CXCL12 rs18011157 polymorphism in patients with non-Hodgkin's lymphoma: Is it associated with poor outcome?

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.

Association between the neutrophil-to-lymphocyte ratio, a new marker of systemic inflammation, and restless legs syndrome.

INTRODUCTION: Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is characterised by abnormal sensations in the legs as well as dysaesthesia. Although the aetiology of RLS has not yet been determined, it may be associated with systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a new and simple marker indicating systemic inflammation. The present study aimed to investigate the relationship between systemic inflammation and RLS through the use of the NLR. METHODS: A total of 75 newly diagnosed patients with RLS and 56 healthy control subjects were included in the study. Baseline NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The NLRs of the two groups were compared. RESULTS: There were no significant differences in gender and age between the two groups. The NLR was 1.96 ± 0.66 in the patient group and 1.67 ± 0.68 in the control group (p = 0.005). Receiver operating characteristic analysis was performed to determine the cut-off value of NLR to predict RLS. The NLR was predictive at 1.58 with a 64% sensitivity and 50% specificity (95% confidence interval 0.55-0.74, area under curve 0.648 ± 0.05). The NLR was found to be statistically higher in patients with RLS and may be used to predict RLS. CONCLUSION: The aetiology of RLS remains undetermined. The present study showed that systemic inflammation may play a role in RLS. However, RLS could also be associated with systemic inflammatory diseases. This relationship is supported by high NLR values, which are related to chronic systemic inflammation.

Relationship between primary restless legs syndrome and migraine with aura.

In this study, the prevalence and characteristics of definite migraine in primary restless legs syndrome (pRLS) patients and matched control patients (CPs) were investigated. We evaluated 63 consecutive adult pRLS patients and 141 age- and sex-matched controls in this case-control study. The diagnosis of migraine and its subtypes were defined based on The International Classification of Headache Disorders-II. Only those with "definite" migraine were included in the study. The mean age of 63 adult pRLS patients (15 men and 48 women) who participated in the study was 49.4 years. A total of 27 patients (42.9%) had definite migraine. Of these migraineurs, seven (11.1%) were without aura and 20 (31.8%) were with aura. The mean age of the 141 matched CPs was 48.7 years. A total of 32 CPs (22.7%) experienced migraine. Among these 32 migraineurs, 28 (19.9%) were without aura and four (2.8%) were with aura. Migraine and migraine with aura were significantly more common in pRLS patients than in CPs. pRLS patients with migraine were more anxious and experienced a shorter duration of RLS symptoms than pRLS patients without migraine. Migraineurs in the pRLS group tended to have high scores for severity of migraine headache by Visual Analog Scale score and high levels of disability by Migraine Disability Assessment grading than those in the control group. pRLS patients showed a positive association with definite migraine headaches. In contrast to results highlighted in recent studies, we found a strong link between migraine with aura and pRLS.

Is JAK2V617F Mutation the Only Factor for Thrombosis in Philadelphia-Negative Chronic Myeloproliferative Neoplasms?

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.

Usefulness of the platelet-to-lymphocyte ratio in predicting the severity of carotid artery stenosis in patients undergoing carotid angiography.

Carotid artery stenosis (CAS) is primarily caused by atherosclerotic plaque. Progressive inflammation may contribute to the rupture of an atherosclerotic plaque. The platelet-to-lymphocyte ratio (PLR) is a new and simple marker that indicates inflammation. In this study, we aimed to investigate the use of the PLR to determine the severity of CAS. One hundred forty patients were chosen from among patients who underwent carotid angiography in our institution. Symptomatic patients with stenosis >50% in the carotid arteries and asymptomatic patients with stenosis >80% were diagnosed via carotid angiography as having critical stenosis. Patients were classified into two groups. Group 1 included patients who had critical CAS, whereas Group 2 included patients with noncritical CAS, as determined by carotid angiography. Correlations between the PLR and the severity of CAS were analyzed. There were no significant differences in sex and age between the two groups. The PLR was 162.5 ± 84.7 in the noncritical CAS group patients and 94.9 ± 60.3 in the critical CAS group patients (p < 0.0001). The PLR value of 117.1 had 89% sensitivity and 68% specificity for CAS [95% confidence interval, 0.043-0.159; area under the curve, 0.101 ± 0.03)]. In this study, we have shown that PLR values may be associated with critical stenosis in at least one of the carotid arteries. Furthermore, PLR values may be used to predict critical stenosis in the carotid arteries.

