Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury After Massive Burns.

BACKGROUND Acute kidney injury (AKI) is a common and serious complication after massive burn injury. One of the postulated etiologies is destruction of the extracellular matrix of nephrons, caused by a local imbalance between matrix metalloproteinases (MMPs) and specific inhibitors. The aim of this study was to analyze the dynamics of tissue inhibitors of metalloproteinases (TIMPs) during the first 5 days after massive thermal injury and the relationship with the risk of AKI. MATERIAL AND METHODS Thirty-three adults (22 men, 11 women) with severe burns were enrolled in the study. The values of TIMPs 1 to 4 were measured in blood serum and urine using the multiplex Luminex system. The associations between TIMPs and the risk of AKI were analyzed by using the generalized linear mixed models for repeated measurements. RESULTS Significant changes in serum and urine activities of TIMPs were confirmed, especially during the first 2 days after burn injury. Almost half of patients presented renal problems during the study. Significant differences between values of TIMPs in AKI and non-AKI status were also observed. However, a significant relationship between concentration of TIMPs and risk of AKI was confirmed only for urine TIMP-1 and serum TIMP-3. CONCLUSIONS The evaluation of TIMPs in the early stage after burn injury has potential benefits. The important roles of urine TIMP-1 and serum TIMP-3, as novel markers of the risk of AKI development, were confirmed. Other parameters require further analysis.

Archetype analysis and the PHATE algorithm as methods to describe and visualize pregnant women's levels of physical activity knowledge.

The knowledge of physical activity (PA) recommended for pregnant women and practical application of it has positive impact on the outcome. Nevertheless, it is estimated that in high-income countries over 40% of pregnant women are insufficiently physically active. One of the reasons is insufficient knowledge pregnant women have about allowed effort during pregnancy and both recommended and not recommended physical activities. Description of knowledge about physical activity the women have and distinguishing patterns of their knowledge is becoming an increasingly important issue. A common approach to handle survey data that reflect knowledge involves clustering methods or Principal Component Analysis (PCA). Nevertheless, new procedures of data analysis are still being sought. Using survey data collected by the Institute of Mother and Child Archetypal analysis has been applied to detect levels of knowledge reflected by answers given in a questionnaire and to derive patterns of knowledge contained in the data. Next, PHATE (Potential of Heat-diffusion for Affinity-based Trajectory Embedding) algorithm has been used to visualize the results and to get a deeper insight into the data structure. The results were compared with picture derived from PCA. Three archetypes representing three patterns of knowledge have been distinguished and described. The presentation of complex data in a low dimension was obtained with help of PHATE. The formations revealed by PHATE have been successfully described in terms of knowledge levels reflected by the survey. Finally, comparison of PHATE with PCA has been shown. Archetype analysis combined with PHATE provides novel opportunities in examining nonlinear structure of survey data and allows for visualization that captures complex relations in the data. PHATE has made it possible to distinguish sets of objects that have common features but were captured neither by Archetypal analysis nor PCA. Moreover, for our data, PHATE provides an image of data structure which is more detailed than interpretation of PCA.

Long-term pulmonary outcomes of young adults born prematurely: a Polish prospective cohort study PREMATURITAS 20.

BACKGROUND: The long-term consequences of prematurity are often not sufficiently recognized. To address this gap, a prospective cohort study, which is a continuation of the multicenter Polish study PREMATURITAS, was conducted, utilizing unique clinical data from 20 years ago. OBJECTIVE: The main goal was to evaluate lung function, detect any structural abnormalities using lung ultrasound, and assess psychological well-being in young adults born between 24 and 34 weeks of gestational age (GA). Additionally, the study aimed to investigate potential associations between perinatal risk factors and abnormalities observed in pulmonary function tests (PFTs) during adulthood. METHODS: The young survivors underwent a comprehensive set of PFTs, a lung ultrasound, along with the quality of life assessment. Information regarding the neonatal period and respiratory complications was obtained from the baseline data collected in the PREMATURITAS study. RESULTS: A total of 52 young adults, with a mean age of 21.6 years, underwent PFTs. They were divided into two groups based on GA: 24-28 weeks (n = 12) and 29-34 weeks (n = 40). The subgroup born more prematurely had significantly higher lung clearance index (LCI), compared to the other subgroup (p = 0.013). LCI ≥ 6.99 was more frequently observed in the more premature group (50% vs. 12.5%, p = 0.005), those who did not receive prenatal steroids (p = 0.020), with a diagnosis of Respiratory Distress Syndrome (p = 0.034), those who received surfactant (p = 0.026), and mechanically ventilated ≥ 7 days (p = 0.005). Additionally, elevated LCI was associated with the diagnosis of asthma (p = 0.010). CONCLUSIONS: The findings suggest pulmonary effects due to prematurity persist into adulthood and their insult on small airway function. Regular follow-up evaluations of young survivors born preterm should include assessments of PFTs. Specifically, the use of LCI can provide valuable insights into long-term pulmonary impairment.

