FG-4592 protected haematopoietic system from ionising radiation in mice.

Ionising radiation exposure can lead to acute haematopoietic radiation syndrome. Despite significant advancements in the field of radioprotection, no drugs with high efficacy and low toxicity have yet been approved by the Food and Drug Administration. FG-4592, as a proline hydroxylase inhibitor, may play an important role in radioprotection of the haematopoietic system. Mice were peritoneal injected with FG-4592 or normal saline. After irradiation, the survival time, body weight, peripheral blood cell and bone marrow cell (BMC) count, cell apoptosis, pathology were analysed and RNA-sequence technique (RNA-Seq) was conducted to explore the mechanism of FG-4592 in the haematopoietic system. Our results indicated that FG-4592 improved the survival rate and weight of irradiated mice and protected the spleen, thymus and bone marrow from IR-induced injury. The number of BMCs was increased and protected against IR-induced apoptosis. FG-4592 also promoted the recovery of the blood system and erythroid differentiation. The results of RNA-Seq and Western blot showed that the NF-κB signalling pathway and hypoxia-inducible factor-1 (HIF-1) signalling pathway were upregulated by FG-4592. Meanwhile, RT-PCR results showed that FG-4592 could promote inflammatory response significantly. FG-4592 exhibited radioprotective effects in the haematopoietic system by promoting inflammatory response and targeting the NF-κB, HIF signalling pathway.

Risk factors analysis of lateral cervical lymph node metastasis in papillary thyroid carcinoma: a retrospective study of 830 patients.

OBJECTIVE: The aim of this study is to investigate the risk factors for lateral cervical lymph node metastasis in papillary thyroid carcinoma (PTC). METHODS: Clinicopathological data (age, gender, Hashimoto's thyroiditis, preoperative circulating tumor cells (CTCs), multifocal, maximum lesion diameter, invaded capsule, T stage, and lymph node metastasis) of 830 PTC patients diagnosed and treated in Meizhou People's Hospital from June 2021 to April 2023 were collected. The related factors of lateral cervical lymph node metastasis were analyzed. RESULTS: There were 334 (40.2%), and 103 (12.4%) PTC patients with central lymph node metastasis, and lateral cervical lymph node metastasis, respectively. Compared with patients without lateral cervical lymph node metastasis, PTC patients with lateral cervical lymph node metastasis had a higher proportion of multifocal, maximum lesion diameter > 1 cm, invaded capsule, T3-T4 stage. Regression logistic analysis showed that male (odds ratio (OR): 2.196, 95% confidence interval (CI): 1.279-3.769, p = 0.004), age < 55 years old (OR: 2.057, 95% CI: 1.062-3.988, p = 0.033), multifocal (OR: 2.759, 95% CI: 1.708-4.458, p < 0.001), maximum lesion diameter > 1 cm (OR: 5.408, 95% CI: 3.233-9.046, p < 0.001), T3-T4 stage (OR: 2.396, 95% CI: 1.241-4.626, p = 0.009), and invaded capsule (OR: 2.051, 95% CI: 1.208-3.480, p = 0.008) were associated with lateral cervical lymph node metastasis. CONCLUSIONS: Male, age < 55 years old, multifocal, maximum lesion diameter > 1 cm, T3-T4 stage, and invaded capsule were independent risk factors for lateral cervical lymph node metastasis in PTC.

Roxadustat protect mice from DSS-induced colitis in vivo by up-regulation of TLR4.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) is growing in the population. At present, the etiology of inflammatory bowel disease remains unclear, and there is no effective and low-toxic therapeutic drug. The role of the PHD-HIF pathway in relieving DSS-induced colitis is gradually being explored. METHODS: Wild-type C57BL/6 mice were used as a model of DSS-induced colitis to explore the important role of Roxadustat in alleviating DSS-induced colitis. High-throughput RNA-Seq and qRT-PCR methods were used to screen and verify the key differential genes in the colon of mice between normal saline (NS) and Roxadustat groups. RESULTS: Roxadustat could alleviate DSS-induced colitis. Compared with the mice in the NS group, TLR4 were significantly up-regulated in the Roxadustat group. TLR4 KO mice were used to verify the role of TLR4 in the alleviation of DSS-induced colitis by Roxadustat. CONCLUSION: Roxadustat has a repairing effect on DSS-induced colitis, and may alleviate DSS-induced colitis by targeting the TLR4 pathway and promote intestinal stem cell proliferation.

Evaluating Urban Building Damage of 2023 Kahramanmaras, Turkey Earthquake Sequence Using SAR Change Detection.

