Blood Concentrations of Lead, Cadmium, and Mercury Are Associated With Alcohol-Related Liver Disease.

BACKGROUND: An association between environmental pollutants and alcohol-related liver disease (ALD) has not been determined until now. The objectives of this study were to examine the association of the pollutants with ALD, and whether the pollutants together increased the risk of ALD. METHODS: Data were extracted from the Korea National Health and Nutrition Examination Survey (2010-2013 and 2016-2017; n = 11,993). Blood levels of lead, cadmium, and mercury were measured. ALD was defined by a combination of excessive alcohol consumption and ALD/non-alcoholic fatty liver disease index > 0. The aspartate aminotransferase-to-platelet ratio index and fibrosis (FIB)-4 score were used to evaluate ALD FIB. RESULTS: The odds ratios (ORs) of ALD for the highest versus the lowest quartiles of exposure were for lead, 7.39 (95% confidence interval [CI], 5.51-9.91); cadmium, 1.68 (95% CI, 1.32-2.14); and mercury, 5.03 (95% CI, 3.88-6.53). Adjusting for age, gender, smoking, occupation, education, and personal income attenuated the associations but indicated significant positive trends (all Ptrend < 0.001). A positive additive interaction between cadmium and lead was observed. The relative excess OR due to the interaction was 0.96 (95% CI, 0.41-1.51); synergy index = 2.92 (95% CI, 0.97-8.80). Among 951 subjects with ALD, advanced FIB was associated with lead and cadmium (OR, 3.46, 95% CI, 1.84-6.53; OR, 8.50, 95% CI, 2.54-28.42, respectively), but not with mercury. The effect estimates for lead and cadmium remained significant even after adjustment for daily alcohol intake. CONCLUSION: Blood levels of lead, cadmium, and mercury were significantly associated not only with the risk of ALD but also with ALD FIB. Cadmium and lead have synergistic effects that increase the risk of ALD.

Serum phosphorus and subclinical coronary atherosclerosis in asymptomatic subjects without kidney dysfunction.

BACKGROUND AND AIMS: There is limited data on the association between serum phosphorus concentration (SPC) and subclinical coronary atherosclerosis in low-risk asymptomatic subjects without kidney dysfunction. MATERIALS AND METHODS: We retrospectively analyzed 1,636 Korean individuals (mean age 52.6 ± 7.6 years; males: 712 (43.5%)) without traditional cardiovascular risk factors (CVRFs) and kidney dysfunction who voluntarily underwent coronary computed tomography angiography (CCTA) as part of a general health examination. Traditional CVRFs were defined as follows: systolic/diastolic blood pressure ≥ 140/90 mmHg, fasting blood glucose ≥ 126 mg/dL, hemoglobin A1c ≥ 6.5%, total cholesterol ≥ 240 mg/dL, low-density lipoprotein cholesterol ≥ 160 mg/dL, high-density lipoprotein cholesterol < 40 mg/dL, body mass index ≥ 25.0 kg/m2, currently smoking, and medical history of hypertension, diabetes, and hyperlipidemia. Study participants were stratified into tertiles according to their SPC levels (≤ 3.2, 3.3 - 3.6, and ≥ 3.7 mg/dL). RESULTS: 297 (18.2%) study participants had subclinical coronary atherosclerosis, characterized by any coronary plaque on CCTA. In multivariable regression analysis, the risk of subclinical coronary atherosclerosis increased in the second (odds ratio (OR): 1.629; 95% confidence interval (CI): 1.149 - 2.308; p = 0.006) and third (OR: 1.645; 95% CI: 1.093 - 2.476; p = 0.017) SPC tertiles compared to the first SPC tertile. In addition, the risk of calcified plaque increased in the second (OR: 1.605; 95% CI: 1.124 - 2.292; p = 0.009) and third (OR 1.790; 95% CI 1.179 - 2.716; p = 0.006) SPC tertiles. CONCLUSION: In low-risk asymptomatic Korean individuals without kidney dysfunction, a higher SPC level was an independent predictor of subclinical coronary atherosclerosis.

Clinical Course of Terminal Ileal Ulcers Observed Incidentally During Colonoscopy.

