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Background/Aims: Pregnancy-associated plasma protein A (PAPP-A) is a biomarker related to vascular damage. The aim of the study was to focus on PAPP-A and related parameters and their relationship to the prognosis of long-term hemodialysis (HD) patients. Methods: This is a prospective observational cohort study which included 261 long-term HD patients followed up for 5 years and 66 healthy subjects. PAPP-A, placental growth factor (PlGF), matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-4 (IGFBP-4), and cardiac, nutritional and inflammatory parameters were measured at the beginning of the study and tested as predictors of mortality. Results: PAPP-A, PlGF, IGF-1, IGFBP-4 and MMP-2 were significantly increased in HD patients compared to controls (PAPP-A 27.6 ± 15.5 mIU/l in HD vs. 9.4 ± 2.5 mIU/l in controls, p < 0.001). Increased PAPP-A was a significant independent predictor of overall mortality and mortality due to infection in the multivariate Cox analysis [HR (95% CI): 1.237 (1.060-1.444), p = 0.007, and 1.416 (1.115-1.798), p = 0.004, per standard deviation, respectively]. PAPP-A was not related to cardiovascular mortality. Conclusion: Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). Methods A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65–79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. Results Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P  < .0001; 200.5 vs 830.0 mg/L, P  < .0001; and 126.0 vs 408.0 mg/L, P  < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10–13 h after dose administration was dependent on eGFR (r2 = 0.6144, P  < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. Conclusion Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity. [ABSTRACT FROM AUTHOR]

Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose. [ABSTRACT FROM AUTHOR]

Background. Dialysis patients are at high risk of cardiovascular complications. Pregnancy-associated plasma protein A (PAPP-A) as well as sRAGE (soluble receptor for advanced glycation end products) are new biomarkers related to cardiovascular disease. The aim of our study was to describe their intra- and inter-individual variability. Methods. The studied group consisted of 21 chronic hemodialysis patients. PAPP-A, sRAGE and selected routine parameters were measured monthly during a 1-year prospective study. Results. Our results show high intra-individual variability of both PAPP-A and sRAGE. Both PAPP-A and sRAGE were closely linked to serum transferrin levels. Additionally, sRAGE was significantly associated with leukocyte count and haemoglobin. Conclusion. Our study demonstrates high intra-individual variability of PAPP-A and sRAGE in stable clinical status. This finding could be helpful for further evaluation of the significance of PAPP-A and sRAGE in chronic kidney disease. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: EN-RAGE is extracellular newly identified receptor for advanced glycation end-products binding protein playing a role in inflammation. The aim was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis patients (HD). Design and methods: This is a prospective observational cohort study in 261 HD patients followed up for five years. Laboratory parameters were measured at the beginning of the study. Results: EN-RAGE was slightly but unsignificantly increased in HD patients compared with healthy controls and correlated significantly with inflammatory markers. Univariate Cox analysis demonstrated EN-RAGE as a significant predictor for mortality due to infection (HR (95%CI): 1.305 (1.063–1.602), per standard deviation, p=0.01), but this significance disappeared in multivariate Cox analysis when CRP was included into the model. Conclusions: Our study demonstrates EN-RAGE as an inflammatory biomarker. It is related to mortality of HD patients due to infection, but in our study, it did not provide additional information to CRP. [Copyright &y& Elsevier]

Our study presents a novel collagen wound dressing prepared from freshwater fish skin (Cyprinus Carpio) collagen type I. Half of the sponges were cross-linked with carbodiimide. The cross-linked and non-cross-linked collagen sponges were subsequently impregnated with gentamicin and lyophilized thus allowing for the attainment of the appropriate gentamicin content without the removal thereof during the cross-linking stage. The structure was evaluated via micro-CT and infrared spectrometry and the structural stability and gentamicin release properties were evaluated in phosphate buffer solution. The sponges were further tested via a rat model of an infected wound with Pseudomonas aeruginosa inoculation and compared with a reference commercial product. The sponges thus prepared provided a degree of open porosity that was comparable to or higher than that of the reference commercial product. Spectrometry analysis revealed that the cross-linked collagen sponge and reference commercial product sponge preserved their secondary collagen structure after 168 h while early accelerated degradation was observed with respect to the non-cross-linked collagen sponge. Gentamicin was released rapidly from all the sponges. Compared to those animals with gentamicin-containing sponges or gentamicin administered intramuscularly, the animals with the cross-linked collagen sponge without gentamicin exhibited marked clinical and laboratory infection signs. Both the administration routes (intramuscular and via gentamicin-containing sponges) provided similar gentamicin plasma levels. The resulting highly homogeneous product which was characterized by excellent structural and clinical properties proved effective in terms of the treatment of a surgical wound infection in a rat model. We demonstrated that all the gentamicin was released from the sponge and was absorbed in the systemic circulation. This is the first time that Cyprinus Carpio collagen has been used in the preparation of wound dressings. Thus, gentamicin-containing sponges provide a promising tool for the treatment and prevention of surgical site infections. [ABSTRACT FROM AUTHOR]

Procalcitonin (PCT) levels can distinguish between infectious and non-infectious systemic inflammatory response. However, there are some differences between Gram-negative (G−), Gram-positive (G+), and fungal bloodstream infections, particularly in different cytokine profiles, severity and mortality. The aim of current study was to examine whether PCT levels can serve as a distinguishing mark between G+, G−, and fungal sepsis as well. One hundred and sixty-six septic patients with positive blood cultures were examined on C-reactive protein (CRP) and PCT on the same date of blood culture evaluation. The median (interquartile range, IQR) of CRP and PCT in G+, G−, and fungal cohorts and comparison of measured values between groups were made using the Kruskal-Wallis test with subsequent Bonferroni's corrections, with p < 0.05. In 83/166 (50 %) of blood cultures, G+ microbes, 78/166 (47 %) G− rods, and 5/166 (3 %) fungi were detected. PCT concentrations (ng/ml) were significantly higher in G− compared to other cohorts: 8.90 (1.88; 32.60) in G−, 0.73 (0.22; 3.40) in G+, and 0.58 (0.35; 0.73) in fungi ( p < 0.00001). CRP concentrations did not differ significantly in groups. Significantly higher PCT levels could differentiate G− sepsis from G+ and fungemia. In contrast to CRP, PCT is a good discriminative biomarker in different bloodstream infections. [ABSTRACT FROM AUTHOR]

Background: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. Methods: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. Results: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. Conclusions: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the κ/λ ratio cannot be measured with high precision, κ and λ FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres. [ABSTRACT FROM AUTHOR]

Presents a study examining the association of antineutrophil cytoplasmic antibodies (ANCA) with exposure to asbestos among workers. Use of indirect immunofluorescence; Determination of the occurrence of ANCA-related diseases; Comparison with the influence of silica on the development of disease.