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.

Cushing's Disease: Long-Term Effectiveness and Safety of Osilodrostat in a Polish Group of Patients with Persistent Hypercortisolemia in the Experience of a Single Center.

Osilodrostat is a potent oral steroidogenesis inhibitor that has emerged as the new medical agent for patients with Cushing's disease (CD) requiring long-term medical therapy for hypercortisolemia control. Its efficacy and safety have been assessed in clinical trials; however, real-world evidence is still scarce. This study aimed to investigate the long-term treatment (156 weeks) clinical and biochemical effect of osilodrostat in six patients with CD at a single center in Poland, initially participating in the LINC4 study. At week 36, all six patients met the key secondary endpoint of the LINC4 trial, achieving normalization of median urinary free cortisol. Osilodrostat treatment allowed for complete disease control in all patients and none of the patients was excluded due to the lack of treatment effectiveness in 156 weeks of follow-up. All patients demonstrated significant improvement from baseline on most metabolic and cardiovascular parameters, which was most evident at week 36 and sustained throughout the study period. This study supports and strengthens the role of osilodrostat as an effective long-term medical treatment in patients with CD. We also present three patient case histories in detail to highlight the clinical situations that endocrinologists might face during osilodrostat therapy.

Resistin Contribution to Cardiovascular Risk in Chronic Kidney Disease Male Patients.

BACKGROUND: Resistin is a molecule that belongs to the Resistin-Like Molecules family (RELMs), the group of proteins taking part in inflammatory processes. Increased resistin concentrations are observed in cardiovascular complications. Resistin contributes to the onset of atherosclerosis and intensifies the atherosclerotic processes. The aim of this study was to investigate the relationship between resistin and cardiovascular (CV) risk in men with chronic kidney disease (CKD) not treated with dialysis. MATERIALS AND METHODS: One hundred and forty-two men were included in the study: 99 men with eGFR lower than 60 mL/min/1.73 m2 and 43 men with eGFR ≥ 60 mL/min/1.73 m2. CV risk was assessed. Serum resistin, tumor necrosis factor-alpha (TNF-alpha) and plasminogen activator inhibitor-1 (PAI-1) were measured among other biochemical parameters. RESULTS: We observed that resistin concentrations were significantly higher in patients with CKD compared to individuals with eGFR ≥ 60 mL/min/1.73 m2 (p = 0.003). In CKD, after estimating the general linear model (GLM), we found that resistin is associated with CV risk (p = 0.026) and PAI-1 serum concentrations (0.012). The relationship of PAI-1 with resistin depends on the level of CV risk in CKD (p = 0.048). CONCLUSIONS: Resistin concentrations rise with the increase of CV risk in CKD patients and thus resistin may contribute to the progression of cardiovascular risk in this group of patients. The relationship between resistin and CV risk is modified by PAI-1 concentrations.

Associations between Oxidant/Antioxidant Status and Circulating Adipokines in Non-Obese Children with Prader-Willi Syndrome.

Oxidative stress is implicated in the pathophysiology of Prader-Willi syndrome (PWS), but there are no data on these disorders in non-obese children with PWS. Therefore, the presented study examined total oxidant capacity (TOC), total antioxidant capacity (TAC), the oxidative stress index (OSI), and adipokine levels in 22 non-obese children with PWS during dietary intervention and growth hormone treatment compared with 25 non-obese healthy children. Serum concentrations of TOC, TAC, nesfatin-1, leptin, hepcidin, ferroportin, and ferritin were determined using immunoenzymatic methods. We found that TOC concentrations were higher by 50% (p = 0.006) in patients with PWS than in healthy children, but no significant differences in TAC concentrations were observed between these groups. The OSI was higher in children with PWS than in the controls (p = 0.002). We found positive associations between TOC values and the percentage of the Estimated Energy Requirement, body mass index (BMI) Z-score, percentage of fat mass, and leptin, nesfatin-1, and hepcidin concentrations in patients with PWS. A positive association was also found between the OSI and nesfatin-1 levels. These observations suggest that higher daily energy intake and weight gain may be accompanied by an increasing prooxidant state in these patients. Adipokines such as leptin, nesfatin-1, or hepcidin may also play a role in the prooxidant state in non-obese children with PWS.