On February 6, 2023 (local time), two earthquakes (Mw7.8 and Mw7.7) struck central and southern Turkey, causing extensive damage to several cities and claiming a toll of 40,000 lives. In this study, we propose a method for seismic building damage assessment and analysis by combining SAR amplitude and phase coherence change detection. We determined building damage in five severely impacted urban areas and calculated the damage ratio by measuring the urban area and the damaged area. The largest damage ratio of 18.93% is observed in Nurdagi, and the smallest ratio of 7.59% is found in Islahiye. We verified the results by comparing them with high-resolution optical images and AI recognition results from the Microsoft team. We also used pixel offset tracking (POT) technology and D-InSAR technology to obtain surface deformation using Sentinel-1A images and analyzed the relationship between surface deformation and post-earthquake urban building damage. The results show that Nurdagi has the largest urban average surface deformation of 0.48 m and Antakya has the smallest deformation of 0.09 m. We found that buildings in the areas with steeper slopes or closer to earthquake faults have higher risk of collapse. We also discussed the influence of SAR image parameters on building change recognition. Image resolution and observation geometry have a great influence on the change detection results, and the resolution can be improved by various means to raise the recognition accuracy. Our research findings can guide earthquake disaster assessment and analysis and identify influential factors of earthquake damage.

How Temperature Influences Sleep.

Sleep is a fundamental, evolutionarily conserved, plastic behavior that is regulated by circadian and homeostatic mechanisms as well as genetic factors and environmental factors, such as light, humidity, and temperature. Among environmental cues, temperature plays an important role in the regulation of sleep. This review presents an overview of thermoreception in animals and the neural circuits that link this process to sleep. Understanding the influence of temperature on sleep can provide insight into basic physiologic processes that are required for survival and guide strategies to manage sleep disorders.

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.

Characteristics of healthcare workers who died during the fight against COVID-19 in China.

Coronavirus disease 2019 (COVID-19), first reported in December 2019 in Wuhan, China, has progressed to a pandemic associated with substantial morbidity and mortality. Little is known about the healthcare workers who died fighting the disease in China. This paper analyzed the data of 78 Chinese healthcare workers who died in the fight against COVID-19 between 23 January and 2 June, 2020, and revealed the following characteristics. First, compared to the number of deaths directly attributable to COVID-19, more healthcare workers died from pre-existing disease attack induced by excessive fatigue or died from accidents. Second, the median age of the healthcare workers who died directly from COVID-19 was younger than that of the Wuhan non- healthcare workers who died of COVID 19. Third, although more women than men were involved in fighting the pandemic, more men died. Fourth, more healthcare workers died in Hubei than in other provinces. Fifth, most of the healthcare workers who died directly from COVID-19 were non-professionals.

Clinical and predictive value of simplified creatinine index used as muscle mass surrogate in end-stage kidney disease haemodialysis patients-results from the international MONitoring Dialysis Outcome initiative.

BACKGROUND: Protein-energy wasting, muscle mass (MM) loss and sarcopenia are highly prevalent and associated with poor outcome in haemodialysis (HD) patients. Monitoring of MM and/or muscle metabolism in HD patients is of paramount importance for timely detection of muscle loss and to intervene adequately. In this study we assessed the reliability and reproducibility of a simplified creatinine index (SCI) as a surrogate marker of MM and explored its predictive value on outcome. METHOD: We included all in-centre HD patients from 16 European countries with at least one SCI. The baseline period was defined as 30 days before and after the first multifrequency bioimpedance spectroscopy measurement; the subsequent 7 years constituted the follow-up. SCI was calculated by the Canaud equation. Multivariate Cox proportional hazards models were applied to assess the association of SCI with all-cause mortality. Using backward analysis, we explored the trends of SCI before death. Bland-Altman analysis was performed to analyse the agreement between estimated and measured MM. RESULTS: We included 23 495 HD patients; 3662 were incident. Females and older patients have lower baseline SCI. Higher SCI was associated with a lower risk of mortality [hazard ratio 0.81 (95% confidence interval 0.79-0.82)]. SCI decline accelerated ∼5-7 months before death. Lean tissue index (LTI) estimated by SCI was correlated with measured LTI in both sexes (males: R2 = 0.94; females: R2 = 0.92; both P < 0.001). Bland-Altman analysis showed that measured LTI was 4.71 kg/m2 (±2 SD: -12.54-3.12) lower than estimated LTI. CONCLUSION: SCI is a simple, easily obtainable and clinically relevant surrogate marker of MM in HD patients.

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.

Impacts of dialysis adequacy and intradialytic hypotension on changes in dialysis recovery time.

