Challenges of Predicting Arteriovenous Access Survival Prior to Conversion from Catheter.

OBJECTIVE: The decision to convert from catheter to arteriovenous access is difficult yet very important. The ability to accurately predict fistula survival prior to surgery would significantly improve the decision making process. Many previously investigated demographic and clinical features have been associated with fistula failure. However, it is not conclusively understood how reliable predictions based on these parameters are at an individual level. The aim of this study was to investigate the probability of arteriovenous fistula maturation and survival after conversion using machine learning workflows. METHODS: A retrospective cohort study on multicentre data from a large North American dialysis organisation was conducted. The study population comprised 73 031 chronic in centre haemodialysis patients. The dataset included 49 variables including demographic and clinical features. Two distinct feature selection and prediction pipelines were used: LASSO regression and Boruta followed by a random forest classifier. Predictions were facilitated for re-conversion to catheter within one year. Additionally, all cause mortality predictions were conducted to serve as a comparator. RESULTS: In total, 38 151 patients (52.2%) had complete data and made up the main cohort. Sensitivity analyses were conducted in 67 421 patients (92.3%) after eliminating variables with a high proportion of missing data points. Selected features diverged between datasets and workflows. A previously failed arteriovenous access appeared to be the most stable predictor for subsequent failure. Prediction of re-conversion based on the demographic and clinical information resulted in an area under the receiver operating characteristic curve (ROCAUC) between 0.541 and 0.571, whereas models predicting all cause mortality performed considerably better (ROCAUC 0.662 - 0.683). CONCLUSION: While group level depiction of major adverse outcomes after catheter to arteriovenous fistula or graft conversion is possible using the included variables, patient level predictions are associated with limited performance. Factors during and after fistula creation as well as biomolecular and genetic biomarkers might be more relevant predictors of fistula survival than baseline clinical conditions.

Real-time prediction of intradialytic hypotension using machine learning and cloud computing infrastructure.

BACKGROUND: In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. METHODS: We developed a machine learning model to predict IDH in in-center hemodialysis patients 15-75 min in advance. IDH was defined as systolic blood pressure (SBP) <90 mmHg. Demographic, clinical, treatment-related and laboratory data were retrieved from electronic health records and merged with intradialytic machine data that were sent in real-time to the cloud. For model development, dialysis sessions were randomly split into training (80%) and testing (20%) sets. The area under the receiver operating characteristic curve (AUROC) was used as a measure of the model's predictive performance. RESULTS: We utilized data from 693 patients who contributed 42 656 hemodialysis sessions and 355 693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15-75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. CONCLUSIONS: Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies.

Assembly and co-occurrence patterns of rhizosphere bacterial communities are closely linked to soil fertility during continuous cropping of cut chrysanthemum (Chrysanthemum morifolium Ramat).

AIMS: Continuous cropping is known to have profound effects on the soil microbial community in different planting systems. However, we lack an understanding of how different years of continuous cropping affects rhizosphere soil bacterial community co-occurrence pattern and assembly processes in the cut chrysanthemum (Chrysanthemum morifolium Ramat.) field. METHODS AND RESULTS: We collected the soils from cut chrysanthemum rhizospheres with planting for 1 year (PY1) and continuous cropping for 6 years (CY6) and 12 years (CY12). Real-time quantitative PCR and flow cytometry (FCM) techniques were used to test the 16S rRNA gene copy number and bacterial cell count, respectively. The bacterial community structure was analysed by using high-throughput sequencing technology. The CY12 had a significantly decreased soil fertility index and rhizosphere bacterial living cell counts and gene copy numbers compared to CY6 and PY1 (P < 0.05). The rhizosphere bacterial community dissimilarity increased as the continuous cropping years increased. Three main ecological clusters (modules #1, #2, and #3) were observed in the bacterial co-occurrence network across all samples, and only the relative abundance of module #1 (enriched in the CY12) was significantly correlated with soil fertility (P < 0.05). Moreover, the rhizosphere bacterial community assembly was primarily governed by the deterministic process under 12 years of continuous cropping. CONCLUSIONS: Soil fertility decline correlates with ecological network modularization and the deterministic assembly process of the rhizosphere bacterial community of cut chrysanthemum during continuous cropping.

Gut Microbiome-Derived Uremic Toxin Levels in Hemodialysis Patients on Different Phosphate Binder Therapies.