Circulating Levels of Nesfatin-1 and Spexin in Children with Prader-Willi Syndrome during Growth Hormone Treatment and Dietary Intervention.

BACKGROUND: Despite observable improvement in the treatment outcomes of patients with Prader-Willi syndrome (PWS), adequate weight control is still a clinical problem. Therefore, the aim of this study was to analyze the profiles of neuroendocrine peptides regulating appetite-mainly nesfatin-1 and spexin-in children with PWS undergoing growth hormone treatment and reduced energy intake. METHODS: Twenty-five non-obese children (aged 2-12 years) with PWS and 30 healthy children of the same age following an unrestricted age-appropriate diet were examined. Serum concentrations of nesfatin-1, spexin, leptin, leptin receptor, total adiponectin, high molecular weight adiponectin, proinsulin, insulin-like growth factor-I, and total and functional IGF-binding protein-3 concentrations were determined using immunoenzymatic methods. RESULTS: The daily energy intake in children with PWS was lower by about 30% (p < 0.001) compared with the controls. Daily protein intake was similar in both groups, but carbohydrate and fat intakes were significantly lower in the patient group than the controls (p < 0.001). Similar values for nesfatin-1 in the PWS subgroup with BMI Z-score < -0.5 and the control group, while higher values in the PWS subgroup with BMI Z-score ≥ -0.5 (p < 0.001) were found. Spexin concentrations were significantly lower in both subgroups with PWS than the controls (p < 0.001; p = 0.005). Significant differences in the lipid profile between the PWS subgroups and the controls were also observed. Nesfatin-1 and leptin were positively related with BMI (p = 0.018; p = 0.001, respectively) and BMI Z-score (p = 0.031; p = 0.027, respectively) in the whole group with PWS. Both neuropeptides also correlated positively in these patients (p = 0.042). CONCLUSIONS: Altered profiles of anorexigenic peptides-especially nesfatin-1 and spexin-in non-obese children with Prader-Willi syndrome during growth hormone treatment and reduced energy intake were found. These differences may play a role in the etiology of metabolic disorders in Prader-Willi syndrome despite the applied therapy.

Comparable Hemodilution with Hypertonic Glucose in Patients with and without Type-2 Diabetes Mellitus during Hemodialysis.

(1) Background: It was examined whether glucose-induced changes in the relative blood volume are suitable to identify subjects with and without type-2 diabetes mellitus (T2D) during hemodialysis. (2) Methods: The relative blood volume was continuously recorded during hemodialysis and perturbed by the infusion of glucose comparable to the dose used for intravenous glucose tolerance tests. Indices of glucose metabolism were determined by the homeostatic model assessment (HOMA). Body composition was measured by a bioimpedance analysis. The magnitude and the time course of hemodilution were described by a modified gamma variate model and five model parameters. (3) Results: A total of 34 subjects were studied, 14 with and 20 without T2D. The magnitude of the hemodilution and the selected model parameters correlated with measures of anthropometry, body mass index, absolute and relative fat mass, volume excess, baseline insulin concentration, and HOMA indices such as insulin resistance and glucose disposition in a continuous analysis, but were not different in a dichotomous analysis of patients with and without T2D. (4) Conclusions: Even though the parameters of the hemodilution curve were correlated with measures of impaired glucose metabolism and body composition, the distinction between subjects with and without T2D was not possible using glucose-induced changes in the relative blood volume during hemodialysis.

