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Hemorrhage is a frequent complication in patients with acute leukemias as a result of chemotherapy-induced myelosuppression. Gastrointestinal bleeding in thrombocytopenic patients carries a high mortality. Patients are generally managed with red blood cell, platelet suspensions, and fresh frozen plasma; and sometimes with pharmacologic and endoscopic interventions. If these therapeutic measures fail, patients might be treated with hemostatic drugs, one example of which is recombinant activated factor VII (rFVIIa). This drug is recommended for all kinds of bleeding in hemophiliacs with inhibitors; it is also being used for the treatment of bleeding in thrombocytopenia and platelet function disorders. We present our 44-year-old female patient who had gastrointestinal system bleeding after remission induction therapy for acute myeloid leukemia. Thrombocytopenia was refractory to apheresis platelets; and gastrointestinal bleeding could be controlled only after the administration of a single dose (35 microg/kg, total dose 2.4 mg) of rFVIIa. Our experience indicates that rFVIIa might be a novel treatment alternative in massive bleeding in leukemic patients with thrombocytopenia or platelet function disorders. [ABSTRACT FROM AUTHOR]

Myeloid blast-phase chronic myeloid leukemia (MBP-CML) is a rare disease with a dismal prognosis. It is twice as common as lymphoid blast-phase CML, and its prognosis is poorer. Despite the success with tyrosine kinase inhibitors in the treatment of chronic-phase CML, the same does not hold true for MBP-CML. In addition to the Philadelphia chromosome, other chromosomal and molecular changes characterize rapid progression. Although some progress in elucidating the biology of MBP-CML has been made, there is need to discover more in order to develop more satisfactory treatment options. Currently, most common treatment options include tyrosine kinase inhibitors (TKIs) as monotherapy or in combination with acute myeloid leukemia-based intensive chemotherapy regimens. Some patients may develop resistance to TKIs via BCR-ABL1-dependent or BCR-ABL1-independent mechanisms. In this paper, we provide an overview of the biology of MBP-CML, the current treatment approaches, and mechanisms of resistance to TKIs. In order to improve treatment responses in these patients, more emphasis should be placed on understanding the biology of myeloid blastic transformation in CML and mechanisms of resistance to TKIs. Although patient numbers are small, randomized clinical trials should be considered.

On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% [95% confidence interval (CI), 30-46] in the asciminib arm versus 16% (95% CI, 8-26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34-64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications., (©2024 American Association for Cancer Research.)

Summary: Cancer drug development remained robust in 2023. Highlights of U.S. drug approvals this year include new immunotherapies and targeted drug development in adult and pediatric patients as well as patients with rare diseases., (©2023 American Association for Cancer Research.)

The cancer treatment landscape has changed dramatically since the turn of the century, resulting in substantial improvements in outcomes for patients. This Review summarizes trends in the approval of oncology therapeutic products by the United States Food and Drug Administration (FDA) from January 2000 to October 2022, based on a categorization of these products by their mechanism of action and primary target. Notably, the rate of oncology indication approvals has increased in this time, driven by approvals for targeted therapies, as has the rate of introduction of new therapeutic approaches. Kinase inhibitors are the dominant product class by number of approved products and indications, yet immune checkpoint inhibitors have the second most approvals despite not entering the market until 2011. Other trends include a slight increase in the share of approvals for biomarker-defined populations and the emergence of tumour-site-agnostic approvals. Finally, we consider the implications of the trends for the future of oncology therapeutic product development, including the impact of novel therapeutic approaches and technologies., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The FDA has an accelerated approval program for drugs that have been identified as promising treatments for serious conditions when the available data suggest that the benefits outweigh the foreseeable risks. All of the currently available treatment options for chronic myeloid leukemia (CML) initially went through the accelerated approval program. Here, a group of academic CML experts, patient panelists, and members from the FDA convened to discuss the utility of the accelerated approval program as it pertains to CML, and the utility of this program in future drug development in this disease. The results of that discussion are summarized here., (©2022 American Association for Cancer Research.)

In 2022, cancer drug development continued to progress rapidly despite the lingering COVID-19 pandemic. Highlights of U.S. drug approvals for oncology indications this year include ongoing development in rare diseases and molecular subgroups, improved dosage optimization, and updated data for drugs granted accelerated approval, with confirmatory studies demonstrating verification of clinical benefit in some instances, as well as indication withdrawal when clinical benefit was not verified., (©2022 American Association for Cancer Research.)

Objective: We studied CXCL12-related rs18011157 polymorphism in non-Hodgkin lymphoma (NHL) patients. We also determined the effect of this polymorphism on clinical features and outcome of NHL., Methods: We included 90 NHL patients (54 males, 36 females) and 88 healthy controls (54 males, 34 females). CXCL12-related rs18011157 polymorphism was determined by polymerase chain reaction., Results: rs18011157 polymorphism was significantly more frequent in NHL patients with GA genotype than in healthy controls (37.8% vs. 20.5%, P = 0.011). The frequency of patients with initially high lactate dehydrogenase (LDH) level (65.8% vs. 38.5%) and extranodal involvement (61.1% vs. 43.8%) was significantly higher in the GA plus AA genotype groups when considered altogether (P = 0.01 and 0.09). Poor prognostic factors in univariate analysis were the presence of B symptoms, initially high International Prognostic Index (IPI), splenomegaly, nonresponse to first-line therapy, the presence of early relapse, and carrying A allele (GA plus AA genotypes). The independent prognostic factors in multivariate analysis were only early relapse and an initially high IPI score., Discussion: CXCL12 rs1801157 polymorphism which was found to be associated with extranodal involvement and increased LDH in NHL might be a marker of poor prognosis in patients with GA and AA genotypes., Conclusions: CXCL12-related rs18011517 polymorphism was more frequent in NHL patients: it might be associated with NHL pathogenesis and outcome., Competing Interests: There are no conflicts of interest

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma and four cases of PCNSL have previously been described in association with mycophenolate mofetil. We report the fifth case of PCNSL in a patient with lupus nephropathy while on mycophenolate mofetil treatment.

