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Purpose Mannose-binding lectin (MBL) is a serine protease belonging to the collectins and an important factor in the inherited immune system. We aimed to reveal the distribution of different MBL2 genotypes in patients diagnosed with acute bronchiolitis and pneumonia. Material and methods A total of 147 patients who applied to Pediatric Emergency between 01.12.2019-31.12.2020 included in the study. Patients were divided into two subgroups: Bronchiolitis and pneumonia. Results AA genotype was found to be significantly higher in healthy controls (p = 0.039). In pneumonia group, both AB/BB genotype was significantly higher compared to healthy controls (p = 0.001). While AA genotype was more common in patients with acute bronchiolitis, AB/BB genotypes were more common in the pneumonia group (p = 0.001). The presence of fever, crepitation, tachypnea, pathological x-ray finding and high leukocyte count are significantly more common in patients with AA genotype, while more than 3 days of follow-up duration and severe clinical picture were more common in patients with AB/BB genotypes (p Conclusions Genotypes with low MBL expression were significantly more common in patients with pneumonia and severe infection. All these results reveal the importance of MBL polymorphisms and expression in infections.

For COVID-19 (Coronavirus Disease-2019) cases, detecting host-based factors that predispose to infection is a very important research area. In this study, the aim is to investigate the MBL2 and NOS3 gene polymorphisms in COVID-19 patients with lung involvement, whose first nasopharyngeal PCR results were negative. Seventy-nine patients diagnosed with COVID-19 between April-June 2020 who were admitted to a university hospital, and 100 healthy controls were included. In the first statistical analysis performed between PCR-positive, CT-negative and PCR-negative, CT-positive patients; the AB of MBL2 genotype was significantly higher in the first group (p = 0.049). The B allele was also significantly higher in the same subgroup (p = 0.001). The absence of the AB genotype was found to increase the risk of CT positivity by 6.9 times. The AB genotype of MBL2 was higher in healthy controls (p = 0.006). The absence of the AB genotype was found to increase the risk of CT positivity; also, it can be used for early detection and isolation of patients with typical lung involvement who had enough viral loads, but whose initial PCR results were negative.

Multiple myeloma (MM) is a disease caused by malignant plasma cells, causing free light chain release accompanying the increase in monoclonal immunoglobulin. Cytochrome P450 (CYP) is one of the large and functional enzyme families composed of various hemoproteins. This protein network has been shown to play a role in many treatment steps in current practices. We aimed to investigate the relationship between genotypes of CYP3A4*1B and treatment response and prognosis of MM. Seventy-two patients diagnosed with MM between January 2016 and 2020 and 100 healthy people to create a control group participated in our study. Genotypes were classified in 3 separate groups as NN, MN, and MM. Both PFS and OS were significantly higher in the NN genotype (p = 0.001, p = 0.014). Being under the age of 65 was 27.988 times more protective for OS and 4.496 times for PFS (p = 0.006, p = 0.017). NN genotype was shown to be 41.666-fold protective for OS and 3.144-fold protective for PFS (p = 0.004, p = 0.030). This study demonstrated that CYP3A4*1B NN genotype, which is an important cytochrome p450 member for the treatment of MM, was 41.666-fold protective for OS and 3.144-fold protective for PFS. It was shown in this study for the first time in the literature as a valuable contribution.

Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Findings: Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Interpretation: Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. Funding: European Myeloma Network and Janssen Research and Development., European Myeloma Network and Janssen Research and Development.

The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Thus, we aimed to determine the impact and safety of BV as maintenance after ASCT in real-world patients. Seventy-five patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease presenting with variable and various clinical findings. PNH might be overlooked and diagnosis may be delayed due to low awareness about PNH. This is the first multicenter study in Turkey, investigating the efficiency of diagnostic screening of PNH by multiparameter flow cytometry (FCM) according to consensus guidelines. Methods We evaluate the efficiency of consensus clinical indications for PNH testing with FCM in 1689peripheral blood samples from 20 centers between January 2014 and December 2017. Results Overall, at the 20 centers contributing to this study, PNH clone were detected in 62/1689 samples (3.6%) by FCM test. 75.8% (n = 47) of patients with PNH clone had aplastic anemia, 3.2% (n = 2) had Coombs (-) hemolytic anemia, 6.5% (n = 4) had unexplained cytopenia, 3.2% (n = 2) had MDS with refractory anemia, 1.6% (n = 1) had hemoglobinuria and 9.7% (n = 6) had others (elevated LDH, splenomegaly, etc.). In contrast, we detect no PNH clone test in patients who were screened for unexplained thrombosis. Conclusions Our study showed that current clinical indications for PNH testing are highly efficient and diagnostic screening of suspected patients for PNH with FCM is recommended. However, advanced screening algorithms are required for patients presenting with unexplained thrombosis and normal complete blood count.

