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.

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.

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.

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.

The prognostic role of BRAF and WNT pathways activation in kinase inhibitors-naïve clinical stage III cutaneous melanoma.

The results of local-regional advanced melanoma (stage III) management are still not satisfactory. Particularly, there is no personalized treatment in stage III melanoma patients due to the lack of useful classical pathological markers for prognostication of indolent or aggressive course of the disease. The aim of this study was to explore melanoma genomic landscape by means of the mutational profiling of 50 genes influencing carcinogenesis pathways in the randomly selected 93 kinase inhibitor-naïve (KI-naïve) stage III patients. The genomic alterations were found in 27 out of 50 tested genes and at least one pathogenic variant was detected in 77 out of 93 cases (82.7%). Survival rate was negatively affected by the presence of the somatic mutations in AKT1, ATM, CDH1 and SMARCB1, while the BRAF+ status in KI-naïve stage III population correlated with the longer median overall survival. Genomic alterations in WNT pathway correlated with extranodal adipocyte tissue involvement (P = 0.027) and higher number of metastatic lymph nodes (P = 0.045). In terms of survival, the Cox model confirmed the worse prognosis in patients with mutation in the WNT pathway [hazard ratio (HR) = 2.9, P = 0.017], and better prognosis in cases with mutations in BRAF pathway (HR = 0.5, P = 0.004). WNT/ß-catenin pathway alteration was associated with more advanced/aggressive disease. From this perspective, the concept of blocking the activity of the WNT pathway in selected cases appears promising and complementary to the BRAF inhibition therapeutic option for the future.

MGMT expression in pituitary corticotroph adenomas and its relationship to clinical, pathological, and ultrastructural parameters in patients with Cushing's disease.

INTRODUCTION: Transsphenoidal surgery is the treatment of choice in Cushing's disease (CD), although even late recurrences occur in some patients. Low expression of O-6-methylguanine-DNA methyltransferase (MGMT) has been linked to a high risk of relapse in pituitary tumours, but the evidence for corticotroph adenomas is limited. Therefore, we investigated whether MGMT expression was associated with CD remission or clinicopathological markers of tumour aggressiveness among patients with corticotroph adenomas. MATERIAL AND METHODS: We included 72 consecutive patients (83% female, mean age ±SD: 44.15 ±15.15 years) with CD, who underwent transsphenoidal adenomectomy between 2012 and 2018. The invasiveness of corticotroph tumours was assessed based on the Knosp scale. Immunohistochemistry was used to analyse MGMT expression as well as the proliferation markers (Ki-67, p53, mitotic index). Electron microscopy was used to categorise tumours into densely or sparsely granulated. Early biochemical remission was evaluated in all patients 6 months after pituitary surgery. RESULTS: Early remission was observed in 47 (65%) patients 6 months after surgery. MGMT expression was > 75% in half of all tumours, < 25% in 14 tumours, and 25-50% or 50-75% in 11 tumours. Lower MGMT expression was associated with a larger tumour diameter (p = 0.001), higher adrenocorticotropic hormone (ACTH) concentration (p = 0.002), higher p53 expression (p = 0.026), and higher frequency of sparsely granulated corticotroph adenomas (p = 0.009). Low MGMT expression was significantly related to lower frequency of early clinical remission (p = 0.005). CONCLUSIONS: MGMT predicted the outcomes of transsphenoidal surgery for CD. Pituitary corticotroph adenomas with low MGMT expression may be associated with increased invasiveness and poorer prognosis.

Blood neutrophil-to-lymphocyte ratio is associated with prognosis in advanced gastrointestinal stromal tumors treated with imatinib.