Treatment with tyrosine kinase inhibitors (TKIs) has dramatically changed the life expectancy of chronic myeloid leukaemia (CML) patients. Although the impact of first-generation TKIs on quality of life (QoL) was shown in CML, the effects of new generic formulations of imatinib mesylate (IM) are unclear. We evaluated differences in QoL under treatment with first- or second-generation TKIs. Fifty-two patients diagnosed with CP-CML completed the European Organization for Research and Treatment of Cancer Quality of Life Questionaire-C30, Hospital Anxiety and Depression Scale, and General Health Questionnaire. General QoL scores were similar between groups. There was a significant difference in the frequency of diarrhoea between IM group and the group using new generic formulations of IM (P = 0.012). General QoL score tended to be higher in patients with disease duration longer than 3 years (P = 0.052). GHQ, anxiety and depression scores correlated positively with symptom scales and negatively with functional subscales.CML patients using new generic formulations of IM reported a higher frequency of diarrhoea than patients using original IM and second-generation TKIs that could result in more drug discontinuation., (© 2015 John Wiley & Sons Ltd.)

Objectives: This study aims to evaluate the mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR) in gouty arthritis (GA) and rheumatoid arthritis (RA) patients, as well as their relationship with atherosclerotic cardiovascular mortality (ACVM)., Patients and Methods: The study included 122 GA patients (96 males, 26 females; mean age 64.6±13.4 years; range 34 to 82 years), 82 RA patients (40 males, 42 females; mean age 62.1±12.1 years; range 29 to 83 years), and 61 healthy controls (34 males, 27 females; mean age 65.3±4.8 years; range 33 to 80 years). Clinical and ACVM data were obtained from medical charts. Erythrocyte sedimentation rate, C-reactive protein, MPV, and NLR were recorded at the time of diagnosis and one month after therapy., Results: Mean platelet volume in GA (8.49±1.5) and RA (7.98±0.99) groups were significantly lower than in healthy controls (9.8±15) (p<0.001). NLR in healthy controls (1.9±0.74) was significantly lower than in GA (3.6±2.3) and RA (3.7±2.5) groups (p<0.001). After treatment, MPV did not change significantly in GA and RA groups (p values >0.05); however, NLR decreased in both groups (p<0.001). Nine GA and 12 RA patients died from ACVM during follow-up. GA patients with ACVM were older and had more frequent hypertension, higher MPV, and higher intercritical CRP level. In multivariate analysis, MPV was an independent poor prognostic factor for ACVM in GA patients., Conclusion: Gouty arthritis and RA patients had significantly lower MPV and significantly higher NLR than controls. MPV might be used as a potential biomarker for the development of ACVM in GA., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

We aimed to evaluate the relationship between some important genetic variations and expressions of these genes in our SLE population. We also determined their association with clinical parameters. Eighty-four SLE patients (79 F, 5 M) and 105 healthy controls (98 F, 7 M) were included in the study. rs13277113, rs2736340, rs7829816, rs6983130, rs2613310, and rs704853 polymorphisms, gene expressions of Src family kinases (Blk, Hck, Lck, and Lyn), and Syk kinases (Syk, ZAP70) were studied by real-time PCR. The heterozygous genotypic pattern (GA) for rs13277113 polymorphism was more frequent in patients with SLE when compared to that in controls (48.8 vs. 31.4%, p = 0.035). Other genotype variants were similar in SLE patients and controls. In the SLE group, the heterozygous genotype for rs13277113 was significantly less frequent in active SLE patients (58.8 vs. 26.7%, p = 0.01). SLE flares according to the SELENA-SLEDAI flare index were significantly more frequent in GA (rs13277113) (70 vs. 37%) and CT (rs2736340) genotypes (66.7 vs. 35.2%) than those in other genotypes (p values <0.01). The relative expression of Blk gene was significantly decreased in the SLE group as compared to that in controls (0.52 times, 95%CI 0.19-0.85). The gene expressions of Blk and ZAP70 were significantly lower in SLE patients who had flares according to the SELENA-SLEDAI flare index when compared to those in others (p values 0.01 and 0.017). We observed more frequent heterozygous GA genotypic pattern (rs13277113) in our SLE patients compared to that in controls; and it was associated with disease flares. Blk gene expression in SLE was lower, especially in relapsing patients.

Aim: There is significant autoantibody production in systemic lupus erythematosus (SLE) and scleroderma (SSc); microchimerism is also thought to play a role in pathogenesis. We determined the frequency of anti-HLA antibodies in SLE and SSc patients and evaluated associated clinical factors., Methods: We included 77 SLE patients, 46 SSc patients and 53 healthy controls into the study. Clinical data about the patients were obtained from hospital records. Anti-human leukocyte (anti-HLA) antigen antibody analysis of sera was performed by applying Lifecodes anti-HLA Class I and Class II Screening kits based on xMAP technology., Results: The frequencies of class I and II anti-HLA antibodies were significantly higher in SLE (27.3% and 41.6%) and SSc (26.1% and 41.3%) groups than in healthy controls (1.9% and 5.7%) (all P < 0.001). Frequencies of thrombocytopenia (P = 0.021), anti-ribonucleoprotein (P = 0.037) and anti-Ro (P = 0.027) were significantly higher in the class I antibody-positive SLE group; however, pericarditis was less frequent (P = 0.05). On the other hand, the class II antibody-positive SLE group had more frequent anti-ribosomal P antibody (P = 0.038), but less frequent active disease (P = 0.038). In the SSc group, class I antibody-positive patients had more frequent digital ulcers (P = 0.048) and anti-centromere antibodies (P = 0.01). There was no association of anti-HLA antibodies with pulmonary hypertension and interstitial fibrosis in SSc patients., Conclusions: Both class I and class II antibodies were found to be significantly increased in SLE and SSc. Rather than major organ involvement, anti-HLA antibodies were associated with the presence of other antibodies in both diseases., (© 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Background: In this study, we determined the frequency of migraine headache in iron-deficiency anemia (IDA) patients and whether it was related to anxiety, depression, and somatization., Methods: We included 127 consecutive IDA patients into the study. All patients were asked validated questions about headache and migraine face-to-face. They were administered validated questionnaires for anxiety-depression The Hospital Anxiety and Depression Scale and somatization. The quality of life (QoL) disturbance associated with headache was marked on a 0-10 VAS., Results: Of all IDA patients, 79.5 % defined headache at any time of their life. In addition, 36.2 % of all IDA patients defined the criteria for migraine. IDA patients with migraine were more frequently smokers and had significantly lower hemoglobin and mean corpuscular volume values (p values < 0.05). The IDA group with migraine had significantly higher mean anxiety score (p = 0.046) and headache-related QoL disturbance score (p = 0.021) than the IDA group without migraine. Migraine patients with aura had lower hemoglobin values (p = 0.02), higher depression scores (p = 0.005), and higher migraine-related QoL disturbance scores than others., Conclusions: IDA patients have a high frequency of migraine headache. The presence of anxiety and depression have great influence on the presence of migraine in IDA patients.