BACKGROUND: Dialysis recovery time (DRT) surveys capture the perceived time after HD to return to performing regular activities. Prior studies suggest the majority of HD patients report a DRT > 2 h. However, the profiles of and modifiable dialysis practices associated with changes in DRT relative to the start of dialysis are unknown. We hypothesized hemodialysis (HD) dose and rates of intradialytic hypotension (IDH) would associate with changes in DRT in the first years after initiating dialysis. METHODS: We analyzed data from adult HD patients who responded to a DRT survey ≤180 days from first date of dialysis (FDD) during 2014 to 2017. DRT survey was administered with annual KDQOL survey. DRT survey asks: "How long does it take you to be able to return to your normal activities after your dialysis treatment?" Answers are: < 0.5, 0.5-to-1, 1-to-2, 2-to-4, or > 4 h. An adjusted logistic regression model computed odds ratio for a change to a longer DRT (increase above DRT > 2 h) in reference to a change to a shorter DRT (decrease below DRT < 2 h, or from DRT > 4 h). Changes in DRT were calculated from incident (≤180 days FDD) to first prevalent (> 365-to- ≤ 545 days FDD) and second prevalent (> 730-to- ≤ 910 days FDD) years. RESULTS: Among 98,616 incident HD patients (age 62.6 ± 14.4 years, 57.8% male) who responded to DRT survey, a higher spKt/V in the incident period was associated with 13.5% (OR = 0.865; 95%CI 0.801-to-0.935) lower risk of a change to a longer DRT in the first-prevalent year. A higher number of HD treatments with IDH episodes per month in the incident period was associated with a 0.8% (OR = 1.008; 95%CI 1.001-to-1.015) and 1.6% (OR = 1.016; 95%CI 1.006-to-1.027) higher probability of a change to a longer DRT in the first- and second-prevalent years, respectively. Consistently, an increased in incidence of IDH episodes/months was associated to a change to a longer DRT over time. CONCLUSIONS: Incident patients who had higher spKt/V and less sessions with IDH episodes had a lower likelihood of changing to a longer DRT in first year of HD. Dose optimization strategies with cardiac stability in fluid removal should be tested.

Prediction of Mortality and Hospitalization Risk Using Nutritional Indicators and Their Changes Over Time in a Large Prevalent Hemodialysis Cohort.

OBJECTIVE(S): Malnutrition and protein-energy wasting are associated with morbidity and mortality in hemodialysis patients. Existing nutritional scores rely primarily on cross-sectional data. Using readily available nutritional indicators, we developed models to predict the risk of mortality and hospitalization in prevalent hemodialysis patients. DESIGN AND METHODS: In this retrospective study, we constructed prediction models of 1-year mortality and hospitalization using generalized linear models, generalized additive models (GAM), classification tree, and random forest models. The models were compared using area under the receiver-operating characteristics curve (AUC) and calibration curves. Model predictors included nutritional and inflammation indicators, demographics, comorbidities, and slopes of all continuous variables over 6 months. Patients were randomly split in the ratio 2:1:1 into training, testing, and validation cohorts, respectively. We included patients with hemodialysis vintage ≥1 year from Fresenius Medical Care North America clinics from July 2011 to December 2012 (N = 21,802 in mortality analysis; N = 13,892 in hospitalization analysis).The outcome variables were 1-year mortality and hospitalization. RESULTS: For mortality prediction, GAM was the best model (AUC = 0.85, 95% confidence interval = 0.83-0.86), comprised of neutrophil-to-lymphocyte ratio slope, serum bicarbonate slope, and vintage as nonlinear predictors, and age, serum albumin, and creatinine as linear predictors. For hospitalization prediction, GAM was also the best model (AUC = 0.70, 95% confidence interval = 0.62-0.79) and included neutrophil-to-lymphocyte ratio slope, bicarbonate slope, volume of urea distribution, vintage, and phosphate slope as nonlinear predictors, in addition to albumin, congestive heart failure, age, phosphate, equilibrated normalized protein catabolic rate, and creatinine as linear predictors. Both models demonstrated good calibration, with mild overestimation of hospitalization risk at the highest risk interval. CONCLUSIONS: The GAM model can accurately predict the risk of mortality and hospitalization. Application of these prediction models could inform allocation of nutritional interventions to patients at highest nutritional risk.

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.

BACKGROUND: Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative. METHODS: All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group. RESULTS: We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results. CONCLUSION: Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.

Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

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.

Pre-dialysis fluid status, pre-dialysis systolic blood pressure and outcome in prevalent haemodialysis patients: results of an international cohort study on behalf of the MONDO initiative.