INTRODUCTION: Neutrophil-to-lymphocyte ratio (NLR) was shown to be prognostic in several solid malignancies. There are limited data about predictive/prognostic value of NLR during targeted therapy of patients with advanced gastrointestinal stromal tumors (GIST). The aim of this study was to asses a clinical value of this ratio in patients with advanced GIST. METHODS: Between 2001 and 2016, 385 patients with metastatic/unresectable GIST treated initially with imatinib were included in the analysis. In all patients, the NLR was assessed at the baseline, after 3 months of treatment, and upon disease progression (or last observation). The cutoff values for NLR were set at 2.7 and 5.4. Kaplan-Meier survival probability estimation with log-rank test and Cox proportional hazards model were used for analysis. RESULTS: Median progression-free survival (PFS) on imatinib treatment was 44.8 months, 5-year rate 43%; median overall survival (OS) 87.2 months, 10-year rate 36.3%. NLR >2.7 at baseline was significantly associated with poorer OS and PFS: median OS was 89.3 months (95% confidence interval [CI] 80.2-115) for NLR ratio ≤2.7 vs 59.4 months (95% CI 48.6-82) for NLR >2.7 (p < .001); median PFS was 59.4 vs 32.7 (p < .001), respectively. In multivariate model adjusted for mitotic index and driver mutation in the tumor (KIT exon 11 mutation versus other), NLR ratio was proven to be statistically significant (hazard ratio 1.09; 95% CI 1.01-1.19; p = .030). Among patients with disease progression, NLR >2.7 assessed at the third month of treatment was linked with significantly shorter median time to progression (7.5 vs 19 months). CONCLUSIONS: Our results demonstrate the usefulness of NLR as a prognostic and predictive marker as well as a marker for treatment monitoring in patients with advanced GIST treated with imatinib.

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.

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.

Comparison of body composition and adipokine levels between thin and normal-weight prepubertal children / Comparação da composição corporal e dos níveis de adipocina entre crianças pré-púberes magras e com peso normal

Abstract Objective: Thinness can have substantial consequences for child development and health. Adipokines, including leptin and adiponectin, play a significant role in the regulation of important metabolic functions. The aim of this study was to investigate associations between body composition and serum leptin and adiponectin levels in thin and normal-weight children. Methods: The authors examined 100 healthy prepubertal children, who were divided into two subgroups: thin (n = 50) and normal-weight children (n = 50). Body composition was assessed by dual-energy X-ray absorptiometry. Serum concentrations of adipokines were determined by immunoenzymatic assays. Results: Thin children had a similar body height but significantly lower (p < 0.0001) body weight, body mass index, fat mass, lean mass, and bone mineral content compared with normal-weight children. Serum concentrations of leptin were about 2-fold lower (p < 0.0001) in thin vs. normal-weight subjects. Serum levels of total adiponectin, adiponectin multimers, and soluble leptin receptor (sOB-R) were similar in both groups. The leptin/soluble leptin receptor ratio and leptin/adiponectin ratios were lower (p < 0.0001) in thin vs. normal-weight children. In both groups of children, it was found that body composition parameters were positively related with leptin but not with adiponectin levels. Additionally, bone mineral content was positively related with body mass index, fat mass, lean mass, and leptin level in thin and normal-weight children. Conclusions: Prepubertal thin children have disturbances in body composition and adipokine profile. Early recognition of thinness and determination of body composition parameters and adipokine levels can be useful in medical and nutritional care of thin children for the optimization of bone mineral accrual.

Resumo Objetivo: A magreza pode ter consequências substanciais para o desenvolvimento e a saúde das crianças. As adipocinas, inclusive a leptina e a adiponectina, desempenham um papel significativo na regulação de importantes funções metabólicas. O objetivo do estudo foi investigar as associações entre a composição corporal e os níveis séricos de leptina e adiponectina em crianças magras e com peso normal. Métodos: Examinamos 100 crianças pré-púberes saudáveis, divididas em dois subgrupos: crianças magras (n = 50) e com peso normal (n = 50). A composição corporal foi avaliada pelo método de absorciometria de dupla energia de raios X. As concentrações séricas das adipocinas foram determinadas por ensaios imunoenzimáticos. Resultados: As crianças magras apresentaram altura semelhante, porém peso corporal (p < 0,0001), índice de massa corporal (IMC), massa gorda, massa magra e conteúdo mineral ósseo (CMO) significativamente menores em comparação com crianças com peso normal. As concentrações séricas de leptina foram aproximadamente duas vezes mais baixas (p < 0,0001) em indivíduos magros do que em crianças com peso normal. Os níveis séricos de adiponectina total, multímeros de adiponectina e receptor de leptina solúvel (sOB-R) foram semelhantes em ambos os grupos. Os índices de leptina/sOB-R e leptina/adiponectina foram inferiores (p < 0,0001) em crianças magras do que crianças com peso normal. Em ambos os grupos de crianças descobrimos que os parâmetros de composição corporal estavam positivamente relacionados à leptina, porém não aos níveis de adiponectina. Além disso, observamos que o CMO estava positivamente relacionado ao IMC, à massa gorda, à massa magra e ao nível de leptina em crianças magras e com peso normal. Conclusões: As crianças pré-púberes magras têm alterações na composição corporal e no perfil de adipocinas. O reconhecimento precoce da magreza e a determinação dos parâmetros de composição corporal e dos níveis de adipocina podem ser úteis no cuidado médico e nutricional de crianças magras para aprimoramento do acúmulo mineral ósseo.