The most common genetic disorder in Philadelphia negative chronic myeloproliferative neoplasms is the JAK2-V617F mutation. In the present study, we aimed to determine risk factors for thrombosis in patients with essential thrombocytosis and polycythemia vera. We screened the medical records of 101 patients. Risk factors which may predict thrombosis were recorded. Venous thrombosis (VT) before diagnosis was significantly higher in JAK2 positive patients. VT after diagnosis was similar in JAK2 positive and negative groups, and was significantly higher in elderly patients. Treatment places importance on the JAK2 mutation under unmodifiable cardiovascular risk factors such as advanced age after diagnosis.

Epidemiological data about antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is very limited. Until now, there has been no study about the epidemiology of AAV in Turkey. In this study, we evaluated the frequency of AAV in the northeastern part of Turkey. The general clinical features of patients diagnosed with AAV at our center within the last 10 years (2004-2014) were retrospectively recorded down. The incidence rates and the prevalence per 1,000,000 population aged ≥16 years were calculated. In addition, we evaluated the clinical features and survival rates of AAV patients. There were 30 patients with granulomatous polyangiitis (GPA), 15 with microscopic polyangiitis (MPA), and 5 with eosinophilic polyangiitis (EGPA). The overall prevalence of AAV in our region was 69.3/1,000,000 in individuals ≥16 years. Males had a similar prevalence (73.2/1,000,000) with females (65.4/1,000,000). The mean annual incidence rate was 8.1/million for all AAV. The annual incidence of AAV in females was 6.9/million; in males, it was 9.2/million. The annual incidence for GPA was calculated as 4.8/1,000,000, the incidence for MPA was 2.4/1,000,000, and the incidence for CSS was 0.8/1,000,000. Ten-year survival of patients with AAV was 65.3 %. The only independent poor prognostic factor in Cox's multivariate analysis was advanced age at the time of diagnosis (OR 7.5, 95 % CI 10.6-526, p = 0.043). The frequency of all AAV in northwestern Turkey was similar to that in southern Europe; however, it was lower than the frequency in Northern Europe.

In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

Objective/background: Myelodysplastic syndromes (MDSs) are a group of monoclonal hematopoietic diseases consisting of a number of various entities. The presence of differences in chromosomal content of cells within the same individual is known as chromosomal mosaicism. The impact of mosaic pattern on the prognosis of MDS has been unclear. In this study, we aimed to determine the impact of mosaic pattern on the survival of patients with MDS., Methods: We retrospectively evaluated 119 patients diagnosed with MDS at the Trakya University Faculty of Medicine, Department of Hematology. Giemsa-Trypsin-Giemsa banding was used to evaluate chromosomal abnormality. The effect of chromosomal abnormality mosaicism on overall survival and transformation to acute leukemia was evaluated by Kaplan-Meier survival analysis., Results: The mean age at diagnosis was 66.3years, and the mean disease duration was 24.2months. Chromosomal abnormality was observed in 32.5% of patients. Patients with chromosomal abnormalities comprising at least 50% metaphases had significantly lower overall survival than patients with abnormality comprising up to 50% of all abnormal metaphases (p=.003). There were no differences in transformation to acute leukemia among patients with higher and lower chromosomal mosaicism (p=.056)., Conclusion: The most important outcome of this study was to demonstrate worse overall survival rates in MDS patients with higher abnormal chromosomal mosaicism than patients with lesser abnormal chromosomal mosaicism. Higher levels of abnormal chromosomal mosaicism did not predict transformation to acute leukemia. The cause of worse outcomes of patients with higher abnormal chromosomal mosaicism may be related to clonal mass., (Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.)

Systemic lupus erythematosus (SLE) is an autoimmune disease characterised by the production of autoantibodies and the involvement of multiple organ systems. Systemic sclerosis (SSc) is another autoimmune disease that causes fibrosis. We will aim to analyse the role of killer cell immunoglobulin-like receptor (KIR) genotypes and their existence with the respective HLA ligands in patients with SLE and SSc. Forty-five SLE, 25 SSc and 40 healthy controls were included. We examined the presence/absence of KIR2DL1, 2DL2, 2DL3, 2DL4, 2DL5A, 2DL5B, 2DS1, 2DS1, 2DS2, 2DS3, 2DS4, 2DS5, 3DL1, 3DL2, 3DL3, 3DS1, 2DP1, 3DP1 and their known HLA ligands. In the SLE group, the KIR2DL5, KIR2DL5B and KIR2DS3 genes were significantly more frequent, and KIR2DL3 gene was significantly less than in controls (p values <0.05). In SSc patients, the KIR2DS3 gene was more frequent than in controls (p = 0.032). The KIR2DL3 gene was detected more frequently in controls while KIR2DS3 gene was more frequent in the patient group when SLE and SSc patients were combined (p values < 0.05). The KIR2DS2/HLA-C and KIR2DS2/HLA-C combinations were significantly more in both SLE and SSc groups than in controls. The KIR2DL2 and KIR2DL5B genes were protective from neurologic involvement in SLE patients (p values <0.05). The variations of some KIR genes such as KIR2DL5, KIR2DL5B, KIR2DS3 and KIR2DL3 may have a role in the pathogenesis of SLE and SSc. Also, the presence of KIR2DL2 and KIR2DL5B may cause major organ involvement, like neurologic involvement, in SLE.