Hematopoietic stem cell transplantation (HSCT) is a choice of treatment for malignant and non-malignant diseases. After HSCT, some complications may develop in patients. Cardiac complications are particularly important. The aim of this study was to investigate whether systolic pulmonary artery pressure (PAP) is a marker for overall survival (OS) in HSCT patients.In our study, 428 HSCT patients were evaluated. Ejection fraction (EF) and PAP values were investigated during symptom-oriented echocardiography in the pre-HSCT and post-HSCT periods.Pre-HSCT EF values were similar between the groups. In patients with autologous HSCT (auto-HSCT) (PAP25 mmHg), it was found that the 5-year mortality rate was 48.6%, while in the other group (PAP25 mmHg) the 5-year mortality was 25.5%. There was a significant association between 5-year mortality rate and PAP level (p0.046) in the auto-HSCT group. OS was 38% in the pre-auto-HSCT period with PAP values of25 mmHg, while OS was 61% in the pre-auto-HSCT period with PAP values of25 mmHg (p0.001). We determined that there was a statistically significant difference between OS and PAP levels in patients with auto-HSCT. Five-year mortality rate and OS were not significantly different in patients undergoing allogeneic HSCT (allo-HSCT) (p0.05).Our results suggest that pre-HSCT PAP value is an important risk factor for mortality and OS in patients undergoing auto-HSCT.Hematopoietik kök hücre transplantasyonu (HKHT) malign ve non-malign hastalıklarda kullanılan bir tedavi seçeneğidir. Nakil sonrasında bir çok komplikasyon gelişmektedir. Kardiyak komplikasyonlar önemli bir yer tutmaktadır. Bu çalışmanın amacı, sistolik pulmoner arter basıncının (PAB) nakil yapılan hastaların sağkalımına olan etkisini araştırmaktır.Çalışmamızda 428 HKHT yapılan hasta değerlendirildi. Ejeksiyon fraksiyonu (EF) ve PAB değerleri, semptom oryante ekokardiyografi ile post ve pretransplantasyon dönemde değerlendirildi.Karşılaştırılan gruplar arasında pre-HKHT döneminde EF değerleri açısından farklılık saptanmadı. Beş yıllık mortalite otolog HKHT yapılan hastalarda PAB değeri 25 mmHg üzeri olanlarda %48,6, diğer grupta %25,5 olarak gözlendi ve istatistiksel olarak p0,046 olarak hesaplandı. Total sağkalıma bakıldığında otolog HKHT yapılan hastalarda; nakil öncesi PAB değeri 25 mmHg üzeri olanlarda %38 iken; nakil öncesi PAB değeri 25 mmHg altında olan grupta sağkalım %61 olarak saptandı ve bu durum istatistiksel olarak anlamlı hesaplandı (p0,001). Aynı verileri değerlendirerek total sağkalım ve PAB değeri arasında otology HKHT yapılan hastalarda anlamlı ilişki oldugunu, allojenik HKHT yapılanlar arasında istatistiksel olarak anlamlı ilişki olmadığını tespit etmiş bulunmaktayız.Çalışmamızın sonuçlarına göre HKHT öncesi ve sonrası ölçülen PAB değeri hastalarda total sağkalım ve mortalite üzerine önemli etkisi olan bir faktör olarak karşımıza çıkmaktadır.