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.

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission - a prospective, controlled study.

INTRODUCTION: Effective transsphenoidal surgery (TSS) for Cushing`s disease (CD) normalizes cortisol levels and reduces complications of hypercortisolism. However, there is evidence of increased cardiovascular morbidity even after successful surgery. OBJECTIVE: A prospective, controlled study on the dynamics of fibrinogen and D-dimer levels with a six-month follow-up after an effective TSS for CD. MATERIAL AND METHODS: Forty patients with CD and forty healthy age- and sex-matched subjects were included. We assessed ACTH, urinary and serum cortisol, and fibrinogen and D-dimer levels before TSS and during follow-up. RESULTS: Baseline BMI (P < 0.001), fibrinogen (P = 0.002), and D-dimer (P = 0.001) levels in CD patients were significantly higher than those in healthy controls. High fibrinogen levels in the CD group were independent of BMI, and were positively associated with hsCRP (rS = 0.61, P < 0.001) and arterial hypertension (P = 0.029). After the six-month follow-up we confirmed a sustained difference between the remission group and controls in fibrinogen and D-dimer levels (P = 0.001 and P = 0.017, respectively). CONCLUSIONS: Despite early biochemical remission of CD the levels of fibrinogen and D-dimer failed to decrease. This probably contributes to the high risk of thrombotic events and indicates the need for a close follow-up for signs of thromboembolic and cardiovascular complications in patients with early CD remission. (Endokrynol Pol 2016; 67 (3): 283-291).

Clinicopathological predictive factors in the early remission of corticotroph pituitary macroadenomas in a tertiary referral centre.

OBJECTIVE: Corticotroph macroadenomas are a rare cause of Cushing's disease (CD), but their properties are not well-recognised. The aim of this study was to evaluate the clinical and pathological aspects of corticotroph macroadenomas with particular emphasis on proliferation markers and their associations with the efficacy of surgical treatment. DESIGN: A prospective cohort study was conducted in a tertiary referral centre in Poland. METHODS: In total, 59 patients with CD (20 macroadenomas and 39 microadenomas) were included in this study. Hormonal and imaging parameters, histopathological and ultrastructural features of the corticotroph tumours and the early surgical outcomes were evaluated. RESULTS: ACTH and ACTH/cortisol ratios were higher in macroadenomas (P<0.001 and P=0.002 respectively). Greater tumour volumes were associated with higher Ki-67 and p53 expression (Ptrend=0.009 and Ptrend=0.024 respectively) and the rates of sparsely granulated adenomas (Ptrend=0.036). Immediate postoperative remission and early biochemical remission rates were lower in macroadenomas compared to microadenomas (P<0.001). A logistic regression model showed that the immediate postoperative remission or early biochemical remission depended on tumour volume (P=0.005 and P=0.006 respectively) and invasiveness based on Knosp grades 3 and 4 for macroadenomas and a lack of surgical pseudocapsule for microadenomas (P=0.004 and P=0.007 respectively). CONCLUSION: Corticotroph macroadenomas differ from the more common microadenomas not only in terms of hormonal and imaging characteristics but also in terms of immunohistochemical and ultrastructural features and proliferation markers. The early effectiveness of surgery depends primarily on tumour volume and invasiveness.

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.

First year survival of patients on maintenance dialysis treatment in Poland.

