Rare diagnosis of an Epstein-Barr virus-positive extracavitary/solid variant of primary effusion lymphoma by duodenal endoscopic biopsy in a human immunodeficiency virus-seronegative and immunocompetent patient: A case report.

Primary effusion lymphoma and its tissue-based subtype extracavitary/solid variant was first described in human immunodeficiency virus (HIV)-seropositive patients. We report the case of a 50-year-old HIV-seronegative male patient who presented with icterus and cholestasis. Computed tomography revealed a 80 × 56 mm abdominal mass. Fine-needle aspiration biopsy was performed from the celiac lymph nodes and pancreatic head, under endoscopic ultrasonography guidance. A duodenal endoscopic biopsy was taken from the infiltration area, and a core biopsy was performed for the portal hilar mass. All biopsies showed similar cytohistopathological features. LCA-positive lymphoid neoplasia had a plasmacytoid/anaplastic morphology and null cell phenotype. HHV-8 and Epstein-Barr virus-encoded small RNAs (EBER) were diffuse positive. The patient, who did not have an effusion, was diagnosed with an extracavitary/solid variant of primary effusion lymphoma. Virus-associated lymphoproliferative disorders should be considered in the differential diagnosis of patients without a history of immunosuppression or HIV infection.

The role of IgG4-positive plasma cell population in classic Hodgkin lymphoma.

The effect of IgG4, which constitutes the least of the IgG subclasses, on the pathogenesis and prognosis of lymphoma or solid tumors is one of the research topics of interest in recent years. The role of IgG4, which has been reported to suppress antitumor immunity, in classic Hodgkin's lymphoma (cHL), which is recognized by its pathognomonic microenvironment, is not yet clearly known. The aim of this study was to determine IgG4-positive plasma cell density in the cHL microenvironment and to compare it with histopathological and clinical parameters. In addition, the role of the increase in IgG4-positive cells in the development of relapse after treatment was also investigated. A retrospective cross-sectional study. Ninety-four patients with the initial diagnosis of cHL who had no comorbidity or no treatment history and forty-one reactive lymph nodes with follicular hyperplasia findings were included in the study. Three hot-spot areas were identified with reference to the IgG4 sections. Mean IgG4-positive plasmacyte counts and IgG4/IgG ratios were determined and compared with histopathological characteristics. The mean IgG4 + plasma cell count was 33.57 in cHL cases and 47.04 in the control group (p = 0.233). IgG4/IgG ratio was significantly higher in cHL compared with the control group (0.27 vs. 0.21, p = 0.021). The IgG4/IgG ratio was found to be higher in younger patients with classic Hodgkin lymphoma, with a low correlation (p = 0.028, r = - 0.226). There was no relationship with gender, lymph node location, histological subtype, EBV positivity and bone marrow infiltration. It was observed that IgG4/IgG ratio was higher in early-stage patients (p = 0.022). No significant IgG4 + cell increase was detected in the initial diagnosis and relapse slides of six patients who developed relapse after standard treatment, resulting in a cure. Novel therapeutic modalities targeting microenvironmental components have been reported to show dramatic effects, particularly in relapsed or refractory patients. Detailed characterization of the cHL inflammatory milieu will be useful for the identification of alternative targets. IgG4 subclass antibodies, which have been described to have anti-inflammatory effects, may have prognostic significance in a proportion of cHL patients.

Evaluation of trace elements in essential thrombocytosis and reactive thrombocytosis.

