The Effect of FcγRIIIA Gene Polymorphism on the Treatment of Diffuse Large B-cell Non-Hodgkin Lymphoma: A Multicenter Prospective Observational Study.

OBJECTIVE: The curative treatment approach for diffuse large B-cell lymphoma (DLBCL) is controversial even in the rituximab (R) era. The aim of this study was to examine the FcγRIIIA gene polymorphism distribution of DLBCL patients who had been treated with R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Furthermore, we investigated the impact of FcγRIIIA gene polymorphism on the overall response rate (ORR) and overall survival (OS). MATERIALS AND METHODS: Patients from 3 centers in the Aegean region of Turkey who had newly diagnosed CD20-positive DLBCL were enrolled in the study. The single nucleotide polymorphisms of the FcγRIIIA gene were analyzed by real time-PCR. The response to treatment was determined in the middle and at the end of the protocol. During 2 years of follow-up, the patients were clinically and radiologically evaluated for disease status every 3 months. RESULTS: Thirty-six patients were included in the study and the distributions of F/F, V/F, and V/V types of alleles of FcγRIIIA were 25%, 50%, and 25%, respectively. Twenty-seven patients were considered as evaluable according to ORR and OS. The patients' ORR was 87.5%, 100%, and 50% in the F/F, V/F, and V/V allele groups, respectively. We did not establish any statistically significant differences among the 3 alleles groups in respect to ORR (p=0.93). The OS within 2 years in the F/F, V/F, and V/V allele groups was 62.5%, 100%, and 100%, respectively. The OS in the F/F allele group was found to be lower than in the other 2 allele groups (p=0.01). CONCLUSION: The distribution of gene polymorphisms in our study group was similar to those of previous studies. While ORR was similar between the groups, our results highlight a lower OS in F/F patients compared to other allele groups of FcγRIIIA.

IPSET-Thrombosis Better Identifies Thrombosis-Free Survival: A Turkish Cohort.

INTRODUCTION: Essential thrombocythemia (ET) is the most common of the myeloproliferative neoplasms. For better predicting the occurrence of thrombotic events, an International Prognostic Score of Thrombosis for ET (IPSET-Thrombosis) was recently developed. We aimed to investigate the validity of IPSET-Thrombosis in a Turkish patient cohort and to compare the efficacy of IPSET-Thrombosis and conventional risk scoring systems in predicting thrombosis-free survival. PATIENTS AND METHODS: We retrospectively evaluated the clinical characteristics and risk factors for thrombosis in 112 Turkish patients. Median thrombosis-free survival and Harrell C concordance indexes were calculated for both conventional and IPSET-Thrombosis. RESULTS: Median age of 112 patients included in the study was 61 (range, 27-90) years at the time of diagnosis. When patients were stratified according to the conventional risk stratification system, 43.8% of patients were in the low-risk group and 56.2% in the high-risk group. A total of 22.4% of low-risk and 42.9% of high-risk patients had at least one thromboembolic event. When patients were stratified according to the IPSET-Thrombosis, 33% were in the low-risk group, 26.8% in the intermediate-risk group, and 40.2% in the high-risk group. Considering IPSET-Thrombosis risk groups, 5.4% of low-risk, 26.7% of intermediate-risk, and 66.2% of high-risk patients had at least one thromboembolic event. Regarding IPSET-Thrombosis risk groups, 10-year thrombosis-free survival was 86.8% for low-risk, 39.4% for intermediate-risk, and 32.9% for high-risk groups (P < .001). Harrell C concordance indexes of conventional and IPSET-Thrombosis were 0.60 and 0.77, respectively. CONCLUSION: By validating the reproducibility of IPSET-Thrombosis in Turkish ET patients, we found that IPSET-Thrombosis identifies thrombosis-free survival better than the conventional risk stratification system.

Hyperglycemia is associated with lower levels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor in wound fluid.

AIMS: Wounds in patients with hyperglycemia show impaired healing. Plasminogen activation is crucial in several overlapping phases of wound healing process. In this study, we aimed i) to compare acute wound fluid in patients with hyperglycemia and normoglycemia, ii) to focus on the elements of plasminogen activation in the wound fluid, and iii) to determine if the acute wound fluid characteristics are associated with surgical site infections. METHODS: In a cohort of 54 patients, a closed suction drain was placed in the wound above the anterior abdominal wall fascia under the skin in order to collect postoperative acute wound fluid samples for 3 following days after colorectal surgery. Patients were classified as normoglycemic (n=25) or hyperglycemic (n=29; 17 with type 2 diabetes and 12 with stress induced hyperglycemia). Surgical site infection was defined according to the Centers for Disease Control criteria. The levels of urokinase-type plasminogen activator (uPA), urokinase-type plasminogen activator receptor (uPAr), plasminogen activator inhibitor-1 (PAI-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and fibroblast growth factor-1 (FGF-1) were measured in the wound fluid. RESULTS: Compared to normoglycemic subjects, patients with hyperglycemia had significantly lower levels of uPA and uPAr in the wound fluid despite similar or even higher circulating levels. There was no significant difference in IL-1ß, TNF-α, PAI-1 and FGF-1 levels. In the whole study population, the wound fluid levels of uPA and uPAr were negatively correlated with circulating glucose levels. No difference was detected in the wound fluid characteristics of patients with and without surgical site infection. CONCLUSION: Patients with hyperglycemia exhibit decreased levels of uPA and uPAr in the wound fluid, suggesting a local failure in plasminogen activation at the wound site.

Circulating apelin levels are associated with cardiometabolic risk factors in women with previous gestational diabetes.