Socioeconomic disparities in changes to preterm birth and stillbirth rates during the first year of the COVID-19 pandemic: a study of 21 European countries.

BACKGROUND: Despite concerns about worsening pregnancy outcomes resulting from healthcare restrictions, economic difficulties and increased stress during the COVID-19 pandemic, preterm birth (PTB) rates declined in some countries in 2020, while stillbirth rates appeared stable. Like other shocks, the pandemic may have exacerbated existing socioeconomic disparities in pregnancy, but this remains to be established. Our objective was to investigate changes in PTB and stillbirth by socioeconomic status (SES) in European countries. METHODS: The Euro-Peristat network implemented this study within the Population Health Information Research Infrastructure (PHIRI) project. A common data model was developed to collect aggregated tables from routine birth data for 2015-2020. SES was based on mother's educational level or area-level deprivation/maternal occupation if education was unavailable and harmonized into low, medium and high SES. Country-specific relative risks (RRs) of PTB and stillbirth for March to December 2020, adjusted for linear trends from 2015 to 2019, by SES group were pooled using random effects meta-analysis. RESULTS: Twenty-one countries provided data on perinatal outcomes by SES. PTB declined by an average 4% in 2020 {pooled RR: 0.96 [95% confidence intervals (CIs): 0.94-0.97]} with similar estimates across all SES groups. Stillbirths rose by 5% [RR: 1.05 (95% CI: 0.99-1.10)], with increases of between 3 and 6% across the three SES groups, with overlapping confidence limits. CONCLUSIONS: PTB decreases were similar regardless of SES group, while stillbirth rates rose without marked differences between groups.

Clarity and consistency in stillbirth reporting in Europe: why is it so hard to get this right?

BACKGROUND: Stillbirth is a major public health problem, but measurement remains a challenge even in high-income countries. We compared routine stillbirth statistics in Europe reported by Eurostat with data from the Euro-Peristat research network. METHODS: We used data on stillbirths in 2015 from both sources for 31 European countries. Stillbirth rates per 1000 total births were analyzed by gestational age (GA) and birthweight groups. Information on termination of pregnancy at ≥22 weeks' GA was analyzed separately. RESULTS: Routinely collected stillbirth rates were higher than those reported by the research network. For stillbirths with a birthweight ≥500 g, the difference between the mean rates of the countries for Eurostat and Euro-Peristat data was 22% [4.4/1000, versus 3.5/1000, mean difference 0.9 with 95% confidence interval (CI) 0.8-1.0]. When using a birthweight threshold of 1000 g, this difference was smaller, 12% (2.9/1000, versus 2.5/1000, mean difference 0.4 with 95% CI 0.3-0.5), but substantial differences remained for individual countries. In Euro-Peristat, missing data on birthweight ranged from 0% to 29% (average 5.0%) and were higher than missing data for GA (0-23%, average 1.8%). CONCLUSIONS: Routine stillbirth data for European countries in international databases are not comparable and should not be used for benchmarking or surveillance without careful verification with other sources. Recommendations for improvement include using a cut-off based on GA, excluding late terminations of pregnancy and linking multiple sources to improve the quality of national databases.

Assessment of the correlation of commonly used laboratory tests with clinical activity, renal involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies.