BACKGROUND: Trace elements (TE) are vital for cellular mechanisms at biological, chemical and molecular levels. The effects of TE in diagnosis, progression and treatment of essential thrombocytosis (ET), which is one of the chronic myeloproliferative neoplasms is a rare clonal stem cell disease characterized by increased thrombocyte numbers with impaired function, have not been elucidated in detail yet. The aim of the present study was to investigate the effects of TE alterations in an ET model and the efficacy of TE in ET treatment protocol by means of a vast number of TE. METHODS: Study groups were categorized as patients with ET diagnosis (ET group, n:30), patients with reactive thrombocytosis secondary to iron deficiency anemia (IDA-RT) (IDA-RT group, n:30) and healthy controls (HC group, n:30). Serum levels of copper (Cu), iron (Fe), cobalt (Co), chromium (Cr), aluminum (Al), silicon (Si), nickel (Ni), zinc (Zn), selenium (Se), manganese (Mn), boron (B) and magnesium (Mg) were analyzed utilizing inductively coupled plasma-optical emission spectrophotometer instrument (ICP-OES). Statistical analysis was evaluated using SPSS 23.0. RESULTS: ET group had statistically higher serum levels of Co and Mg (p < 0.05), Ni and Mn (p < 0.001), and lower Si (p < 0.05) than IDA-RT group. ET group had statistically higher serum levels of Co and Mn (p < 0.05), and Ni (p < 0.001), and lower Al, Si and Se (p < 0.001) than HC group. Serum levels of Fe, Al and Se (p < 0.001), and Mg (p < 0.01), and Zn (p < 0.05) in IDA-RT group were significantly lower than HC group. CONCLUSION: This novel study pointed out that alterations of many serum TE by means of both increment or decrement might have close relationship with mechanisms and complications of ET onset and follow-up. We consider that further research of TE would elucidate ethiopathogenesis and prognosis of ET. Thus, analysis of serum trace elements in essential thrombocytosis patients may be an important protocol by means of diagnosis, treatment and follow-up intervals.

Real-Life Experience Regarding Clinical Characteristics and Treatment Outcome in Non-Cutaneous Peripheral T-Cell Lymphomas: A Multicenter Study of the Turkish Hematology Research and Education Group (ThREG)

Objective: Peripheral T-cell lymphomas (PTCLs) are an uncommon and quite heterogeneous group of disorders, representing only 10%-15% of all non-Hodgkin lymphomas. Although both molecular and clinical studies have increased in recent years, we still have little knowledge regarding real-life practice with PTCLs. In this study, we aimed to investigate the clinical characteristics and treatment outcomes of a large population-based cohort of patients presenting with systemic non-cutaneous PTCL. Materials and Methods: We conducted a multicenter retrospective analysis of 190 patients consecutively diagnosed and treated with non-cutaneous PTCLs between 2008 and 2016. Results: Considering all first-line treatment combinations, the overall response rate was 65.9% with 49.4% complete remission (n=81) and 16.5% partial response (n=27). The 5-year overall survival and event-free survival rates were significantly different between the transplant and non-transplant groups (p<0.01, and p=0.033, respectively). Conclusion: The retrospective analysis of a large volume of real-life data on the Turkish experience regarding non-cutaneous PTCL patients showed consistent results compared to other unselected PTCL cohorts with some minor differences in terms of survival and transplantation outcomes. The long-term outcome of patients who receive autologous hematopoietic cell transplantation as part of upfront consolidation or salvage therapy is favorable compared to patients who are unable to receive high-dose therapy.

Early Suspicion of Heparin-Induced Thrombocytopenia for Successful Free Flap Salvage: Reports of Two Cases.

Heparin-induced thrombocytopenia (HIT) is an underestimated complication of heparin treatment. Flap loss and related morbidity (even mortality) are caused by occlusion of the capillary vessels by a highly immunogenic complex formed by adherence of antiheparin antibodies to platelet factor 4. Early suspicion and effective treatment of HIT developing in two free flaps are described. We report on the management of two patients with HIT. Both patients were treated successfully by early suspicion and hematology consultation. Heparin products were discontinued; the patients were switched to a nonheparin anticoagulant. We emphasize the importance of early diagnosis, hematologist assessment, and a change to a nonheparin anticoagulant to prevent flap failure and possibly the catastrophic consequences of such failure.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Determination of cerebral blood flow velocity and microembolic signals in essential thrombocytosis by transcranial doppler ultrasonography.

OBJECTIVES: The goal of treatment in essential thrombocytosis (ET) is to prevent vascular complications such as thrombosis and hemorrhage. This study aimed to evaluate the risk of cerebrovascular microembolism in ET patients due to detection of microembolic signals (MES) and measure cerebral blood flow velocity (CBFV) by Transcranial Doppler (TCD) ultrasonography. MATERIAL AND METHODS: In this prospective case-control study, forty patients with diagnosed ET and age and sex-matched forty healthy controls were examined by the TCD sonography. RESULTS: The ET group had a higher rate of MES (8/40) in the right MCA than that in the control group (none), as measured by TCD. Five patients had MES at the left MCA compared to that in no subjects in the control group. The comparison of the ET and control groups in terms of CBFV parameters showed significantly lower end-diastolic FV at the right MCA in the ET group compared to that in the control group (p < 0.05). On the other hand; both pulsatility and resistance indices in the right and left MCA and the ratios of systolic to diastolic blood flow rates in the right and left MCA were significantly higher in the ET group than that in the control group. DISCUSSION: This study revealed that MES seems to be more common in patients with ET despite treatment. We could suggest that ET patients should be monitored more closely to address the potential risk of developing a cerebrovascular disease, which can be estimated by detection MES and raised CBFV, combine antiplatelet therapies to standard treatments.

