Investigation of the value of hematological biomarkers in the clinical differential diagnosis of IgG4-RD.

BACKGROUND: IgG4- related disease (IgG4- RD) is a systemic fibroinflammatory disease whose pathogenesis has not been completely elucidated. Due to the novelty and complexity of the diagnostic criteria, it is difficult to distinguish from the diseases included in the differential diagnosis without tissue biopsy. This study aimed to discover new biomarkers that can help for disease diagnosis and its differential diagnosis by reviewing the relationships between neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI). METHODS: Thirty IgG4- RD, 38 granulomatous polyangiitis (GPA), and 46 sarcoidosis patients presenting to the Rheumatology Clinic meeting the criteria of 2019 American College of Rheumatology, 2012 International Chapel Hill and 1999 American Thoracic Society meeting, respectively, and 27 healthy control subjects were included. We collected data on complete blood count with automated differential values including NLR, PLR, SII, and SIRI. RESULTS: The SII and PLR values were significantly higher in patients with IgG4-RD compared to healthy controls, (SII median (minmax) 572 (102-5583) vs. 434 (172-897), PLR median (min-max) 130 (56.8-546) vs. 104 (57.5- 253) p < 0.001). SII value was found to have a significant positive correlation with CRP in IgG4-RD disease (r = 0.371; p = 0.043). While SII, SIRI, NLR, PLR parameters were not significant between the IgG4-RD and sarcoidosis groups, SII, SIRI, NLR, PLR were significantly higher in patients with GPA than in IgG4-RD patients (p < 0.001). DISCUSSION: This is the first study to review the SII, SIRI, NLR, and PLR in IgG4-RD. The obtained results suggest that the SII could beused as a new tool, for differential diagnosis and activity of the IgG4-RD.

Prevalence and Time Course of Thiamine Deficiency in Critically Ill Children: A Multicenter, Prospective Cohort Study in Turkey.

OBJECTIVES: To determine the prevalence and time course of thiamine deficiency (TD) in PICU patients. DESIGN: Multicenter, prospective, cohort study between May 2019 and November 2019. SETTING: Three university-based tertiary care, mixed medical-surgical PICUs in Ankara, Turkey. PATIENTS: PICU patients 1 month to 18 years old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 476 patients and grouped them by TD status on days 1 and 3 of the PICU admission. There might be a risk of unintended bias since we excluded 386 patients because of the absence of consent, inadequate blood samples, loss of identifier information, and recent vitamin supplementation. On day 1, TD was present in 53 of 476 patients (11.1%) and median (minimum-maximum) thiamine levels were 65.5 ng/mL (5-431 ng/mL). On day 3, TD was present in 27 of 199 patients (13.6%) with repeated measurement. The median (minimum-maximum) thiamine levels were 63 ng/mL (13-357 ng/mL). The time course of TD from day 1 to day 3 in these 199 patients was as follows. In 21 of 199 patients (10.6%) with TD on day 1, 11 of 21 (52%) continued to have TD on day 3 and the other 10 of 21 patients (48%) improved to no longer having TD. In 178 of 199 patients (89.4%) without TD on day 1, 16 of 178 (9%) went on to develop TD by day 3, and the other 162 of 178 (91%) continued to have normal thiamine status. CONCLUSIONS: In the PICU population in three centers in Turkey, the prevalence of TD in the sample of patients was 11.1%. In those TD patients who had serial studies, we also identified that by day 3 some continued to be TD, and some patients improved to normal thiamine status. Of concern, however, is the population who develop TD over the course of PICU stay.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

OBJECTIVE: The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. METHOD: Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. RESULTS: Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. CONCLUSION: Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Diagnostic utility of serum biomarkers in large vessel vasculitis and their correlation with positron emission tomography.