Could the mosaic pattern of chromosomal abnormality predict overall survival of patients with myelodysplastic syndrome?

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.

Is iron-deficiency anemia associated with migraine? Is there a role for anxiety and depression?

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.

Gastrointestinal symptoms are closely associated with depression in iron deficiency anemia: a comparative study.

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.

Assessment of cytokine levels and hs-CRP in bipolar I disorder before and after treatment.

We aimed to assess the relationship between cytokine levels and the severity of the manic period in medication free patients. 30 Medication free patients and 28 healthy subjects (HS) were recruited. Plasma levels of pro-inflammatory, anti-inflammatory, inflammatory cytokines, and hs-CRP levels were investigated upon hospital admission, after six weeks follow up in bipolar disease manic episode and the results were compared to HS. The severity of the manic episodes was assessed according to the Young mania rating scale. TNF-α, INF-γ, IL-6 and hs-CRP levels were significantly higher in patients with manic episode of bipolar I disorder before treatment than HS. After treatment the levels of TNF-α, INF-γ, IL-6 and hs-CRP were observed to be significantly decreased. There was no difference between the levels of anti-inflammatory cytokines in patients before or after treatment of bipolar disorder and HS. hs-CRP was observed to be the only parameter correlated with clinical response. The most significant outcome of this study is the correlation between clinical outcome and hs-CRP levels in treatment naive manic episode bipolar type I patients. hs-CRP is the most consistent indicator according to pro-inflammatory, inflammatory and anti-inflammatory cytokines, in predicting treatment outcomes.

Natural killer cell killer immunoglobulin-like gene receptor polymorphisms in non-Hodgkin lymphoma: possible association with clinical course.

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.

Decreased dickkopf-1 levels in chronic lymphocytic leukemia and increased osteopontin levels in non-Hodgkin's lymphoma at initial diagnosis: Could they be playing roles in pathogenesis?

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.

Immune thrombocytopenia: epidemiological and clinical features of 216 patients in northwestern Turkey.

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.

A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye.

Multiple myeloma (MM), the second most common hematological malignancy, is caused by the accumulation of monoclonal plasma cells in bone marrow. It accounts for 10-15% of deaths from hematological malignancies and approximately 2% of deaths from cancer. The median age at presentation is 70 years old. The diagnosis is incidental in 30% of cases. MM is often discovered through routine blood screening with a large gap between the total protein and the albumin levels. Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye). Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR) to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma.

PECAM-1 gene polymorphisms and soluble PECAM-1 level in rheumatoid arthritis and systemic lupus erythematosus patients: any link with clinical atherosclerotic events?

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.

Tissue factor pathway inhibitor and thrombin-activatable carboxypeptidase B for prediction of early atherosclerosis in gouty arthritis.

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.

Brucellosis triggering hemolytic anemia in glucose-6-phosphate dehydrogenase deficiency.

OBJECTIVES: To present a case of acute brucellosis triggering acute hemolytic anemia in a subject with glucose-6-phosphate dehydrogenase (G6PD) deficiency. CLINICAL PRESENTATION AND INTERVENTION: A 17-year-old male patient presented with fever, malaise and jaundice. His blood and bone marrow cultures yielded Brucella species. In addition, he was found to have acute hemolytic anemia due to previously undiagnosed G6PD deficiency. He was started on folic acid supplementation and given a combination of doxycycline and rifampicin for 6 weeks. His response to antibiotic therapy was optimal; the hemolytic anemia resolved. There were no further episodes of hemolysis. CONCLUSION: This case showed that the differential diagnosis of acute hemolytic anemia in subjects with G6PD deficiency should include brucellosis, especially in regions where the infection is endemic.

Systemic antineutrophil cytoplasmic antibody vasculitis in a patient with chronic lymphocytic leukemia: quite a rare diagnosis.

There might be rheumatic manifestations of malignant diseases, especially those of the hematological type. Until now, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in chronic lymphocytic leukemia (CLL) has been reported on only very few occasions. Here, we present our patient with Rai stage II CLL who came to us with constitutional symptoms. She turned out to have hematuria with dysmorphic erythrocytes and developed hemoptysis. She had pulmonary-renal syndrome and was diagnosed with p-ANCA positive microscopic polyangiitis. She is currently using prednisolone and cyclophosphamide and undergoing regular hemodialysis. Constitutional symptoms in patients with hematological malignancies should make the physicians consider systemic vasculitis after exclusion of disease-related complications.