Alterations of the Adipo-Myokine Irisin in Sepsis and Septic Shock: Diagnostic and Prognostic Implications.

Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum irisin and its kinetics in critically ill patients with sepsis and septic shock with regard to sepsis severity and outcome. We enrolled 102 critically ill patients with sepsis or septic shock within 48 h of diagnosis and 102 age- and gender-matched healthy controls. Irisin was determined in serum upon enrollment in all participants and one week later in patients using an immunoenzymatic method. The outcome of sepsis was recorded 28 days after enrollment. At enrollment, circulating irisin was significantly lower in patients than controls (22.3 ± 6.8 µg/L vs. 28.1 ± 6.7 µg/L, p < 0.001), and increased significantly one week later (22.3 ± 6.8 µg/L vs. 26.6 ± 9.5 µg/L, p < 0.001). Irisin was significantly lower in patients who presented with septic shock than those with sepsis, and in non-survivors than survivors both at enrollment and one week later. However, kinetics of irisin did not differ between the groups (p > 0.05). Patients with higher circulating irisin during the first week of sepsis had a better outcome (p < 0.001). Lower irisin was independently associated with 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26-0.77, p = 0.004 and one week after: HR 0.37, 95% C.I. 0.23-0.58, p < 0.001). Irisin was negatively correlated with severity scores, metabolic, and inflammatory biomarkers. Circulating irisin decreases early in sepsis and is an independent predictor of 28-day mortality. Irisin may be a promising diagnostic and prognostic sepsis biomarker; nevertheless, larger studies are needed to explore its role in sepsis.

Diagnostic and Prognostic Value of Serum Omentin-1 in Sepsis: A Prospective Study in Critically Ill Patients.

Background and Objectives: Omentin-1, also known as intelectin-1, is a novel adipokine with anti-inflammatory activities implicated in inflammatory diseases and sepsis. We aimed to explore serum omentin-1 and its kinetics in critically ill patients early in sepsis and its association with severity and prognosis. Materials and Methods: Serum omentin-1 was determined in 102 critically ill patients with sepsis during the first 48 h from sepsis onset and 1 week later, and in 102 age- and gender-matched healthy controls. The outcome of sepsis at 28 days after enrollment was recorded. Results: Serum omentin-1 at enrollment was significantly higher in patients compared to controls (763.3 ± 249.3 vs. 451.7 ± 122.3 µg/L, p < 0.001) and it further increased 1 week after (950.6 ± 215.5 vs. 763.3 ± 249.3 µg/L, p < 0.001). Patients with septic shock (n = 42) had higher omentin-1 compared to those with sepsis (n = 60) at enrollment (877.9 ± 241.2 vs. 683.1 ± 223.7 µg/L, p < 0.001) and 1 week after (1020.4 ± 224.7 vs. 901.7 ± 196.3 µg/L, p = 0.007). Furthermore, nonsurvivors (n = 30) had higher omentin-1 at sepsis onset (952.1 ± 248.2 vs. 684.6 ± 204.7 µg/L, p < 0.001) and 1 week after (1051.8 ± 242 vs. 908.4 ± 189.8 µg/L, p < 0.01). Patients with sepsis and survivors presented higher kinetics than those with septic shock and nonsurvivors (Δ(omentin-1)% 39.8 ± 35.9% vs. 20.2 ± 23.3%, p = 0.01, and 39.4 ± 34.3% vs. 13.3 ± 18.1%, p < 0.001, respectively). Higher omentin-1 at sepsis onset and 1 week after was an independent predictor of 28-day mortality (HR 2.26, 95% C.I. 1.21-4.19, p = 0.01 and HR: 2.15, 95% C.I. 1.43-3.22, p < 0.001, respectively). Finally, omentin-1 was significantly correlated with the severity scores, the white blood cells, coagulation biomarkers, and CRP, but not procalcitonin and other inflammatory biomarkers. Conclusions: Serum omentin-1 is increased in sepsis, while higher levels and lower kinetics during the first week of sepsis are associated with the severity and 28-day mortality of sepsis. Omentin-1 may be a promising biomarker of sepsis. However, more studies are needed to explore its role in sepsis.