Objective/Background: Lymphoma is seen as a highly treatable and curable malignancy with aggressive treatment methods. Efficacy is often limited by toxicity and many patients need alternative treatment strategies as they cannot tolerate existing high cytotoxic approaches. Our aim is to compare BEAM [carmustine (BCNU), etoposide, cytarabine (ARA-C, cytosine arabinoside), and melphalan] and mitoxantrone–melphalan (Mx-Mel) regimens utilized in our patients with a diagnosis of lymphoma who underwent autologous stem cell transplantation (ASCT), and to demonstrate that the Mx-Mel regimen has similar but less toxic results than the BEAM regimen we have been using frequently as standard conditioning regimen. Methods A total of 101 patients with lymphoma who underwent ASCT were included in our study. The BEAM regimen included BCNU, etoposide, ARA-C, and melphalan. The Mx-Mel regimen included mitoxantrone and melphalan. Results Of 101 patients included in the study, 60 (59.4%) received BEAM and 41 (40.6%) received Mx-Mel (40.6%) conditioning regimen. The median time to neutrophil engraftment was 10 (range: 9–20) days and 12 (range: 9–12) days in the BEAM and Mx-Mel arms, respectively; it was statistically significantly shorter in the BEAM arm (p = .001). Conclusion This study demonstrates that the Mx-Mel regimen has similar efficacy and toxicity compared with the BEAM regimen. Although time to neutrophil engraftment was shorter in the BEAM arm, it did not result as significant transplant-related complications between the two regimens. The Mx-Mel regimen is seen as a good alternative with low toxicity and high efficacy.

Context The AETHERA trial reported an increased progression-free survival (PFS) when brentuximab vedotin (BV) was used as maintenance therapy in high-risk Hodgkin lymphoma (HL) after autologous stem cell transplantation (ASCT). Objective To determine the impact and safety of BV as maintenance after ASCT in real-world patients. Design Patients with relapsed/refractory HL started on BV consolidation therapy after ASCT due to high risk of relapse, between January 2016 and July 2019, from 25 institutions, were retrospectively analyzed. Setting All patients were followed by the bone marrow transplantation team of their hospital. Patients or Other Participants Seventy-five patients were included in the study. The median follow-up time was 26 months. The most common high-risk features were primary refractory or relapsed disease Interventions BV consolidation was initiated within 6 months of ASCT and administered at a dose of 1.8 mg/kg intravenous infusion over 30 min every 3 weeks for up to 16 cycles in an outpatient setting. Main Outcome Features The primary endpoint of the study was PFS; secondary endpoints were safety and overall survival (OS). Results At the time of analysis, 42 patients completed consolidation courses, and BV was discontinued in 33 patients. Fifty patients had an ongoing response (CR in 41, PR in six, and SD in three patients), 25 had progressed. Ten died in the follow-up, eight with progressive disease and two due to infection while in CR. The 2-years PFS and OS rates were 67.75% (95% CI:0.55–0.77) and 87.61% (95% CI:0.76–0.94), respectively. Seventeen patients (23%) received BV in the pre-ASCT treatment lines, and there was no survival difference between the BV naive and BV exposed groups. The most common adverse events were neutropenia (27%) and peripheral neuropathy (21%). Sixteen patients (21.3%) experienced grade 3 or 4 toxicity. BV was discontinued due to AE in 12 patients. Conclusions Consolidation with BV after ASCT can achieve a 2-year PFS of 67.75% (95% CI: 0.55–0.75) with an acceptable toxicity profile.

ObjectiveMultiple myeloma (MM) arises from malignant plasma cells as a single clone in the bone marrow. Accumulating evidences have reported that there is an association betweenmiR-196a2(rs11614913) variant and various cancers while there were unverified and inconsistent results in MM. The goal of this study is to investigate the impact of themiR-196a2 variant on clinical findings and susceptibility in MM. Two hundred MM patients (156 patients under transplantation of autologous stem cell) and 200 healthy controls included in this study.ResultsThe statistical analysis showed no significant relationship for allele and frequencies ofmiR-196a2genotype between patients and controls (p > 0.05). Log-rank test showed that gender has highly significant impact on both OS and PFS (p = 0.027, p = 0.045).In the univariate analysis, TT genotype (p = 0.022), and CT/TT (p = 0.008) had better OS. In the multivariate analysis, CC/CT-TT were associated with positively OS (p = 0.041). Currently, the most valuable prognostic markers in MM that has clinical implication are genetic abnormalities. It can be concluded from the results thatmiR-1962avariant is effective in prognosis of the MM. It is believed that these findings will help us understand the molecular basis of disease.