PURPOSE: Women with previous gestational diabetes mellitus (pGDM) are at high risk for type 2 diabetes and cardiovascular disorders. In this study, we aimed to compare plasma apelin levels between women with and without pGDM, and to investigate the possible association of apelin with cardiometabolic risk factors. METHODS: Among 252 consecutive Caucasian women with GDM being included in a prospective postpartum follow-up protocol, 141 women eligible for the study protocol were enrolled. Control group consisted of 49 age- and body mass index-matched healthy women without pGDM. Circulating apelin, IL-6 and plasminogen activator inhibitor levels, and carotid intima media thickness (IMT) were measured. To evaluate carbohydrate intolerance, 75-g oral glucose tolerance test was performed. Fasting insulin and lipids were measured, and homeostasis model assessment index was calculated. RESULTS: Plasma apelin levels were reduced in women with pGDM (p < 0.001). In multiple regression analysis, apelin was negatively associated with fasting (r (2) 0.090, ß -0.273, p = 0.001) and post-load glucose (r (2) 0.061, ß -0.187, p = 0.022), serum IL-6 (r (2) 0.082, ß -0.234, p = 0.002), and carotid IMT (r (2) 0.057, ß -0.168, p = 0.033). CONCLUSIONS: Our results suggested that suppressed apelin levels were associated with increased cardiovascular risk in women with pGDM.

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Non-alcoholic steatohepatitis (NASH) lacks effective medical treatment. Since tumor necrosis factor alpha (TNF-α) plays an important role in NASH pathogenesis, we aimed to investigate drugs affecting TNF-α as possible treatment options during the development of NASH. MATERIALS AND METHODS: A total of 35 rats were divided into five groups and evaluated over a 6 week period. One group received a normal diet alone or in combination with the administration of infliximab, adalimumab or pentoxifylline. RESULTS: NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received anti-TNF agents. No statistically significant differences were observed between the three agents in terms of the histological NASH score. CONCLUSION: Our study showed that the anti-TNF agents infliximab, adalimumab, and pentoxifylline effectively suppress TNF-α. Although these drugs did not prevent the development of NASH, they were able to slightly reverse the NASH histopathology score and positively affect liver function tests.

Insulin need in gestational diabetes is associated with a worse cardiovascular risk profile after pregnancy.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) treated with insulin are more likely to develop type 2 diabetes after pregnancy compared to mild GDM cases treated with medical nutrition treatment (MNT) alone. We aimed to compare levels of subclinical atherosclerosis markers in women with previous GDM treated with insulin and MNT alone. METHODS: Eighty-one women with previous GDM (45 treated with insulin, 36 treated with MNT) and 35 age-matched lean controls were included. Fasting glucose, insulin and lipids, circulating fibrinogen, CRP, PAI-1 and IL-6 levels were assayed. Carotid intima media thickness (IMT) was measured. RESULTS: Women with previous GDM treated with insulin in pregnancy had significantly higher fasting glucose, plasma PAI-1 levels and carotid IMT compared to women treated with MNT alone. In multiple regression analysis, insulin need in pregnancy was associated with increased carotid IMT and plasma PAI-1 levels (corrected for age, BMI, postpartum duration, fasting glucose and lipids; model r(2)=0.132; beta=0.297, p=0.014 for carotid IMT; model r(2)=0.198; beta=0.345, p=0.003 for PAI-1). CONCLUSION: Women with previous GDM treated with insulin in pregnancy had a worse cardiovascular risk profile compared to mild GDM patients. An intensive preventive approach for cardiovascular disorders is particularly essential for this subgroup of women.

Plasma thrombin-activatable fibrinolysis inhibitor levels are not associated with glucose intolerance and subclinical atherosclerosis in women with previous gestational diabetes.

We aimed to determine plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in women with previous gestational diabetes mellitus (GDM) and to evaluate the possible association of plasma TAFI with glucose intolerance and markers of subclinical atherosclerosis. This cross-sectional study was performed in 111 women with previous GDM and 60 controls. Glucose intolerance was evaluated. Homeostasis model assessment score was calculated. Circulating lipids, interleukin-6, matrix metalloproteinase-1, fibrinogen, plasminogen activator inhibitor-1, and TAFI antigen levels were assayed. Carotid intima media thickness (IMT) was measured. Women with previous GDM had increased levels of atherosclerosis markers and carotid IMT. On the other hand, plasma TAFI antigen levels were similar (P = .395). Thrombin-activatable fibrinolysis inhibitor was not associated with the indices of insulin resistance, glucose intolerance, markers of atherosclerosis, and carotid IMT. Our data demonstrated that plasma TAFI was not altered in women with previous GDM. TAFI was not associated with glucose intolerance and subclinical atherosclerosis.

Role of transforming growth factor-beta 1 gene polymorphisms in childhood idiopathic thrombocytopenic purpura.

PURPOSE: To investigate whether transforming growth factor-beta 1 (TGF-beta 1) gene polymorphisms have a role in the development, clinical progress, and treatment response in children with idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Thirty-five children with acute ITP, 40 children with chronic ITP, and 97 healthy children were enrolled. After genomic DNA was extracted, TGF-beta 1 gene 509 (C-->T), codon 25 (Arg-->Pro), and codon 10 (Leu-->Pro) polymorphisms were studied using a coupled polymerase chain reaction-restriction enzyme digestion method. RESULTS: The genotype and allele frequencies of TGF-beta 1 polymorphisms between acute ITP, chronic ITP, and control group did not differ significantly. No significant association was found between TGF-beta 1 polymorphisms and therapy response. CONCLUSIONS: These results demonstrate that the frequency of TGF-beta1 gene 509 (C-->T), codon 25 (Arg-->Pro), and codon 10 (Leu-->Pro) polymorphisms and alleles do not play a role as a genetic risk factor in the development and clinical progress of ITP. Different results may be obtained with further studies involving larger patient populations and other TGF-beta 1 gene polymorphisms.