Lower circulating omentin-1 is independently linked to subclinical hypothyroidism reflecting cardiometabolic risk: an observational case-control and interventional, longitudinal study.

BACKGROUND: Omentin-1, a newly discovered adipokine, is implicated in the modulation of the adipose phenotype, ameliorating systemic metabolism and exhibiting anti-atherogenic, anti-oxidative, cardioprotective, anti-inflammatory and insulin-sensitizing properties. Our goal was to explore circulating omentin-1 in subclinical hypothyroidism (SH) and determine its correlations with cardiometabolic risk factors. METHODS: In a large case-control and interventional longitudinal study, serum omentin-1, metabolic and lipid parameters, inflammatory biomarkers, classic adipocytokines and cardiovascular risk factors were assessed in 120 consecutive patients with SH and 120 healthy controls matched on age, gender and date of blood draw. Sixteen patients with SH were administered L-T4 and, after six months, circulating omentin-1 and other biomarkers were determined. RESULTS: SH subjects presented significantly decreased circulating omentin-1 than control individuals (P<0.001). In all study participants, omentin-1 was negatively correlated with TSH, anti-thyroid antibodies, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, adipokines and cardiovascular risk factors, including Framingham score and apolipoprotein B. Omentin-1 was positively associated with adiponectin and HDL-C. Circulating omentin-1 was independently associated with SH occurrence, above and beyond clinical and cardiometabolic factors (P=0.04). TSH was a negative independent predictor of serum omentin-1 levels (P<0.001). L-T4 treatment did not alter considerably the lower omentin-1 levels in treated SH patients (P=0.07). CONCLUSIONS: Omentin-1 may be a useful non-invasive biomarker reflecting cardiometabolic risk as well as a promising therapeutic target. More mechanistic and larger prospective studies shedding light on the pathogenetic role of omentin-1 in SH are required to confirm these findings.

Circulating Chemerin and Its Kinetics May Be a Useful Diagnostic and Prognostic Biomarker in Critically Ill Patients with Sepsis: A Prospective Study.

Chemerin, a novel adipokine, is a potent chemoattractant molecule with antimicrobial properties, implicated in immune responses. Our aim was to investigate circulating chemerin and its kinetics, early in sepsis in critically ill patients and its association with severity and prognosis. Serum chemerin was determined in a cohort of 102 critically ill patients with sepsis during the first 48 h from sepsis onset and one week later, and in 102 age- and gender-matched healthy controls. Patients were followed for 28 days and their outcomes were recorded. Circulating chemerin was significantly higher in septic patients at onset compared to controls (342.3 ± 108.1 vs. 200.8 ± 40.1 µg/L, p < 0.001). Chemerin decreased significantly from sepsis onset to one week later (342.3 ± 108.1 vs. 308.2 ± 108.5 µg/L, p < 0.001), but remained higher than in controls. Chemerin was higher in patients presenting with septic shock than those with sepsis (sepsis onset: 403.2 ± 89.9 vs. 299.7 ± 99.5 µg/L, p < 0.001; one week after: 374.9 ± 95.3 vs. 261.6 ± 91.9 µg/L, p < 0.001), and in nonsurvivors than survivors (sepsis onset: 427.2 ± 96.7 vs. 306.9 ± 92.1 µg/L, p < 0.001; one week after: 414.1 ± 94.5 vs. 264.2 ± 79.9 µg/L, p < 0.001). Moreover, patients with septic shock and nonsurvivors, presented a significantly lower absolute and relative decrease in chemerin one week after sepsis onset compared to baseline (p < 0.001). Based on ROC curve analyses, the diagnostic performance of chemerin (AUC 0.78, 95% CI 0.69-0.87) was similar to C-reactive protein (CRP) (AUC 0.78, 95% CI 0.68-0.87) in discriminating sepsis severity. However, increased chemerin at sepsis onset and one week later was an independent predictor of 28-day mortality (sepsis onset: HR 3.58, 95% CI 1.48-8.65, p = 0.005; one week after: HR 10.01, 95% CI 4.32-23.20, p < 0.001). Finally, serum chemerin exhibited significant correlations with the severity scores, white blood cells, lactate, CRP and procalcitonin, as well as with biomarkers of glucose homeostasis, but not with cytokines and soluble urokinase-type plasminogen activator receptor (suPAR). Circulating chemerin is increased early in sepsis and its kinetics may have diagnostic and prognostic value in critically ill patients. Further studies are needed to shed light on the role of chemerin in sepsis.