BACKGROUND: Cecal intubation is essential during colonoscopy, and observation of the terminal ileum is performed in most clinical practices. However, data on terminal ileal (TI) ulcers observed incidentally during colonoscopy are rare. AIM: We aimed to identify the characteristics and clinical course of TI ulcers observed incidentally during colonoscopy. METHODS: Between January 2008 and December 2018, medical records from multi-centers reporting asymptomatic subjects who underwent biopsy on TI ulcers during colonoscopy were retrospectively reviewed. The characteristics of endoscopic findings and clinical course of TI ulcers were analyzed, and the factors affecting the clinical course of TI ulcers were evaluated. RESULTS: The median follow-up durations from first to second colonoscopy and from second to third colonoscopy were 20 months (interquartile range, 12-36) and 24 months (interquartile range, 12-34), respectively. A total of 134 subjects were included in the analysis. The histopathologic findings of TI ulcers were mostly chronic or active ileitis/inflammation (92.7%). On the second colonoscopy, 59 (44.0%) patients had no ulcers, 38 (28.4%) showed a decrease in size or number, and 37 (27.6%) patients showed no change in ulcers. Among 62 subjects who underwent a third colonoscopy, 14 (10.4%) had decreased size or number, 10 (7.5%) had no ulcer change, and two (1.5%) had increased ulcer size or number. In multivariate logistic regression analysis, a star shape was the only factor affecting continuation without improvement of incidental TI ulcers. CONCLUSIONS: Most TI ulcers observed incidentally showed no unusual findings on biopsy and improved on follow-up colonoscopy without treatment.

Estimation of population-based utility weights for health states of chronic kidney disease, dialysis and kidney transplantation.

AIM: This study aimed to determine the utility of chronic kidney disease (CKD)-related health states in the Korean general population by using the standard gamble (SG) method. METHODS: Seven hypothetical CKD-related health states were developed and revised based on previous publications. Data from 242 individuals from the Korean general population were obtained via computer-assisted personal interviews and used to evaluate the CKD-related health states by using the visual analogue scale (VAS) and SG methods. Mean and median utility values were calculated for each health state. To assess the reliability of the valuation, some samples were retested and evaluated using intraclass correlation coefficients (ICC). RESULTS: In all health states, the utility weights from SG were higher than those from VAS. The difference in utility values between the two valuation methods ranged from 0.258 to 0.308. The utility value of CKD grade 3 was the highest and that of peritoneal dialysis (PD) was the lowest. The utility weights tended to decrease in accordance with the progression of CKD. CKD grade 3 was assigned a SG utility value of 0.878, whereas PD was assigned 0.507. The SG utility values of predialysis end-stage renal disease, haemodialysis, kidney transplantation (KT), and post-KT recovery states were 0.666, 0.547, 0.748 and 0.827, respectively. The mean ICC (SD) at the individual level was 0.746 (0.281) for the SG scores. CONCLUSION: Our results could be used to measure the burden of kidney disease or to evaluate the economic efficiency of CKD-related interventions.

A Validation Study of the Inbrain CST: a Tablet Computer-based Cognitive Screening Test for Elderly People with Cognitive Impairment.