BACKGROUND: The aim of the study was to assess the correlation of commonly used laboratory tests with clinical activity, degree of kidney involvement and treatment of systemic small-vessel vasculitis with the presence of ANCA antibodies. METHODS: The study included 28 patients with active AAV (BVAS ≥ 3). The following tests were performed: MPO-ANCA, PR3-ANCA, peripheral blood count, ESR, CRP, procalcitonin, creatinine, GFR, urea, albumin, fibrinogen, d-dimer, components of the C3 and C4 complement systems, urinalysis with sediment evaluation and diurnal proteinuria. The assessments were conducted twice: at study entry (A0) and after 6 months (A6) (BVAS = 0). RESULTS: At the time of inclusion in the study, the mean creatinine concentration was 3.39 mg/dl (GFR 33.17 ml/min/1.73 m²), after achieving remission in 11 patients (39.3 %) GFR remained below 30 ml/min/1.73 m², 4 patients (14.3 %) continued renal replacement therapy, and 3 patients (10.7 %) with advanced renal failure died. Microscopic hematuria occurred in 80.9 % of the studied population, withdrew in most patients, strongly correlated with renal involvement p < 0.001 and was not related to disease severity p = 0.147. CRP, ESR, fibrinogen, d-dimer, albumin and hemoglobin in the peripheral blood showed a strong correlation with the clinical activity of AAV and well identified severe patients. High procalcitonin concentrations correlated with a severe form of the disease, pulmonary involvement with respiratory failure and alveolar hemorrhage (mean 3.41 ng/ml, median 0.91 ng/ml, SD 7.62, p = 0.000), and were associated with the occurrence of infectious complications and the need to administer antibiotic therapy. ANCA antibodies were useful in the evaluation of patients with AAV, the amount of antibodies did not correlate with the severity of vasculitis (p = 0.685) and the results in many patients did not match the expected assumptions. CONCLUSIONS: CRP, ESR, fibrinogen, d-dimers, albumin and hemoglobin in the peripheral blood correlate well with the activity of vasculitis and identify severe patients. The resolution of microscopic hematuria suggests remission of the disease in the renal area. Procalcitonin may be slightly increased in patients with active AAV without infection, high concentrations are strongly associated with infectious complications. ANCA antibodies should always be interpreted in the context of the observed clinical symptoms.

Biocompatibility of Hemodialysis.

This study was designed to investigate the biocompatibility of hemodialysis procedures, largely depending on the contact of patient's blood with the dialysis membranes. We addressed the issue by comparing the content of the proteolytic enzymes collagenase and cathepsin B and that of neutrophil myeloperoxidase (MPO) and C-reactive protein (CRP) in the blood before and after a single session treatment and a full course of successive 8-week-long therapies with three types of hemodialysis: low-flux (lfHD), high-flux (hfHD), and post-dilution hemodiafiltration (HDF). The study included 19 patients with chronic nephropathy. We found that collagenase significantly increased after a single session of each type of hemodialysis. Cathepsin B tended to decrease after single sessions; the decrease reached significance only after hfHD. CRP increased significantly after single hfHD and HDF treatments. These changes were meager, with no differences depending on the dialysis type, and their significance was lost after 8-week-long therapy, except the persisting increase in CRP after HDF. Neutrophil MPO apparently was not activated during any type of dialysis, as its content was below the detection threshold. We conclude that all three types of hemodialysis are compatible with the biological system, so that they would rather unlikely lead to clinically harmful effects in chronically hemodialyzed patients. Nonetheless, proteolytic enzymes and myeloperoxidase seem hardly appropriable estimators of hemodialysis biocompatibility due to meager and variable changes. Upregulation of C-reactive protein, on the other hand, expresses a general pro-inflammatory propensity of hemodialysis and is not a suitable estimator of biocompatibility either.

Quantifying the burden of stillbirths before 28 weeks of completed gestational age in high-income countries: a population-based study of 19 European countries.