Changes of Hemodynamic Parameters after Intradialytic Glucose Injection.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of hemodialysis (HD). Current methods of IDH prevention are insufficient. METHODS: We analyzed the intradialytic time course of systolic (SBP), diastolic (DBP), mean arterial (MAP), pulse pressure (PP), and heart rate (HR) in a group of chronic kidney disease (CKD) patients. First, 30 min into HD, a 40% glucose solution was injected into the venous line of the extracorporeal circulation at a dose of 0.5 g/kg of dry weight. Pressures and HR were measured in frequent intervals. Relative volume overload was determined by bioimpedance spectroscopy. RESULTS: Thirty-five participants were studied. SBP increased after 5, 10, and 20 min of glucose infusion. DBP increased after 2 and 3 h and also at the end of HD. PP increased after 5, 10, and 20 min of glucose infusion and fell after the 2nd and 3rd hour and also at the end of HD. MAP increased after 2 and 3 h of glucose injection and at the end of HD. Significant interactions of the time course of SBP, DBP, MAP, with HR at baseline and of the time course of PP with fluid overload were observed. Symptomatic hypotensive episodes were absent. CONCLUSIONS: Glucose infusions during HD prevent symptomatic IDH and do not cause severe hypertensive episodes.

Left Ventricular Diastolic Dysfunction in Chronic Kidney Disease Patients Not Treated with Dialysis.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is observed in the early stages of chronic kidney disease (CKD) and may lead to heart failure with preserved ejection fraction (HFpEF). The purpose of our study was to investigate the association between metabolic, nutritional and inflammatory parameters and LVDD in CKD and non-CKD patients. METHODS: Two groups of patients were recruited to the study: 93 men with CKD and eGFR lower than 60 mL/min/1.73 m2 and 40 men without kidney function decrease with eGFR ≥ 60 mL/min/1.73 m2. Transthoracic echocardiography was performed to evaluate the diastolic function of the left ventricle. Bioimpedance spectroscopy (BIS) was used to measure overhydration and lean body mass. We also measured the serum concentrations of albumin, glucose, haemoglobin A1c (HgbA1c), fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and osteoprotegerin (OPG). RESULTS: We observed that elevated serum fibrinogen and glucose concentrations were associated with LVDD independently of CKD status. Serum fibrinogen concentrations increased with the advancement of LVDD. Low albumin concentrations in CKD were related with LVDD. In the control group, lower muscle mass presented as lean tissue index (LTI) and lean tissue mass (LTM), and overhydration were associated with LVDD. In the group of patients without kidney function decrease the OPG concentrations were significantly higher in those with LVDD, and they rose with the advancement of LVDD. CONCLUSIONS: Elevated inflammatory parameters, increased serum glucose concentrations and worse nutritional status are the states that may impair the diastolic function of the left ventricle in CKD and non-CKD patients. Serum OPG levels are elevated in patients without kidney function decrease and LVDD and its concentrations rise with the advancement of LVDD.

Serum Osteoprotegerin Is an Independent Marker of Left Ventricular Hypertrophy, Systolic and Diastolic Dysfunction of the Left Ventricle and the Presence of Pericardial Fluid in Chronic Kidney Disease Patients.

BACKGROUND: Osteoprotegerin (OPG) is a molecule which belongs to the tumor necrosis factor receptor superfamily. OPG concentration is elevated in patients with left ventricle hypertrophy, heart failure and acute myocardial infarction. OPG concentrations rise in chronic kidney disease (CKD). The aim of this study was to investigate the association between OPG concentrations and cardiovascular complications, such as left ventricle hypertrophy, systolic and diastolic dysfunction of left ventricle and dysfunction of right ventricle in chronic kidney disease patients not treated with dialysis. The relation between OPG and the amount of pericardial fluid was also examined. METHODS: One hundred and one men with CKD stage 3-5 not treated with dialysis were included in the study. Overhydration, body fat mass and lean body mass were measured using bioimpedance spectroscopy (BIS). Echocardiography was performed to evaluate the amount of pericardial fluid and to measure the thickness of the interventricular septum (IVS), systolic and diastolic function of left ventricle, as well as systolic function of right ventricle. RESULTS: We observed a significant positive association between OPG and the thickness of the interventricular septum, the size of the left atrium (LA) and the presence of pericardial fluid. A negative relationship was observed between OPG and ejection fraction (EF). CONCLUSIONS: Our results suggest that OPG can be an independent marker of left ventricular hypertrophy, systolic and diastolic dysfunction of left ventricle and the presence of pericardial fluid in chronic kidney disease patients.

Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience.

Worldwide neonatal screening for congenital hypothyroidism (CH) is a gold standard of active surveillance in newborns. Prompt diagnosis, subsequent timely treatment implementation, and proper dosage of levothyroxine (L-T4) are crucial for normal growth and development, especially of the central nervous system. However, overtreatment may have a potential negative impact on further neurodevelopment. We retrospectively analysed data of 99 newborns with CH diagnosis, referred to the Endocrinology Outpatient Clinic of the Institute of Mother and Child in Warsaw, Poland from the CH screening program from 2017 to 2021. We evaluated the diagnostic process and treatment up to the age of 3 years. We compared groups of children from the first and the second screening groups (FSG, SSG) in the neonatal screening with an evaluation of ultrasound examination (thyroid dysgenesis vs. gland in situ, GIS). The overtreatment and undertreatment risks were assessed and an analysis of the new TSH thresholds was performed. Treatment was implemented at a median of 9 days of life (3 - 27); 8 days (3 - 17) in FSG and 19 (6 - 27) in SSG. The dose of L-T4 differed between FSG and SSG at all three analysed time points (start of the therapy, 12 months, and 3 years) with significantly higher doses in FSG. The same was observed for the patients with thyroid dysgenesis vs. GIS. Screening TSH level was ≥ 28mIU/l in 91.7% of patients with thyroid dysgenesis in comparison to 74.0% of patients with GIS (p= 0.038). The optimally treated group (fT4 in the upper half of the reference range, according to the guidelines) was up to 58.0% of the children during the follow-up. The risk for overtreatment was present in 1/5 of the study group after 12 months and 1/4 after 3 years of L-T4 therapy. Analysis of new TSH thresholds showed an increased prevalence of mild hypothyroidism, GIS, and either euthyroid state or overtreatment while treating with lower L-T4 doses in comparison to the rest of the cohort. The study confirmed the general efficacy of the CH diagnostic pathway and the timely implemented L-T4 therapy. The suspected overtreatment after the first 12 months of L-T4 therapy requires consideration of the earlier diagnosis re-evaluation.

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.

Relationships between Sclerostin, Leptin and Metabolic Parameters in Non-Dialysis Chronic Kidney Disease Males.

Sclerostin is an inhibitor of the Wnt-beta-catenin pathway. The relationship between sclerostin and adipose tissue or between sclerostin and nutritional status has been the subject of research interest in the last decade. Sclerostin concentrations are elevated in patients with chronic kidney disease (CKD). Leptin is an adipocytokine which inhibits food intake by stimulating the satiety center in the hypothalamus. Leptin concentrations rise with the reduction of eGFR (glomerular filtration rate). The aim of this study was to investigate the possible association between sclerostin and leptin, between sclerostin and selected poor prognostic factors of CKD progression, and between sclerostin and nutritional parameters in non-dialysis CKD male patients. 101 men with non-dialysis CKD stage 3-5 were included in the study. Bioimpedance spectroscopy (BIS) was used to measure body composition. Blood samples were drawn to measure the serum concentrations of sclerostin, leptin, creatinine, hemoglobin (Hgb), parathormone (PTH), inflammatory markers, and markers of nutritional status. We also measured homeostatic model assessment of insulin resistance (HOMA-IR) as well as blood pressure. We observed a significant, positive relationship between sclerostin and age, leptin, and glycated hemoglobin (HgbA1c) concentrations. A significant, negative association was observed between sclerostin and eGFR. Sclerostin is associated with leptin in non-dialysis CKD male patients. Sclerostin is also related to metabolic disturbances such as hyperglycemia in this population.

International versus national growth charts for identifying small and large-for-gestational age newborns: A population-based study in 15 European countries.

