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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.

Amyloidosis and its related factors in Turkish patients with familial Mediterranean fever: a multicentre study

OBJECTIVE The primary aim of this study was to investigate the prevalence of amyloidosis and its related factors in a large number of FMF patients. METHODS Fifteen centres from the different geographical regions of Turkey were included in the study. Detailed demographic and medical data based on a structured questionnaire and medical records were collected. The diagnosis of amyloidosis was based on histological proof of congophilic fibrillar deposits in tissue biopsy specimens. RESULTS There were 2246 FMF patients. The male/female ratio was 0.87 (1049/1197). The mean age of the patients was 34.5 years (S.D. 11.9). Peritonitis was the most frequent clinical finding and it was present in 94.6% of patients. Genetic testing was available in 1719 patients (76.5%). The most frequently observed genotype was homozygous M694V mutation, which was present in 413 (24%) patients. Amyloidosis was present in 193 patients (8.6%). Male sex, arthritis, delay in diagnosis, M694V genotype, patients with end-stage renal disease (ESRD) and family history of amyloidosis and ESRD were significantly more prevalent in patients with amyloidosis compared with the amyloidosis-negative subjects. Patients with homozygous M694V mutations had a 6-fold higher risk of amyloidosis compared with the other genotypes (95% CI 4.29, 8.7, P < 0.001). CONCLUSION In this nationwide study we found that 8.6% of our FMF patients had amyloidosis and homozygosity for M694V was the most common mutation in these patients. The latter finding confirms the association of homozygous M694V mutation with amyloidosis in Turkish FMF patients.

Does mean platelet volume influence the attack or attack-free period in the patients with Familial Mediterranean fever?

Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease which is characterized by recurrent attacks of fever and peritonitis, pleuritis, arthritis, or erysipelas-like skin disease. Mean platelet volume (MPV) is a sign of platelet activation. There are limited studies in the literature about MPV levels in FMF patients. We aimed to investigate MPV levels during the attack period (group 1) and attack-free periods (group 2) in FMF patients, and to compare them with healthy controls (group 3). The study consisted of the data of: 60 group 1 patients, 120 group 2 patients, and 75 group 3 patients. 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 lower in FMF patients both in group 1 and group 2 than in group 3 (p = 0.004, p = 0.002, respectively); however, there was no difference among group 1 and group 2 in patients with FMF (p = 0.279). The mean platelet count of group 1 was higher than that of group 3 (p = 0.010). In conclusion, this study results suggested that MPV level did not increase on the contrary, it decreased in patients with FMF both in group 1 and/or group 2 when compared to group 3. It was concluded that the lower MPV level was an expected result of secondary thrombocytosis in FMF patients.

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.

Prevalence of periodontal disease in patients with Familial Mediterranean Fever: A cohort study from central Turkey

OBJECTIVE The aim of this study was to compare the periodontal status in patients with Familial Mediterranean Fever (FMF) and in those without this disease. METHOD AND MATERIALS 84 subjects clinically diagnosed with FMF and 75 systemically healthy controls, matched by age and gender, were recruited. All FMF patients were on a regular daily colchicine treatment and during attack-free periods. Gingival Index (GI), Plaque Index (PI), probing pocket depth (PD), and clinical attachment level (CAL) were measured in all subjects. To evaluate periodontal disease further, patients were stratified into fi ve groups. Education information and smoking habits were recorded. RESULTS The FMF patients and healthy controls were comparable for age, gender, and smoking status (P>.05). The FMF patients had significantly higher PI and GI values and lower PD and CAL values than those of the control group (P<.05). However, there was no significant difference among all groups in terms of periodontal disease severity (P>.05). In the FMF-severe periodontitis group, higher PI and GI values were seen (P<.05). However, there was no significant difference between the FMF-severe periodontitis group and the controls with severe periodontitis regarding the PD and CAL values (P>.05). CONCLUSION Patients with FMF using colchicine did not manifest higher attachment loss compared to age- and sex-matched systemically healthy controls.

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.

A Nationwide Experience With The Off‐label Use of Interleukin‐1 Targeting Treatment in Familial Mediterranean Fever Patients

Approximately 30–45% of patients with familial Mediterranean fever (FMF) have been reported to have attacks despite colchicine treatment. Currently, data on the treatment of colchicine‐unresponsive or colchicine‐intolerant FMF patients are limited; the most promising alternatives seem to be anti–interleukin‐1 (anti–IL‐1) agents. Here we report our experience with the off‐label use of anti–IL‐1 agents in a large group of FMF patients.

Alpha-Fetoprotein Response After Locoregional Therapy for Hepatocellular Carcinoma

TO THE EDITOR: We read with great interest the report by Riaz et al, in which they demonstrated that the response of serum alphafetoprotein (AFP) level after locoregional therapy in patients with hepatocellular carcinoma (HCC) was a useful surrogate marker to determinate tumor response and survival. In this study, AFP response was seen in 81 (64.8%) of 125 patients treated with chemoembolization and radioembolization. Also, the authors reported that AFP response was a prognostic factor for overall survival in univariate and multivariate analyses. It is still unclear whether serial AFP measurement or AFP/tumor volume for monitoring treatment response in patients with HCC should be used. Some studies have shown that serum AFP level might be used as a surrogate marker for response to systemic chemotherapy. A significant correlation between serum AFP levels and both size and number of HCC lesions has been reported. AFP/tumor volume may be a better prognostic indicator for patients with HCC than serum AFP value alone. Also, significant correlation between higher AFP levels and higher stages has been reported. Because the results of a multivariate analysis give important messages to readers, the analysis should be carefully used. For accurately interpreted results of a study, the sample size should be sufficient to perform multivariate analysis. Some authors have recommended that a minimum of 20 patients per predictor should be used for an accurately interpreted multivariate analysis. Also, each parameter considered to be a prognostic factor must be evaluated before univariate or multivariate analysis is performed, because one factor may interact with the others. We think that the statistical assessment is the most important limitation of the study by Riaz et al. The study included a total of 125 patients and six prognostic factors, such as stage, performance status, Child Pugh class, WHO response, European Association for the Study of the Liver response, and AFP response, which were evaluated for multivariate analysis. We think that the sample size of the study was quite small for multivariate analysis, and the interaction probability among prognostic factors analyzed in the study was quite high. We believe that this problematic issue may have affected the results presented in the report.

Validity and reliability of medication adherence scale in FMF (adult version)

MASIF (Medication Adherence Scale in FMF) is an instrument designed to measure adherence to treatment in children with Familial Mediterranean Fever (FMF). We have developed this scale for children with FMF and found valid and reliable.