BACKGROUND: Computerized versions of cognitive screening test could have advantages over pencil-and-paper versions by eliminating rater-dependent factors and saving the time required to score the tests and report the results. We developed a computerized cognitive screening test (Inbrain Cognitive Screening Test [Inbrain CST]) that takes about 30 minutes to administer on a touchscreen computer and is composed of neuropsychological tests already shown to be sensitive in detecting early cognitive decline in Alzheimer's disease (AD). The aims of this study were to 1) introduce normative data for Inbrain CST, 2) verify its reliability and validity, 3) assess clinical usefulness, and 4) identify neuroanatomical correlates of Inbrain CST. METHODS: The Inbrain CST runs on the Microsoft Windows 10 operating system and comprises 7 subtests that encompass 5 cognitive domains: attention, language, visuospatial, memory, and executive functions. First, we recruited 480 cognitively normal elderly people (age 50-90) from communities nationwide to establish normative data for Inbrain CST. Second, we enrolled 97 patients from our dementia clinic (26 with subjective cognitive decline [SCD], 42 with amnestic mild cognitive impairment [aMCI], and 29 with dementia due to AD) and investigated sensitivity and specificity of Inbrain CST for discriminating cognitively impaired patients from those with SCD using receiver operating characteristic (ROC) curve analyses. Third, we compared the Inbrain CST scores with those from another neuropsychological test battery to obtain concurrent validity and assessed test-retest reliability. Finally, magnetic resonance imaging (MRI)-based cortical thickness analyses were performed to provide anatomical substrates for performances on the Inbrain CST. RESULTS: First, in the normative sample, the total score on the Inbrain CST was significantly affected by age, years of education, and gender. Second, Inbrain CST scores among the three patient groups decreased in the order of SCD, aMCI, and AD dementia, and the ROC curve analysis revealed that Inbrain CST had good discriminative power for differentiating cognitively impaired patients from those with SCD. Third, the Inbrain CST subtests had high concurrent validity and test-retest reliability. Finally, in the cortical thickness analysis, each cognitive domain score and the total score of Inbrain CST showed distinct patterns of anatomical correlates that fit into the previously known brain-behavior relationship. CONCLUSION: Inbrain CST had good validity, reliability, and clinical usefulness in detecting cognitive impairment in the elderly. Furthermore, it showed neuroanatomical validity through MRI cortical thinning patterns. These results suggest that Inbrain CST is a useful cognitive screening tool with efficiency and validity to detect mild impairments in cognition in clinical settings.

Current Measurement Transducer Based on Current-to-Voltage-to-Frequency Converting Ring Oscillator with Cascade Bias Circuit.

We propose a ring oscillator (RO) based current-to-voltage-to-frequency (I-V-F) converting current transducer with a cascade bias circuit. The I-V-F converting scheme guarantees highly stable biasing against RO, with a rail-to-rail output operation. This device was fabricated using National NanoFab Center (NNFC) 180 nm complementary metal-oxide-semiconductor (CMOS) technology, which achieves a current resolution of 1 nA in a measurement range up to 200 nA. A noise floor of 11.8 pA/√Hz, maximum differential nonlinearity (DNL) of 0.15 in 1 nA steps, and rail-to-rail output with a 1.8 V power supply is achieved. The proposed transducer can be effectively applied to bio-sensing devices requiring a compact area and low power consumption with a low current output. The fabricated structure can be applied to monolithic-three-dimensional integration with a bio-sensing device.

Fully Automated Lung Lobe Segmentation in Volumetric Chest CT with 3D U-Net: Validation with Intra- and Extra-Datasets.

Lung lobe segmentation in chest CT has been used for the analysis of lung functions and surgical planning. However, accurate lobe segmentation is difficult as 80% of patients have incomplete and/or fake fissures. Furthermore, lung diseases such as chronic obstructive pulmonary disease (COPD) can increase the difficulty of differentiating the lobar fissures. Lobar fissures have similar intensities to those of the vessels and airway wall, which could lead to segmentation error in automated segmentation. In this study, a fully automated lung lobe segmentation method with 3D U-Net was developed and validated with internal and external datasets. The volumetric chest CT scans of 196 normal and mild-to-moderate COPD patients from three centers were obtained. Each scan was segmented using a conventional image processing method and manually corrected by an expert thoracic radiologist to create gold standards. The lobe regions in the CT images were then segmented using a 3D U-Net architecture with a deep convolutional neural network (CNN) using separate training, validation, and test datasets. In addition, 40 independent external CT images were used to evaluate the model. The segmentation results for both the conventional and deep learning methods were compared quantitatively to the gold standards using four accuracy metrics including the Dice similarity coefficient (DSC), Jaccard similarity coefficient (JSC), mean surface distance (MSD), and Hausdorff surface distance (HSD). In internal validation, the segmentation method achieved high accuracy for the DSC, JSC, MSD, and HSD (0.97 ± 0.02, 0.94 ± 0.03, 0.69 ± 0.36, and 17.12 ± 11.07, respectively). In external validation, high accuracy was also obtained for the DSC, JSC, MSD, and HSD (0.96 ± 0.02, 0.92 ± 0.04, 1.31 ± 0.56, and 27.89 ± 7.50, respectively). This method took 6.49 ± 1.19 s and 8.61 ± 1.08 s for lobe segmentation of the left and right lungs, respectively. Although various automatic lung lobe segmentation methods have been developed, it is difficult to develop a robust segmentation method. However, the deep learning-based 3D U-Net method showed reasonable segmentation accuracy and computational time. In addition, this method could be adapted and applied to severe lung diseases in a clinical workflow.