INTRODUCTION: Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients. METHODS: Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly. RESULTS: The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, p < 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5-7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups. CONCLUSION: There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels.

The time of onset of intradialytic hypotension during a hemodialysis session associates with clinical parameters and mortality.

Intradialytic hypotension (IDH) is a common complication of hemodialysis, but there is no data about the time of onset during treatment. Here we describe the incidence of IDH throughout hemodialysis and associations of time of hypotension with clinical parameters and survival by analyzing data from 21 dialysis clinics in the United States to include 785682 treatments from 4348 patients. IDH was defined as a systolic blood pressure of 90 mmHg or under while IDH incidence was calculated in 30-minute intervals throughout the hemodialysis session. Associations of time of IDH with clinical and treatment parameters were explored using logistic regression and with survival using Cox-regression. Sensitivity analysis considered further IDH definitions. IDH occurred in 12% of sessions at a median time interval of 120-149 minutes. There was no notable change in IDH incidence across hemodialysis intervals (range: 2.6-3.2 episodes per 100 session-intervals). Relative blood volume and ultrafiltration volume did not notably associate with IDH in the first 90 minutes but did thereafter. Associations between central venous but not arterial oxygen saturation and IDH were present throughout hemodialysis. Patients prone to IDH early as compared to late in a session had worse survival. Sensitivity analyses suggested IDH definition affects time of onset but other analyses were comparable. Thus, our study highlights the incidence of IDH during the early part of hemodialysis which, when compared to later episodes, associates with clinical parameters and mortality.

Artificial intelligence enabled applications in kidney disease.

Artificial intelligence (AI) is considered as the next natural progression of traditional statistical techniques. Advances in analytical methods and infrastructure enable AI to be applied in health care. While AI applications are relatively common in fields like ophthalmology and cardiology, its use is scarcely reported in nephrology. We present the current status of AI in research toward kidney disease and discuss future pathways for AI. The clinical applications of AI in progression to end-stage kidney disease and dialysis can be broadly subdivided into three main topics: (a) predicting events in the future such as mortality and hospitalization; (b) providing treatment and decision aids such as automating drug prescription; and (c) identifying patterns such as phenotypical clusters and arteriovenous fistula aneurysm. At present, the use of prediction models in treating patients with kidney disease is still in its infancy and further evidence is needed to identify its relative value. Policies and regulations need to be addressed before implementing AI solutions at the point of care in clinics. AI is not anticipated to replace the nephrologists' medical decision-making, but instead assist them in providing optimal personalized care for their patients.

Effect of Statewide Lockdown in Response to COVID-19 Pandemic on Physical Activity Levels of Hemodialysis Patients.

BACKGROUND/OBJECTIVES: On March 22, 2020, a statewide stay-at-home order for nonessential tasks was implemented in New York State. We aimed to determine the impact of the lockdown on physical activity levels (PAL) in hemodialysis patients. METHODS: Starting in May 2018, we are conducting an observational study with a 1-year follow-up on PAL in patients from 4 hemodialysis clinics in New York City. Patients active in the study as of March 22, 2020, were included. PAL was defined by steps taken per day measured by a wrist-based monitoring device (Fitbit Charge 2). Average steps/day were calculated for January 1 to February 13, 2020, and then weekly from February 14 to June 30. RESULTS: 42 patients were included. Their mean age was 55 years, 79% were males, and 69% were African Americans. Between January 1 and February 13, 2020, patients took on average 5,963 (95% CI 4,909-7,017) steps/day. In the week prior to the mandated lockdown, when a national emergency was declared, and in the week of the shutdown, the average number of daily steps had decreased by 868 steps/day (95% CI 213-1,722) and 1,222 steps/day (95% CI 668-2300), respectively. Six patients were diagnosed with COVID-19 during the study period. Five of them exhibited significantly higher PAL in the 2 weeks prior to showing COVID-19 symptoms compared to COVID-19 negative patients. CONCLUSION: Lockdown measures were associated with a significant decrease in PAL in hemodialysis patients. Patients who contracted COVID-19 had higher PAL during the incubation period. Methods to increase PAL while allowing for social distancing should be explored and implemented.

Transmission of SARS-CoV-2 considering shared chairs in outpatient dialysis: a real-world case-control study.