OBJECTIVES: To investigate the association between vascular inflammation, as detected by positron emission tomography (PET) imaging and interleukin-6 (IL-6), pentraxin3, and B-cell-activating factor (BAFF) in subjects with LVV. METHODS: The study included newly diagnosed giant cell arteritis (GCA, n = 27) or Takayasu arteritis (n = 9) patients and healthy control (HC, n = 31) subjects. PET scan and blood samples were obtained before the introduction of treatments. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay kits. RESULTS: Thirty-six patients with LVV (20 females, 16 males; age 64.5 ± 16.6 years) and 31 HC (14 females, 17 males; age 37.1 ± 9.6 years) were included. Serum levels of IL-6, PTX3, and BAFF were increased in patients with newly diagnosed LVV compared with healthy control subjects. In receiver operating characteristics (ROC) analysis, serum IL-6 and BAFF provided excellent discrimination of newly diagnosed LVV patients from HC (area under the ROC curve of >0.90 and >0.80, respectively). None of the inflammatory markers correlated with vascular inflammatory activity determined by PET scanning. CONCLUSIONS: Our results suggest that IL-6 and BAFF may serve as markers of large vessel vasculitis, while PTX3 is not useful. None of the inflammatory markers correlated with PET assessed vasculitis activity.

FGF23, alpha-Klotho and vitamin D mediated calcium-phosphate metabolism in haemodialysis patients.

BACKGROUND: Klotho is a prote˝in that acts as a co-receptor for FGF23. FGF23-Klotho axis has great importance regarding the regulation of mineral metabolism by kidneys. In this study, we analysed FGF23, Klotho, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, parathormone, Calcium and Phosphate levels of haemodialysis patients in order to investigate the nature of the mineral metabolism disruption in chronic kidney diseases. METHODS: Sixty haemodialysis patients and 34 healthy controls were included in the study. Serum iFGF, cFGF, and soluble Klotho were analysed using ELISA kits. Moreover, 1,25-dihydroxyvitamin D3 was determined using LCMS/MS. Calcium, phosphate, iPTH and 25-hydroxyvitamin D were measured using autoanalyzers. RESULTS: In haemodialysis patients, iFGF23, cFGF23, iPTH and P levels were significantly higher, and 1,25-dihydroxyvitamin D3, Klotho and Ca levels were significantly lower compared with the control group. There was no significant difference in the 25-hydroxyvitamin D levels. CONCLUSIONS: Our study showed that lack of sufficient amounts of Klotho is crucial for mineral metabolism disruptions seen as a complication of chronic kidney diseases. Despite the high levels of the hormone, FGF23 is unable to accomplish its function properly, likely due to deteriorated kidney function in haemodialysis patients.

Serum defensin levels in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. METHODS: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. RESULTS: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). CONCLUSIONS: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. TRIAL REGISTRATION: This study is not a clinical trial study.

Early Diagnostic Markers for Detection of Acute Kidney Injury in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

OBJECTIVES: Acute kidney injury is a relatively frequent complication of allogenic hematopoietic stem cell transplant, resulting in increased risk of morbidity and mortality. Early diagnosis and management of acute kidney injury is of great importance for prevention of poor outcomes in these transplant recipients. MATERIALS AND METHODS: Fifty consecutive patients, hospitalized for allogenic hematopoietic stem cell transplant at the Bone Marrow Transplantation Unit of Gazi University Faculty of Medicine, were included in this prospective study. Serial measurements of serum creatinine and creatinine clearance were obtained before administration of conditioning regimen and at 0, 7, 14, 21, and 28 days after start of conditioning. Blood and urine samples were also obtained for the measurement of serum cystatin C and urine neutrophil gelatinase-associated lipocalin levels before conditioning and 24 hours before each serum creatinine measurement. RESULTS: During the median 25 days of follow-up, acute kidney injury developed in 19 patients: 10 patients had stage 1, 7 had stage 2, and 2 had stage 3 acute kidney injury according to the Acute Kidney Injury Network classification. There were significant positive correlations between serum cystatin C levels and serum creatinine levels and negative correlations with creatinine clearance levels at each time point (P < .001), whereas no statistically significant associations were observed with urinary neutrophil gelatinase-associated lipocalin levels. Both univariate and multivariate Cox regression models showed a statistically significant association between serum cystatin C levels and development of acute kidney injury, whereas urine neutrophil gelatinase-associated lipocalin levels did not show any significant associations. CONCLUSIONS: Serum cystatin C levels might be a useful marker for early detection of acute kidney injury in adult allogenic hematopoietic stem cell transplant recipients. Close monitoring of kidney function by sensitive biomarkers might provide early recognition and timely management of acute kidney injury in high-risk patient populations.

