Ali Ugur Uslu

Two new inflammatory markers associated with Disease Activity Score‐28 in patients with rheumatoid arthritis: neutrophil‐lymphocyte ratio and platelet‐lymphocyte ratio

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with unknown etiology and systemic involvement. Neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) are two new inflammatory markers used in the assessment of systemic inflammation. The aim here is to study NLR and PLR in patients with RA to investigate their relation with Disease Activity Score of 28 joints (DAS‐28).

Is Neutrophil/Lymphocyte Ratio Associated with Subclinical Inflammation and Amyloidosis in Patients with Familial Mediterranean Fever?

Background. The purpose of the present study is to determine the association between neutrophil/lymphocyte ratio and both subclinical inflammation and amyloidosis in familial Mediterranean fever. Methods. Ninety-four patients with familial Mediterranean fever and 60 healthy volunteers were included in the study. Of the patients, 12 had familial Mediterranean fever related amyloidosis. The neutrophil/lymphocyte ratio of the patients was obtained from the hematology laboratory archive. Results. The neutrophil/lymphocyte ratio was significantly higher among persons with familial Mediterranean fever compared to healthy individuals (P < 0.0001). Also, neutrophil/lymphocyte ratio was significantly higher in patients with amyloidosis than in amyloidosis-free patients (P < 0.0001). Since NLR was evaluated in nonamyloid and amyloid stages of the same patient population (type 1 phenotype), we obtained significant statistical differences (1.95 ± 0.30 versus 2.64 ± 0.48, P < 0.05, resp.). With the cutoff value of neutrophil/lymphocyte ratio >2.21 and AUC = 0.734 (P = 0.009), it was a reliable marker in predicting the development of amyloidosis. Conclusion. The neutrophil/lymphocyte ratio, an emerging marker of inflammation, is higher in patients with familial Mediterranean fever in attack-free periods. The neutrophil/lymphocyte ratio may be a useful marker in predicting the development of amyloidosis.

Endocan Levels and Subclinical Atherosclerosis in Patients With Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. A major cause of morbidity and mortality in SLE is accelerated atherosclerosis. Endothelial-specific molecule 1 (endocan) is a potential predictor of vascular events and is expressed in response to inflammatory cytokines in endothelial cells. We investigated the relationship between endocan and carotid intima–media thickness (cIMT) as a marker of early atherosclerosis. We included 44 women with SLE and 44 healthy women as controls. Disease severity of SLE was evaluated using the SLE Disease Activity Index. Endocan, C-reactive protein, erythrocyte sedimentation rate (ESR), and lipid panel were measured. The cIMT was 0.70 (range: 0.45-1.20) mm in patients with SLE and 0.40 (0.25-0.60) mm in controls (P < .001). Endocan value was 1.6 ± 0.9 ng/mL in controls and 2.2 ± 1.0 ng/mL in patients with SLE (P = .014). Endocan levels were positively correlated with cIMT (r = .469, P < .001), body mass index (r = .373, P = .013), and ESR (r = .393, P = .008). Endocan level may be associated with subclinical atherosclerosis in SLE. Consequently, endocan levels may be a promising clinical tool for patients with SLE as a guide for preventive strategy.

Novel myokine: irisin may be an independent predictor for subclinic atherosclerosis in Behçet's disease

