Estimation of homeostatic dysregulation and frailty using biomarker variability: a principal component analysis of hemodialysis patients.

Increased intraindividual variability in several biological parameters is associated with aspects of frailty and may reflect impaired physiological regulation. As frailty involves a cumulative decline in multiple physiological systems, we aimed to estimate the overall regulatory capacity by applying a principal component analysis to such variability. The variability of 20 blood-based parameters was evaluated as the log-transformed coefficient of variation (LCV) for one year's worth of data from 580 hemodialysis patients. All the LCVs were positively correlated with each other and shared common characteristics. In a principal component analysis of 19 LCVs, the first principal component (PC1) explained 27.7% of the total variance, and the PC1 score exhibited consistent correlations with diverse negative health indicators, including diabetes, hypoalbuminemia, hyponatremia, and relative hypocreatininemia. The relationship between the PC1 score and frailty was subsequently examined in a subset of the subjects. The PC1 score was associated with the prevalence of frailty and was an independent predictor for frailty (odds ratio per SD: 2.31, P = 0.01) using a multivariate logistic regression model, which showed good discrimination (c-statistic: 0.85). Therefore, the PC1 score represents principal information shared by biomarker variabilities and is a reasonable measure of homeostatic dysregulation and frailty.

A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study).

OBJECTIVE: To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4-9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP). DESIGN: A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4-9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps. RESULTS: A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI -1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps). CONCLUSIONS: The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4-9 mm colorectal polyps. (Study registration: UMIN000018328).

Aging and death-associated changes in serum albumin variability over the course of chronic hemodialysis treatment.

BACKGROUND: Several epidemiological studies have demonstrated associations between variability in a number of biological parameters and adverse outcomes. As the variability may reflect impaired homeostatic regulation, we assessed albumin variability over time in chronic hemodialysis (HD) patients. METHODS: Data from 1346 subjects who received chronic HD treatment from May 2001 to February 2015 were analyzed according to three phases of HD treatment: post-HD initiation, during maintenance HD treatment, and before death. The serum albumin values were grouped according to the time interval from HD initiation or death, and the yearly trends for both the albumin levels and the intra-individual albumin variability (quantified by the residual coefficient of variation: Alb-rCV) were examined. The HD initiation and death-associated changes were also analyzed using generalized additive mixed models. Furthermore, the long-term trend throughout the maintenance treatment period was evaluated separately using linear regression models. RESULTS: Albumin levels and variability showed distinctive changes during each of the 3 periods. After HD initiation, albumin variability decreased and reached a nadir within a year. During the subsequent maintenance treatment period (interquartile range = 5.2-11.0 years), the log Alb-rCV showed a significant upward trend (mean slope: 0.011 ± 0.035 /year), and its overall mean was -1.49 ± 0.08 (equivalent to an Alb-rCV of 3.22%). During the 1-2 years before death, this upward trend clearly accelerated, and the mean log Alb-rCV in the last year of life was -1.36 ± 0.17. The albumin levels and variability were negatively correlated with each other and exhibited exactly opposite movements throughout the course of chronic HD treatment. Different from the albumin levels, albumin variability was not dependent on chronological age but was independently associated with an individual's aging and death process. CONCLUSION: The observed upward trend in albumin variability seems to be consistent with a presumed aging-related decline in homeostatic capacity.