Background: Pre-dialysis fluid overload (FO) associates with mortality and causes elevated pre-dialysis systolic blood pressure (pre-SBP). However, low pre-SBP is associated with increased mortality in haemodialysis patients. The objective of this study was to investigate the interaction between pre-dialysis fluid status (FS) and pre-SBP in association with mortality. Methods: We included all patients from the international Monitoring Dialysis Outcome Initiative (MONDO) database with a pre-dialysis multifrequency bioimpedance spectroscopy measurement in the year 2011. We used all parameters available during a 90-day baseline period. All-cause mortality was recorded during 1-year follow-up. Associations with outcome were assessed with Cox models and a smoothing spline Cox analysis. Results: We included 8883 patients. In patients with pre-dialysis FO (>+1.1 to +2.5 L), pre-SBP <110 mmHg was associated with an increased risk of death {hazard ratio (HR) 1.52 [95% confidence interval (CI) 1.06-2.17]}. An increased risk of death was also associated with pre-dialysis fluid depletion (FD; <-1.1 L) combined with a pre-SBP <140 mmHg. In normovolemic (NV) patients, low pre-SBP <110 mmHg was associated with better survival [HR 0.46 (95% CI 0.23-0.91)]. Also, post-dialysis FD associated with a survival benefit. Results were similar when inflammation was present. Only high ultrafiltration rate could not explain the higher mortality rates observed. Conclusion: The relation between pre-SBP and outcome is dependent on pre-dialysis FS. Low pre-SBP appears to be disadvantageous in patients with FO or FD, but not in NV patients. Post-dialysis FD was found to associate with improved survival. Therefore, we suggest interpreting pre-SBP levels in the context of FS and not as an isolated marker.

The Association of Weekly pre-Hemodialysis Systolic Blood Pressure and Following Week Mortality.

BACKGROUND/AIMS: Few studies examine the impact of systolic blood pressure (SBP) on mortality in the incident hemodialysis (HD) period, and throughout the first HD year. This large retrospective observational study analyzes the impact of "current" and cumulative low preSBP <110 mmHg (L), and variations in preSBP on short-term (1 week) mortality over the first HD year. METHODS: Weekly mean preSBP for HD weeks 1 to 51 was categorized into L or high preSBP>=110 mmHg (H) for each patient. A generalized linear model (GLM) was used to compute the probability of death in the following week. The model includes age, gender, race and three preSBP-related parameters: (a) percent of prior weeks with L preSBP; (b) percent of prior weeks with switching between L to H; (c) "current" week's preSBP as a binary variable. Separate models were constructed that include demographics and BP-related parameters (a), (b), and (c) separately. RESULTS: In a model combining (a), (b), and (c) above, "current" week L preSBP is associated with increased odds ratio for following week mortality throughout the first HD year. The percent of prior week's L and more switching between L and H are less significantly associated with short-term mortality. In models including (a), (b), and (c) separately, "current" L preSBP is associated with higher mortality. CONCLUSION: This study confirms an association of L preSBP with increased short-term mortality which is maintained over the first HD year. Percent of L preSBP in prior weeks, switching between L and H, and "current" week L are all associated with short-term mortality risk, but "current" week L preSBP is most significant.

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.

Effect of Change in Fluid Status Evaluated by Bioimpedance Techniques on Body Composition in Hemodialysis Patients.

OBJECTIVE: This prospective study uses calf bioimpedance spectroscopy (cBIS) to guide the attainment of dry weight (DWcBIS) in chronic hemodialysis (HD) patients. The primary aim of this study was to evaluate whether body composition is altered when fluid status is reduced to DWcBIS. METHODS: Target post-HD weight was gradually reduced from baseline (BL) until DWcBIS was achieved. DWcBIS was defined as the presence of both flattening of the curve of extracellular resistance and the attainment calf normalized resistivity in the normal range during the dialysis treatment. Extracellular volume (ECV), intracellular volume, and total body water (TBW) were measured using whole body BIS (Hydra 4200). Fluid overload, lean body mass, and fat mass were calculated according to a body composition model. RESULTS: Seventy-three patients enrolled and 60 completed the study (55 ± 13 years, 49% male). Twenty-eight patients (25% diabetes) achieved DWcBIS, whereas 32 patients (47% diabetes) did not. Number of treatment measurements were 16 ± 10 and 12 ± 13 studies per patient in the DWcBIS and non-DWcBIS groups, respectively. Although significant decreases in body weight and ECV were observed, lean body mass and FM did not differ significantly in both groups from BL to the end of study. ECV, ECV/TBW, and fluid overload were higher in the non-DWcBIS than in the DWcBIS group both at BL and at the end of study. Ratios of intradialytic changes in calf normalized resistivity, ECV, and ECV/TBW to ultrafiltration volume were significantly lower in diabetic than in non-diabetic patients. CONCLUSIONS: This study shows that decreasing fluid status by gradual reduction of post-HD weight in both DWcBIS and Non-DWcBIS groups did not affect body composition significantly over a period of about 4 weeks.