed Tomography-Based Volumetric Measurements: Role of Remaining Kidney Volume.

Kidney volume in healthy living donors may serve as a surrogate marker of renal function. Here, we evaluated whether preserved kidney volume correlated with and could predict donor renal function at 2 years postdonation using the CKD-EPI estimated glomerular filtration rate equation. Healthy living donors (n = 208) with computed tomography volume measurements were evaluated for renal function before and after donation. Preserved kidney volume was adjusted to body surface area. Demographic characteristics (including race/ethnicity and sex) and renal function variables of donors were analyzed for postdonation renal function. Donor mean age was 39.4 ± 10.7 years (36.2% males, 91.9% white). Median adjusted preserved kidney volume was 180.6 mL. At 2 years postdonation, median estimated glomerular filtration rate was 62.4 mL/min (interquartile range, 54.8-73.2 mL/min). Predonation estimated glomerular filtration rate, age, and adjusted preserved kidney volume were found to be inde-pendent predictors of 2-year estimated glomerular filtration rate (P < .001). We further analyzed data by stratifying preserved kidney volumes into tertiles. Mean 2-year estimated glomerular filtration rates were 57.9 ± 12, 65 ± 16, and 73 ± 17 mL/min for lowest to highest tertile groups, respectively (P < .05). The odds ratio of having a 2-year postdonation estimated glomerular filtration rate of < 60 mL/min for donors in the lowest tertile group was 3.51 (95% confidence interval, 1.9-6.4; P < .001), whereas the risk for donors in the highest tertile group was 0.23 (95% confidence interval, 0.12-0.44; P< .001). Sensitivity analysis result was 0.764 (95% confidence interval, 0.69-0.82; P = .005) for adjusted preserved kidney volume and estimated glomerular filtration rate of < 60 mL/min. Remaining kidney volume before donation correlated with and predicted estimated glomerular filtration rate after donation. Remaining kidney volume should be assessed when selecting kidneys from healthy donors.

The ratio of fasting plasma glucose to hemoglobin A1c as a predictor of all-cause mortality in individuals with normal glucose levels: The Jichi Medical School cohort study.

Objectives:The fasting plasma glucose/hemoglobin A1c ratio is considered a marker associated with glucose metabolism disorders, including fasting hyperglycemia. However, it remains unclear whether this ratio can be used for the prevention of deaths in individuals with normal fasting plasma glucose levels. This study aimed to see the predictive value of the fasting plasma glucose/hemoglobin A1c ratio for all-cause mortality in a general population with normal fasting plasma glucose levels.Methods:The study investigated prospectively a cohort of 1087 multi-regional, community-dwelling Japanese participants (women, 69.2%) for a follow-up period of 11.3 years. We included individuals with fasting plasma glucose levels <6.11 mmol/L and excluded those meeting the diabetes criteria. All-cause mortality was the primary outcome and hazard ratios were calculated using the Cox proportional hazard model after dividing the fasting plasma glucose/hemoglobin A1c ratios into tertiles.Results:There were 54 deaths (25 women) during the follow-up period. The high tertile group had a significantly higher hazard ratio for all-cause mortality than the low tertile group in women (multivariate-adjusted hazard ratio = 4.45; 95% confidence interval = 1.26–15.72), but not clearly in men.Conclusion:The data of the population-based cohort study suggest that a high fasting plasma glucose/hemoglobin A1c ratio can predict all-cause mortality in women with normal fasting plasma glucose levels.