Histologic diagnosis of pancreatic masses using 25-gauge endoscopic ultrasound needles with and without a core trap: a multicenter randomized trial.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with 25-gauge needles yields small volume samples that are mainly processed for cytology. Using 25-gauge needles with a core trap may overcome this limitation. This trial compared 25-gauge needles with and without a core trap in terms of their ability to obtain histologic samples from solid pancreatic masses. PATIENTS AND METHODS: Consecutive patients with solid pancreatic masses who presented to eight Japanese referral centers for EUS-FNA in April - September 2013 were randomized to undergo sampling with a 25-gauge needle with a core trap (ProCore) or a standard 25-gauge needle. Tissue samples were fixed in formalin and processed for histologic evaluation. For the purpose of this study only samples obtained with the first needle pass were used for comparison of: (i) accuracy for the diagnosis of malignancy, (ii) rate of samples with preserved tissue architecture adequate for histologic evaluation, and (iii) sample cellularity. RESULTS: A total of 214 patients were enrolled. Compared to the first pass with a standard needle (n = 108), the first pass with the ProCore needle (n = 106) provided samples that were more often adequate for histologic evaluation (81.1 % vs. 69.4 %; P = 0.048) and had superior cellularity (rich/moderate/poor, 36 %/27 %/37 % vs. 19 %/26 %/55 %; P = 0.003). There were no significant differences between the two needles in sensitivity (75.6 % vs. 69.0 %, P = 0.337) and accuracy (79.2 % vs. 75.9 %, P = 0.561) for the diagnosis of malignancy. CONCLUSIONS: In patients with solid pancreatic masses, a 25-gauge EUS-FNA needle with a core trap provides histologic samples of better quality than a standard 25-gauge needle. There was no difference in accuracy for the diagnosis of malignancy between the needles. CLINICAL TRIAL NUMBER: UMIN000010021.

High-gamma power changes after cognitive intervention: preliminary results from twenty-one senior adult subjects.

INTRODUCTION: Brain-imaging techniques have begun to be popular in evaluating the effectiveness of cognitive intervention training. Although gamma activities are rarely used as an index of training effects, they have several characteristics that suggest their potential suitability for this purpose. This pilot study examined whether cognitive training in elderly people affected the high-gamma activity associated with attentional processing and whether high-gamma power changes were related to changes in behavioral performance. METHODS: We analyzed (MEG) magnetoencephalography data obtained from 35 healthy elderly subjects (60-75 years old) who had participated in our previous intervention study in which the subjects were randomly assigned to one of the three types of intervention groups: Group V trained in a vehicle with a newly developed onboard cognitive training program, Group P trained with a similar program but on a personal computer, and Group C was trained to solve a crossword puzzle as an active control group. High-gamma (52-100 Hz) activity during a three-stimulus visual oddball task was measured before and after training. As a result of exclusion in the MEG data analysis stage, the final sample consisted of five subjects in Group V, nine subjects in Group P, and seven subjects in Group C. RESULTS: Results showed that high-gamma activities were differently altered between groups after cognitive intervention. In particular, members of Group V, who showed significant improvements in cognitive function after training, exhibited increased high-gamma power in the left middle frontal gyrus during top-down anticipatory target processing. High-gamma power changes in this region were also associated with changes in behavioral performance. CONCLUSIONS: Our preliminary results suggest the usefulness of high-gamma activities as an index of the effectiveness of cognitive training in elderly subjects.

Effects of Different Types of Cognitive Training on Cognitive Function, Brain Structure, and Driving Safety in Senior Daily Drivers: A Pilot Study.

BACKGROUND: Increasing proportion of the elderly in the driving population raises the importance of assuring their safety. We explored the effects of three different types of cognitive training on the cognitive function, brain structure, and driving safety of the elderly. METHODS: Thirty-seven healthy elderly daily drivers were randomly assigned to one of three training groups: Group V trained in a vehicle with a newly developed onboard cognitive training program, Group P trained with a similar program but on a personal computer, and Group C trained to solve a crossword puzzle. Before and after the 8-week training period, they underwent neuropsychological tests, structural brain magnetic resonance imaging, and driving safety tests. RESULTS: For cognitive function, only Group V showed significant improvements in processing speed and working memory. For driving safety, Group V showed significant improvements both in the driving aptitude test and in the on-road evaluations. Group P showed no significant improvements in either test, and Group C showed significant improvements in the driving aptitude but not in the on-road evaluations. CONCLUSION: The results support the effectiveness of the onboard training program in enhancing the elderly's abilities to drive safely and the potential advantages of a multimodal training approach.

Variability of laboratory parameters is associated with frailty markers and predicts non-cardiac mortality in hemodialysis patients.