Association of baseline histopathology and kidney donor risk index with graft outcomes in deceased donor kidney transplantation
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BACKGROUND: Donor organ quality is a key determinant of graft outcomes in deceased donor kidney transplantation (DDKT). The predictive values of baseline histopathology and several clinical scoring systems for long-term graft outcomes have been evaluated, but the results remain controversial. MATERIALS AND METHODS: We screened 167 patients who underwent DDKT at Ulsan University Hospital from April 2003 to June 2016. Among them, 66 patients who underwent baseline kidney biopsy and whose kidney donor risk index (KDRI) was available were included in this analysis. All baseline biopsies were rescored according to the updated Banff classification. RESULTS: Median follow-up was 22 months. Mean age of recipients and donors was 51.4 and 44.7 years, respectively. Mean KDRI was 1.40 ± 0.44. During follow-up, delayed graft function and biopsy-proven acute rejection (BPAR) developed in 7 and 11 patients, respectively. Graft failure occurred in 2 patients. In Cox regression analysis, interstitial fibrosis/tubular atrophy (IFTA) (hazard ratio (HR) = 3.59; p = 0.049) was a significant risk factor for BPAR. In multivariate linear regression, age (standardized ß (SB) = -0.282; p = 0.002), BPAR (SB = -0.406; p < 0.001), KDRI (SB = -0.277; p = 0.003), and IFTA (SB = -0.298; p = 0.001) were significant predictors of last-visit estimated glomerular filtration rate (eGFR). CONCLUSION: Several clinical and pathologic parameters, such as KDRI and IFTA, may be helpful for predicting long-term graft outcomes, including BPAR and last-visit eGFR, in DDKT.
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Cost-utility analysis of the National Health Screening Program for chronic kidney disease in Korea.

AIM: Although a National Health Screening Program (NHSP) for chronic kidney disease (CKD) has been implemented in Korea since 2002, its cost-effectiveness has never been determined. This study aimed to estimate the cost-utility of NHSP for CKD in Korea. METHODS: A Markov decision analytic model was constructed to compare CKD screening strategies of the NHSP with no screening. We developed a model that simulated disease progression in a cohort aged 20-120 years or death from the societal perspective. RESULTS: Biannual screening starting at age 40 for CKD by proteinuria (dipstick) and estimated glomerular filtration ratio had an ICUR of $66 874/QALY relative to no screening. The targeted screening strategy had an ICUR of $37 812/QALY and $40 787/QALY for persons with diabetes and hypertension, respectively. ICURs improved with lower cost strategies. The most influential parameter that might make screening more cost-effective was the effectiveness of treatment on CKD to decrease disease progression and mortality. CONCLUSIONS: The Korean NHSP for CKD is more cost-effective for patients with diabetes or hypertension than the general population, consistent with prior studies. Although it is too early to conclude the cost-effectiveness of the Korean NHSP for CKD, this study provides evidence that is useful in evaluating the cost-effectiveness of CKD interventions.

Predictors of High-Risk Adenoma Occurrence at Surveillance Colonoscopy in Patients Who Undergo Colorectal Adenoma Removal.