BACKGROUND: To inform the on-going debate about the use of universal prescriptive versus national intrauterine growth charts, we compared perinatal mortality for small and large-for-gestational-age (SGA/LGA) infants according to international and national charts in Europe. METHODS: We classified singleton births from 33 to 42 weeks of gestation in 2010 and 2014 from 15 countries (N = 1,475,457) as SGA (birthweight <10th percentile) and LGA (>90th percentile) using the international Intergrowth-21st newborn standards and national charts based on the customised charts methodology. We computed sex-adjusted odds ratios (aOR) for stillbirth, neonatal and extended perinatal mortality by this classification using multilevel models. FINDINGS: SGA and LGA prevalence using national charts were near 10% in all countries, but varied according to international charts with a north to south gradient (3.0% to 10.1% and 24.9% to 8.0%, respectively). Compared with appropriate for gestational age (AGA) infants by both charts, risk of perinatal mortality was increased for SGA by both charts (aOR[95% confidence interval (CI)]=6.1 [5.6-6.7]) and infants reclassified by international charts from SGA to AGA (2.7 [2.3-3.1]), but decreased for those reclassified from AGA to LGA (0.6 [0.4-0.7]). Results were similar for stillbirth and neonatal death. INTERPRETATION: Using international instead of national charts in Europe could lead to growth restricted infants being reclassified as having normal growth, while infants with low risks of mortality could be reclassified as having excessive growth. FUNDING: InfAct Joint Action, CHAFEA Grant n°801,553 and EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking ConcePTION grant n°821,520. AH received a PhD grant from EHESP.

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.

The Effect of 6 Months' Treatment With Pasireotide LAR on Glucose Metabolism in Patients With Resistant Acromegaly in Real-World Clinical Settings.

Objective: The aim of the study was to evaluate glucose metabolism, as measured by glycated hemoglobin (HbA1c) levels and the need for antidiabetic medical treatment, in patients with acromegaly resistant to first-generation somatostatin receptors ligands (SRLs) treated with pasireotide long-acting release (LAR) in real-world clinical practice. Biochemical control of acromegaly, as measured by growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, was also assessed. Study Design: Two-center retrospective cohort of consecutive patients with acromegaly treated with first-generation SRLs at maximum doses, who had not achieved biochemical disease control. After SRLs were discontinued, patients were given pasireotide LAR 40 mg i.m. every 28 days. The dose was increased to 60 mg i.m. in patients for whom adequate control was not achieved after 3 months. Patients were given dietary and lifestyle advice, and antihyperglycemic treatment was modified as needed. Main Outcome Measures: Biochemical disease control parameters (GH and IGF-1 concentration), as well as HbA1c level at baseline and after 6 months. Results: In total, 39 patients with acromegaly were enrolled. GH concentration decreased (Δme =-1.56 µg/L, range -21.38-3.62, p <0.001) during 6 months of pasireotide LAR treatment. A worsening of metabolic status was observed, with an increase of median HbA1c (Δme =0.40%, range -0.20%-2.30%, p <0.001), and antihyperglycemic treatment intensification in 23 (59.0%) patients. The median decline in IGF-1 concentration was: -283.0 µg/L, range -682.7-171.6, p <0.001. IGF-1 reached the age- and gender-specific upper level of normal in 23 (59%) patients. Conclusions: Pasireotide LAR is an effective therapeutic option in patients with acromegaly refractory to first-generation SRLs. However, this therapy may result in pasireotide LAR-associated hyperglycemia, which requires early and aggressive antidiabetic medical therapy to prevent glucose homeostasis alterations.

Glucose tolerance in patients with and without type 2 diabetes mellitus during hemodialysis.