Introduction Post-transplant lymphoproliferative disease (PTLD), a lymphoid proliferation observed after the solid organ transplantation or allogeneic stem cell transplant, is an important and mortal complication that can occur during the post-transplant period. Classical Hodgkin lymphoma-like PTLD is the least form of PTLD. We are presenting an adult case of classical Hodgkin lymphoma-like PTLD which was successfully treated with nivolumab. Case report A 31-year-old female was diagnosed with primary myelofibrosis and we performed allogeneic stem cell transplantation from her HLA fully matched brother in 2015. Two years after transplant, classical Hodgkin lymphoma-like PTLD was diagnosed. The patient was resistant to six cycles of ABVD chemotherapy and four cycles of brentuximab vedotin. Management and outcome After the failure of ABVD and brentuximab vedotin, we started nivolumab therapy at a dose of 3 mg/kg every 2 weeks. After six cycles, we achieved a PET negative complete remission. After 10 cycles of nivolumab, the patient is still followed with a complete remission. Still, there is no evidence of acute or chronic GvHD, and therefore no need for immunosuppressive treatment. No auto-immune complication was observed. It is planned to give nivolumab treatment to the patient until the progression. Discussion Our case has depicted that the classical Hodgkin lymphoma type PTLD may be resistant to the conventional treatments and anti-CD30 brentuximab vedotine. In such cases, nivolumab may be an effective and worth assessing agent in terms of both activity and safety profile.

Objectives Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ≤ 0.1% on the International Scale [BCR-ABL1IS]) by 12 months. Methods Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. This study is registered with ClinicalTrials.gov (NCT01274351). Results Of 112 patients enrolled, 66.1% (80% CI, 59.7-72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1IS ≤0.0032%) by 12 months. During the first year of treatment, one patient progressed to blast crisis and two patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. Conclusion These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP with low and intermediate risk.

The basic underlying factor for cardiovascular diseases is atherosclerosis, which is a multifactorial disease driven by environmental and genetic factors. We aimed to study the genetic polymorphism in mannose binding lectin-2 (MBL2) and macrophage migration inhibitory factor (MIF) in the arteries of patients with atherosclerotic lesions who underwent cardiac valve replacement for cardiac valve stenosis. Thirty-five patients (38.9 %) operated with coronary bypass surgery (coronary group, CG), 55 (61.1 %) patients operated with aortic or mitral valve replacement (valve group, VG) and 100 healthy controls were analyzed for codon 54 A/B polymorphism in the MBL2 gene and –173 G/C polymorphism in the MIF gene by using the method of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The comparison of the healthy control group with CG and VG in terms of the MBL2 genotypes revealed significantly lower AA genotype and A allele ratios. The comparison of the healthy control group with CG and VG in terms of the MIF genotypes showed significantly lower GG genotype and G allele ratios. We suggest that the lower frequency of the GG genotype/G allele of the MIF gene and of the AA genotype/A allele of the MBL2 gene may be associated with the ethiopathogenesis of CG and VG patients.

Objective: Ankylosing spondylitis (AS) is a chronic inflammatory disorder. MicroRNAs (miRNAs) can function as either oncogenes or tumor suppressor genes. Altered miRNA expression has been implicated in the pathogenesis of several diseases. Therefore, we aimed to explore the effects of miR-196a2T/C (rs11614913) variant profile on susceptibility to AS in a Turkish population. Materials and Methods: Blood samples were collected from 78 AS patients and 79 healthy controls. miR-196a2T/C variant was genotyped by PCR-RFLP. Odds ratio (OR) with 95% confidence interval (95%CI) were calculated using the χ2 test. Results: The frequency of T/C and T/T genotypes of the miR196a2T/C were higher in AS patients compared to healthy controls (p=0.034 and p=0.028, respectively). The subjects carrying the miR-196a2T/C variant T/T genotype showed a 2.542-fold increased AS risk than the control group. However, no difference was observed in the allele frequencies of miR-196a2T/C between AS patients and the controls. It was found that C/C genotype of miR-196a2T/C variant was more frequent in AS patients with enthesitis than AS patients without enthesitis (p=0.042). Conclusion: The miR-196a2T/C variant represents a genetic risk factor for increased susceptibility to AS and is associated with enthesitis in the Turkish population.