The Effect of Smoking on Mitochondrial Biogenesis in Patients With Graves Ophthalmopathy.

PURPOSE: To evaluate the effects of cigarette smoking on oxidative stress (OS) and mitochondrial biogenesis related parameters in patients Graves Ophthalmopathy (GO). METHODS: Patients with moderate-to-severe GO according to the European Group on Graves Orbitopathy (EUGOGO) criteria were prospectively enrolled in this study. Age- and sex-matched healthy volunteers who applied to outpatient clinic due to refractive problems consisted the control group. Participants were divided into 4 groups based on their diagnosis and smoking status: group 1 (n = 30) smoker GO patients, group 2 (n = 30) nonsmoker GO patients, group 3 (n = 30) smoker healthy controls, and group 4 (n = 30) nonsmoker healthy controls. In the sera, total antioxidant status, total oxidant status and OS index values, peroxisome proliferator-activated receptor-γ coactivator 1-α, mitochondrial transcriptional factor A levels, and paraoxonase-1 enzyme activity were evaluated. RESULTS: Total oxidant status and OS index values were the highest in group 1 compared to other groups (p = 0.031, p = 0.042; respectively). There was no statistically significant difference in total antioxidant status and peroxisome proliferator-activated receptor-γ coactivator 1α levels among the groups (p = 0.521, p = 0.388; respectively). Paraoxonase-1 enzyme activity was the lowest in group 1 and highest in group 4 (p = 0.024). The levels of mitochondrial transcriptional factor A was the lowest in group 1 compared to other groups (p = 0.012). CONCLUSIONS: Cigarette smoking in GO patients seems to be a risk factor that increases OS, and therefore, it may have an unfavorable impact on the mitochondrial biogenesis.

Serum defensin levels in patients with systemic sclerosis

Abstract Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of skin and lung as well as involvement of kidney, gastrointestinal system and heart. Aetiology and exact mechanism of disease is poorly understood. The association between antimicrobial peptides (AMPs) and other diseases such as idiopathic pulmonary fibrosis, diffuse panbronchiolitis, pulmoner alveolar proteinosis and psoriasis have been reported. A small number of studies have examined the role of AMPs on autoimmune diseases which has not been studied in scleroderma yet. We aimed to investigate AMP serum levels and their association with disease characteristics of SSc. Methods: Forty-two patients (40 female, mean age 42 years) and 38 healthy subjects (32 female, mean age 38 years) were enrolled. For SSc patients, the following data were recorded: disease subset (limited/diffuse), autoantibodies (antinuclear, anti-centromere (ACA), and anti-SCL-70), blood tests, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), modified Rodnan skin score, presence and history of digital ulcers, kidney, gastrointestinal disease and lung involvement assessed by computed tomography and pulmonary function tests. Association between serum AMPs and disease characteristics were analysed. Results: Twenty-nine of the patients had diffuse (69%) and 13 of the patients had limited (31%) systemic sclerosis. Average disease duration was 5.5 years. Pulmonary involvement was detected in 20 patients (47.6%). Serum concentration of alpha defensin was higher than healthy subjects (563 ± 415 vs 377 ± 269 ng/mL, p = 0.02). However, no difference was observed for beta-1 and beta-2 defensins in SSc patients and healthy controls. In sub-group analysis patients with interstitial lung disease had higher levels of alpha defensin than those without lung involvement (684 ± 473 vs 430 ± 299 ng/ml, p = 0.04). There was also correlation between alfa defensin serum concentrations and CRP (r = 0.34). Conclusions: Alpha defensin levels are increased in scleroderma patients and correlated with lung involvement indicating a role in the pathogenesis of disease. Trial registration: This study is not a clinical trial study.(AU)

Acute effects of different doses of malathion on the rat liver.