AIMS: The disposal of a glucose bolus was studied to identify glucose metabolism in patients with and without type 2 diabetes mellitus (T2DM) during their regular hemodialysis (HD) treatment. METHODS: Plasma glucose, insulin, and c-peptide concentrations were measured during a 60 min observation phase following a rapid glucose infusion (0.5 g/kg dry weight). Glucose disposition and elimination rates were determined from kinetic analysis, and insulinogenic index was calculated. Insulin resistance (RHOMA) was determined by homeostatic model assessment (HOMA). RESULTS: 35 HD patients (14 with T2DM) distinguished by a higher age (median: 70 vs. 55 y, p < 0.01) in T2DM patients were studied. Glucose kinetic data showed only small differences between patients with or without T2DM, but as RHOMA measured in all patients increased, a larger fraction of glucose was removed by the extracorporeal system (r = 0.430, p = 0.01). One hour after glucose bolus injection the glucose level was not different from that before HD also in patients with T2DM (p = 0.115). CONCLUSIONS: The larger glucose amount recovered in dialysate in patients with increasing RHOMA indicates that impaired glucose disposal could be measured during HD using a non-invasive dialysis quantification approach without blood sampling. Glucose infusion during HD is safe also in patients with T2DM.

Associations Between Antioxidant Vitamin Status, Dietary Intake, and Retinol-binding Protein 4 Levels in Prepubertal Obese Children After 3-month Weight Loss Therapy

Objective: Adiposity is associated with increased oxidative stress, leading to changed fat-soluble vitamin concentrations. The aim of this study was to determine whether weight loss alters fat-soluble vitamin status and whether these alterations are associated with dietary intake, anthropometric parameters and adipokines in obese children. Methods: Vitamin A and E concentrations were measured using high-pressure liquid chromatography in 60 obese children before and after weight loss therapy. Retinol-binding protein 4 (RBP4), leptin, soluble leptin receptor (sOB-R), and high molecular weight adiponectin concentrations were determined by immunoenzymatic assays. Results: The intake of vitamin E was lower in obese children with weight loss after therapy (p=0.038). In this group, an increase was found in the vitamin A/lipids (p=0.022) and the vitamin E/lipids (p=0.008) ratios but due to the reduction in triglyceride levels. In the obese group, changes in vitamin E level were positively correlated with changes in dietary vitamin E (p=0.017) and the leptin/sOB-R ratio (p=0.046). Changes in vitamin A level were positively correlated with changes in dietary vitamin A (p=0.001) and RBP4 concentration (p=0.023). Associations between changes in RBP4 level with the changes in body mass index (BMI) (p=0.011) and total cholesterol concentration (p=0.023) but not with changes in vitamin A concentration were found in the obese after therapy. Conclusion: An increased risk of vitamin E deficiency may occur in children losing weight during lifestyle intervention. Changes in BMI value may influence changes in RBP4 concentrations and consequently the vitamin A status in obese children after therapy.

Prolactinomas: Prognostic Factors of Early Remission After Transsphenoidal Surgery.

Background and Objective: Most patients with prolactinomas receive pharmacological treatment only, resulting in limited research on the predictors of successful prolactinoma surgery. In this study, we analyzed whether early postoperative serum prolactin concentrations and selected tumor characteristics could predict early, hormonal remission after removal of prolactinomas. Methods: We prospectively enrolled 48 consecutive patients with prolactinomas who underwent transsphenoidal resection performed by the same surgeon. Early remission, defined as a lack of hyperprolactinemia symptoms and normalization of serum prolactin concentration, was ascertained in all patients at 3 months. We evaluated the invasiveness of prolactinomas on the Knosp grading scale and measured serum prolactin concentrations on the first postoperative day. Routine immunohistochemical analysis, evaluation for plurihormonality, and assessment of the Ki-67 proliferation index (<3 or ≥3% of positive nuclei) were performed in all tumor samples. Results: Of 48 patients, 38 (79%) achieved early biochemical remission at 3 months. Patients in early remission at 3 months had lower serum prolactin concentrations on the first postoperative day than patients with recurrent or persistent hyperprolactinemia (p < 0.001). Using univariate logistic regression, larger maximum tumor diameter (p = 0.014), higher Knosp grade (p < 0.001), and plurihormonality predicted remission at 3 months (p = 0.021). However, using multivariate stepwise logistic regression, only the Knosp grade remained significant (p < 0.001). Conclusions: Radiological assessment of prolactinoma invasiveness (Knosp grades) and early postoperative serum prolactin concentrations are important predictors of early remission following transsphenoidal prolactinoma resection.