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that may lead to weakness and death of patients, if unrecognized and untreated. Although consensus guidelines were reviewed recently for the diagnostic screening of PNH with multi-parameter flow cytometry (FCM), until now, no study has investigated the efficiency of such clinical indications in older patients. Methods: Overall, 20 centers participated in the study and a total of 1,689 patients were included, 313 of whom were at geriatric age and 1,376 were aged 18 - 64 years. We evaluated the efficiency of consensus clinical indica-tions for PNH testing using FCM in peripheral blood samples and compared the results of older patients and pa-tients aged 18 - 64 years. Results: PNH clones were detected positive in 7/313 (2.2%) of the older patients. Five (74.4%) of the patients with PNH clones had aplastic anemia, 1 had unexplained cytopenia, and 1 patient had myelodysplastic syndrome (MDS) with refractory anemia. PNH clones were not detected in any older patients who were screened for unex-plained thrombosis, Coombs (-) hemolytic anemia, hemoglobinuria, and others (e.g., elevated lactate dehydroge-nase (LDH), splenomegaly). We detected PNH clones in 55/1376 (4%) samples of the patients aged under 65 years. Forty-two (76.4%) patients with PNH clones had aplastic anemia, 2 patients had Coombs (-) hemolytic anemia, 3 patients had unexplained cytopenia, 1 patient had MDS with refractory anemia, 1 patient had hemoglobinuria, and 6 (10.9%) had others (e.g., elevated LDH, splenomegaly). PNH clones were not detected in any patients who were screened for unexplained thrombosis. There was no statistical difference between the geriatric population and patients aged 18 - 64 years in terms of clinical indications for PNH screening with FCM (p = 0.49). Conclusions: Our results showed that the current clinical indications for PNH screening with FCM were also effi-cient in older patients. We suggest that older patients with unexplained anemia, myelodysplastic syndrome with refractory anemia, and unexplained cytopenia should be screened for PNH with FCM to identify patients who would benefit from treatment. © 2020 Verlag Klinisches Labor GmbH. All rights reserved.

Background: Addictive substances are known to result in oxidative stress (OS). OS enhances the generation of free radicals and reactive oxygen species (ROS) and reduces antioxidant capacity. Peroxides and oxygen radicals, including hydrogen peroxide and superoxide and radical nitrogen species, including nitric oxide (NO), are parts of the ROS. Gene variants of the endothelial nitric oxide (eNOS) affect the plasma levels of NO. This study aimed to investigate whether there was an association between eNOS variants and substance use disorders (SUDs) risk in the Turkish population. Methods: Two eNOS variants (G894T and 27 bp VNTR 4b/a in intron 4) were examined in 216 SUD patients and 140 healthy controls. The eNOS variants were assessed with the PCR based on the RFLP analysis. Since the patient group consisted only of men, the control group was examined as a mixed and male-only. Results: The eNOS G894T homozygous T/T genotype revealed a significant association with susceptibility to SUD. The patients carrying T/T genotype had SUD risk 1.054 times as much as the controls and male controls had (p=0.004 and p=0.038, respectively). eNOS 4a/4a genotype increased in patients as compared to male controls (p=0.048). The homozygous 4b/4b genotype was higher in the male control group than in SUD patients (p=0.029). eNOS VNTR 4a allele was more prevalent in the patients than in both controls and male controls (p=0.026 and p=0.0033, respectively). Conclusion: This study is one of the first studies investigating the relationship between two eNOS gene variants and SUD in our country. Our findings show that eNOS G894T and VNTR variants may be the significant risk factor for SUDs in Turkish subjects.