AIM OF THE STUDY: Our study was designed to evaluate the acute effects of malathion on rat liver tissues. MATERIAL AND METHODS: The animals were divided into 4 groups of 6 animals/each. Group 1 (control group) received corn oil, while groups 2, 3, and 4 were given malathion dissolved in corn oil at a dose of 100, 200 and 400 mg/kg, respectively. 24 hours after malathion administration, animals were sacrificed and liver tissues were collected. The liver tissues were then analysed biochemically and histopathologically. RESULTS: Butyrylcholinesterase levels in groups 2, 3 and 4 were significantly lower than that of group 1. Total oxidant status and tumour necrosis factor alpha level were significantly increased in group 4 compared to group 1. Catalase activities of groups 3 and 4 were significantly higher than that of group 1. Arylesterase activity was significantly decreased in groups 3 and 4 compared to group 1. In groups 3 and 4, some vacuoles in hepatocytes were revealed and hydropic degeneration was observed in group 4. CONCLUSIONS: Acute administrations of malathion results in hepatotoxicity in a dose-dependent manner.

Hypothalamic Energy Regulatory Peptides in Chronic Kidney Disease.

Loss of appetite affects one-third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti-related peptide (AgRP) with neuropeptide-Y (NPY) and anorexigenic melanocyte-stimulating hormone-α (MSH-α) with cocaine- and amphetamine-regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis-stimulating agent (ESA) therapy. The cross-sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo- or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients.

Evaluation of growth in children and adolescents after renal transplantation.

Büyükkaragöz B, Bakkaloglu SA, Tuncel AF, Kadioglu-Yilmaz B, Karcaaltincaba D, Pasaoglu H. Evaluation of growth in children and adolescents after renal transplantation. Turk J Pediatr 2019; 61: 217-227. Despite the advances in the last decades, it is well-known that optimal growth is usually not achieved in children with chronic kidney disease (CKD) even after successful renal transplantation (RTx). In this study, our aim was to evaluate growth patterns and factors affecting growth in pediatric and adolescent renal transplant recipients (RTR). Thirty-seven prevalent RTR with mean age of 17.0±2.9 years and mean post-RTx duration of 4.2±2.0 years were evaluated. Growth parameters, height velocities and factors affecting growth at the time of RTx (baseline) and in the post-RTx follow-up were also retrospectively assessed. Cumulative corticosteroid (CS) doses were calculated. Mean height and weight standard deviation score (SDS) values were negative (-1.4±1.1 and -1.2±1.5, respectively), whereas height SDS was positive in 16% of the patients. Mean weight, height, and BMI (body mass index) SDS of the RTR were significantly higher than the values at transplantation (p < 0.001 for weight and height SDS; p < 0.05 for BMI SDS). Height SDS was < -2.0 in 19% of the patients while 60% at the baseline. Main factors associated with post-RTx height SDS were pre-RTx height SDS (B: 0.448, p < 0.01) and CKD duration (B: -0.01, p < 0.05). Although it was much better than the pre-RTx period, the present study reveals that post- RTx growth was less than anticipated. As well as minimizing post-RTx CS doses and preserving graft function in the post-RTx follow-up, performing early transplantation and all efforts for minimizing pre-RTx growth deficit are crucial for an optimal post-RTx growth.

Relationship between obesity and iron deficiency anemia: is there a role of hepcidin?

