Growth differentiation factor-15 serum concentrations reflect disease severity and anemia in patients with inflammatory bowel disease.

BACKGROUND: Population of patients with inflammatory bowel disease (IBD) is burdened by various extraintestinal manifestations which substantially contribute to greater morbidity and mortality. Growth-differentiation factor-15 (GDF-15) is often over-expressed under stress conditions, such as inflammation, malignancies, heart failure, myocardial ischemia, and many others. AIM: To explore the association between GDF-15 and IBD as serum concentrations of GDF-15 were shown to be an independent predictor of poor outcomes in multiple diseases. An additional aim was to determine possible associations between GDF-15 and multiple clinical, anthropometric and laboratory parameters in patients with IBD. METHODS: This cross-sectional study included 90 adult patients diagnosed with IBD, encompassing both Crohn's disease (CD) and ulcerative colitis (UC), and 67 healthy age- and sex-matched controls. All patients underwent an extensive workup, including colonoscopy with subsequent histopathological analysis. Disease activity was assessed by two independent gastroenterology consultants specialized in IBD, employing well-established clinical and endoscopic scoring systems. GDF-15 serum concentrations were determined following an overnight fasting, using electrochemiluminescence immunoassay. RESULTS: In patients with IBD, serum GDF-15 concentrations were significantly higher in comparison to the healthy controls [800 (512-1154) pg/mL vs 412 (407-424) pg/mL, P < 0.001], whereas no difference in GDF-15 was found between patients with CD and UC [807 (554-1451) pg/mL vs 790 (509-956) pg/mL, P = 0.324]. Moreover, multiple linear regression analysis showed that GDF-15 levels predict CD and UC severity independent of age, sex, and C-reactive protein levels (P = 0.016 and P = 0.049, respectively). Finally, an association between GDF-15 and indices of anemia was established. Specifically, negative correlations were found between GDF-15 and serum iron levels (r = -0.248, P = 0.021), as well as GDF-15 and hemoglobin (r = -0.351, P = 0.021). Accordingly, in comparison to IBD patients with normal hemoglobin levels, GDF-15 serum levels were higher in patients with anemia (1256 (502-2100) pg/mL vs 444 (412-795) pg/mL, P < 0.001). CONCLUSION: For the first time, we demonstrated that serum concentrations of GDF-15 are elevated in patients with IBD in comparison to healthy controls, and the results imply that GDF-15 might be involved in IBD pathophysiology. Yet, it remains elusive whether GDF-15 could serve as a prognostic indicator in these patients.

The Importance of Increased Serum GFAP and UCH-L1 Levels in Distinguishing Large Vessel from Small Vessel Occlusion in Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is one of the leading causes of morbidity worldwide, thus, early recognition is essential to accelerate treatment. The only definite way to diagnose AIS is radiological imaging, which is limited to hospitals. However, two serum neuromarkers, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), have been proven as indicators of brain trauma and AIS. We aimed to investigate the potential utility of these markers in distinguishing between large vessel occlusion (LVO) and small vessel occlusion (SVO), considering differences in treatment. Sixty-nine AIS patients were included in our study and divided into LVO and SVO groups based on radiological imaging. Control group consisted of 22 participants without history of neurological disorders. Results showed differences in serum levels of both GFAP and UHC-L1 between all groups; control vs. SVO vs. LVO (GFAP: 30.19 pg/mL vs. 58.6 pg/mL vs. 321.3 pg/mL; UCH-L1: 117.7 pg/mL vs. 251.8 pg/mL vs. 573.1 pg/mL; p < 0.0001), with LVO having the highest values. Other prognostic factors of stroke severity were analyzed and did not correlate with serum biomarkers. In conclusion, a combination of GFAP and UCH-L1 could potentially be a valuable diagnostic tool for differentiating LVO and SVO in AIS patients.

Effects of Moderate Consumption of Red Wine on Hepcidin Levels in Patients with Type 2 Diabetes Mellitus.

Iron overload is often associated with type 2 diabetes (T2D), indicating that hepcidin, the master regulator of iron homeostasis, might be involved in diabetes pathogenesis. Alcohol consumption may also result in increased body iron stores. However, the moderate consumption of wine with meals might be beneficial in T2D. This effect has been mainly attributed to both the ethanol and the polyphenolic compounds in wine. Therefore, we examined the effects of red wine on hepcidin in T2D patients and non-diabetic controls. The diabetic patients (n = 18) and age- and BMI-matched apparently healthy controls (n = 13) were men, aged 40−65 years, non-smoking, with BMI < 35 kg/m2. Following a 2-week alcohol-free period, both groups consumed 300 mL of red wine for 3 weeks. The blood samples for the iron status analysis were taken at the end of each period. The red wine intake resulted in a decrease in serum hepcidin in both the diabetic subjects (p = 0.045) and controls (p = 0.001). The levels of serum ferritin also decreased after wine in both groups, reaching statistical significance only in the control subjects (p = 0.017). No significant alterations in serum iron, transferrin saturation, or soluble transferrin receptors were found. The suppression of hepcidin, a crucial iron-regulatory hormone and acute-phase protein, in T2D patients and healthy controls, is a novel biological effect of red wine. This may deepen our understanding of the mechanisms of the cardiometabolic effects of wine in T2D.