BACKGROUND: International comparisons of stillbirth allow assessment of variations in clinical practice to reduce mortality. Currently, such comparisons include only stillbirths from 28 or more completed weeks of gestational age, which underestimates the true burden of stillbirth. With increased registration of early stillbirths in high-income countries, we assessed the reliability of including stillbirths before 28 completed weeks in such comparisons. METHODS: In this population-based study, we used national cohort data from 19 European countries participating in the Euro-Peristat project on livebirths and stillbirths from 22 completed weeks of gestation in 2004, 2010, and 2015. We excluded countries without national data for stillbirths by gestational age in these periods, or where data available were not comparable between 2004 and 2015. We also excluded those countries with fewer than 10 000 births per year because the proportion of stillbirths at 22 weeks to less than 28 weeks of gestation is small. We calculated pooled stillbirth rates using a random-effects model and changes in rates between 2004 and 2015 using risk ratios (RR) by gestational age and country. FINDINGS: Stillbirths at 22 weeks to less than 28 weeks of gestation accounted for 32% of all stillbirths in 2015. The pooled stillbirth rate at 24 weeks to less than 28 weeks declined from 0·97 to 0·70 per 1000 births from 2004 to 2015, a reduction of 25% (RR 0·75, 95% CI 0·65-0·85). The pooled stillbirth rate at 22 weeks to less than 24 weeks of gestation in 2015 was 0·53 per 1000 births and did not significantly changed over time (RR 0·97, 95% CI 0·80-1·16) although changes varied widely between countries (RRs 0·62-2·09). Wide variation in the percentage of all births occurring at 22 weeks to less than 24 weeks of gestation suggest international differences in ascertainment. INTERPRETATION: Present definitions used for international comparisons exclude a third of stillbirths. International consistency of reporting stillbirths at 24 weeks to less than 28 weeks suggests these deaths should be included in routinely reported comparisons. This addition would have a major impact, acknowledging the burden of perinatal death to families, and making international assessments more informative for clinical practice and policy. Ascertainment of fetal deaths at 22 weeks to less than 24 weeks should be stabilised so that all stillbirths from 22 completed weeks of gestation onwards can be reliably compared. FUNDING: EU Union under the framework of the Health Programme and the Bridge Health Project.

Protein-Bound Solute Clearance During Hemodialysis.

Indoxyl sulfate (IS) and p-cresol sulfate (p-CS) are protein-bound solutes that accumulate in the blood serum in chronic kidney disease and have a detrimental effect on the kidney and other organs' function. This study seeks to define the effectiveness of IS and p-CS clearance after single dialysis sessions and after 8-week-long cycles of hemodialysis using the following different dialysis modalities in succession: low-flux hemodialysis (lfHD), high-flux hemodialysis (hfHD), and post-dilution hemodiafiltration (HDF). We also investigated to what extent IS and p-CS serum content would associate with some other biochemical indices in patients with chronic kidney diseases. The study included 21 uremic patients. We found that a single session of each modality effectively decreased the content of both IS and p-CS, with the predominance of p-CS decrease. There were no appreciable differences depending on the modality of hemodialysis chosen. However, the leaching effect tended to wear off with the weeks' long dialysis cycles. We further found that a greater inflammation-prone level of hsCRP evoked by dialysis led to a greater removal of solutes, and thus their decrease in the serum, during a single dialysis session. Reversely, a greater protein level might result in a greater solute binding and a decrease in removal. We conclude that there are no major differences in the serum clearance of IS and p-CS depending on the dialysis modality. These protein-bound toxins are significantly cleared from the serum already during the first dialysis session, but their level tends to revert during weeks' long dialysis sessions.

Copeptin Blood Content as a Diagnostic Marker of Chronic Kidney Disease.

Plasma content of copeptin increases with the advancement of chronic kidney disease (CKD). The purpose of this study was to evaluate copeptin content as a potential marker of CKD, as a single pathology or with coexisting heart failure. Seventy-six patients were divided into the following groups: Group 1 (control), without CKD and heart failure; Group 2, CKD stage 3a; Group 3, CKD stage 3b; Group 4, CKD stage 4; Group 5, CKD stage 5; and Group 6, CKD stage 3b and heart failure. For all patients, plasma concentrations of copeptin, creatinine, urea, cystatin C, sodium, C-reactive protein (CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and blood pH were assessed. We found that plasma content of creatinine, urea, CRP, cystatin, NT-proBNP, and copeptin increased with CKD progression. Heart failure in CKD patients was not the cause of an appreciable increase of copeptin level. Copeptin/creatinine, copeptin/cystatin C ratios, and especially copeptin/eGFR ratio enhanced copeptin prognostic sensitivity concerning renal failure in CKD, compared with copeptin alone. The copeptin×NT-proBNP ratio decreased along CKD progression, reaching a nadir in the accompanying heart failure. In contradistinction, copeptin×NT-proBNP/creatinine ratio increased along CKD progression, reaching a peak in the accompanying heart failure. We conclude that copeptin is an important marker in CKD, but not so concerning heart failure in the disease. A decrease in copeptin×NT-proBNP and an increase in copeptin×NT-proBNP/creatinine ratio are useful markers of cardiac function decline in CKD.