OBJECTIVES: Iron deficiency is common in obese children although the underlying mechanism is unclear. The aim of this study was to investigate the associations between iron parameters, leptin, hepcidin and adiponectin levels in obese children. METHODS: A total of 237 children, ranging in age from 5 to 18 years, 180 with primary obesity and 57 healthy children and adolescents, were enrolled. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, leptin, hepcidin and adiponectin levels were studied. RESULTS: White blood cell and platelet count, iron-binding capacity, high-sensitive C-reactive protein, leptin and hepcidin values in the obese group were higher than those of the control group (p < 0.001, p = 0.002, p < 0.001, p < 0.001, p < 0.001 and p < 0.001, respectively). However, mean corpuscular volume, adiponectin and transferrin saturation values in the obese group were lower than in the control group (p = 0.026, p = 0.003, and p < 0.001, respectively). No significant differences were found in terms of hemoglobin, serum ferritin, iron and IL-6 levels. CONCLUSIONS: Our study suggests that hepcidin levels do not contribute to the development of iron deficiency anemia in pediatric obese individuals.

The role of inflammatory biomarkers in CHD-associated pulmonary hypertension in children.

OBJECTIVE: The present study aims to identify the role of inflammatory markers such as C-reactive protein, interleukin-6, and fractalkine in CHD-associated pulmonary hypertension in children. METHODS: This is a prospective review of 37 children with CHD-related pulmonary hypertension, 21 children with congenital heart defects, and 22 healthy children. RESULTS: Serum C-reactive protein and interleukin-6 levels were significantly higher in the children with CHD-related pulmonary hypertension (respectively, p=0.049 and 0.026). Serum C-reactive protein concentrations correlated negatively with ejection fraction (r=-0.609, p=0.001) and fractional shortening (r=-0.452, p=0.007) in the pulmonary hypertension group. Serum fractalkine concentrations correlated negatively with ejection fraction (r=-0.522, p=0.002) and fractional shortening (r=-0.395, p=0.021) in the children with pulmonary hypertension. Serum interleukin-6 concentrations also correlated negatively with Qs (r=-0.572, p=0.021), positively with Rs (r=0.774, p=0.001), and positively with pulmonary wedge pressure (r=0.796, p=0.006) in the pulmonary hypertension group. A cut-off value of 2.2 IU/L for C-reactive protein was able to predict pulmonary hypertension with 77.5% sensitivity and 77.5% specificity. When the cut-off point for interleukin-6 concentration was 57.5 pg/ml, pulmonary hypertension could be predicted with 80% sensitivity and 75% specificity. CONCLUSION: Inflammation is associated with the pathophysiology of pulmonary hypertension. The inflammatory markers C-reactive protein and interleukin-6 may have a role in the clinical evaluation of paediatric pulmonary hypertension related to CHDs.

Increased serum YKL-40 level is associated with the presence and severity of metabolic syndrome.

OBJECTIVE: Metabolic syndrome (MS) is defined by a cluster of interdependent physiological, biochemical, and clinical risk factors and linked to a state of chronic inflammation. YKL-40 is known as an inflammatory glycoprotein, which is secreted by various cell lines during inflammation. Thus, we aimed to assess the association of serum YKL-40 levels with the presence and severity of MS. METHODS: In this prospective cross-sectional study, a total of 177 consecutive patients [n=114 MS present and n=63 MS absent] were enrolled. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Serum YKL-40 and hs-CRP levels were measured for all participants. RESULTS: Serum YKL-40, hs-CRP and white blood cell count (WBC) were significantly higher in the MS present group (p<0.05). There was a graded relationship between increasing number of MS components and serum YKL-40 level (p<0.05). In addition, serum YKL-40 level was positively correlated with hs-CRP level (r=0.467, p<0.001) and WBC count (r=0.251, p=0.001). In multivariable regression analysis, serum YKL-40 [1.022 (1.011-1.033), p<0.001] and hs-CRP [1.346 (1.111-1.632), p=0.002] were remained as independent predictors for the presence of MS. In the ROC curve analysis, using a cut-off level of 147.0, YKL-40 well predicted the presence of MS with a sensitivity of 73.7% and specificity of 69.8% (AUC: 0.785; 95% CI: 0.718-0.853, p<0.001). CONCLUSION: In this study, we demonstrated that serum YKL-40 level was significantly associated with the presence of MS. According to these findings, we concluded that serum YKL-40 may be a novel and useful indicator for MS.

RANKL/Osteoprotegerin System and Bone Turnover in Hashimoto Thyroiditis.