OBJECTIVES: Surveillance colonoscopy is recommended after polypectomy because adenoma recurrence is common. The aim of this study was to evaluate the predictors of high-risk adenoma occurrence at surveillance colonoscopy in patients who undergo colorectal adenoma removal and to clarify the association between age and recurrent colorectal adenoma. METHODS: This retrospective study included 563 patients who had colorectal adenomas at baseline colonoscopy and who underwent surveillance colonoscopy. The risk factors for recurrent adenoma were evaluated and the 5-year cumulative incidence rates of overall and high-risk adenoma were compared according to age group. RESULTS: During a mean follow-up period of 3.1 years, 305 (54.2%) patients had overall adenoma recurrence, and 80 (14.2%) patients had high-risk adenoma at surveillance colonoscopy. In a multivariate analysis, old age (≥60 years) and presence of multiple adenomas (3 or more) were significantly associated with high-risk adenoma (p = 0.002 and p = 0.006 respectively). The 5-year cumulative incidence rates of high-risk adenoma were 7.4, 16.7, and 24.1% in the < 50, 50-59, and ≥60 years group respectively (p < 0.001). CONCLUSIONS: Old age (≥60 years) and presence of multiple adenomas (3 or more) were strongly associated with the occurrence of high-risk adenoma at surveillance colonoscopy. The 5-year cumulative incidence of high-grade adenoma was significantly high in the old age group.

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism.

OBJECTIVE: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. METHODS: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. RESULTS: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. CONCLUSION: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Risks of colorectal advanced neoplasia in young adults versus those of screening colonoscopy in patients aged 50 to 54 years.

BACKGROUND AND AIM: The role of screening or diagnostic colonoscopy to detect advanced neoplasia in young cohorts of age < 50 is unclear. This study compared the risk of colorectal neoplasia in a young age cohort against that in 50-54s screening cohort. METHODS: A multi-center retrospective study was conducted at 14 university hospitals to compare the detection rates of neoplasia and advanced neoplasia in screening or diagnostic colonoscopy in the young cohort of < 50s against those in screening colonoscopy in the 50-54s cohort. RESULTS: Among 10 477 eligible subjects, 9765 subjects were enrolled after excluding 712 subjects. Advanced neoplasia detection rates in the young screening cohort was significantly lower than that in the 50-54s screening cohort (5.9% vs 9.3%, P < 0.001). Compared with 50-54s screening cohort, the risk of advanced neoplasia was significantly reduced by 23%, 53%, and 54% in the 45-49s, 40-44s, and 20-39s screening cohorts, respectively. The detection rates of advanced neoplasia in the young diagnostic cohort was 5.0%, which was much lower than 11.8% in 50-54s screening cohort (P < 0.001). Compared with the 50-54s screening cohort, the risk of advanced neoplasia was significantly reduced by 50%, 66%, and 71% in the 45-49s, 40-44s, and 20-39s diagnostic cohorts, respectively. CONCLUSIONS: Colonoscopy to detect advanced neoplasia in young adults aged < 50 years should be reconsidered as their risk of advanced neoplasia on screening or diagnostic colonoscopy was much lower than those of 50-54s screening cohort; however, colonoscopy screening may be justified for high-risk 45-49s cohorts.

Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis.

BACKGROUND: The inverse association between body mass index (BMI) and mortality observed in patients treated with maintenance hemodialysis (MHD), also known as the obesity paradox, may be a result of residual confounding. Marginal structural model (MSM) analysis, a technique that accounts for time-varying confounders, may be more appropriate to investigate this association. We hypothesize that after applying MSM, the inverse association between BMI and mortality in MHD patients is attenuated. METHODS: We examined the associations between BMI and all-cause mortality among 123 624 adult MHD patients treated during 2001-6. We examined baseline and time-varying BMI using Cox proportional hazards models and MSM while considering baseline and time-varying covariates, including demographics, comorbidities and markers of malnutrition and inflammation. RESULTS: The patients included 45% women and 32% African Americans with a mean age of 61(SD 15) years. In all models, BMI showed a linear incremental inverse association with mortality. Compared with the reference (BMI 25 to <27.5 kg/m(2)), a BMI of <18 kg/m(2) was associated with a 3.2-fold higher death risk [hazard ratio (HR) 3.17 (95% CI 3.05-3.29)], and mortality risks declined with increasing BMI with the greatest survival advantage of 31% lower risk [HR 0.69 (95% CI 0.64-0.75)] observed with a BMI of 40 to <45 kg/m(2). CONCLUSIONS: The linear inverse relationship between BMI and mortality is robust across models including MSM analyses that more completely account for time-varying confounders and biases.