The effect of weight loss on body composition, serum bone markers, and adipokines in prepubertal obese children after 1-year intervention.

Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. MATERIALS AND METHODS: We determined serum leptin, soluble leptin receptor, adiponectin, bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), sclerostin, body composition, and bone mineral density (BMD) in 40 obese prepubertal children before and after therapy. The control group, matched for sex and age, consisted of 40 non-obese children. RESULTS: We found that values of the total body less head-bone mineral content (TBLH-BMC) and TBLH-BMD were significantly increased, but TBLH-BMD Z-score was decreased by 25% (p = 0.002) in obese children with weight loss after therapy. We observed increases of CTX-I to OC ratio (p = 0.009), and Gla-OC concentrations (p = 0.049). Changes in TBLH-BMD Z-score in patients were positively correlated with changes in BMI Z-score (p = 0.001), percentage of fat mass (p = 0.004), and BALP activity (p = 0.01). Changes in BALP activity were negatively correlated (p < 0.001) with changes in adiponectin concentrations, while changes in sclerostin levels were positively correlated (p = 0.001) with leptin changes. CONCLUSIONS: We suggest that alterations in adipokines metabolism were associated with a lower rate of bone mineral accrual as a result of decreased bone formation rather than increased bone resorption. The lower rate of bone mass accrual in weight losing children may be an effect of reduced BALP levels related to increase in adiponectin levels.

The levels of bone alkaline phosphatase (BALP) and soluble epidermal growth factor receptor-2 (ECD/HER-2) in pediatric patients with osteosarcoma during clinical treatment.

OBJECTIVE: Aim: The aim of this study was to assess the usefulness of bone-specific alkaline phosphatase (BALP) and the extracelluar domain of human epidermal growth factor receptor 2 (ECD/HER-2) measurements in pediatric patients with osteosarcoma as prospective prognostic and predictive markers for monitoring the treatment and early detection of disease recurrence. PATIENTS AND METHODS: Material and methods: We studied 22 patients (5 girls, 17 boys) aged 7-20 years with osteosarcoma (OS) treated at the Institute of Mother and Child in Warsaw. All the patients were evaluated for the serum levels of BALP and ECD/HER-2 before treatment, during pre- and postoperative chemotherapy and after the completion of treatment. Healthy children (n=22) were the reference group. The levels of BALP and ECD/HER-2 were measured using immunoenzymatic methods. RESULTS: Results: The values of BALP and ECD/HER-2 proteins were higher (p<0.01; p<0.05, respectively) in patients with osteosarcoma at the time of diagnosis compared with the control group. The values of both markers significantly decreased during chemotherapy in most patients with remission. In contrast to ECD/HER-2, the value of BALP after therapy was higher in patients with progression than with remission (p<0.001). CONCLUSION: Conclusions: Our results demonstrate the different pattern of BALP and ECD/HER-2 proteins during clinical treatment in patients with osteosarcoma. Higher values of BALP may characterize the progression of the disease and unfavourable prognosis. Further longitudinal studies are necessary to confirm the prognostic values of BALP and ECD/HER-2 proteins in this group of patients.

[Infant and neonatal deaths in poland in 1995-2015].