BACKGROUND: SARS-CoV-2 can remain transiently viable on surfaces. We examined if use of shared chairs in outpatient hemodialysis associates with a risk for indirect patient-to-patient transmission of SARS-CoV-2. METHODS: We used data from adults treated at 2,600 hemodialysis facilities in United States between February 1st and June 8th, 2020. We performed a retrospective case-control study matching each SARS-CoV-2 positive patient (case) to a non-SARS-CoV-2 patient (control) treated in the same dialysis shift. Cases and controls were matched on age, sex, race, facility, shift date, and treatment count. For each case-control pair, we traced backward 14 days to assess possible prior exposure from a 'shedding' SARS-CoV-2 positive patient who sat in the same chair immediately before the case or control. Conditional logistic regression models tested whether chair exposure after a shedding SARS-CoV-2 positive patient conferred a higher risk of SARS-CoV-2 infection to the immediate subsequent patient. RESULTS: Among 170,234 hemodialysis patients, 4,782 (2.8 %) tested positive for SARS-CoV-2 (mean age 64 years, 44 % female). Most facilities (68.5 %) had 0 to 1 positive SARS-CoV-2 patient. We matched 2,379 SARS-CoV-2 positive cases to 2,379 non-SARS-CoV-2 controls; 1.30 % (95 %CI 0.90 %, 1.87 %) of cases and 1.39 % (95 %CI 0.97 %, 1.97 %) of controls were exposed to a chair previously sat in by a shedding SARS-CoV-2 patient. Transmission risk among cases was not significantly different from controls (OR = 0.94; 95 %CI 0.57 to 1.54; p = 0.80). Results remained consistent in adjusted and sensitivity analyses. CONCLUSIONS: The risk of indirect patient-to-patient transmission of SARS-CoV-2 infection from dialysis chairs appears to be low.

Di-(2-ethylhexyl) phthalate (DEHP) exposure suppressed the community diversity and abundance of ammonia-oxidizers and mitigated N2O emissions in an alkaline soil.

Phthalic acid esters (PAEs) pollution has become an increasing issue worldwide, but little is known about its effects on ammonia-oxidizers and nitrous oxide (N2O) in the soil environment. Here, a 50-day soil microcosm experiment was conducted using low and high doses bis (2-Ethylhexyl) phthalate (DEHP) to estimate the effect of DEHP exposure on soil N2O emissions and the nitrifying community in calcareous soil. The results showed that DEHP exposure at 10 and 100 mg kg-1 doses significantly reduced N2O by 67.5% and 73.6%, respectively, relative to the DEHP absent treatment. The microbial biomass carbon and nitrogen (MBC and MBN) were consistently and significantly decreased with DEHP exposure at 5, 22, and 50 days after incubation, especially with high-dose. The bipartite association networks showed that DEHP exposure changed the compositions of both ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) communities. Moreover, the AOA and AOB amoA gene abundances were significantly decreased by DEHP addition to the soil (P < 0.05). Random forest modeling showed that the AOB Shannon index and pH were the most important biotic and abiotic factors affecting N2O emissions in the soil with DEHP exposure, respectively. Partial least squares path modeling (PLS-PM) demonstrated that the reduction of N2O emissions due to DEHP exposure was mainly ascribed to the changes of the AOB community. The results from this study highlight the toxicity of DEHP on the ammonia oxidizers, and its mitigating effect on N2O emissions in the soil where ammonia-oxidation is largely driven by AOB.

Association of all-cause mortality with pre-dialysis systolic blood pressure and its peridialytic change in chronic hemodialysis patients.

BACKGROUND: Pre-dialysis systolic blood pressure (pre-HD SBP) and peridialytic SBP change have been associated with morbidity and mortality among hemodialysis (HD) patients in previous studies, but the nature of their interaction is not well understood. METHODS: We analyzed pre-HD SBP and peridialytic SBP change (calculated as post-HD SBP minus pre-HD SBP) between January 2001 and December 2012 in HD patients treated in US Fresenius Medical Care facilities. The baseline period was defined as Months 4-6 after HD initiation, and all-cause mortality was noted during follow-up. Only patients who survived baseline and had no missing covariates were included. Censoring events were renal transplantation, modality change or study end. We fitted a Cox proportional hazard model with a bivariate spline functions for the primary predictors (pre-HD SBP and peridialytic SBP change) with adjustment for age, gender, race, diabetes, access-type, relative interdialytic weight gain, body mass index, albumin, equilibrated normalized protein catabolic rate and ultrafiltration rate. RESULTS: A total of 172 199 patients were included. Mean age was 62.1 years, 61.6% were white and 55% were male. During a median follow-up of 25.0 months, 73 529 patients (42.7%) died. We found that a peridialytic SBP rise combined with high pre-HD SBP was associated with higher mortality. In contrast, when concurrent with low pre-HD SBP, a peridialytic SBP rise was associated with better survival. CONCLUSION: The association of pre-HD and peridialytic SBP change with mortality is complex. Our findings call for a joint, not isolated, interpretation of pre-HD SBP and peridialytic SBP change.