Circulating Omentin-1 as a Biomarker at the Intersection of Postmenopausal Breast Cancer Occurrence and Cardiometabolic Risk: An Observational Cross-Sectional Study.

Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL (p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes (p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79-0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.

Molecular Epidemiology of Multi-Drug Resistant Pseudomonas aeruginosa Isolates from Hospitalized Patients in Greece.

Resistant Pseudomonas aeruginosa isolates are one of the major causes of both hospital-acquired infections (HAIs) and community-acquired infections (CAIs). However, management of P. aeruginosa infections is difficult as the bacterium is inherently resistant to many antibiotics. In this study, a collection of 75 P. aeruginosa clinical isolates from two tertiary hospitals from Athens and Alexnadroupolis in Greece was studied to assess antimicrobial sensitivity and molecular epidemiology. All P. aeruginosa isolates were tested for susceptibility to 11 commonly used antibiotics, and the newly introduced Double Locus Sequence Typing (DLST) scheme was implemented to elucidate the predominant clones. The tested P. aeruginosa isolates presented various resistant phenotypes, with Verona Integron-Mediated Metallo-ß-lactamase (VIM-2) mechanisms being the majority, and a new phenotype, FEPR-CAZS, being reported for the first time in Greek isolates. DLST revealed two predominant types, 32-39 and 8-37, and provided evidence for intra-hospital transmission of the 32-39 clone in one of the hospitals. The results indicate that DLST can be a valuable tool when local outbreaks demand immediate tracking investigation with limited time and financial resources.

Circulating plasminogen activator inhibitor-1 activity: a biomarker for resectable non-small cell lung cancer?

PURPOSE: Plasminogen activator inhibitor-1 (PAI-1) participates in thrombotic, fibrinolytic, inflammatory and metabolic cascades. Since previous studies have focused on tissue and blood level concentrations, our goal was to investigate for the first time the independent relationship between plasma PAI-1 activity in resectable non small cell lung cancer (NSCLC) taking into consideration its several interfaces and study its diagnostic and prognostic potential. METHODS: In an adequately powered case-control study, plasma PAI-1 activity, metabolic parameters, classic adipokines, hemostatic, inflammatory and tumor biomarkers were measured in 110 consecutive patients with resectable NSCLC and 110 healthy subjects matched on age, sex and date of blood draw. RESULTS: NSCLC patients exhibited significantly higher PAI-1 activity compared to controls (p<0.001). In NSCLC cases, PAI-1 activity correlated with somatometric variables, insulin, WBC, antithrombin III, protein C, plasminogen, IL-6 and tumor size (p<0.05). Plasma PAI-1 activity was independently associated with NSCLC beyond risk factors associated with NSCLC (OR:6.9, 95%CI:2.9-16.6, p<0.001). Plasminogen activity and body mass index emerged as independent predictors of PAI-1 activity in cases. Due to its high specificity, PAI-1 activity could represent a potentially useful parameter in ruling out NSCLC, alone or in combination with serum tumor markers associated with NSCLC. CONCLUSIONS: PAI-1 activity, reflecting PAI-1 functionality, may represent a potentially useful biomarker in NSCLC associated with thrombotic, tumor-promoting and metabolic networks. More clinical studies are needed to explore whether PAI-1 activity may be a practical biomarker in the risk assessment of NSCLC, at the crossroads of hemostasis and metabolism.