AIM: The aim of the study was the analysis of trends of infant and neonatal mortality in Poland in 1995-2015, overall and by gestational age, main groups of causes and age at death. MATERIAL AND METHODS: Data from birth and death certificates from 1995, 2000, 2005, 2010, 2014 and 2015 were used. Infant, neonatal, postneonatal, perinatal and gestational age - specific mortality rates were presented. Main groups of causes of deaths were determined according to the International Classification of Diseases ICD-10. RESULTS: In Poland, in 1995-2015 infant mortality decreased more than three-fold, similarly to neonatal and postneonatal mortality. Early neonatal mortality decreased almost four-fold, stillbirths rate - two-fold and perinatal mortality - almost three-fold. The progress, to the greatest extend was related to preterm births. Infant mortality in this group decreased from 128.5 per 1000 preterm live births in 1995 to 36.8 in 2015. The main causes of all infant deaths are perinatal conditions and congenital anomalies. CONCLUSIONS: The decrease of infant and neonatal mortality has been continued in the last twenty years and affected mainly preterm births born from the shorter and shorter gestations, what implicates growing demand for long lasting health care and rehabilitation. Deaths of infants and neonates born at term and not related to congenital anomalies are relatively rare and need individual assessment.

[The influence of hypothyroidism on the conversion and binding of thyroid hormones in patients with end-stage renal disease]. / Wplyw niedoczynnosci tarczycy u chorych ze schylkowa niewydolnoscia nerek na wspólczynniki konwersji i wiazania hormonów tarczycy.

Hypothyroidism in patients with renal failure (RF) causes many metabolic and clinical problems, and both these diseases can mutually exacerbate their disturbances. AIM: The aim of this study was to evaluate the effect of hypothyroidism, and end-stage renal disease (ESRD) on conversion of thyroid hormones (TH) in patients with ESRD treated with chronic hemodialysis (HD). MATERIALS AND METHODS: The study was performed in 74 patients, including 41 women (K) and 33 men (M) aged 28-83 y.o. in 4 groups: G1 - 12 people with ESRD treated with HD and with newly diagnosed hypothyroidism without substitution (6 K and M 6) aged 66,83±12,90 y.o., G2 - 26 patients with ESRD treated with HD without hypothyroidism (10 F, 16 M) aged 58,85±15,52 y.o., G3 - 11 hypothyroid patients without RF (9 K, 2 M) aged 54,73±21,26 y.o., G4 - 25-persons from control group of healthy subjects (16 M, 9 M) aged 51,24±12,58 y.o. In all subjects the concentration of TSH and TH (T4, T3, fT4, TSH, FT3, rT3) were measured and values of conversion factors (T3/T4, FT3/ fT4, rT3/fT4 and rT3/fT3) and binding TH to protein factors (fT4/T4 and fT3/T3) were calculated. RESULTS: Lower concentration of T3 (p=0.012), fT3 (p<0.001) i fT4 (p=0.014) was found in patients without hypothyroidism than in healthy subjects. Renal failure with concomitant hypothyroidism intensify the disturbances of T4 to T3 conversion (p=0.034) and hypothyroidism with concomitant renal failure disrupts binding of T3 to proteins (p=0.001). FT3 to fT4 ratio in renal failure with concomitant hypothyroidism group was significantly lower than in each other group. rT3 concentrations were the highest in healthy subjects. CONCLUSIONS: Concomitance of hypothyroidism and end-stage renal disease reduces the conversion of thyroxine to triiodothyronine, but does not increase the production of rT3. Hypothyroidism significantly increases the disorders of thyroid hormones in end-stage renal disease. There is decreased tendency to bind of thyroid hormone to protein in hypothyroidism in patients with end-stage renal disease.

The clinical significance of changes in ezrin expression in osteosarcoma of children and young adults.

Ezrin is a protein that functions as a cross-linker between actin cytoskeleton and plasma membrane. Its clinical role in osteosarcoma is unclear. The aim of this study was to investigate, in osteosarcoma, the prognostic value of ezrin expression at biopsy and changes in expression levels after preoperative chemotherapy. Thirty-eight newly diagnosed osteosarcoma patients aged 6-23 years were included. At diagnosis, 20 patients had localized disease, the others had distant metastases. Median follow-up was 75 months (range 13-135). Ezrin expression was assessed immunohistochemically in biopsy tissue and primary tumour specimens resected after chemotherapy. The influence on survival of changes in ezrin expression after chemotherapy was analysed. Ezrin expression was significantly higher after preoperative chemotherapy and changes compared to biopsy tissue were significantly lower in patients with early progression than in patients with relapse or no further evidence of disease (p = 0.006 and p = 0.002, respectively). Similarly, ezrin expression was higher after preoperative chemotherapy and exhibited less change in expression in deceased patients compared to patients surviving more than 5 years (both p = 0.001). Ezrin expression at biopsy was significantly associated with both histopathological aggressiveness (p < 0.001) and tumour size (p = 0.037). The results of this study provide evidence that changes in overexpression of ezrin due to preoperative chemotherapy could be a useful predictive and prognostic marker in patients with osteosarcoma.