No differences in splenic emptying during on-transient supine cycling between aerobically trained and untrained participants.

PURPOSE: The role of splenic emptying in O2 transport during aerobic exercise still remains a matter of debate. Our study compared the differences in spleen volume changes between aerobically trained and untrained individuals during step-transition supine cycling exercise at moderate-intensity. We also examined the relationship between spleen volume changes, erythrocyte release, and O2 uptake parameters. METHODS: Fourteen healthy men completed all study procedures, including a detailed medical examination, supine maximal O2 uptake ([Formula: see text] max.) test, and three step-transitions from 20 W to a moderate-intensity power output, equivalent to [Formula: see text] uptake at 90% gas exchange threshold. During these step-transitions pulmonary [Formula: see text], near-infrared spectroscopy of the vastus lateralis, and cardiovascular responses were continuously measured. In parallel, minute-by-minute ultrasonic measurements of the spleen were performed. Blood samples were taken before and immediately after step-transition cycling. RESULTS: On average, [Formula: see text] max. was 10 mL kg min-1 (p = 0.001) higher in trained compared to their aerobically untrained peers. In response to supine step-transition cycling, the splenic volume was significantly reduced, and the largest reduction (~ 106 to 115 mL, ~ 38%, p = 0.001) was similar in both aerobically trained and untrained individuals. Erythrocyte concentration and platelet count transiently increased after exercise cessation, with no differences observed between groups. However, the vastus lateralis deoxygenation amplitude was 30% (p = 0.001) greater in trained compared to untrained individuals. No associations existed between: (i) spleen volumes at rest (ii) spleen volume changes (%), (iii) resting hematocrit and oxygen uptake parameters. CONCLUSION: Greater splenic emptying and subsequent erythrocyte release do not lead to a slower [Formula: see text], regardless of individual [Formula: see text] max. readings.

The Relationship of Vitamin D Status, Adherence to the Mediterranean Diet, and Physical Activity in Obese Children and Adolescents.

Vitamin D deficiency is associated with a range of chronic diseases, including childhood obesity. Prevalence of vitamin D deficiency in obese children and adolescents ranges from 6.5% to 57%. This cross-sectional study included 92 obese patients with body mass index z-score >2 and 39 subjects in the control group. Anthropometric and laboratory patient assessment were performed, including the fasting 25-hydroxyvitamin D (25(OH)D). Adherence to the Mediterranean diet was assessed by Mediterranean Diet Quality Index for children and adolescents (KIDMED index), while physical activity was evaluated by Physical Activity Questionnaire (PAQ). Serum levels of 25(OH)D were significantly lower in obese subjects compared to the control group (52.0 ± 17.93 vs. 64.09 ± 25.82 nmol/L, P = .003). The subgroup of obese patients with metabolic syndrome (MS) had significantly lower levels of serum vitamin D when compared to the subgroup of obese patients without MS and the control group (46.99 ± 17.11 vs. 54.58 ± 17.93 vs. 64.09 ± 25.82 nmol/L, P = .003). Obese patients with MS had lower PAQ score when compared to obese without MS and the control group (2.32 ± 0.55 vs. 2.49 ± 0.67 vs. 2.85 ± 0.63 nmol/L, P = .002), while no significant differences were observed in the KIDMED index (4.23 ± 1.81 vs. 4.21 ± 2.13 vs. 4.87 ± 2.29, P = .251), respectively. PAQ score was in positive correlation with serum levels of 25(OH)D (r = 0.305, P < .001). This study demonstrated that obese children and adolescents have significantly lower values of serum 25(OH)D. The positive correlation between vitamin D and PAQ score points to the importance of physical activity in the prevention of further cardiovascular complications and MS.

Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT-HF study.