Hypothyroidism is associated with changes in bone metabolism. The impact of hypothyroidism and the associated autoimmunity on the mediators of bone turnover in Hashimoto's thyroiditis (HT) is not known. In this study, we assessed the levels of OPG, RANKL, and IL-6 along with markers of bone formation as osteocalcin (OC) and markers of bone resorption as type 1 collagen C telopeptide (CTX) and tartrate-resistant acid phosphatase isoform 5b (TRAcP 5b) in 30 hypothyroid and 30 euthyroid premenopausal HT patients and 20 healthy premenopausal controls. We found that TRAcP 5b (p = 0.006), CTX (p = 0.01), OC (p = 0.017), and IL-6 (p < 0.001) levels were lower in the hypothyroid group compared to euthyroid HT patients and controls. OPG levels were higher (p < 0.001) and RANKL levels were lower (p = 0.021) in hypothyroid and euthyroid HT patients compared to controls. TSH was negatively correlated with IL-6 (rho = -0.434, p < 0.001), OC (rho = -0.313, p = 0.006), TRAcP 5b (rho = -0.335, p = 0.003), and positively correlated with OPG (rho = 0.248, p = 0.029). RANKL/OPG ratio was independently associated with the presence of HT. In conclusion, bone turnover is slowed down by hypothyroidism in premenopausal patients with HT. Thyroid autoimmunity might have a unique impact on OPG/RANKL levels apart from the resultant hypothyroidism.

Echocardiographic epicardial adipose tissue measurements provide information about cardiovascular risk in hemodialysis patients.

Epicardial adipose tissue (EAT) is a cardiovascular risk predictor in general population. However, its value has not been well validated in maintainance hemodialysis (MHD) patients. We aimed to assess associations of EAT with cardiovascular risk predictors in nondiabetic MHD patients. In this cross-sectional study, we measured EAT thickness by transthoracic echocardiography in 50 MHD patients (45.8 ± 14.6 years of age, 37 male). Antropometric measurements, bioimpedance analysis, left ventricular (LV) mass, carotis intima media thickness, blood tests, homeostasis model assessment for insulin resistance (HOMA-IR) and hemodialysis dose by single-pool urea clearence index (spKt/V) were determined. The mean EAT thickness was 3.28 ± 1.04 mm. There were significant associations of EAT with body mass index (ß = 0.590, P < 0.001), waist circumference (ß = 0.572, P < 0.001), body fat mass (ß = 0.562, P < 0.001), percentage of body fat mass (ß = 0.408, P = 0.003), percentage of lean tissue mass (ß = -0.421, P = 0.002), LV mass (ß = 0.426, P = 0.002), carotis intima media thickness (ß = 0.289, P = 0.042), triglyceride/high-density lipoprotein cholesterol ratio (ß = 0.529, P < 0.001), 1/HOMA-IR (ß = -0.386, P = 0.006), and spKt/V (ß = -0.311, P = 0.028). No association was exhibited with visfatin C, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-alpha (for all, P > 0.05). Body mass index, waist circumference, body fat mass, percentage of lean tissue mass, LV mass, triglyceride/high-density lipoprotein cholesterol ratio, HOMA-IR, and spKt/V appeared as independent predictors of EAT. EAT was significantly associated with body fat measures, cardiovascular risk predictors, and dialysis dose in MHD patients.

Association between Plasma Endothelin-1, Transforming Growth Factor-ß, Fibroblast Growth Factor, and Nitric Oxide Levels and Liver Injury in Hematopoietic Stem Cell Transplantation Recipients with Persistent Iron Overload after Transplantation.