Challenges in early diagnosis of primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma: a case series of four patients.

BACKGROUND: Primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma (AECTCL) is a rare and aggressive lymphoma characterised by ulcerated lesions and a poor prognosis. OBJECTIVES: To present a case series of four previously misdiagnosed AECTCL patients and discuss the importance of early diagnosis. MATERIALS AND METHODS: All patients in this study were identified from the database of the Dermatology Department of the Medical School of Bezmialem Vakif University, based on clinical and histopathological diagnosis of AECTCL between 2010 and 2018. RESULTS: AECTCL cases may mimic many benign dermatoses and accurate diagnosis may be delayed. CONCLUSION: Because of its poor prognosis, early diagnosis of AECTCL may be helpful in improving the likelihood of patient survival, but further study is needed to address the challenges in diagnosing this rare and aggressive lymphoma.

Is rituximab therapy a risk factor for development of melanoma?

In the literature, there are reports about dermoscopic and size changes of nevi in patients undergoing biologic therapy and chemotherapeutics. There has not been any established data for melanoma and Rituximab therapy. Sixteen patients, with 94 nevi were included in this study. Dermoscopic images of follow-up visits, which were performed at baseline, 3, 6, and 12 months after treatment, were evaluated. Suspicious lesions were excised. There was no increase in total nevus count. Although 61.7% of the 94 nevi have shown a stable duration without size changes, 26.5% had enlarged, and 11.7% had become smaller during our 1-year experience of dermoscopic monitoring. There was not any pattern transformation. Atypical dots and clods appeared in 17% of nevi. All of the excised nevi were comparable with Clark nevi, there was no clue for melanoma development. According to our results, we found that Rituximab therapy influences nevus morphology, but there is no evidence that this was linked to melanoma development.

Evolution of Hematological Parameters During the First 2 Years After Laparoscopic Sleeve Gastrectomy: Results of a Retrospective Study.

PURPOSE: Laparoscopic sleeve gastrectomy (LSG) is one of the most effective bariatric surgery methods of treatment for obesity. It can cause nutritional deficiencies and lead to anemia at the same time. The aim of the present study is to retrospectively investigate whether the supplement treatment administration to cases that underwent LSG is sufficient in terms of the hematological parameters. MATERIAL AND METHODS: A total of 494 obese patients between 18 and 65 years who underwent LSG were recruited to the study. Vitamin B12, iron, and folic acid replacement therapy are prescribed to all patients who can be followed-up at regular intervals. We compared hemogram, iron studies, vitamin B12, and folic acid values of these patients at preoperative and at first visit (1 month), 3, 6, 12, and 24 months post-surgery. RESULTS: The number of patients with anemia and vitamin B12 and folic acid deficiencies decreased significantly during the follow-up with supplementation. Postoperative leucocyte and thrombocyte levels were significantly lower than the preoperative levels. CONCLUSION: Our study indicates that the proper supplementation therapy in patients attending regular follow-up helps to keep hematological parameters within the normal range and to improve anemia and deficiencies of vitamin B12 and folic acid. Compliance with follow-up programs is essential after costly and invasive treatments such as sleeve gastrectomy to improve the well-being of patients in the long-term and to maximize compliance.

Treatment modalities of non-Hodgkin lymphoma patients over 65 years of age: A two-center experience.

