Ayse Balkarli

Incidence of Cyclophosphamide-induced Urotoxicity and Protective Effect of Mesna in Rheumatic Diseases

Objective. To assess bladder toxicity of cyclophosphamide (CYC) and uroprotective effect of mesna in rheumatic diseases. Methods. Data of 1018 patients (725 women/293 men) treated with CYC were evaluated in this retrospective study. All of the following information was obtained: the cumulative CYC dose, route of CYC administration, duration of therapy, concomitant mesna usage, and hemorrhagic cystitis. Cox proportional hazard model was used for statistics. Results. We identified 17 patients (1.67%) with hemorrhagic cystitis and 2 patients (0.19%) with bladder cancer in 4224 patient-years. The median time for diagnosis to hemorrhagic cystitis was 10 months (4–48) and bladder cancer was 8 years (6–10.9). There were 583 patients (57.2%) who received mesna with intravenous CYC therapy. We observed similar incidence rate for hemorrhagic cystitis in both patient groups concomitantly treated with or without mesna [9/583 (1.5%) vs 8/425 (1.8%) respectively, p = 0.08]. Cumulative CYC dose (HR for 10-g increments 1.24, p < 0.001) was associated with hemorrhagic cystitis. Conclusion. Cumulative dose was the only risk factor for hemorrhagic cystitis in patients treated with CYC. No proof was obtained for the uroprotective effect of mesna in our cohort.

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND Adult-onset Stills disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.

Synaptosomal-associated protein 25 (Snap-25) gene Polymorphism frequency in fibromyalgia syndrome and relationship with clinical symptoms

BackgroundSNAP-25 protein is contributory to plasma membrane and synaptic vesicle fusions that are critical points in neurotransmission. SNAP-25 gene is associated with behavioral symptoms, personality and psychological disorders. In addition, SNAP-25 protein can be related to different neurotransmitter functions due to its association with vesicle membrane transition and fusion. This is important because neurologic, cognitive, and psychologic disorders in fibromyalgia syndrome (FMS) can be related to this function. This relationship may be enlightening for etiopathogenesis of FMS and treatment approaches. We aimed to study a SNAP-25 gene polymorphism, which is related to many psychiatric diseases, and FMS association in this prospective study.MethodsWe included 71 patients who were diagnosed according to new criteria and 57 matched healthy women in this study. Both groups were evaluated regarding age, height, weight, BMI, education level, marital and occupational status. A new diagnosis of FMS was made from criteria scoring, SF-36, Beck depression scale, and VAS that were applied to the patient group. SNAP-25 gene polymorphism and disease activity score correlations were compared.ResultsMean age was 38±5,196 and 38.12±4.939 in patient and control groups, respectively (p=0.542). No significant difference was found between groups regarding age, height, weight, BMI, education level, marital or occupational status (p > 0.05). Ddel T/C genotype was significantly higher in the patient group (p = 0.009). MnlI gene polymorphism did not show a correlation with any score whereas a significant correlation was found between Ddel T/C genotype and Beck depression scale and VAS score (p < 0.05).ConclusionFMS etiopathogenesis is not clearly known. Numerous neurologic, cognitive and psychological disorders were found during studies looking at cause. Our study showed increased SNAP-25 Ddel T/C genotype in FMS patients compared to the control group, which is related to behavioral symptoms, personality and psychological disorders in FMS patients.