Graft-versus-host disease, iron overload, and infections are the major causes of liver dysfunction in allogeneic hematopoietic stem cell transplantation (AHSCT) recipients. We investigated the relationship between serum iron parameters and the levels of transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF), endothelin-1 (ET-1), and nitric oxide (NO) as predictors of chronic liver injury in 54 AHSCT recipients who survived at least a year after transplantation. Serum samples from patients were obtained for the evaluation of ET-1, TGF-ß, FGF, NO, and nontransferrin bound iron at the first year follow-up visit using commercially available ELISA kits. Patients were categorized depending on serum ferritin and transferrin saturation levels. The parameters were compared between the groups, and survival analysis was also performed. Most of the AHSCT recipients (81.5%) were in complete remission during the study. After a median follow-up time of 73 months (range, 13 to 109 months), 72.2% of the patients were alive. Mean serum levels of ET-1, NO, TGF-ß, and FGF were 81.54 ± 21.62 µmol/mL, 31.82 ± 26.42 µmol/mL, 2.56 ± 0.77 ng/mL, and 50.31 ± 32.69 pg/mL, respectively. Nineteen patients (35.2% of the cohort) had serum ferritin levels higher than 1000 ng/mL. Mean serum levels of ET-1, NO, TGF-ß, and FGF were similar in patients with serum ferritin levels below or above 1000 ng/mL (P > .05). Serum ferritin levels were positively correlated with serum alanine aminotransferase (r = .284, P = .042) and γ-glutamyl transferase (r = .271, P = .05) levels and were negatively correlated with serum albumin levels (r = .295, P = .034). There was a significant positive correlation between serum transferrin saturation and alanine aminotransferase levels (r = .305, P = .03). Serum ET-1 level was positively correlated with alkaline phosphatase levels (r = .304, P = .026). In univariate Cox regression analysis serum levels of iron parameters, ET-1, NO, TGF-ß, and FGF did not have an impact on overall survival (P > .05). The probability of progression-free survival was also similar in patients with ferritin levels above or below 1000 ng/mL (P = .275). The probability of survival was similar in patients with transferrin saturation ≥70% and <70% (P > .05). Serum iron parameters showed a positive correlation with liver injury. However, there was no correlation between fibrogenic cytokines and liver transaminases. Our results suggest that iron overload at least with the current levels of ferritin might have a relatively benign course. Prospective randomized trials will guide the actual role of iron chelation in the post-transplantation setting.

Inflammatory markers, oxidative stress, and antioxidant capacity in healthy allo-HSCT donors during hematopoietic stem cell mobilization.

The aim of this study is to investigate the impact of mobilization with granulocyte colony stimulating factor (G-CSF) and apheresis procedure on inflammatory and oxidative stress markers, and antioxidant capacity in healthy allo-HSCT donors. The study was conducted in the Stem Cell Transplantation Unit of Gazi University Hospital between October 2010 and March 2011, and 25 consecutive allo-HSCT donors were included. The alteration in the serum levels of iron, iron binding capacity, albumin, ferritin, IL-6, hs-CRP, TAC, MDA, and AOPP were determined at five different time points. (1) Prior to the first dose of G-CSF (T0), (2) preapheresis (on the fourth day of G-CSF before the apeheresis procedure) (T1), (3) immediately postapheresis (T2), (4) 24 h postapheresis (T3), and (5) a week after apheresis (T4). Serum ferritin levels increased steadily after administration of G-CSF and remained high up toT4. Both serum IL-6 and hs-CRP levels began to increase in the T1 sampling and reached to a maximum level at T3 and decreased even below the basal levels at T4. Serum AOPP levels decreased at preapheresis and postapheresis time points, while they increased at T3 and T4 samples. Serum MDA levels decreased at T1, T2, T3, and T4 samples. Serum TAC increased significantly and steadily at all time points post G-CSF. In conclusion; mobilization with G-CSF and apheresis caused a transient inflammatory reaction and a protein limited oxidative stress in healthy allo-HCT donors.