Rebamipide attenuates 5-Fluorouracil-induced small intestinal mucositis in a mouse model.

5-Fluorouracil (5-FU)-induced intestinal mucositis is one of the most common morbidities in chemotherapy and involves the reactive oxygen species (ROS) system, apoptosis, and inflammatory cytokines. Rebamipide exerts a mucosal-protective effect, mediated through several mechanisms. The aim of this study was to evaluate the effects of rebamipide in 5-FU-induced mouse small-intestinal mucositis. BALB/c mice were assigned randomly to four groups; (1) control group (n=10; receiving saline orally for 6 d), (2) rebamipide group (n=10; 150 mg/kg rebamipide for 6 d orally), (3) 5-FU group (n=10; 30 mg/kg 5-FU for 5 d, intraperitoneally (i.p.)), and (4) rebamipide +5-FU group (n=10; 150 mg/kg rebamipide for 6 d orally and 30 mg/kg 5-FU for 5 d, i.p.). Body weights and diarrhea scales were assessed. At day 5, the mice were sacrificed. Small intestinal tissue was used for: (1) hematoxylin and eosin (HE) staining for determination of small intestinal villi height, (2) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay, (3) immunohistochemistry for inducible nitric oxide synthase (iNOS), F4/80, and transforming growth factor (TGF)-ß1, (4) measurement of serum and tissue GSH levels, and (5) measurement of serum tumor necrosis factor (TNF)-α levels. Rebamipide attenuated the severity of mucosal injury reflected by body weight changes, degrees of diarrhea, and heights of villi. Rebamipide reduced the expression of iNOS and TGF-ß1, apoptosis, macrophage accumulation, serum TNF-α levels, and prevented reductions in serum and tissue glutathione (GSH) levels by 5-FU administration. These results suggest that rebamipide promotes several mechanisms of mucosal protection and attenuated the 5-FU-induced mucosal injury. In conclusion, administration of rebamipide may have significant protective effects against 5-FU-induced intestinal mucositis.

Safety and efficacy of a novel, fenestrated aortic arch stent graft with a preloaded catheter for supraaortic arch vessels: an experimental study in Swine.

Thoracic endovascular aortic repair (TEVAR) shows limitations in cases in which the aortic pathology involves the aortic arch. The study aims were to test a fenestrated aortic arch stent graft (FASG) with a preloaded catheter for the supraaortic arch vessels and to perform a preclinical study in swine to evaluate the safety and efficacy of this device. Six FASGs with 1 preloaded catheter and 5 FASGs with 2 preloaded catheters were advanced through the iliac artery in 11 swines. The presence of endoleaks and the patency and deformity of the grafts were examined with computed tomography (CT) at 4 weeks postoperatively. A postmortem examination was performed at 8 weeks. The mean procedure time for the one and two FASG groups was 30.2 (27.9-34.5) min and 43.1 (39.2-53.7) min. The mean time for the selection of the carotid artery was 4.8 (4.2-5.5) min and 6.2 (4.6-9.4) min. Major adverse event was observed in one of 11 pigs. One pig died at 4 weeks likely because of the effects of the high dose of ketamine, while the remaining 10 pigs survived 8-week. For both the one and two FASG groups, no endoleaks, no disconnection, no occlusion of the stent grafts were observed in the CT findings and the postmortem gross findings. The procedure with the FASG could be performed safely in a relatively short procedure time and involved an easy technique. The FASG is found to be safe and convenient in this preclinical study with swine.

Effect of age and dialysis vintage on obesity paradox in long-term hemodialysis patients.