Background: Apelin/APJ system regulates angiogenesis and is overexpressed in some malignancies. Apelin can induce lymphangiogenesis and lymph node metastasis., Objective: We evaluated apelin levels in multiple myeloma (MM) and non-Hodgkin lymphoma (NHL); and analyzed the association between apelin levels and clinical findings., Methods: We included consecutive 29 MM, 31 NHL patients, and 19 healthy controls. Patients' demographic and clinical features, treatment modalities, and responses were recorded from hospital records. Plasma apelin was determined by enzyme-linked immunosorbent assay (ELISA)., Results: MM patients had significantly higher plasma apelin level than NHL and healthy control groups (p< 0.001). Apelin level in NHL group was similar to controls (p> 0.05). ROC curve analysis showed that the area under the curve value for apelin level in MM was 0.842 ng/ml (95%CI: 0.739-0.945, p< 0.001). Plasma apelin level ≥ 0.827 ng/ml had 76% sensitivity and 86% specificity for the diagnosis of MM. Multivariate Cox regression analysis showed that MM patients with high apelin level had better prognosis and patients with advanced stage of disease (ISS-3) had significantly poor prognosis when compared to others. In the MM group, apelin level correlated negatively with LDH (r = -0.39, p= 0.038)., Conclusions: In MM, plasma apelin level was significantly higher than in NHL and control groups. Apelin could be playing a role in MM pathogenesis; and apelin level could be used as a diagnostic and prognostic biomarker in MM.

Objectives: Adult-onset Still's disease (AOSD) is a rare disease that is classified among the multifactorial autoinflammatory disorders. It is characterised by fever, arthritis and, a typical salmon-coloured rash, and is accompanied by fever at nights. Currently, there is limited data on the prevalence of AOSD., Methods: Patients diagnosed with AOSD at the Department of Rheumatology of Trakya University Medical Faculty, between 2003 to 2014 were reviewed retrospectively. Patients' clinical features, laboratory measurements, demographics, treatments, follow-up durations, disease courses, outcomes and complications were evaluated., Results: Our study included 42 patients with AOSD of whom, 32 (76.2%) were females and 10 (23.8%) were males (female to male ratio: 3.2). Over the course of the study, the annual incidence of AOSD was 0.62/100,000; and the overall prevalence was 6.77/100,000. The most common findings were fever (97.6%), arthralgia (95.2%), arthritis (76.2%), rash (73.8%) and sore throat (40.5%)., Conclusions: In our hospital-based study on AOSD which is a disease with very limited epidemiological data, the frequency of AOSD was found to be significantly higher than in other series. Female gender was more common in our series; and polycyclic pattern was more common in patients with longer follow-ups.

Objectives: The pathogenesis of fibrosis in scleroderma (SSc) is unknown. TGF-β and platelet-derived growth factor are important in the development of fibrosis and tyrosine kinases are involved in these pathways. The possible antifibrotic effects of various kinase inhibitors in SSc have been studied before. Spleen tyro-sine kinase (Syk) is a protein tyrosine kinase which activates intracellular signal transduction pathways; and has been claimed to be involved in the pathogenesis of systemic autoimmune diseases. Inhibition of Syk suppresses IgE- and IgG-associated FcR signal activation in various cell types; and suppresses experimental arthritis and skin and kidney disease in lupus-prone mice. We investigated the ability of a small drug, the Syk inhibitor, fostamatinib, to protect mice from bleomycin-induced SSc., Methods: Four study groups of BALB/c mice were included into this study: control, bleomycin (administered subcutaneously to BALB/c mice for 21 days), bleomycin and fostamatinib (mice fed with chow containing a Syk inhibitor for 21 days), and fostamatinib alone groups. Skin and lung tissue specimens were obtained and evaluated histologically., Results: Treatment with fostamatinib significantly reduced skin thickness and fibrosis. Mice treated with fostamatinib also displayed less fibrosis and inflammation in the lung tissue. Following fostamatinib treatment, Syk, phospho-Syk, and TGF-β expression decreased in both skin and lung tissues., Conclusions: The Syk inhibitor fostamatinib prevented bleomycin-induced fibrosis and inflammation in the skin and in the lung. The anti-fibrotic effect of fostamatinib is linked to reduced Syk phosphorylation and TGF-β expression. The Syk pathway appears as a potential molecular target for therapeutic intervention in SSc.

Aims We determined plasma levels of dickkopf-1 (DKK-1) and osteopontin (OPN) which have roles in the Wnt pathway in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) patients and in healthy controls. We also tested whether DKK-1 and OPN levels could be of clinical or prognostic significance in CLL and NHL. Methods We included 36 CLL, 24 NHL patients, and 21 healthy controls. Patients' clinical and demographic features, treatment modalities, and response to treatment were recorded. DKK-1 and OPN levels in plasma obtained at initial diagnosis were determined with enzyme-linked immunosorbent assay. Results CLL patients had significantly lower DKK-1 levels than NHL and control groups (P levels, respectively, 0.048 and 0.017). OPN level was significantly higher in NHL group than in CLL and control groups (P values, 0.017 and <0.001). CLL patients with early and late Rai stages of disease had similar DKK-1 and OPN levels. After a median follow-up of 48 months, 13 CLL patients died. Univariate analysis showed that advanced Rai stages and older age were significantly poor prognostic factors. DKK-1 level in CLL patients who have died was significantly lower than those who were alive (P = 0.035). NHL patients with extranodal involvement had significantly higher OPN levels than those with no involvement (P = 0.04). Conclusions Our results demonstrated that the Wnt pathway inhibitor DKK-1 was decreased in CLL. OPN was increased in NHL and associated with extranodal involvement. In order to reveal the pathogenic and clinical roles of DKK-1 and OPN in CLL and NHL, larger studies need to be conducted.