Thiol/disulfide homeostasis in patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients.Ankylosing spondylitis (AS) is a chronic inflammatory disease. In many inflammatory diseases, increased production of pro-inflammatory cytokines is associated with an increase in oxidative stress mediators. Thiol/disulfide homeostasis is a marker for oxidative stress. The aim of this study was to examine the dynamic thiol/disulfide homeostasis in AS. Sixty-nine patients with AS and 60 age- and sex-matched controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and visual analogue scale (VAS) were used to determine the disease activity. Native thiol, total thiol, and disulfide levels were measured with a novel automated method recently described by Erel and Neselioglu. The aforementioned method is also optionally manual spectrophotometric assay. The total thiol levels were significantly lower in the AS group compared with the control group (p = 0.03). When the patients were divided into active (n = 35) and inactive (n = 34) subgroups using BASDAI scores, the native plasma thiol and total thiol levels were significantly lower in the active AS patients compared to the inactive AS patients (p = 0.02, p = 0.03 respectively). There was a negative correlation between the plasma native thiol levels and VAS, BASDAI scores. Thiol/disulfide homeostasis may be used for elucidating the effects of oxidative stress in AS. Understanding the role of thiol/disulfide homeostasis in AS might provide new therapeutic intervention strategies for patients.

Leptin and leptin receptors in salivary glands of primary Sjögren’s syndrome

BACKGROUND The role of leptin in primary Sjögrens syndrome (SS) pathogenesis is unknown. The aim of this study was to investigate the expression of leptin and leptin receptor (LEPR) in minor salivary glands in patients with SS. MATERIALS AND METHODS The expression of leptin and LEPR in minor salivary gland specimens obtained from patients with primary SS (n=50) and control subjects (n=50) were examined using immunohistochemical staining. RESULTS Acinar cells, epithelial cells and adipocytes in salivary glands can express leptin and LEPR. It was observed that there was intense staining in the focal lymphocytic infiltration areas in SS patients. The intensity of leptin and LEPR staining under microscopy (400×) were graded semiquantitatively as negative, mild, moderate or strongly positive, and scored as 1, 2 or 3, respectively. The expression levels of leptin and LEPR in patients with primary SS were not higher than in controls. There was no significant difference in degrees of leptin and LEPR staining, staining intensity, and immunoreactive scores between groups. The expression of leptin and LEPR were not correlated with autoantibodies such as RF, ANA, anti-Ro, and/or anti-La positivity. CONCLUSIONS These findings indicate that leptin and its receptors do not play an important role in primary SS pathophysiology.

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.

An evaluation of the functional and radiological results of percutaneous vertebroplasty versus conservative treatment for acute symptomatic osteoporotic spinal fractures

PURPOSE This study aimed to compare the results of the two different treatment regimens (percutaneous vertebroplasty (PV) and conservative treatment (CT)) regarding to efficacy, quality of life, functional and radiological results in patients with acute osteoporotic vertebral compression fractures (OVF). METHODS The study comprised 83 patients who presented with complaints of OVF associated with osteoporosis and were treated with CT (37) or PV (46). All patients were evaluated according to preoperative and postoperative visual analogue scale (VAS), Oswestry disability index (ODI) and plain radiographs. RESULTS All patients in VP group reported a significant decrease in pain at 1st day postoperative. While Pain relief and functional outcomes were significantly better in PV group than CT at 1st and 3rd months according to VAS and ODI scores, there were no statistically significant differences between the groups at 6th months follow-up. The mean preoperative local sagittal Cobb angle (LSCA) and the mean vertebra corpus mid-level height (MVCH) were 42.3° and 14.6 mm in the PV group, while they were measured as 39.8° and 15.7 mm in CT group, respectively. 15.6° decreasing the LSCA and 10.2 mm increasing MVCH were noted in the PV group at the 6th month follow-up. While LSCA increased 19.1° and MVCH decreased 7.6mm in CT group at same time period (p<0.001). CONCLUSIONS Compared to the CT group, PV provides a rapid decrease of pain and an early return to daily life activities. Although improvement was observed on the radiological findings following treatment in the PV group, PV may not enhance the quality of life in patients with acute OVF at 6th months follow up.