OBJECTIVE: This study was conducted with the aim of making the contribution to a decision for treatment and determination of the modalities in patients diagnosed with non-Hodgkin lymphoma which increasingly become widespread in the geriatric population. MATERIALS AND METHODS: Ninety-one patients aged over 65 years diagnosed with lymphoma and treated in Bezmialem Vakif University Medical Faculty Hospital and Haseki Training and Research Hospital between 2008 and 2013 were retrospectively evaluated. Finally, 63 patients for whom data could be reached were included in the study. RESULTS: Examining the results, histological diagnoses of our patients were as follows: diffuse large B-cell lymphoma (50.8%), follicular lymphoma (23.8%), marginal zone lymphoma (12.7%), mantle cell lymphoma (4.8%), T-cell lymphoma (4.8%), lymphoplasmacytic lymphoma (1.6%) and small lymphocytic lymphoma (1.6%). Stages at the time of diagnosis were early stage by 33.3% and late stage by 66.7%. Of the patients, 36.5% had a low-intermediate and 63.5% a high-intermediate International Prognostic Index score. According to the Eastern Cooperative Oncology Group scoring, 34.9% of the patients have an Eastern Cooperative Oncology Group score of 2-4. Activities of daily living score of 33.3% patients was under 5. Looking at the responses to treatment, the complete response was found in 50.8%, partial response in 4.8%, stable disease in 1.6% and progressive disease in 9.5% of the patients. The mean follow-up duration of patients was found as 25.2 months and disease-free survival after remission as 20.2 months. CONCLUSION: We found that we have achieved a complete remission in more than half of our patients (50.8%). Based on this, treatment should aim remission in elderly patients.

A Multi-Center Study on the Efficacy of Eltrombopag in Management of Refractory Chronic Immune Thrombocytopenia: A Real-Life Experience

Objective: The aim of the present study was to evaluate the efficacy and safety of eltrombopag, an oral thrombopoietin receptor agonist, in patients with chronic immune thrombocytopenia (ITP). Materials and Methods: A total of 285 chronic ITP patients (187 women, 65.6%; 98 men, 34.4%) followed in 55 centers were enrolled in this retrospective cohort. Response to treatment was assessed according to platelet count (/mm3) and defined as complete (platelet count of >100,000/mm3), partial (30,000-100,000/mm3 or doubling of platelet count after treatment), or unresponsive (<30,000/mm3). Clinical findings, descriptive features, response to treatment, and side effects were recorded. Correlations between descriptive, clinical, and hematological parameters were analyzed. Results: The median age at diagnosis was 43.9±20.6 (range: 3-95) years and the duration of follow-up was 18.0±6.4 (range: 6-28.2) months. Overall response rate was 86.7% (n=247). Complete and partial responses were observed in 182 (63.8%) and 65 (22.8%) patients, respectively. Thirty-eight patients (13.4%) did not respond to eltrombopag treatment. For patients above 60 years old (n=68), overall response rate was 89.7% (n=61), and for those above 80 years old (n=12), overall response rate was 83% (n=10). Considering thrombocyte count before treatment, eltrombopag significantly increased platelet count at the 1st, 2nd, 3rd, 4th, and 8th weeks of treatment. As the time required for partial or complete response increased, response to treatment was significantly reduced. The time to reach the maximum platelet levels after treatment was quite variable (1-202 weeks). Notably, the higher the maximum platelet count after eltrombopag treatment, the more likely that side effects would occur. The most common side effects were headache (21.6%), weakness (13.7%), hepatotoxicity (11.8%), and thrombosis (5.9%). Conclusion: Results of the current study imply that eltrombopag is an effective therapeutic option even in elderly patients with chronic ITP. However, patients must be closely monitored for response and side effects during treatment. Since both response and side effects may be variable throughout the follow-up period, patients should be evaluated dynamically, especially in terms of thrombotic risk factors.

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study.

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment. We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1-75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Preparation and characterization of amine functional nano-hydroxyapatite/chitosan bionanocomposite for bone tissue engineering applications.

In this study, three different types of scaffolds including a uniquely modified composite scaffold - namely chitosan (CTS), nano-hydroxyapatite/chitosan composite (CTS+nHAP), and amine group (NH2) modified nano-hydroxyapatite/chitosan composite (CTS+nHAP-NH2) scaffolds - were synthesized for bone tissue engineering (BTE) purposes. As results of the study, it was found that all scaffold types were biodegradable with CTS and CTS+nHAP scaffolds losing up to 15% of their initial weight, while the CTS+nHAP-NH2 scaffold showing 10% of weight loss after six weeks of lysozyme treatment. In addition, all three types of scaffolds were shown to be biocompatible, and amongst them CTS+nHAP-NH2 scaffolds supported the most cell proliferation in WST-1 assay and expressed the least and acceptable level of cytotoxicity in lactate dehydrogenase (LDH) test for human bone mesenchymal stem cells (hBM-MSCs). Finally, during osteoinductivity assessment, CTS+nHAP-NH2 nearly tripled initial alkaline phosphatase (ALP) activity when whereas both CTS and CTS+nHAP scaffolds only doubled. These results indicate that all synthesized scaffold types under investigation have certain potential to be used in bone tissue engineering approaches with CTS+nHAP-NH2 scaffold being the most promising and applicable one. In the future, we plan to intensify our studies on osteogenic differentiation on our scaffolds on a detailed molecular level and to include in vivo studies for pre-clinical purposes.