All-cause mortality in relation to changes in relative blood volume during hemodialysis.

BACKGROUND: Relative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown. METHODS: Intradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan-Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis. RESULTS: We studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93-96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42-0.79)]; second hour, 89-94% [HR 0.54 (95% CI 0.39-0.75)]; third hour, 86-92% [HR 0.46 (95% CI 0.33-0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors. CONCLUSION: Specific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients.

Tracking Arteriovenous Fistula Maturation: A Novel Approach.

BACKGROUND: The time between the creation of an arteriovenous fistula (AVF) and its successful use is significantly longer in hemodialysis (HD) patients in the United States compared to those in other countries, and there is an urgent need to reduce the residence time of central-venous catheters (CVC). METHODS: Successful AVF creation and maturation results in typical hemodynamic changes, such as an increase in cardiac output and upper body blood flow (UBBF). In patients with CVC as vascular access, we measured once per minute intradialytic central-venous oxygen saturation (ScvO2) and hemoglobin levels simultaneously using the Crit-Line Monitor. Under conditions of stable upper body oxygen consumption and arterial oxygen saturation, ScvO2 and hemoglobin concentration allows the calculation of estimated UBBF (eUBBF). In a quality improvement project, we used ScvO2 and eUBBF to track the hemodynamic changes accompanying AVF maturation. RESULTS: Out of 11 patients (9 incident to HD, 1 female, age 61 ± 13 years), AVF maturation was successful in 9. In 1 patient, the AVF did not mature. One patient died from sudden cardiac death with a maturing AVF. In the 9 patients with successful AVF maturation, ScvO2 increased from 60.9 ± 2.7% prior to AVF creation to 73.4 ± 3.6% a week after AVF creation (19.6 ± 6.3% increase). eUBBF increased from 1.3 ± 0.3 to 2.2 ± 0.6 L/min (62.7 ± 37.5% increase); no material ScvO2 or eUBBF changes occurred in the other 2 patients. CONCLUSION: Our results indicate the potential utility of ScvO2 and eUBBF to track the hemodynamic response to AVF maturation. To what extent these insights translate into shortening of the time between AVF creation and successful cannulation warrants further investigations.

Association of Central Venous Oxygen Saturation Variability and Mortality in Hemodialysis Patients.

BACKGROUND: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality. METHODS: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2. RESULTS: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 >  11% was associated with a significantly increased HR for all-cause mortality. CONCLUSION: High ScvO2 variability during dialysis is associated with increased all-cause mortality.

Rapid, Stoichiometric, Site-Specific Modification of Aldehyde-Containing Proteins Using a Tandem Knoevenagel-Intra Michael Addition Reaction.

A site-specific modification of aldehyde-containing proteins using a tandem Knoevenagel-intra Michael addition reaction was developed. The reaction featured fast kinetics (50 M-1 s-1) and favorable stoichiometry. Various functionalities could be introduced into the protein with little impact on its function and conformation. The reaction was successfully applied in the labeling of living cells.

Intradialytic hypertension is associated with low intradialytic arterial oxygen saturation.