Protective effect of adrenomedullin on contrast induced nephropathy in rats / Efecto protector de la adrenomedulina en la nefropatía inducida por contraste en ratas

Background and aims: Contrast-induced nephropathy (CIN) has a growing incidence in which renal vasoconstriction and medullary hypoxia are important mechanisms. Therapeutic approaches are very restricted and there is a considerable interest in advancing preventive strategies. Adrenomedullin is a relatively novel peptide having antioxidant, vasoactive and vasodilatory properties. We aimed to investigate whether adrenomedullin might have a preventive role against the development of experimental CIN. Methods: Wistar albino rats (n=24) were allocated randomly into four equal groups of 6 each; Control (C), Adrenomedullin (A), Contrast Media (CM) and Adrenomedullin plus Contrast Media (ACM). All rats were deprived of water from day 1 to day 4 during 72 hours. Then, intravenous administrations of chemicals were performed. Adrenomedullin was given at dose of 12µg/kg to groups A and ACM. A single dose of high-osmolar contrast media; diatrizoate (Urografin 76%, Schering AG, Germany) was injected to groups CM and ACM at dose of 10mL/kg. On day 1 and 6 blood samples were drawn for renal function tests and inflammatory markers including TNF-α IL-1β, IL-6 and IL-18. After sacrification, kidney histologies were examined with hematoxylin-eosin staining. Results: Compared to CM group, serum cystatin-C levels on 6th day were found significantly lower in ACM group (p<0.05). Additionally, daily protein excretion rates, absolute changes in daily urine output and creatinine clearance values were significantly lower in ACM group than those in CM group (p<0.05). In histopathological evaluation, regarding the degree of tubular damage and medullary congestion scores, ACM group had slightly better scores compared to CM group; however the differences did not reach significance as shown in inflammatory markers. Conclusion: This study demonstrated a beneficial impact of adrenomedullin on deteriorated renal function tests in an experimental CIN model. Adrenomedullin might be a candidate agent for prophylaxis of CIN. However, further studies are needed to shed more light on this issue

Antecedentes y objetivos: La incidencia de la nefropatía inducida por contraste (NIC) está aumentando y la vasoconstricción renal y la hipoxia medular son mecanismos importantes. Los enfoques terapéuticos son muy limitados y existe un gran interés en avanzar en las estrategias preventivas. La adrenomedulina es un péptido relativamente nuevo con propiedades antioxidantes, vasoactivas y vasodilatadoras. Nuestro objetivo es investigar si la adrenomedulina puede jugar un papel preventivo frente al desarrollo de la NIC experimental. Métodos: Se distribuyeron ratas Wistar albinas (n = 24) de forma aleatoria en cuatro grupos de 6: control (C), adrenomedulina (A), medio de contraste (MC) y adrenomedulina más medio de contraste (AMC). Las ratas no ingirieron agua desde el día 1 al día 4 (durante 72 horas). Posteriormente, se les administraron las sustancias de forma intravenosa. Los grupos A y AMC recibieron una dosis de adrenomedulina de 12 µg/kg. Los grupos MC y AMC recibieron una única dosis de medio de contraste de alta osmolaridad: 10 ml/kg de diatrizoato (Urografin 76 %, Schering AG, Alemania). Los días 1 y 6 se tomaron muestras de sangre para realizar análisis de función renal y de marcadores inflamatorios, incluidos el TNF-α, IL-1β, IL-6 e IL-18. Tras el sacrificio, se examinaron las histologías renales con tinción hematoxilina-eosina. Resultados: En comparación con el grupo MC, los niveles de cistatina C sérica fueron significativamente inferiores en el grupo AMC (P < 0,05). Además, la tasa de excreción diaria de proteínas, los cambios absolutos en el gasto urinario diario y los valores de aclaramiento de la creatinina fueron significativamente inferiores en el grupo AMC que en el grupo MC (P < 0,05). En la evaluación histopatológica, en lo que respecta al grado de daño tubular y los valores de congestión medular, el grupo AMC presentaba niveles ligeramente mejores en comparación con el grupo MC. Sin embargo, según los marcadores inflamatorios, las diferencias no presentaron significación estadística. Conclusión: El estudio ha demostrado que la adrenomedulina resulta beneficiosa en los análisis de función renal deteriorada en un modelo experimental de NIC. Por lo tanto, la adrenomedulina puede ser un candidato para la profilaxis de la NIC. No obstante, se necesitan más estudios que arrojen luz sobre este tema