ADIPOQ -11377C>G Polymorphism Increases the Risk of Adipokine Abnormalities and Child Obesity Regardless of Dietary Intake.

OBJECTIVE: The aim of the present study was to verify whether selected functional single nucleotide polymorphisms in LEP, LEPR, and ADIPOQ loci are associated with the development of obesity and serum levels of the respective adipokines in prepubertal white children with obesity. METHODS: Frequencies of -2548G>A LEP (rs7799039), Q223R (rs1137101) and K656N (rs8129183) LEPR, and -11377C>G (rs266729) and -11426A>G (rs16861194) ADIPOQ polymorphisms were analyzed by restriction fragment length polymorphism in 101 obese (standard deviation score [SDS]-body mass index [BMI] >2) and 67 normal-weight (SDS-BMI <- 1 + 1 >) children. Serum adipokine concentrations were measured using the enzyme-linked immunosorbent assay method. RESULTS: The GC/GG genotypes of -11377C>G ADIPOQ polymorphism were associated with a higher risk of obesity (P = 0.022, odds ratio 2.08 [95% confidence interval 1.11-3.90]). Individuals carrying the GG genotype had a higher leptin/total adiponectin ratio by 25% than CC homozygotes (P trend = 0.05). In the multivariate linear regression model, we found differences among particular genotypes of this polymorphism in concentrations of high molecular weight (HMW) adiponectin (P trend = 0.043) and HMW/total adiponectin ratio (P trend = 0.048), with the lowest values in GG homozygotes. Positive correlations between SDS-BMI and dietary reference intake percentage were observed in individuals homozygous for allele C (r = 0.403, P = 0.01) and CG heterozygotes (r = 0.428, P = 0.004). No significant correlations between both parameters were found in the GG homozygotes. CONCLUSIONS: Among the analyzed polymorphisms, only -11377C>G ADIPOQ single nucleotide polymorphism was associated with obesity during the prepubertal period. Adipokine abnormalities coexisting with the lack of relations between SDS-BMI and dietary intake may predict a higher risk of future obesity-related disorders in obese children carrying the GG genotype than in those with other genotypes.

Socioeconomic inequalities in stillbirth rates in Europe: measuring the gap using routine data from the Euro-Peristat Project.

BACKGROUND: Previous studies have shown that socioeconomic position is inversely associated with stillbirth risk, but the impact on national rates in Europe is not known. We aimed to assess the magnitude of social inequalities in stillbirth rates in European countries using indicators generated from routine monitoring systems. METHODS: Aggregated data on the number of stillbirths and live births for the year 2010 were collected for three socioeconomic indicators (mothers' educational level, mothers' and fathers' occupational group) from 29 European countries participating in the Euro-Peristat project. Educational categories were coded using the International Standard Classification of Education (ISCED) and analysed as: primary/lower secondary, upper secondary and postsecondary. Parents' occupations were grouped using International Standard Classification of Occupations (ISCO-08) major groups and then coded into 4 categories: No occupation or student, Skilled/ unskilled workers, Technicians/clerical/service occupations and Managers/professionals. We calculated risk ratios (RR) for stillbirth by each occupational group as well as the percentage population attributable risks using the most advantaged category as the reference (post-secondary education and professional/managerial occupations). RESULTS: Data on stillbirth rates by mothers' education were available in 19 countries and by mothers' and fathers' occupations in 13 countries. In countries with these data, the median RR of stillbirth for women with primary and lower secondary education compared to women with postsecondary education was 1.9 (interquartile range (IQR): 1.5 to 2.4) and 1.4 (IQR: 1.2 to 1.6), respectively. For mothers' occupations, the median RR comparing outcomes among manual workers with managers and professionals was 1.6 (IQR: 1.0-2.1) whereas for fathers' occupations, the median RR was 1.4 (IQR: 1.2-1.8). When applied to the entire set of countries with data about mothers' education, 1606 out of 6337 stillbirths (25 %) would not have occurred if stillbirth rates for all women were the same as for women with post-secondary education in their country. CONCLUSIONS: Data on stillbirths and socioeconomic status from routine systems showed widespread and consistent socioeconomic inequalities in stillbirth rates in Europe. Further research is needed to better understand differences between countries in the magnitude of the socioeconomic gradient.