Behçets disease (BD) is a vasculitic and inflammatory disease causing endothelial dysfunction. Irisin is a metabolic hormone related to insulin resistance and endothelial functions. In this study, we investigated the relationship between irisin and carotid intima-media thickness (cIMT), which is a marker of atherosclerosis in patients with BD. 48 patients with BD and 50 healthy individuals were enrolled in the study. Disease severity was evaluated by BD current activity form. Irisin, glucose, insulin, C reactive protein, erythrocyte sedimentation rate and lipid panel were examined in all patients. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was used to calculate insulin resistance. A simple and inexpensive cIMT test was used as indicator of atherosclerosis. cIMT was 0.62 (0.45–1.05) mm in the patients, while it was 0.38 (0.25–0.65) mm in the control group (p<0.001). Irisin value was found to be 197.3 (24.8–834.2) ng/mL in the control group, while it was 85.4 (4.7–471.1) ng/mL in the patient group (p=0.007). There was a negative correlation between irisin level and cIMT (r=−0.511, p<0.001) and HOMA-IR (r=−0.371, p=0.009). Decreased irisin levels (OR 0.996, 95% CI 0.992 to 1.000, p=0.041), male gender (OR 7.634, 95% CI 1.415 to 41.191, p=0.018), and HOMA-IR (OR 2.596, 95% CI 1.451 to 4.643, p=0.001) are independent risk factors for cIMT in patients with BD. We detected a very strong relationship between cIMT, which is an indicator of subclinical atherosclerosis, and decreased irisin levels in patients with BD. BD is characterized by chronic inflammation, and low serum irisin levels in BD may be related to atherosclerosis.

Ischemia-Modified Albumin and Atherosclerosis in Patients With Familial Mediterranean Fever.

The constriction of vessels due to atherosclerotic lesions causes hypoxia/ischemia and oxidative changes resulting in transformation of free albumin to ischemia-modified albumin (IMA) in the circulation and increased carotid intima–media thickness (cIMT). We investigated the reliability of IMA increase in evaluating atherosclerosis in patients with familial Mediterranean fever (FMF) compared with cIMT. Patients with FMF (n = 58) diagnosed by the Tel-Hashomer criteria in attack-free period and 38 healthy people were included in the study. Patient demographics as well as the clinical and laboratory characteristics of the healthy controls and patients with FMF were noted. The IMA levels and cIMT in patients with FMF were 0.30 ± 0.09 absorbance units (ABSUs) and 1.12 ± 0.27 mm, respectively, and in the control group, IMA levels and cIMT were 0.25 ± 0.07 ABSU and 0.74 ± 0.26 mm, respectively. The IMA levels and cIMT were significantly higher in patients with FMF than in controls (P = .020 and P < .0001, respectively). The IMA values showed positive correlation with cIMT in patients with FMF(r = .302, P = .041). Our results reveal that IMA—an oxidative stress marker—may be an indicator of atherosclerosis in patients with FMF. This finding deserves further investigation.

The relationship between red cell distribution width and homozygous M694V mutation in familial Mediterranean fever patients.

BACKGROUND AND OBJECTIVE Familial Mediterranean fever (FMF) is characterized by recurrent and self-limiting attacks with peritonitis, pleuritis, arthritis, and erysipelas-like erythema. We aimed to investigate the red cell distribution width (RDW) level as an inflammatory marker in FMF patients compared with normal subjects. DESIGN AND SETTINGS A retrospective study of FMF patients at the Department of Gastroenterology, Cumhuriyet University, between November 2011-February 2013. METHODS A total of 249 FMF patients and 131 age- and sex-matched control participants were included in the currrent study. RDW levels were also analyzed by standard methods. Each patient was given 2 mL of blood sample to obtain genomic DNA. RESULTS Statistically significant differences were observed in RDW values between the FMF patients and the control group. Also, RDW levels were higher in the FMF patients with the homozygous M94V mutation compared with those with other mutations. The receiver-operating characteristic curve analysis suggested that the optimum RDW cutoff point for the FMF patients was 13.95, with a sensitivity, specificity, negative predictive value, and positive predictive value of 70%, 64%, 68%, and 66%, respectively (area under the curve: 0.711, 95% confidence interval 0.627–0.795, P<.0001). CONCLUSION We suggest that RDW may show subclinical inflammation in FMF patients. RDW may be a promising marker in predicting the homozygous M694V mutation in FMF patients.

The Relationship Between Atherogenic Index and Carotid Artery Atherosclerosis in Familial Mediterranean Fever: A Pilot Study.