Cholesterol Levels in Patients with Chronic Lymphocytic Leukemia.

Low cholesterol levels may be accompanied by solid tumors or hematological malignancies such as multiple myeloma. Decreased cholesterol levels have been reported in some experimental studies about chronic lymphocytic leukemia (CLL). It may be associated with tumoral cell metabolism. Herein, we examine blood lipid profiles of patients with newly diagnosed CLL (284 male, 276 female, mean age 64 ± 11 years) as defined by National Cancer Institute criteria. The control group consisted of 71 healthy subjects with mean age 55 ± 9 years (28 male, 43 females). 60% of patients with Binet A, while 25% were Binet C. Decreased levels of total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) were observed in patients with CLL than control group (p < 0,001). There was no statistical significance between CLL and control group for triglycerides (TG) and very low density lipoprotein (VLDL), also between HDL-C, VLDL, TG and grades. Cholesterol may metabolized by abnormal lymphocytes in CLL patients.

Mean Platelet Volume in Heterozygous Beta Thalassaemia.

BACKGROUND/AIM: It is not known why cerebrovascular and cardiovascular ischaemic events are less frequently observed in heterozygous beta thalassaemia (HBT) patients than in the general population. However, we previously reported that serum levels of some platelet function markers, i.e. soluble CD40 ligand and soluble P-selectin, are lower in patients with HBT than in controls. A high mean platelet volume (MPV) is an indicator of in vivo platelet activation and may indicate a tendency to thrombosis. We investigated whether MPV is lower in HBT patients than in controls. METHODS: Forty-eight patients with HBT were compared with 51 controls matched for gender, age, and BMI for MPV in a cross-sectional study. RESULTS: The MPV was within the normal range and higher in the HBT group (9.64 ± 1.20 vs. 9.07 ± 082 fL, p = 0.006). The 2 groups were similar in terms of atherosclerosis risk factors and medications. After linear regression analysis, the MPV was correlated with HBT, sensitive CRP, and BMI. CONCLUSION: The higher MPV in patients with HBT could indicate platelet activation, and this may represent a dilemma. Higher MPV in the HBT group might have resulted from higher sympathetic nervous system activity, mild ineffective erythropoiesis, and haemolysis.

Could Heterozygous Beta Thalassemia Provide Protection Against Multiple Sclerosis?

BACKGROUND Heterozygous beta thalassemia (HBT) has been proposed to increase the risk of developing autoimmune disease. Our aim in this study was to examine the prevalence of HBT among multiple sclerosis (MS) patients. MATERIAL AND METHODS HBT frequency was investigated in our MS group (243 patients with MS). Hemoglobin electrophoresis (HE) was carried out if MS patients had a mean corpuscular volume of (MCV) <80 fL and a mean corpuscular hemoglobin level of (MCH) <27 pg/L according to a complete blood count (CBC). If MCV was lower than 80 fL, MCH was lower than 27 pg/L, and Hemoglobin A2 equal to or higher than 3.5%, a diagnosis of HBT was established. The frequency of patients with HBT in our MS patient group was statistically compared with the prevalence of HBT in the city of Istanbul, where our MS patients lived. RESULTS The HBT prevalence was 0.823% (2 patients) in the MS patient group. The prevalence of HBT in Istanbul has been reported to be 4.5%. According to the z-test, the HBT prevalence in our MS patient group was significantly lower than that in Istanbul (Z=6.3611, two-sided p value <0.0001, 95% confidence interval of prevalence of HBT in our MS patient group: 0.000998-0.029413). CONCLUSIONS Contrary to our hypothesis at the outset of study, the reduced HBT prevalence in the MS group compared to HBT frequency in the city of Istanbul might indicate that HBT is protective against MS.