BACKGROUND: In contrast to the general population, higher body mass index (BMI) is associated with greater survival in patients receiving hemodialysis (HD; "obesity paradox"). We hypothesized that this paradoxical association between BMI and death may be modified by age and dialysis vintage. STUDY DESIGN: Retrospective observational study using a large HD patient cohort. SETTING & PARTICIPANTS: 123,383 maintenance HD patients treated in DaVita dialysis clinics between July 1, 2001, and June 30, 2006, with follow-up through September 30, 2009. PREDICTORS: Age, dialysis vintage, and time-averaged BMI. Time-averaged BMI was divided into 6 subgroups; <18.5, 18.5-<23.0, 23.0-<25.0, 25.0-<30.0, 30.0-<35.0, and ≥35.0kg/m(2). BMI category of 23-<25kg/m(2) was used as the reference category. OUTCOMES: All-cause, cardiovascular, and infection-related mortality. RESULTS: Mean BMI of study participants was 27±7kg/m(2). Time-averaged BMI was <18.5 and ≥35kg/m(2) in 5% and 11% of patients, respectively. With progressively higher time-averaged BMI, there was progressively lower all-cause, cardiovascular, and infection-related mortality in patients younger than 65 years. In those 65 years or older, even though overweight/obese patients had lower mortality compared with underweight/normal-weight patients, sequential increases in time-averaged BMI > 25kg/m(2) added no additional benefit. Based on dialysis vintage, incident HD patients had greater all-cause and cardiovascular survival benefit with a higher time-averaged BMI compared with the longer term HD patients. LIMITATIONS: Causality cannot be determined, and residual confounding cannot be excluded given the observational study design. CONCLUSIONS: Higher BMI is associated with lower death risk across all age and dialysis vintage groups. This benefit is more pronounced in incident HD patients and those younger than 65 years. Given the robustness of the survival advantage of higher BMI, examining interventions to maintain or even increase dry weight in HD patients irrespective of age and vintage are warranted.

Dose of hemodialysis and survival: a marginal structural model analysis.

BACKGROUND: Observational studies have consistently demonstrated the survival benefits of a greater dialysis dose in maintenance hemodialysis (MHD) patients, whereas randomized controlled trials have shown conflicting results. The possible causal impact of dialysis dose on mortality needs to be investigated using rich cohort data analyzed with novel statistical methods such as marginal structural models (MSMs) that account for time-varying confounding and exposure. METHODS: We quantified the effect of delivered dose of hemodialysis (HD) [single-pool Kt/V (spKt/V)] on mortality risk in a contemporary cohort of 68,110 patients undergoing HD 3 times weekly (7/2001- 9/2005). We compared conventional Cox proportional hazard and MSM survival analyses, accounting for time-varying confounding by applying longitudinally modeled inverse-probability-of-dialysis-dose weights to each observation. RESULTS: In conventional Cox models, baseline spKt/V showed a weak negative association with mortality, while higher time-averaged spKt/V was strongly associated with lower mortality risk. In MSM analyses, compared to a spKt/V range of 1.2 - <1.4, a spKt/V range of <1.2 was associated with a higher risk of mortality [HR (95% CI) 1.67 (1.54 - 1.80)], whereas mortality risks were significantly lower with higher spKt/V [HRs (95% CI): 0.74 (0.70-0.78), 0.63 (0.59-0.66), 0.56 (0.52-0.60), and 0.56 (0.52-0.61) for spKt/V ranges of 1.4 - <1.6, 1.6-<1.8, 1.8 - <2.0, and ≥2.0, respectively]. Thus, MSM analyses showed that the greatest survival advantage of a higher dialysis dose was observed for a spKt/V range of 1.8-<2.0, and the dialysis dose-mortality relationship was robust in almost all subgroups of patients. CONCLUSIONS: Higher HD doses were robustly associated with greater survival in MSM analyses that more fully and appropriately accounted for time-varying confounding.

Impact of age, race and ethnicity on dialysis patient survival and kidney transplantation disparities.