AIMS: Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in-hospital death as well as the association between sST2 and CST among AWHF patients. METHODS AND RESULTS: A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non-survivors and survivors. Predictive values of sST2 and CST for in-hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in-hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and C-reactive protein. The in-hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non-survivors than survivors [146.6 (inter-quartile range, IQR 65.9-156.2) vs. 35.3 (IQR 20.6-64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9-28.0) vs. 5.6 (IQR 3.4-9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in-hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48-15.20, P = 0.005, and FC 6.58, 95% CI 1.66-21.78, P = 0.003, respectively], while NT-proBNP was not a significant predictor (FC 1.57, 95% CI 0.51-3.99, P = 0.142). In classifying non-survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819-1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792-1.000, P < 0.001), while NT-proBNP yielded AUC of 0.735 (95% CI 0.516-0.954, P = 0.036). High-sensitivity cardiac troponin I and C-reactive protein were not found as significant classifiers of in-hospital death (AUC 0.719, 95% CI 0.509-0.930, P = 0.075, and AUC 0.682, 95% CI 0.541-0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (ß = 0.437, P < 0.001). CONCLUSIONS: Elevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in-hospital death (CATSTAT-HF ClinicalTrials.gov Number NCT03389386).

Serum adropin levels are reduced in patients with inflammatory bowel diseases.

Adropin is a novel peptide mostly associated with energy homeostasis and vascular protection. To our knowledge, there are no studies that investigated its relationship with inflammatory bowel diseases (IBD). The aim of this study was to compare serum adropin levels between 55 patients with IBD (30 Ulcerative colitis (UC) patients, 25 Crohn's disease (CD) patients) and 50 age/gender matched controls. Furthermore, we explored adropin correlations with IBD severity scores, hsCRP, fecal calprotectin, fasting glucose and insulin levels. Serum adropin levels were significantly lower in patients with IBD in comparison with the control group (2.89 ± 0.94 vs 3.37 ± 0.60 ng/mL, P = 0.002), while there was no significant difference in comparison of UC patients with CD patients (P = 0.585). Furthermore, there was a negative correlation between adropin and fecal calprotectin (r = -0.303, P = 0.025), whereas in the total study population, we found a significant negative correlation with fasting glucose levels (r = -0.222, P = 0.023). A multivariable logistic regression showed that serum adropin was a significant predictor of positive IBD status when enumerated along with baseline characteristics (OR 0.455, 95% CI 0.251-0.823, P = 0.009). Our findings imply that adropin could be involved in complex pathophysiology of IBD, but further larger scale studies are needed to address these findings.

Comparison of inflammatory stress response between laparoscopic and open approach for pediatric inguinal hernia repair in children.

BACKGROUND: The aim of this study was to compare inflammatory stress response between laparoscopic percutaneous inguinal ring suturing (PIRS) and open modified Marcy technique for pediatric inguinal hernia repair. METHODS: From May 2017 to April 2018, 32 male children with median age of 4.5 years undergoing inguinal hernia repair were included in randomized controlled trial. The patients were divided in two groups, by using random number generator, depending on surgical approach. The blood was tested in three time frames for white blood cells count (WBC), C-reactive protein (CRP), Interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RESULTS: Significant increase in concentration for all inflammatory biomarkers, that occur over time, has been found (p < 0.001 for all). Additionally, it was also found that the type of surgery significantly influenced the level of WBC, CRP, and IL-6 with Marcy showing a higher level of inflammatory response (WBC 11.4 ± 3.1 × 109/L; CRP 11.5 mg/L; IL-6 11.0 pg/mL) than the PIRS (WBC 7.6 ± 1.6 × 109/L; CRP 0.8 mg/L; IL-6 2.0 pg/mL) (p < 0.001 for all). Similar pattern was also found for TNF-α (Marcy 16.8 pg/mL; PIRS 10.1 pg/mL), but correlation between surgery type and concentration of this biomarker was significant only at the 0.1 level (p = 0.055). The mean operation time was significantly shorter (9 ± 2 min) in PIRS group compared to Marcy group (25 ± 7 min) (p < 0.001). Significantly lower median of visual analog scale score (VAS) was found in PIRS group (VAS = 2) compared to Marcy group (VAS = 6) (p < 0.001). CONCLUSIONS: Use of laparoscopic (PIRS) technique in children shows significantly lower surgical stress in comparison to open hernia repair.

Adropin and Inflammation Biomarker Levels in Male Patients With Obstructive Sleep Apnea: A Link With Glucose Metabolism and Sleep Parameters.