BACKGROUND: The levels of many laboratory parameters are associated with the outcomes of dialysis patients, but the significance of their variability has not been well studied. METHODS: A total of 384 patients receiving stable hemodialysis treatment during 2002 were followed up for mortality until the end of 2013. The within-patient coefficients of variation (CV) were calculated for 13 laboratory parameters from 1 year of data. We defined variability as CV and analyzed the survival of the patients according to the baseline CV values of each parameter by proportional hazard modeling. RESULTS: During the 11-year observation period, 125 patients died. Higher CV levels for eight parameters, namely, blood urea nitrogen (BUN), sodium, hemoglobin, creatinine, total protein, albumin, potassium and phosphate, were significantly associated with all-cause mortality. The adjusted hazard ratios for a high BUN-CV (>15 %) and a high Na-CV (>1.3 %) against a lower CV were 1.92 (95 % CI 1.31-2.81) and 1.95 (1.36-2.80), respectively. The increased mortality risk associated with each variability was attributed to excess non-cardiac deaths. The CV values of most parameters were correlated with each other and often exhibited negative associations with age, diabetes, and mobility as well as the levels of hemoglobin, albumin, creatinine, Na, the protein catabolic rate, and the creatinine generation rate. Therefore, a high variability was generally associated with frailty-related adverse prognostic factors. CONCLUSIONS: The variability of several blood parameters had a significant impact on all-cause and non-cardiac mortality. The levels of the variabilities were most likely related to poor physical conditions of the patients.

Hemodialysis patients born with a low birth weight should have a different time course of kidney diseases than those born with a normal birth weight.

Low birth weight (LBW) is thought to be one of the risk factors for the progression of kidney diseases. This study hypothesized that the onset age of kidney disease, the rate of progression of kidney disease, or the age at the time of hemodialysis (HD) induction among HD patients that were born with LBW is different from those without a history of LBW. A questionnaire survey in nine dialysis units in Japan was performed and 427 answer sheets were collected. There were statistically significant differences in the present age, the age of kidney disease onset, and the age of HD induction between LBW group and normal birth weight group (NBW). An analysis limited to participants whose underlying disease was diabetic nephropathy revealed that the duration from the onset of nephropathy to HD induction was much shorter in HD patients with a history of LBW than those with a NBW history. In addition, the Pearson's correlation coefficient between the birth weight and the period from onset of diabetic nephropathy to HD induction was 0.283. Although these results might partly support the primary hypothesis, the necessity to perform other clinical studies is also emphasized.

Efficacy of once-weekly intravenous administration of epoetin-beta as a maintenance treatment for anemia in Japanese hemodialysis patients: a multicenter, open-label clinical study.

Epoetin-beta is extremely useful as a drug for treating anemia in hemodialysis (HD) patients and is widely used for that purpose. The aim of this study was to determine whether once-weekly intravenous administration of epoetin-beta is as effective in maintaining hemoglobin (Hb) concentration as the same weekly dose administered 2 or 3 times per week as maintenance treatment of anemia in HD patients. The subjects were stable HD patients who had been receiving HD for at least 12 months. Using a fixed weekly dose of 3000 or 6000 IU of epoetin-beta, this study evaluated maintenance of improvement of anemia by comparing Hb concentration in the study period (once-weekly) with Hb concentration in the prestudy period (2 or 3 times per week). Of the 112 patients treated with epoetin-beta, 111 patients (full analysis set; 3000 IU, 52 patients; 6000 IU, 59 patients) were evaluated, after excluding one patient whose dose was changed immediately before study initiation. The change in the Hb concentration was maintained within +/-1.5 g/dL in 89.2% of patients (3000 IU, 88.5%; 6000 IU, 89.8%). The mean Hb concentration was 10.42 +/- 0.73 g/dL at study initiation and 10.14 +/- 1.00 g/dL at study completion. Adverse reactions occurred in 9.8% of patients (11 out of 112 patients). The main adverse reactions were malaise and increased blood pressure. Once-weekly intravenous administration of epoetin-beta is useful as maintenance treatment of anemia in HD patients and may be a treatment option.