Background: The pathophysiology of a paradoxical systolic blood pressure (SBP) rise during hemodialysis (HD) is not yet fully understood. Recent research indicated that 10% of chronic HD patients suffer from prolonged intradialytic hypoxemia. Since hypoxemia induces a sympathetic response we entertained the hypothesis that peridialytic SBP change is associated with arterial oxygen saturation (SaO2). Methods: We retrospectively analyzed intradialytic SaO2 and peridialytic SBP change in chronic HD patients with arteriovenous vascular access. Patients were followed for 6 months. We defined persistent intradialytic hypertension (piHTN) as average peridialytic SBP increase ≥10 mmHg over 6 months. Linear mixed effects (LME) models were used to explore associations between peridialytic SBP change and intradialytic SaO2 in univariate and adjusted analyses. Results: We assessed 982 patients (29 872 HD treatments; 59% males; 53% whites). Pre-dialysis SBP was 146.7 ± 26.5 mmHg and decreased on average by 10.1 ± 24.5 mmHg. Fifty-three (5.7%) patients had piHTN. piHTN patients had lower intradialytic SaO2, body weight and interdialytic weight gain. LME models revealed that with every percentage point lower mean SaO2, the peridialytic SBP change increased by 0.46 mmHg (P < 0.001). This finding was corroborated in multivariate analyses. Conclusion: We observed an inverse relationship between intradialytic SaO2 and the blood pressure response to HD. These findings support the notion that hypoxemia activates mechanisms that partially blunt the intradialytic blood pressure decline, possibly by sympathetic activation and endothelin-1 secretion. To further explore that hypothesis, specifically designed prospective studies are required.

Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis patients.

Background: Cardiac disease is highly prevalent in hemodialysis (HD) patients. Decreased tissue perfusion, including cardiac, due to high ultrafiltration volumes (UFVs) is considered to be one of the drivers of cardiac dysfunction. While central venous oxygen saturation (ScvO2) is frequently used as an indicator of cardiac output in non-uremic populations, the relationship of ScvO2 and UFV in HD patients remains unclear. Our aim was to determine how intradialytic ScvO2 changes associate with UFV. Methods: We conducted a 6-month retrospective cohort study in maintenance HD patients with central venous catheters as vascular access. Intradialytic ScvO2 was measured with the Critline monitor. We computed treatment-level slopes of intradialytic ScvO2 over time (ScvO2 trend) and applied linear mixed effects models to assess the association between patient-level ScvO2 trends and UFV corrected for body weight (cUFV). Results: We studied 6042 dialysis sessions in 232 patients. In about 62.4% of treatments, ScvO2 decreased. We observed in nearly 80% of patients an inverse relationship between cUFV and ScvO2 trend, indicating that higher cUFV is associated with steeper decline in ScvO2 during dialysis. Conclusions: In most patients, higher cUFV volumes are associated with steeper intradialytic ScvO2 drops. We hypothesize that in a majority of patients the intradialytic cardiac function is fluid dependent, so that in the face of high ultrafiltration rates or volume, cardiac pre-load and consequently cardiac output decreases. Direct measurements of cardiac hemodynamics are warranted to further test this hypothesis.

Association between Heights of Dialysis Patients and Outcomes: Results from a Retrospective Cohort Study of the International MONitoring Dialysis Outcomes (MONDO) Database Initiative.

BACKGROUND: Tall people have improved metabolic profiles and better cardiovascular outcomes, a relationship inverted in dialysis patients. We investigated the relationship between height and outcomes in incident hemodialysis (HD) patients commencing treatment in an analysis of the international Monitoring Dialysis Outcomes (MONDO) database. METHODS: In this retrospective cohort study, we included incident HD patients commencing treatment between -January 1, 2006 and December 31, 2010 and investigated the association between height and mortality using the MONDO database. A 6-months baseline period preceded 2.5 years of follow-up, during which we recorded patient mortality. Patients were stratified in region-specific deciles of the respective database's population (Asia Pacific, North and South America, and Europe) and we developed Cox-proportional hazard models (additionally adjusted for age, gender, post-dialysis weight, eKt/V, albumin, interdialytic weight gain, phosphorus, and predialysis systolic blood pressure) for each database. RESULTS: We studied 23,353 patients (62 ± 15 years old, 42% female, body mass index 26 ± 6 kg/m2, height 165 ± 10 cm). We found a trend of increasing hazard ratio of death (HR) with increasing height for Asia Pacific, Europe, and South America. In the fully adjusted models, for South America, we found a trend of increasing HR without significance among deciles >5. In Europe, deciles 8-10 had significantly increased HR. No clear trend was found in North America. CONCLUSION: We found an increasing risk of death with increasing height in all regions, except North America. While the reasons remain unclear, further research may be warranted.