STUDY OBJECTIVES: The main objectives of the study were to determine plasma adropin, systemic inflammation biomarker levels, and glucose metabolism parameters in patients with moderate and severe obstructive sleep apnea (OSA) compared to healthy controls. METHODS: In this study, we included 50 male patients with OSA (25 moderate and 25 severe) and 25 age- and sex-matched control subjects. All subjects underwent fasting sampling of peripheral blood for laboratory analyses. RESULTS: Adropin plasma levels were significantly lower in the severe OSA group in comparison with the moderate and control groups (4.50 ± 1.45 versus 6.55 ± 1.68 versus 8.15 ± 1.79 ng/mL, P < .001). Plasma biomarkers of systemic inflammation were significantly increased in patients with moderate OSA (interleukin [IL]-6 and tumor necrosis factor alpha [TNF-α]) and severe OSA (IL-6, TNF-α, high-sensitivity C-reactive protein) when compared with controls (P < .001). Adropin levels showed a significant negative correlation with IL-6 (r = -.419, P < .001), TNF-α (r = -.540, P < .001), fasting glucose (r = -.331, P = .004), hemoglobin A1c (r = -.438, P < .001), homeostatic model assessment insulin resistance index (r = -.213, P = .046), and polysomnographic parameters including apnea-hypopnea index (r = -.615, P < .001) and oxygen desaturation index (r = -.573, P < .001). A multivariate regression analysis showed that plasma adropin remained as a significant negative predictor of severe OSA status, when adjusted for age and body mass index and computed along with other inflammatory biomarkers in the regression model (odds ratio 0.069, 95% confidence interval 0.009-0.517, P = .009). CONCLUSIONS: Plasma adropin concentrations significantly correlate with indices of disease severity in patients with OSA, suggesting that adropin potentially plays an important role in the complex pathophysiology of the disease.

Effects of dexamethasone on early cognitive decline after cardiac surgery: A randomised controlled trial.

BACKGROUND: Postoperative cognitive decline (POCD), a very common complication after cardiac surgery, is characterised by impairment of both memory function and intellectual ability as well as being associated with increased use of healthcare resources. The investigators focused on the role of the inflammatory response to a surgical procedure as a potential factor involved in the pathogenesis of POCD. OBJECTIVE: The use of prophylactic dexamethasone to attenuate the inflammatory response was hypothesised to reduce the risk of POCD. DESIGN: Randomised controlled study. SETTING: Single university teaching hospital, from March 2015 to January 2016. PATIENTS: A total of 169 patients scheduled for elective cardiac surgery were enrolled, and 161 patients were included in the analyses. INTERVENTION: Patients were randomised to receive a single intravenous bolus of 0.1 mg kg dexamethasone (n = 85) or placebo (n = 84) 10 h before the surgery. MAIN OUTCOME MEASURES: The primary outcome measure in both groups was the incidence of POCD on the 6th day after surgery. The investigators also evaluated the effect of dexamethasone on the incidence of systemic inflammatory response syndrome, postoperative C-reactive protein levels and postoperative serum S100ß protein levels. RESULTS: Compared to the placebo group, the dexamethasone group showed statistically significant reductions in the incidence of POCD (relative risk, 0.43; 95% confidence interval, 0.21 to 0.89; P = 0.02), the incidence of systemic inflammatory response syndrome (30.0 versus 58.0%, P < 0.001) and postoperative C-reactive protein levels (P < 0.001). Postoperative S100ß levels were insignificantly lower (P = 0.56) in the dexamethasone group. CONCLUSION: Preoperative administration of dexamethasone reduced the inflammatory response and thereby decreased the risk of early POCD after cardiac surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02767713.

Increase of plasma S100B and neuron-specific enolase in children following adenotonsillectomy: a prospective clinical trial.

S100B protein and neuron-specific enolase (NSE) can be considered the markers of cerebral injury. To our knowledge the association of general anesthesia for elective non-cardiac surgery in children with these markers has not been studied before. The goal of this study was to find out whether these markers change after adenotonsillectomy with general anesthesia. The secondary goal was to determine whether different types of anesthesia, gender, age and body mass index are associated with the change of S100B and NSE after adenotonsillectomy with general anesthesia. This study was designed as a prospective clinical trial. We did a simple pre-post experiment with no control group. In 59 children (aged 6-13, ASA I-II) undergoing adenotonsillectomy and randomized to TIVA or inhalational general anesthesia, plasma S100B and NSE were measured during anesthesia before and after the surgery which lasted a median (interquartile range) of 16.5 (13.0-20.0) min. S100B and NSE assays were performed using the electrochemiluminescence immunoassay. Significance of the differences was assessed by two-tailed asymptotic Wilcoxon signed rank test. Main outcome measures were differences in the levels of S100B and NSE before and after the general anesthesia and surgery. There were significant increases in S100B and NSE levels after the surgery. S100B was increased by 38% (P < 0.001) and NSE was increased by 10% (P < 0.001). Increase of S100B was significantly negatively associated with age (P = 0.023). We have not found significant association of S100B and NSE with any other of the monitored variables. The values of neurological biomarkers S100B and NSE were significantly increased after general anesthesia for elective adenotonsillectomy in children.