Retrospective analysis of demographic and clinical data of all patients starting dialysis over two years in our Department (n = 105) has been conducted. Factors such as type of dialysis treatment, reason of end-stage renal disease, Body Mass Index (BMI), laboratory tests results, number and cause of death during first year of dialysis were taken under consideration. Five patients have been excluded from the analysis of mortality (four received renal transplantation, one changed dialysis center). Twenty tree deaths have been noted during first year of dialysis treatment. Nine of them occurred during the first three months of therapy. The leading cause of death was cardio-vascular events (n = 14, 60.9%), the second was malignancy (8, 34,8%), one patient died due to catheter associated infection. Malignancy as a cause of end-stage renal disease, lack of outpatient nephrology care, acute mode of beginning renal replacement therapy and lack of erythropoiesis stimulating agents therapy were associated with higher risk of all-cause mortality during first year of dialysis. Being under the outpatient nephrology care, etiology of ESRD other than malignancy and erythropoiesis stimulating agents therapy were independently associated with better survival during this period of time. Other independent variables did not reach statistical significance. To conclude, in order to improve one year survival of dialysis patients, outpatient nephrology care with adequate amount of visits and associated dialysis therapy should be employed.

Cushing's Disease: The Relevance of a Combined Dexamethasone Desmopressin Test as a Component of Postoperative Hormonal Evaluation.

Background. The risk of Cushing's disease (CD) recurring may persist for years, even after initially successful surgery. Objective. To prospectively assess the relevance of a combined dexamethasone desmopressin test (CDDT) as a component of postoperative hormonal evaluation, including the dynamics of ACTH and cortisol concentrations. Material and Methods. We included 28 patients after TSS for CD. Eighteen months after surgery the standard hormonal evaluation was performed, followed by a CDDT. Results. Fifteen patients (53.6%) were in remission whereas in 13 subjects (46.4%) hypercortisolemia was confirmed. Positive results of CDDT were observed in 12 noncured patients (92.3%) and in one subject in remission (6.7%). Negative results were obtained in 12 patients with remission (80%) and in one noncured patient (7.7%). With 2 patients in CD remission (13.3%) the test results were inconclusive. We confirmed a high compatibility between CDDT and standard hormonal assessment results (κ = 0.846; P < 0.001). Significant differences in ACTH and cortisol levels at each CDDT time point between the two studied subgroups were shown. Conclusions. A negative CDDT result can be regarded as one of the factors indicative of CD remission during follow-up. Additionally, CDDT can help distinguish persistent hypercortisolemia from naturally recurring adrenal function after TSS.

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.

Body composition parameters and adipokines levels in relation to bone mineral density in patients with malignant bone tumors after treatment.

BACKGROUND: Recent data support the concept that adipokines, which are secreted by fat cells, are important modulators of bone metabolism. The aim of this study was to assess the relationships between body composition parameters, adipokines (leptin, adiponectin) and bone mineral density (BMD) in patients with malignant bone tumors after anticancer therapy. PROCEDURE: The study included 35 patients (median age 14.8 years) with diagnosed malignant bone tumors treated according to obligatory protocols. Total fat mass, lean mass, bone mineral content (BMC) and BMD measurements were performed after treatment completion by dual energy-ray absorptiometry (DXA). Serum concentrations of leptin, leptin receptor and adiponectin were determined using immunoenzymatic assays. The control group consisted of 28 healthy children (median age 14.3 years). RESULTS: Patients with bone tumor after chemotherapy had significantly higher fat mass (P < 0.01), increased ratio of fat mass/lean mass (P < 0.001), and a decrease (P < 0.001) in total body and lumbar spine BMD compared with controls. We observed higher serum leptin concentration (P < 0.01) and lower soluble leptin receptor (P < 0.001) and adiponectin (P = 0.01) in patients than in controls. The ratios of leptin/leptin receptor and leptin/adiponectin were about three-fold higher in patients compared with the control group (P = 0.001). We found a significant positive correlation between BMD and body composition and a negative correlation between BMD and adiponectin in the patients group. CONCLUSIONS: Changes in body composition parameters coexisting with disturbed adipokine levels, especially higher levels of leptin and lower levels of adiponectin, might be associated with bone status in patients treated for malignant bone tumors.