Effects of dialysate to serum sodium (Na+) alignment in chronic hemodialysis (HD) patients: retrospective cohort study from a quality improvement project.

BACKGROUND: Evidence indicates favorable effects of dialysate (DNa+) to serum sodium concentration (SNa+) alignment, however, results from larger sample populations are needed. For this reason, we conducted a retrospective propensity score-matched cohort study from a quality improvement project to investigate the effects of alignment on population of maintenance hemodialysis patients. METHODS: At 4 participating hemodialysis (HD) clinics, patients with SNa+ lower than the standard DNa+ of 137 mEq/L who received HD with DNa+ aligned to the average of the last 4 SNa+ measurements were evaluated (clinicaltrials.gov # NCT01825590 ). In this retrospective data analysis, an intention-to-treat (primary) and an as-treated "intervention" (secondary) cohort were created. "Aligned" patients from both cohorts (N = 163 for the primary and N = 137 for the secondary) were then propensity-score matched in a 1:1 fashion to "unaligned" patients from the Renal Research Institute database. The propensity score was generated based on age, gender, white race, Hispanic ethnicity, absence or presence of diabetes, hemodialysis vintage, interdialytic weight gain (IDWG; as a percentage of postdialysis body weight), catheter as primary dialysis access, predialysis systolic blood pressure, serum sodium concentration, hospitalization count during baseline. T-Test was employed for group comparisons of changes to the primary (volume-related and hemodynamic parameters) and tertiary outcomes. All-cause and fluid overload-related hospitalization admission rates were compared using Wilcoxon Rank Sum test and Cox regression analysis for repeated events. RESULTS: In the primary analysis, aligned and unaligned subjects showed comparable demographics at baseline. Treatment effects were significant for IDWG [-0.12 (95% CI -0.24 to 0) L] and showed decreasing non-significant trends for pre-dialysis hemodynamic parameters. Count comparison and Cox regression analysis showed no clear advantage of alignment in terms of all-cause and fluid overload-related hospitalization. CONCLUSIONS: Results from the largest sodium alignment program to date suggest positive treatment effects on volume-related and hemodynamic parameters, but no clear effect on risk of hospitalization. Well-matched control patients minimized confounding effects. Small effects and lack of significant differences may be explained by a low baseline DNa+ limiting the interventional change.

The investigation of cobalt intercalation underneath epitaxial graphene on 6H-SiC(0 0 0 1).

The intercalation behaviour of cobalt underneath both epitaxial graphene monolayer and bilayer on 6H-SiC(0001) have been investigated by scanning tunneling microscopy (STM) and density functional theory (DFT). Upon deposition, cobalt atoms prefer to agglomerate into clusters on the epitaxial graphene. After annealing the sample to 850 °C, the intercalation of the adsorbed cobalt atoms into both monolayer and bilayer epitaxial graphene on SiC takes place, as observed by the atomically resolved STM images. Further studies based on DFT modeling and simulated STM images show that, resulting from the interplay between the intercalated cobalt atoms and the carbon layers sandwiching it, the most energetically favourable intercalation sites of cobalt atoms underneath monolayer and bilayer graphene differ. Furthermore, the results show energy barriers of 0.60 eV and 0.41 eV for cobalt penetration through mono-vacancy defects at monolayer and bilayer graphene.

Reduced mouse allergen is associated with epigenetic changes in regulatory genes, but not mouse sensitization, in asthmatic children.

Chronic exposure to mouse allergen may contribute greatly to the inner-city asthma burden. We hypothesized that reducing mouse allergen exposure may modulate the immunopathology underlying symptomatic pediatric allergic asthma, and that this occurs through epigenetic regulation. To test this hypothesis, we studied a cohort of mouse sensitized, persistent asthmatic inner-city children undergoing mouse allergen-targeted integrated pest management (IPM) vs education in a randomized controlled intervention trial. We found that decreasing mouse allergen exposure, but not cockroach, was associated with reduced FOXP3 buccal DNA promoter methylation, but this was unrelated to mouse specific IgE production. This finding suggests that the environmental epigenetic regulation of an immunomodulatory gene may occur following changing allergen exposures in some highly exposed cohorts. Given the clinical and public health importance of inner-city pediatric asthma and the potential impact of environmental interventions, further studies will be needed to corroborate changes in epigenetic regulation following changing exposures over time, and determine their impact on asthma morbidity in susceptible children.