Background/objectives: We evaluated the clinical characteristics of patients with haematological malignancies at our centre who were diagnosed with leukaemia cutis (LC). In addition, we describe the spectrum of other skin lesions, including, secondary skin malignancies and nonspecific benign skin lesions in haematological malignancy patients., Methods: We defined 58 skin lesions that developed in 54 inpatients hospitalised in the Department of Haematology, Trakya University Medical Faculty, Turkey. All skin lesions that developed in inpatients between 2006 and 2012 had been evaluated by a dermatologist. The patients' clinical features, skin biopsy results and therapies were obtained from hospital files. The diagnosis of LC was based on clinical features and histopathological examinations of the skin biopsy., Results: There were 11 patients with LC. Six (54.5%) had acute myeloblastic leukaemia. In nine patients (82%), LC was present at the initial presentation. Secondary skin malignancy was detected in 11 patients (five basal cell carcinoma, four Kaposi's sarcoma, one squamous cell carcinoma, one malignant melanoma); and malignancy was present in two patients (18%) at the initial presentation. Nonspecific benign skin lesions, the most frequent of which were drug eruptions, were determined in 32 of our patients. LC had a significantly higher likelihood of being present at initial presentation than other skin lesions (P < 0.01). The median survival in LC patients was quite short (4.5 months)., Conclusions: LC was usually diagnosed at the initial presentation of the patient or during the early course of the disease. Having LC was a poor prognostic factor., (© 2014 The Australasian College of Dermatologists.)

We evaluated the clinical features, treatment modalities, treatment responses, and prognosis of our patients with immune thrombocytopenia (ITP). Furthermore, we estimated the frequency of ITP in the Thrace region of Turkey. Two hundred sixteen patients diagnosed with ITP between 2000 and 2012 at our center were retrospectively evaluated. Patients' clinical features, treatments, and responses to treatment modalities were recorded. The mean annual incidence of ITP was 2.92/100,000 (95%CI: 1.57-4.27). The overall prevalence of ITP was 35.1/100,000 (95%CI: 30.3-39.8). The administration of first-line therapy resulted in complete remission (CR) in 76.5 % of patients and partial remission (PR) in 13.6 %. After 5 years, 33 % of patients who were responsive to first-line therapy were still in relapse-free remission. Of patients who were given second-line therapy, CR was obtained in 71.3 % and PR in 14.9 %. The duration of relapse-free remission was longer with splenectomy than with steroids (p < 0.001). Five years after splenectomy, 62 % of patients were in relapse-free remission; contrarily, this was lower with steroids (36 % at 5 years). The annual incidence and prevalence of ITP in northwestern Turkey was similar to data from western countries-at the lower limit for some countries. Effective treatment strategies seem to be steroids as first-line therapy and splenectomy in refractory cases.

Natural killer (NK) cell killer immunoglobulin-like receptors (KIRs) contribute to the pathogenesis of many diseases. We determined the association between polymorphisms of KIR and their ligands and susceptibility to non-Hodgkin lymphoma (NHL), clinical features and prognosis. We included 90 patients with NHL and 94 controls. In the NHL group, KIR2DS1, HLA-Bw4 (Thr80) and HLA-Bw4 (Thr80)+/Bw4 (Iso80)- ligands were significantly more frequent. Patients with early-stage NHL had more frequent KIR2DL5 and KIR2DL5B than patients with advanced-stage NHL. During a median follow-up of 27 months, 26 patients with NHL died. Poor prognostic factors in univariate analysis were KIR2DL5A, KIR2DS1 and KIR3DS1 genotypes. In multivariate Cox regression analysis, advanced age and early relapse were poor prognostic factors. KIR genes and ligands had no significant effect on survival. The activating KIR2DS1 gene might activate NK cells, contributing to the production of more lymphoma cells. In addition, KIR2DS1, KIR2DL5A and KIR3DS1 might also be associated with a poor prognosis in NHL.

Background and Objectives: Until now, very few studies evaluated the association between gastrointestinal and psychiatric symptoms in iron deficiency anemia (IDA). The study investigated the frequency of functional dyspepsia (FD) in IDA patients and determined its association with depression and somatization., Design and Settings: The study was conducted at the Hematology Department of Trakya University Medical Faculty, which is a tertiary referral center in northwestern Turkey. It was a case-control study., Materials and Methods: A total of 125 consecutive IDA patients and 57 healthy control subjects were included. Patients and controls were questioned about the severity of their gastrointestinal system (GIS)-related symptoms and the presence of constipation and associated symptoms using a visual analog scale. In addition, IDA patients were administered a validated depression scale (Beck Depression Inventory, BDI) and somatization symptoms checklist., Results: IDA patients had more frequent self-reported constipation compared with controls (56% vs 22.8%, P < .001). The mean scores of bloating, dyspepsia, and constipation-related quality of life (QoL) disturbance were significantly higher in the IDA group than in the control group (all P values.

Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.

Objective: In this study, we evaluated the relationship between ferritin levels and disease activation in rheumatoid arthritis (RA) patients., Material and Methods: We included 44 patients with RA, 20 patients with systemic lupus erythematosus (SLE), 25 patients with infection, 22 patients with malignancy, and 20 healthy control subjects. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), whole blood count, and serum iron parameters were determined in all cases. The joint findings in RA patients were recorded, and disease activity score (DAS) was calculated. In SLE patients, antinuclear antibody (ANA) and anti-dsDNA titers and C3 and C4 complement levels were determined. SLE disease activity index (SLEDAI) score was calculated., Results: Serum ferritin levels in the RA, SLE, and control groups were lower than those in the infection and malignancy groups (p<0.05). The ferritin levels in the RA group did not differ significantly from the SLE and control groups. In RA patients, serum ferritin level had a positive correlation with ESR, CRP, RF, platelet count, and DAS score and had a negative correlation with hematocrit (all p values <0.05). In SLE patients, on the other hand, serum ferritin had a positive correlation with ANA, anti-dsDNA, and SLEDAI (all p values <0.05). According to DAS, ferritin level in inactive RA patients was lower than that in active RA patients. When transferrin saturation was considered, iron deficiency anemia was a quite frequent finding in both active and inactive RA patients., Conclusion: Interestingly, we observed that ferritin level in RA patients was similar to the control group; however, it was a good parameter of disease activation. This is because a reduction in storage iron and resultant iron deficiency anemia are very common in RA patients.