Avaliação da frequência e aspectos dos ataques de pacientes com resistência à colchicina em febre familiar do Mediterrâneo (FFM)

INTRODUCTION Colchicine is the mainstay for the treatment of FMF, which is an auto-inflammatory disease mainly with relapsing polyserositis. Despite daily doses of 2mg or more each day, approximately 5% to 10% of the patients continue to suffer from its attacks. In this study, we aimed to investigate the depression and attack features in patients with FMF who have colchicine resistance (CR). PATIENTS E METHODS CR was defined for FMF patients with 2 or more attacks within the last 6 months period while using 2mg/day colchicine. Eighteen patients (9 Female/9 Male) were enrolled into the CR group and 41 patients were enrolled into the control group (12 Male/29 Female). Demographic, clinical e laboratory findings, treatment adherence, and the Beck Depression Inventory (BDI) scores were evaluated. RESULTS The age of onset of FMF was significantly lower in the CR group (12.3 yrs vs. 16.9 yrs, P=0.03). Disease duration was longer in the CR group (P=0.01). Abdominal and leg pain due to exercise were significantly more frequent in the CR group versus controls (83% vs. 51%; P=0.02 e 88% vs. 60%; P=0.04, respectively). Patients with BDI scores over 17 points were more frequent in the CR group compared to controls (50% vs. 34.1%; P<0.001). DISCUSSION We found that: (1) the age of disease onset was lower and (2) the disease duration was longer in CR group. Pleuritic attacks, hematuria e proteinuria were more frequent in CR patients. We propose that depression is an important factor to consider in the susceptibility to CR.

Pain, depression levels, fatigue, sleep quality, and quality of life inelderly patients with rheumatoid arthritis

BACKGROUND/AIM The aim of this study was to evaluate and determine the relationships (if any) among pain, depression levels, fatigue, sleep quality, and quality of life in patients with rheumatoid arthritis (RA) aged 65 years and over, and to compare the results with those of RA patients under 65 years of age. MATERIALS AND METHODS The study included 52 patients with RA aged 65 years and over (Group 1) and 84 patients with RA under 65 years of age (Group 2). Pain, depression levels, fatigue, sleep quality, quality of life, and disease activity of all of the participants were evaluated using a visual analog scale (VAS), the Beck Depression Inventory (BDI), the Checklist Individual Strength (CIS), the Pittsburgh Sleep Quality Index (PSQI), the Short Form-36 (SF-36), and the Disease Activity Score-28, respectively. RESULTS When the two groups were compared, higher scores for the VAS, BDI, total CIS, and PSQI were found in Group 1 compared to Group 2 (P = 0.003, P = 0.003, P = 0.007, and P = 0.001, respectively). The SF-36 subscales of the physical component summary and mental component summary were not statistically significantly different between the two groups (P > 0.05). CONCLUSION This study evaluated the situation in elderly patients with RA and showed that pain, depression level, fatigue, and sleep quality worsen with age.

Effects of Vitamin D Therapy on Quality of Life in Patients with Fibromyalgia

OBJECTIVE The role of vitamin D in the etiopathogenesis of fibromyalgia and non-specific musculoskeletal pain is controversial. In our study, we aimed to investigate the effect of vitamin D therapy on quality of life in patients with fibromyalgia. MATERIALS AND METHODS Seventy patients diagnosed with fibromyalgia and 65 age- and sex-matched controls were included in the study. Patients were grouped as deficient (<20 ng/mL), inadequate (20-30 ng/mL), and sufficient (>30 ng/mL) according to the levels of vitamin D. Vitamin D replacement was performed for patients with deficiencies and inadequacies. Before and after vitamin D therapy, patients filled in the assessment tools, fibromyalgia impact questionnaire (FIQ), Arizona sexual experience scale (ASEX), Beck depression inventory (BDI), visual analog scale (VAS), and short form-36 (SF-36). RESULTS Vitamin D deficiencies and inadequacies were observed in 60% of the patients (n=42). Among patients with low and normal levels of vitamin D, no statistically significant difference was observed in their values. In scales examined after vitamin D replacement therapy, statistically significant differences were observed in the FIQ, BDI, VAS, and SF-36 compared with pre-treatment. CONCLUSION Vitamin D deficiency seems to be linked to the pathogenesis of fibromyalgia. Vitamin D supplementation may improve the quality of life in patients with fibromyalgia.