Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.

BACKGROUND: Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. METHODS: This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. RESULTS: Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). CONCLUSION: T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.

Synthetic Material Abdominal Swabs Reduce Activation of Platelets and Leukocytes Compared to Cotton Materials.

During surgical procedures, cotton abdominal swabs with their high absorptive capacity and malleability are used to retain organs and absorb blood or other body fluids. Such properties of the natural material cotton are advantageous for most operations, but in cardiopulmonary bypass (CPB) surgery, a high blood volume can accumulate in the thoracic cavity that is quickly retransfused via the heart-lung machine (HLM). This common practice is supposed to be safe due to the high anticoagulation. However, in vitro analyses showed that blood cells and plasma proteins were activated despite a high anticoagulation, which can propagate especially an inflammatory response in the patient. Thus, we investigated patients' blood during CPB surgery for inflammatory and coagulation-associated activation after contact to the HLM and either cotton or synthetic abdominal swabs. Contact with cotton significantly increased thrombocyte and neutrophil activation measured as ß-thromboglobulin and PMN-elastase secretion, respectively, compared to synthetic abdominal swabs. Both inflammatory cytokines, interleukin (IL) 1ß and IL6, were also significantly increased in the cotton over the synthetic patient group, while SDF-1α was significantly lower in the synthetic group. Our data show for the first time that cotton materials can activate platelets and leukocytes despite a high anticoagulation and that this activation is lower with synthetic materials. This additional activation due to the material on top of the activation exerted by the tissue contact that blood is exposed to during CPB surgery can propagate further reactions in patients after surgery, which poses a risk for this already vulnerable patient group.

Evolution of body composition and wasting indicators by time of day of haemodialysis.

BACKGROUND: It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates. METHODS: We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011-16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient). RESULTS: Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of -0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators. CONCLUSIONS: This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.

The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients. METHODS: De-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1-Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH). RESULTS: 1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77-1.69 mmol/L during Q1-Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2-62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0-5.3 pills/day during Q1-Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1-2.8 pills/day). CONCLUSION: In this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Serum Uric Acid and Mortality Risk Among Hemodialysis Patients.

INTRODUCTION: Although high serum uric acid (SUA) has been consistently associated with an increased risk of death in the general population and in persons with nondialysis chronic kidney disease (CKD), studies in patients undergoing dialysis are conflicting. It has been postulated that low SUA simply reflects poor nutritional status in dialysis patients. We here characterize the association between SUA and the risk of death in a large dialysis cohort and explore effect modification by underlying nutritional status as reflected by body composition. METHODS: In this retrospective cohort study, we included 16,057 hemodialysis (HD) patients treated during 2007 to 2016 in NephroCare centers as recorded in the European Clinical Database (EuCliD). The association between SUA, all-cause, and cardiovascular (CV)-related mortality was evaluated with competing risk models and characterized with splines. Effect modification was explored by lean tissue index (LTI) and fat tissue index (FTI). RESULTS: During a mean of 1.8 years of follow-up, 2791 patients (17.4%) died. We found a multivariable-adjusted U-shaped pattern between SUA and all-cause mortality. Patients with SUA levels of 6.5 mg/dl (387 µmol/l) were at the lowest risk of death (subdistribution hazard ratio = 0.94 [confidence interval {CI} 0.91; 0.96]). The form of association was not meaningfully affected by underlying LTI and FTI. CONCLUSION: We found a U-shaped pattern between SUA levels and all-cause mortality among HD patients, which was independent of the patients' body composition.

Effects of high-volume online mixed-hemodiafiltration on anemia management in dialysis patients.

BACKGROUND: Anemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF). METHODS: We included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models. RESULTS: Mean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687). CONCLUSIONS: Results of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

A Modern Twist to a Classic Synthetic Route: Ph3Bi-Based Redox Transmetalation Protolysis (RTP) for the Preparation of Barium Metalorganic Species.

This paper reports advances in redox transmetalation/protolysis (RTP) utilizing the readily available Ph3Bi for the synthesis of a series of barium metal-organic species. On the basis of easily available starting materials, an easy one-pot procedure, and workup, we have obtained BaL2 compounds (L = bis(trimethylsilyl)amide, phenyl(trimethylsilyl)amide, pentamethylcyclopentadienide, fluorenide, 2,6-di-isopropylphenolate, and 3,5-diphenylpyrazolate) quantitatively by sonication of an excess of barium metal with triphenylbismuth and HL in perdeuterotetrahydrofuran, as established by NMR measurements. Rates of conversion are affected by both pKa and bulk of HL. Competition occurs from direct reaction of Ba with HL, thereby enhancing the overall conversion, the effect being pronounced for the less bulky and more acidic ligands. Overall, the method significantly adds to the synthetic armory for barium metal-organic/organometallic compounds.