Background: Gouty arthritis (GA) is a chronic inflammatory arthritis in which both clinical and subclinical atherosclerosis are more frequent. The dynamic equilibrium between coagulation and fibrinolysis is impaired in inflammatory diseases. We determined TFPI and TAFI antigen levels in GA patients and evaluated their association with subclinical atherosclerosis., Methods: We included 45 GA patients (41 males, 4 females; mean age: 51.6years) and 25 asymptomatic hyperuricemic (AHU) subjects (19 males, 6 females; mean age: 48.1years). Cardiovascular risk factors were determined. TAFI and TFPI levels were determined by ELISA. B-mode ultrasonography was used to detect subclinical atherosclerosis., Results: Cardiovascular risk factors were similar in both groups. The carotid IMT was significantly higher in GA group than in AHU group (0.74±0.23mm vs. 0.61±0.13mm, p=0.009). TFPI level was significantly higher in GA group than in AHU group (86.2±48.9ng/mL vs. 25.8±21.4ng/mL, p<0.001); TAFI antigen was significantly higher in AHU group (22.6±3.6ng/mL vs. 25.7±5.3ng/mL, p=0.006) than in GA patients. Atherosclerotic plaque formation was more frequent in GA group (p=0.041). When GA patients with and without plaques were compared, the first group had significantly higher mean age (p=0.01) and TFPI level (p=0.028). TFPI level correlated with carotid IMT (r=0.302; p=0.028). Logistic regression analysis showed that age (OR: 1.236, 95%CI: 1.059-1.443, p=0.007) and TFPI (OR: 1.031, 95%CI: 1.008-1.054, p=0.008) were independent risk factors for the presence of plaques., Conclusions: GA patients had more frequent subclinical atherosclerosis than subjects with AHU. Higher TFPI levels in GA patients -probably associated with enhanced endothelial damage- were related to subclinical atherosclerosis. Lower TAFI levels in GA pointed to impaired fibrinolysis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: Macrophage migration inhibitory factor (MIF) and vascular endothelial growth factor (VEGF), as crucial parameters of angiogenesis and inflammation, were evaluated to identify the role of cyclic citrullinated peptide antibodies (anti-CCP) during angiogenesis in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)., Material and Methods: A total of 145 patients with RA, 44 patients with PsA, and 73 healthy subjects were included in this study. The clinical features, total blood counts, and acute phase parameters of RA and PsA patients were recorded. Anti-CCP antibody, VEGF, and MIF levels were determined with enzyme-linked immunosorbent assay (ELISA)., Results: Anti-CCP positivity was significantly higher in the RA group (69%) than in both PsA (20.6%) and controls (8.2%) (p values<0.001). There was no difference between anti-CCP-positive and -negative RA patients regarding the extra-articular manifestations (p>0.05). VEGF and MIF levels were similar in anti-CCP-positive and -negative RA patients (all p values>0.05). The specificity of anti-CCP antibodies for RA was found to be 87.2%. No relationship was found between anti-CCP antibody positivity and clinical features, disease activity, functional disability as assessed by health assessment questionnaire scores, and extra-articular manifestations. There was no relationship between parameters of angiogenesis and anti-CCP antibody positivity. Both RF and anti-CCP antibodies were observed to be positive in most patients with RA., Conclusion: Either RF or anti-CCP antibody was positive in a considerable proportion of our RA patients. Therefore, anti-CCP antibodies are important in the diagnosis of RF-negative patients who present with clinical findings of RA.

Pancreatic involvement in acute lymphoblastic leukaemia (ALL) may go unrecognised. There are only a few paediatric cases; nevertheless, presentation with pancreatic involvement in an adult patient with ALL has been reported rarely. Our 52-year-old male patient came to us with abdominal pain, nausea and vomiting; he had pancreatic enlargement on CT. He was diagnosed with common B-cell ALL with pancreatic involvement. The patient obtained haematological remission and the pancreatic enlargement regressed after chemotherapy, but later he had central nervous system and liver relapses. He died 6 months after diagnosis because of progressive pneumonia and chemotherapy-resistant ALL with multiple extramedullary relapses., (2014 BMJ Publishing Group Ltd.)

There are reports on patients with systemic lupus erythematosus (SLE) with aspergillosis; however, aspergillosis-related pneumothorax has not been reported in SLE. We present a female patient with active SLE who was administered high-dose steroids, developed an opportunistic bacterial infection and had a cavitary pulmonary lesion. Sputum cultures yielded Aspergillus fumigatus. She was administered voriconazole. She developed dyspnoea and chest X-ray showed pneumothorax. She was placed with an underwater drainage chest tube; the pneumothorax and the pulmonary lesion regressed., (2014 BMJ Publishing Group Ltd.)