Familial Mediterranean fever (FMF) is a disease characterized by chronic inflammation. Atherogenic index of plasma (AIP) is a logarithmic value of the triglyceride to high-density lipoprotein cholesterol ratio and it is a good marker for atherosclerotic heart disease and cardiac risk. In this study, we investigated subclinical atherosclerosis and cardiac risks in patients with FMF. Patients with FMF (78 men and 84 women) and healthy controls (74 men and 82 women) were included in this study. The AIP values of the patients were calculated and carotid intima–media thicknesses (cIMTs) were measured. The cIMT (P < .001) and AIP (P < .001) values of patients with FMF were higher than the values of the control group. There was a positive correlation between cIMT and AIP values (r = .304, P < .001). In regression analysis, we detected an independent relationship between cIMT and AIP (β = .248, P = .001). Atherogenic index of plasma may be highly correlated with the subclinical atherosclerosis. Particularly, male patients with FMF may have a high cardiac risk.

The role of neutrophil lymphocyte ratio to leverage the differential diagnosis of familial Mediterranean fever attack and acute appendicitis

Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. Methods: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. Results: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 ± 6.31 vs. 4.16 ± 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). Conclusions: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis.

Do neutrophil gelatinase-associated lipocalin and interleukin-18 predict renal dysfunction in patients with familial Mediterranean fever and amyloidosis?

Abstract Background: The aim of this study was to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) predict renal disfunction in patients with familial Mediterranean fever (FMF). Methods: This prospective study consisted of 102 patients with FMF in attack-free period, and 40 matched healthy controls. Of the patients, nine were diagnosed as amyloidosis. The patients were divided into two groups according to eGFR as below 120 mL per minute and above 120 mL per minute. Also, patients were divided into three groups according to the degree of urinary albumin excretion as normoalbuminuric, microalbuminuric, and macroalbuminuric. The serum levels of IL-18 (sIL-18) and NGAL (sNGAL), and urinary levels of IL-18 (uIL-18) and NGAL (uNGAL) were measured by using ELISA kits. Results: The levels of sIL-18, sNGAL, uIL-18, and uNGAL were detected significantly higher in FMF patients, particularly in patients with amyloidosis, when compared to controls. sNGAL, uIL-18, and uNGAL were significantly higher in patients with eGFR < 120 mL per minute than in patients with eGFR ≥ 120 mL per minute. sNGAL, uIL-18, and uNGAL were correlated significantly with urinary albumin excretion, additionally, were inverse correlated with eGFR. The most remarkable findings of this study are of the higher values of sIL-18, sNGAL, uIL-18, and uNGAL in both normoalbuminuric FMF patients and patients with eGFR ≥ 120 mL per minute. Conclusions: The results of this study suggest that sIL-18, uIL-18, sNGAL, and uNGAL are reliable markers of early renal disfunction in FMF patients, and may let us take measures from the early stage of renal involvement.

Is there a link between mean platelet volume and thrombotic events in antiphospholipid syndrome

Abstract The antiphospholipid syndrome (APS) is an autoimmune disease characterized by the production of antiphospholipid antibodies (aPL) that promote vascular thrombosis and pregnancy loss. APS can occur in the absence of underlying or associated disease (primary APS) or in combination with other diseases (secondary APS). Mean platelet volume (MPV) is largely regarded as a useful surrogate marker of platelet activation. We aimed to investigate if there is a relationship between MPV and thrombotic events in APS. The study consisted of 22 patients and 22 healthy controls. Group 1 is defined as all the patients in the first day of thrombotic event. Group 2 is defined as the same patient population three months after the thrombotic event. The erythrocyte sedimentation rate, C-reactive protein, white blood cell count, platelet count, and MPV levels were retrospectively recorded from patient files. Statistical analyses showed that MPV was significantly higher in group 1 than group 2 (p < 0.0001) and healthy controls (p < 0.05). However, there was no difference between group 2 and healthy controls (p = 0.888). WBC, hemoglobin and other platelet indices such as platelet distribution width and platecrit did not differ in groups. In conclusion, MPV was increased at initial thrombotic event of APS, and then it was normalized three months later by therapeutic interventions. To our knowledge, this is the first study demonstrating a correlation between MPV and thrombotic events in APS.