Comparative biomechanical study on three miniplates osteosynthesis systems for stabilisation of low condylar fractures of the mandible.

Open reduction and fixation of low condylar fractures of the mandible can be achieved by many osteosynthesis systems that differ in size, shape, and site of placement according to the surgical approach. We investigated the maximum load and rigidity of 4 osteosynthesis systems: the standard double 4-hole straight miniplates, the inverted y-miniplate (with and without self-drilling screws), and the TriLock Delta condyle trauma plate. The standard double 4-hole straight miniplate osteosynthesis achieved the best fixation and resistance in view of a mean (SD) maximum load of 539.8 (100.2)N, followed by the inverted y-miniplate with the self-drilling screws (246.5 (23.8)N), the inverted y-miniplate with standard screws (242.4 (27.2)N), and finally the TriLock Delta plate (167.4 (39.2)N). Analysis of the slope of the force-displacement diagram from 80N to 100N in each group showed that the TriLock Delta miniplate had the highest values for rigidity (17.3 (5.1)N/µm), followed by the inverted y-miniplate groups with self-drilling screws (14.1 (6.4)N/µm), and with standard screws (12.6 (2.5)N/µm). The double 4-hole straight miniplate osteosynthesis had the lowest rigidity (8.7 1.4)N/µm). Despite the significant difference in the maximum load between the double 4-hole miniplates and other investigated osteosynthesis patterns, all groups had sufficient load for the fixation of low condylar fractures of the mandible when postoperative bite forces and the slowly increasing voluntary clenching during healing were considered.

Large-scale application of a telephone-based test of cognitive functioning in older adults.

AIMS: The study of cognitive functioning in large epidemiological settings is hampered by a lack of instruments for the remote assessment of cognitive performance, especially when targeting variability across the full range of adult functioning. The present study examined the practicability of such investigations using a recently developed telephone interview (Cognitive Telephone Screening Instrument, COGTEL). METHODS: A subcohort of an ongoing epidemiological study in the elderly German population (ESTHER) was interviewed via telephone by trained personnel. These data were combined with sociodemographic information obtained by standardized self-administered questionnaires, and analysed by tabulation, histograms and regression models. RESULTS: A total of 1,697 interviews could be analysed. The eligible participants had a mean age ± standard deviation of 74.0 ± 2.8 years. The COGTEL total scores closely followed a normal distribution with no evidence of a ceiling effect. In adjusted regression models, COGTEL total and subcomponent scores were negatively associated with age and strongly positively with higher education, whereas the association with sex was less consistent. CONCLUSIONS: The results suggest that the COGTEL can readily be administered to large study populations and produces plausible and informative results. Education should be considered in all investigations using this instrument and requires further in-depth analyses. Future studies will need to elucidate its associations with risk factors and its prognostic potential for cognitive decline and dementia.

Potential novel drug carriers for inner ear treatment: hyperbranched polylysine and lipid nanocapsules.

AIM: Treatment of sensorineural hearing loss could be advanced using novel drug carriers such as hyperbranched polylysine (HBPL) or lipid nanocapsules (LNCs). This study examined HBPL and LNCs for their cellular uptake and possible toxicity in vitro and in vivo as the first step in developing novel nanosized multifunctional carriers. METHOD: Having incubated HBPL and LNCs with fibroblasts, nanoparticle uptake and cell viability were determined by confocal laser scanning microscopy, fluorescence measurements and neutral red staining. In vivo, electrophysiology, confocal laser scanning microscopy and cytocochleograms were performed for nanoparticle detection and also toxicity studies after intracochlear application. RESULTS: Both nanoparticles were detectable in the fibroblasts' cytoplasm without causing cytotoxic effects. After in vivo application they were visualized in cochlear cells, which did not lead to a change in hearing threshold or loss of hair cells. Biocompatibility and traceability were demonstrated for HBPL and LNCs. Thus, they comply with the basic requirements for drug carriers for potential application in the inner ear.