Objectives: We evaluated the frequency of clinical apparent amyloid deposition, clinical features and outcome in our rheumatoid arthritis (RA) patients., Methods: Medical records of 1415 RA patients were examined. During routine follow-up, RA patients with proteinuria on urinalysis, underwent rectal biopsy., Results: Eleven patients (0.78%) were diagnosed with clinical apparent amyloid deposition. While the mean annual incidence of AA amyloidosis between 2001 and 2005 was 0.2%, it was 0.13% between 2006 and 2011. At initial presentation, three RA-related AA amyloidosis patients had nephrotic-range proteinuria and renal insufficiency, four had only nephrotic-range proteinuria, three had non-nephrotic-range proteinuria, and one had non-nephrotic-range proteinuria and renal insufficiency. The mean age in RA patients with AA amyloidosis was 60.8 years and disease duration was 12 years. Ten of 11 cases had positive rheumatoid factor. Two RA patients with AA amyloidosis who had been diagnosed in the pre-anti-TNF era died. Of the rest nine patients with AA amyloidosis, eight were administered anti-TNF therapy and one was given rituximab. In four patients, anti-TNF therapy led to disappearance of clinical features, decrement in proteinuria and resulted in improvement of or at least stabilization of renal functions. One patient using anti-TNF therapy died because of tuberculosis. One patient discontinued anti-TNF therapy and developed end-stage renal disease. Two patients have been started to be given anti-TNF therapy recently. In one patient who was given rituximab, there was regression of proteinuria and improvement in renal functions., Conclusions: We diagnosed a 0.78% frequency of AA amyloidosis in RA. It seems that - other than the risks of infection, tuberculosis - anti-TNF drugs seem to be effective on RA disease activity and also have renoprotective effects in RA patients with AA amyloidosis.

Objective: here have been tremendous changes in treatment and follow-up of patients with chronic myeloid leukemia (CML) in the last decade. Especially, regular publication and updating of NCCN and ELN guidelines have provided enermous rationale and base for close monitorization of patients with CML. But, it is stil needed to have registry results retrospectively to evaluate daily CML practices., Materials and Methods: In this article, we have evaluated 1133 patients' results with CML in terms of demographical features, disease status, response, resistance and use of second-generation TKIs., Results: The response rate has been found relatively high in comparison with previously published articles, and we detected that there was a lack of appropriate and adequate molecular response assessment., Conclusion: We concluded that we need to improve registry systems and increase the availability of molecular response assessment to provide high-quality patient care., Conflict of Interest: None declared.

In this study, we aimed to evaluate the relation between angiogenesis indicators and T helper 17 cytokine group in patients with systemic sclerosis (SSc) which is a disease characterized by impaired angiogenesis and autoimmune response. In our study, patients with SSc are compared with patients with primary Raynaud's phenomenon (RP) and healthy controls. Forty SSc patients, 18 primary RP cases, and 20 healthy controls were included in our study. The demographic and clinical features of patients with SSc were recorded. The serum levels of vascular endothelial growth factor (VEGF), vascular endothelial (VE)-cadherin, interleukin (IL)-20, IL-22, and IL-23 were assessed. In the SSc group, IL-20 level was significantly lower than in both primary RP group and controls (p values <0.001). VE-cadherin level in SSc was significantly higher than in primary RP (p = 0.016). The IL-22 and IL-23 and VEGF levels of SSc, primary RP, and control groups were similar (p values >0.05). In SSc patients, IL-23 correlated negatively with VEGF (r = -0.36, p = 0.025) and positively with VE-cadherin (r = 0.55, p < 0.001). IL-20 levels in SSc patients correlated with disease duration (r = 0.32, p = 0.044). SSc patients with limited involvement had significantly higher VE-cadherin levels than SSc patients with diffuse involvement (p = 0.044). We observed that IL-20 which is an IL-10 group angiogenesis indicator was observed to be suppressed in SSc, suggesting abnormal angiogenesis.

We evaluated the roles of sociocultural status, distress and cognitive functions in rheumatoid arthritis (RA) patients who developed methotrexate (MTX)-related neutropenia. The data of 37 RA patients with MTX-related neutropenia who were being followed up at 3 centers were evaluated. The control group included 74 RA patients. The clinical features, biochemical tests and treatment modalities of the patients were obtained from hospital files. The mini-mental state examination (MMSE) test and the Hospital Anxiety and Depression Scale (HADS) were administered for all RA patients with neutropenia as well as the control group. The frequencies of male patients, illiterate patients, patients living alone, patients with serious visual impairment, those with low income, and patients with high creatinine were significantly higher among RA patients with MTX-related neutropenia than in controls (p values <0.05). The RA patients with MTX-related neutropenia had significantly lower MMSE scores, and significantly higher HADS-A and HADS-D scores than controls (p values <0.05). In addition, the proportion of patients with probable dementia was significantly higher in RA patients with MTX-related neutropenia than in controls (p < 0.001). Twenty-six of the 37 patients (70.3 %) developed neutropenia with daily dosing. Patients who used MTX daily were more likely to be living alone than those using weekly dosing (p = 0.011). Multivariate analysis showed that having probable dementia on the MMSE test (OR 52.6), low income level (OR 56.8) and age (OR 1.12) were independent risk factors for the development of MTX-related neutropenia. The presence of probable dementia on MMSE, low socioeconomical status and older age are associated with serious toxicity in RA patients using MTX. Measures should be taken to prevent wrong MTX dosing by the patients. Compliance and patient education is of major importance, in particular, in the patients presented in this study.

We evaluated the frequency of secondary amyloidosis, associated clinical features, and outcomes in ankylosing spondylitis (AS) patients diagnosed in the last decade. The medical records of AS patients diagnosed at single academic medical center were reviewed for clinical evidence of amyloidosis. During routine follow-up, routine urinalysis was performed at each visit; patients with significant proteinuria underwent rectal biopsy. We diagnosed 8 clinically apparent amyloidosis patients (1.1 %) in our cohort of 730 AS patients (508 males, 222 females). Four patients undergoing hemodialysis were diagnosed secondary amyloidosis. Three patients had nephrotic syndrome and renal dysfunction and one patient had non-nephrotic proteinuria. When AS patients with amyloidosis were compared to AS controls, it was observed that the amyloidosis group was older, had longer disease duration, higher initial BASDAI scores, and ESR values, and more frequent peripheral arthritis (p < 0.05). Logistic regression analysis revealed that the initial BASDAI level was an independent predictor for the development of secondary amyloidosis (OR:2.36). Six patients were administered anti-TNF therapy. The clinical findings resolved in these. In 2 patients with nephrotic syndrome and renal dysfunction, in addition to clinical improvement, there was a decrement in proteinuria; renal function improved or remained stable. Anti-TNF therapy is safe and effective in patients with renal failure, and at an earlier stage, appears effective in improving renal function. The development of proteinuria in AS patients should occasion a search for underlying amyloidosis.