Circulating eNampt and resistin as a proinflammatory duet predicting independently mortality in critically ill patients with sepsis: A prospective observational study.

BACKGROUND: The adipocytokines eNampt and resistin are involved in the regulation of inflammation exerting pro-inflammatory actions. Our aim was to jointly investigate whether circulating eNampt and resistin, and their kinetics predict 28-day mortality of sepsis. METHODS: In a prospective study, serum eNampt and resistin were determined in 102 critically ill patients fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after, and in 102 healthy controls matched on age, gender and month of diagnosis. RESULTS: Serum eNampt and resistin were significantly higher in septic patients than controls (p < 0.001), and higher in septic shock compared to sepsis (p < 0.001). Both eNampt and resistin decreased significantly during the first week of sepsis (p < 0.001). However, patients with septic shock presented a sustained elevation of eNampt and resistin compared to patients with sepsis. Both adipocytokines were positively correlated with sepsis severity scores and lactate. Baseline eNampt was a better discriminator of sepsis and septic shock compared to C-reactive protein and procalcitonin. Serum eNampt and resistin were higher in nonsurvivors than in survivors during the first week of sepsis. Prolonged and sustained elevation of both eNampt and resistin, as reflected by a lower percentage change from their baseline values, was independently associated with 28-day mortality (HR: 0.05, 95% C.I. 0.01-0.28, p = 0.001; HR: 0.19, 95% C.I. 0.07-0.50, p = 0.001, respectively), after adjustment for significant clinical and laboratory biomarkers. CONCLUSION: Circulating eNampt and resistin, and their kinetics may represent useful diagnostic and prognostic biomarkers in critically ill septic patients. More prospective studies are needed to elucidate their ontological and pathophysiological role in sepsis.

Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer.

OBJECTIVES: Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS: In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). RESULTS: NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 µg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. CONCLUSION: Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors.

PURPOSE: Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. METHODS: In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. RESULTS: SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09). CONCLUSIONS: Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.

Serum angiopoietin-2 and CRP levels during COPD exacerbations.

BACKGROUND AND OBJECTIVE: Angiopoietin-2 (Ang-2) is an important mediator of angiogenesis and has been implicated in many inflammatory diseases. COPD is characterized by systemic inflammation, which is enhanced during exacerbations and may be assessed by measuring serum C-reactive protein (CRP). The aim of the study was to evaluate serum CRP and Ang-2 levels on the first (D1) and seventh day (D7) of hospitalization due to a COPD exacerbation and to examine possible associations of CRP and Ang-2 levels and kinetics with the length of hospital stay and outcome. METHODS: We conducted a prospective study and evaluated 90 patients admitted to the hospital with a diagnosis of an acute exacerbation of COPD. A venous blood sample was obtained from all patients on D1 and D7 of hospitalization, for the measurement of Ang-2 and CRP. RESULTS: Serum Ang-2 levels were significantly higher on D1 compared to D7 during the course of COPD exacerbation (p < 0.001). Serum CRP levels were also significantly higher on D1 compared to D7 (p < 0.001). Serum Ang-2 presented a significant positive correlation with CRP levels both on D1 and D7 (r = 0.315 and r = 0.228, respectively). Patients with unfavorable outcome had significantly higher Ang-2 levels both on D1 (p = 0.04) and D7 (p = 0.01). CONCLUSIONS: Serum Ang-2 levels are elevated at the onset of COPD exacerbations and are positively associated with CRP levels. Ang-2 levels decrease during the course of COPD exacerbations in patients with favorable outcome. Serum Ang-2 may serve as a biomarker that could predict the outcome of a COPD exacerbation.