Early and Late Acute Kidney Injury in Severely Burned Patients.

BACKGROUND This study evaluated factors influencing early and late occurrence of AKI in severely burned patients and assessed the relationship between time of occurrence of AKI and mortality of AKI patients. MATERIAL AND METHODS Renal function was evaluated at 3 time points: at admission, at the critical point or middle point of hospitalization, and at the endpoint for which death or a discharge from the center was considered. AKI criteria were: decrease in GFR of less than 60 ml/min at admission, decrease in GFR of more than 75% compared to baseline, and decrease in the daily diuresis of less than 500 ml/24 h. RESULTS At admission, 15.1% of the patients had eGFR <60 ml/min. AKI occurred in 38.5% of cases. The occurrence of AKI was associated with: elderly age (p<0.001), female sex (p=0.017), overweight and obesity (p=0.055); extent and depth of burns, respiratory failure, low protein concentration (for all p<0.001), low blood pressure (p=0.014), and high WBC (p=0.010). Early AKI was detected in 28% of patients. Mortality was 100% with the initial GFR ≥60, 100% with the initial GFR <60 and early deterioration of renal function, 80% with the initial GFR <60 and late worsening, and 60% with the initial GFR <60 and no worsening. Late AKI was observed in 10% of patients and mortality in this group was 79.2%. Mortality in the entire group with AKI was 88.0% versus 24.5%. CONCLUSIONS The frequent occurrence of AKI, especially early, worsens the prognosis for survival. Assessment of renal function should be included in the prognostic scales for burned patients.

The Associations Between Body Cell Mass and Nutritional and Inflammatory Markers in Patients With Chronic Kidney Disease and in Subjects Without Kidney Disease.

OBJECTIVES: Body cell mass (BCM), a component of lean tissue mass (LTM), is a metabolically active part of the body. Lean tissue loss is one of the diagnostic criteria of protein energy wasting. In patients with chronic kidney disease (CKD), a decrease of lean tissue, including BCM, may be replaced by an increase of extracellular water. Bioimpedance spectroscopy (BIS) enables the assessment of the amount of BCM, LTM, and fluid overload. The aim of our study was to assess the relationship between BCM measured by BIS and anthropometric measurements, biochemical markers of nutrition and also inflammatory markers. METHODS: Forty-eight patients treated with hemodialysis (HD; 32 males and 16 females) with a mean age 59.8 ± 15.5 (HD group), 61 patients with CKD Stage 4 to 5 (35 males and 26 females) with a mean age of 60.1 ± 17.7 (predialysis group) and 33 individuals with normal renal function (18 males and 15 women) with a mean age 58.7 ± 17.0 (control group) were included. Body mass index, handgrip strength (HGS), body composition measured by BIS, and biochemical analyses were performed on all of them. RESULTS: Positive correlations were observed between BCM and LTM, HGS, serum creatinine and insulin-like growth factor 1 concentrations in all groups. Serum prealbumin concentration correlated positively with BCM only in the predialysis group (r = 0.406; P = .001). The amount of lymphocytes also correlated passively with BCM in predialysis group (r = 0.314; P = .024). Negative correlations were noted between BCM and fat mass in all groups and between BCM and interleukin 6 concentrations only in the HD group. In this study, BCM neither correlated with body mass index and serum albumin nor with C-reactive protein. CONCLUSIONS: BCM is strongly associated with biochemical determinants of muscle mass (serum creatinine, insulin-like growth factor 1) and muscle function (HGS) in patients treated with HD, with CKD Stage 4 to 5 and in individuals without kidney disease. Its significance requires further investigation.

Serum markers in early-stage and locally advanced melanoma.

The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I-III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7%; 35 patients died; and the 3-year overall survival (OS) rate was 85%. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61% (p = 0.014) and overall survival -88 vs. 82% (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59% of patients with ulceration and in 26% of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I-III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.