We evaluated the incidence of subclinical atherosclerosis and associated factors in our gouty arthritis patients. We included 55 gouty arthritis patients diagnosed at our center within the last 4 years. The control group included 41 patients with rheumatoid arthritis (RA) and 34 patients with asymptomatic hyperuricemia (AHU). Atherosclerotic risk factors were determined in all subjects. Carotid intima-media thickness (IMT) and the presence of plaques were evaluated by B-mode ultrasonography. The carotid IMT in gouty arthritis patients (0.730 ± 0.19) was significantly higher than in AHU subjects (0.616 ± 0.12) (P = 0.004) and tended to be higher than the RA group (0.669 ± 0.17) (P = 0.1). Atheromatous plaques were significantly more frequent in gouty arthritis patients (16 cases, 29.1%) than in RA patients (5 cases, 12.2%) and AHU subjects (3 cases, 8.8%) (P values, 0.05 and 0.023). Gout patients with plaques were older (P = 0.006) and tended to have tophi more frequently (P = 0.06). Logistic regression analysis showed that age (OR: 1.3, 95% CI: 1.02-1.54) and the presence of tophi (OR: 12.5, 95% CI: 1.2-140) were independent risk factors for the presence of plaques. Gouty arthritis bears a higher risk of atherosclerosis than both RA and AHU.

Recently, it has been reported that ankylosing spondylitis (AS) was characterised by endothelial dysfunction and the development of atherosclerotic complications. In this study, we evaluated platelet and endothelial activation parameters in AS patients. Fiftynine AS patients and 22 healthy controls were included. The clinical features and acute phase parameters were evaluated. In all patients and healthy controls, platelet-monocyte complexes (PMC), platelet-neutrophil complexes, basal and ADP-stimulated P-selectin (CD62P) expression were determined by flow cytometry; soluble E-selectin (sE-selectin) and soluble CD40L (sCD40L) were determined by ELISA. AS patients were divided into two groups as active and inactive by using BASDAI. In 15 AS patients, the evaluated parameters were assessed before and after 12 weeks of anti-TNF therapy. PMC and sCD40L levels in AS patients were significantly higher than in the control group (P values 0.013 and 0.016). The evaluated variables were similar in active and inactive AS groups (P > 0.05). There were no significant changes in platelet and endothelial activation parameters in AS patients after anti-TNF therapy (P > 0.05). Platelet activation which is reflected by high levels of PMC and sCD40L might be responsible for the increased frequency of atherosclerosis in AS. The platelet activation in our AS patients was not associated with disease activity and did not improve after anti-TNF therapy.

Background: Acute cerebral ischemia is caused by different pathophysiological mechanisms. The role of platelets and other blood cells can be different among the stroke subtypes., Methods: Seventy-two patients with acute ischemic cerebrovascular disease, including 31 patients with large vessel disease, 21 patients with cardioembolic disease, and 20 patients with small vessel disease, were evaluated. P-selectin (CD62P) expression and platelet leukocyte aggregates were measured with flow cytometry at the acute phase after the ischemic event. Markers were also measured in 37 control subjects. In all subjects, the serum high-sensitivity C-reactive protein (CRP) was also measured., Results: The platelet-monocyte aggregates (PMA) and platelet-granulocyte aggregates (PGA) in the large vessel disease group were higher than in control group (P=0.002, and P<0.0001, respectively). The PMA and PGA in the small vessel disease group were also higher than in the control group (P=0.004 and P<0.0001, respectively). In contrast, in the cardioembolic disease group, the PMA and PGA were not significantly different from the control group. CD62P expression was higher in all of the patient groups relative to the control group (P<0.05 for all comparisons). Serum CRP levels were also higher in all of the patient groups than in the control group (P<0.0001 for all comparisons)., Conclusions: In contrast to large vessel and small vessel disease, it seems that platelet-leukocyte association does not play a crucial role in the pathogenesis of cardioembolic stroke., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We determined platelet-leucocyte complexes, which play roles in the thrombosis-inflammation relationship, in Behçet's disease patients with and without major vascular involvement (MVI) and in healthy controls. We included 36 Behçet's disease patients (22 male, 14 female, mean age: 34.4 +/- 8.3 years) and 20 healthy individuals (14 male, six female, mean age: 31.8 +/- 4.4 years). Whole blood count, CRP and ESR were determined in both groups. Clinical data about the patients were obtained from medical charts. Individuals with hypertension, diabetes, coronary artery disease, and smokers were excluded. Behçet's disease patients with MVI were taken as a separate group (8 male, 5 female, mean age: 37 +/- 8 years). MVI was defined as the presence of pulmonary arterial aneurysm, deep venous thrombosis, vena cava inferior or superior thrombosis, or venous sinus thrombosis. Flow cytometry was used to determine platelet-monocyte complexes (PMC), platelet-neutrophil complexes (PNC), basal and adenosine diphosphate (ADP)-stimulated platelet CD62P expression. Behçet's disease patients with MVI had significantly higher PNC than Behçet's disease patients without MVI and healthy controls (P values = 0.01). PMC levels in Behçet's disease patients with MVI were significantly higher than in healthy controls (P = 0.01). The groups were similar in basal and ADP-stimulated platelet CD62P expression (P values >0.05). Basal and ADP-stimulated CD62P expression, PMC and PNC were not significantly different between active Behçet's disease versus inactive Behçet's disease patients. The evaluated parameters were similar in Behçet's disease patients with and without uveitis, and pathergy-positive and pathergy-negative groups. Our results might suggest that the formation of PMC and PNC might play a role in thrombosis and MVI of Behçet's disease.