BACKGROUND: Prior studies show that African-American and Hispanic dialysis patients have lower mortality risk than whites. Recent age-stratified analyses suggest this survival advantage may be limited to younger age groups, but did not concurrently compare Hispanic, African-American, and white patients, nor account for differences in nutritional and inflammatory status as potential confounders. Minorities experience inequities in kidney transplantation access, but it is unknown whether these racial/ethnic disparities differ across age groups. METHODS: The associations between race/ethnicity with all-cause mortality and kidney transplantation were separately examined among 130,909 adult dialysis patients from a large national dialysis organization (entry period 2001-2006, follow-up through 2009) within 7 age categories using Cox proportional hazard models adjusted for case-mix and malnutrition and inflammatory surrogates. RESULTS: African-Americans had similar mortality versus whites in younger age groups (18-40 years), but decreased mortality in older age groups (>40 years). In contrast, Hispanics had lower mortality versus whites across all ages. In sensitivity analyses using competing risk regression to account for differential kidney transplantation rates across racial/ethnic groups, the African-American survival advantage was limited to >60-years age categories. African-Americans and Hispanics were less likely to undergo kidney transplantation from all donor types versus whites across all ages, and these disparities were even more pronounced for living donor kidney transplantation (LDKT). CONCLUSIONS: Hispanic dialysis patients have greater survival versus whites across all ages; in African-Americans, this survival advantage is limited to patients >40 years of age. Minorities are less likely to undergo kidney transplantation, particularly LDKT, across all ages.

Association of vascular access type with inflammatory marker levels in maintenance hemodialysis patients.

Aggressive NIH is a common histopathological lesion found at the sites of venous stenosis in arteriovenous fistula (AVF) and arteriovenous grafts (AVG). Inflammatory mediators have been proposed to play a pathogenic role in NIH, but there is paucity of data evaluating this hypothesis in clinical studies or in animal models. Serum levels of inflammatory mediators can potentially identify patients at high risk of AVF and AVG dysfunction. In a cross-sectional cohort study of 754 HD patients who were part of the NIED study cohort, we examined the associations between inflammatory markers including serum interleukin (IL) 1ß, IL-6, C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) and type of vascular access. Unadjusted and multivariate-adjusted linear regression models were used. In addition, time-dependent regression model was used to assess the association between inflammatory markers and mortality. We observed that in the multivariate-adjusted model, inflammatory mediators interleukin-6 (IL-6), interleukin-1L-ß (IL-1ß), and C-reactive protein (CRP), the predicted value in hemodialysis patients, are lowest in patients with AVF and highest in central venous catheter (CVC) and AVG even in case-mix and malnutrition-inflammation complex syndrome (MICS)-adjusted models. IL-6 and CRP levels fall consistently in the same patients when AVG or CVC is changed to AVF and increase if the same patient changes access from AVF to AVG or CVC. Obesity is a risk factor for fistula failure and fistulas are associated with the lowest mortality compared with CVC and AVG. We did not find any statistically significant association between tumor necrosis factor-α (TNF- α) and vascular access outcomes. Higher levels of inflammatory mediators seen in CVC and AVG compared with AVF could potentially explain the higher mortality seen in patients with CVC and AVG compared with AVF.

Remote ischemic preconditioning in hemodialysis: a pilot study.

Hemodialysis (HD)-induced myocardial ischemia is associated with an elevated cardiac troponin T, and is common in asymptomatic patients undergoing conventional HD. Remote ischemic preconditioning (RIPC) has a protective effect against myocardial ischemia-reperfusion injury. We hypothesized that RIPC also has a protective effect on HD-induced myocardial injury. Chronic HD patients were randomized to the control group or the RIPC group. RIPC was induced by transient occlusion of blood flow to the arm with a blood-pressure cuff for 5 min, followed by 5 min of deflation. Three cycles of inflation and deflation were undertaken before every HD session for 1 month (total 12 times). The primary outcome was the change in cardiac troponin T (cTnT) level at day 28 from baseline. Demographic and baseline laboratory values were not different between the control (n = 17) and the RIPC groups (n = 17). cTnT levels tended to decrease from day 2 in the RIPC group through to 28 days, in contrast to no change in the control group. There were significant differences in the change of cTnT level at day 28 from baseline [Control, median; -0.002 ng/ml (interquartile range -0.008 to 0.018) versus RIPC, median; -0.015 ng/ml (interquartile range -0.055 to 0.004), P = 0.012]. RIPC reduced cTnT release in chronic conventional HD patients, suggesting that this simple, cheap, safe, and well-tolerated procedure has a protective effect against HD-induced ischemia.