OBJECTIVE An increasing number of epidemiological and molecular evidence proposes that inflammation is a significant factor in the etiology of cancers. Macrophage Migration Inhibitory Factor (MIF) encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation. It has been reported that MIF is linked with a higher risk of several cancer types. In the present study, we investigated the association of MIF rs755622 variant with the risk of breast cancer (BC) and gastrointestinal cancer in a Turkish cohort. METHODS The present study included a total of 153 subjects, which consisted of 33 BC patients, 53 gastrointestinal cancer patients and 67 healthy controls. Genomic DNA extracted from peripheral venous blood. The rs755622 variant of the MIF gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The results were statistically analyzed by calculating the odds ratios (OR) and 95% confidence intervals (CI) using the ?2 test. RESULTS There was a statistical difference between the BC patients and controls for the MIF rs755622 variant. MIF rs755622 GG genotype and G allele were increased in BC patients compared to controls (p=0.016, p=0.017, respectively). No significant difference was observed between gastrointestinal cancer patients and controls for the MIF rs755622 variant (p>0.05). CONCLUSION Our results showed that the MIF rs755622 variant might play a potential role in BC physiopathology. WOS:000565170700006 2-s2.0-85091336939

WOS: 000491229800399 …

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 (

BACKGROUND This study aimed to evaluate whether VNTR variants in the Endothelial Nitric Oxide Synthase (eNOS) and the XRCC4 gene play any role in nicotine dependence (ND) and/or Schizophrenia+ND (Sch+ND) ethiopathogenesis. METHODS Present study included 100 individuals with ND, 60 patients with Sch+ND, and 70 healthy controls. These variants were analyzed using PCR. RESULTS The cases with ND had higher eNOS VNTR-BB genotype than the healthy control subjects (p = 0.001). eNOS-AA genotype was lower in cases with Sch+ND and ND groups compared to the controls (p = 0.001, p = 0.001, respectively). eNOS-B allele was found significantly more frequently in Sch+ND group compared to the controls (p = 0.001). eNOS-A allele was significantly lower in ND group than the controls (p = 0.001). XRCC4-ID genotype was more common in the ND group than the control group (p = 0.001) as heterozygosity disadvantage. XRCC4-DD genotype was more common in the Sch+ND group compared to the controls (p = 0.035). The frequency of XRCC4-I allele was lower in the Sch+ND group compared to the controls (p = 0.012). CONCLUSIONS Our results showed that eNOS and XRCC4 VNTR variants might play a potential role in Sch+ND and/or ND pathophysiology (Tab. 2, Ref. 48).

Introduction: In this study, clinical, laboratory, radiological, and serological examinations of fascioliasis patients were analyzed, and data with a significant impact on differential diagnosis were evaluated. Methodology: Clinical, radiological, and laboratory findings and treatment responses of a total of 22 fascioliasis patients, treated between October 2009 and September 2014, were evaluated. Nineteen patients were diagnosed with fascioliasis at the invasive phase and three patients at the chronic phase. Patients were followed up for clinical, laboratory, and radiology findings for a period of three months to one year after treatment. Results: The most frequent complaints in both groups were abdominal pain, and the most common physical examination finding was epigastric tenderness. In the performed examination, an eosinophil elevation in whole blood count was detected in 19 patients (100%) in the hepatic phase, and in 2 patients (66.6%) in the biliary phase. The results of the Fasciola hepatica indirect hemagglutination assay (IHA) test ordered in the diagnosis were positive in all patients. Treatment with 10 mg/kg/day triclabendazole for two consecutive days was effective. Live parasites were extracted from patients in the biliary phase with endoscopic retrograde cholangiopancreatography. In the follow-ups, remission in IHA titer and clinical and radiological improvement was achieved in all patients. Conclusions: If hypereosinophilia is detected by peripheral smear in patients who are admitted with complaints such as abdominal pain, weakness, nausea, myalgia, and weight loss, radiological evaluation and serological tests should be performed and fascioliasis should be considered in the differential diagnosis.

Hepatic sinusoidal obstruction syndrome (HSOS) is a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively evaluated the incidence, risk factors, treatment and survival for HSOS after allo-HSCT in Turkey. We also reported our experience of defibrotide (DF) for HSOS prophylaxis in high-risk (HR) patients. Across Turkey, 1153 patients from 10 centers were enrolled in the study. We evaluated the medical records of patients who were treated with allo-SCT between January 2012 and December 2015. The study included 1153 patients (687 males/466 females) with median age of 38 (15?71) years. The incidence of HSOS was 7.5 % (n = 86). The incidences of HSOS in the HR/DF+, HR/DF- and standard risk (SR) group were 8%, 66.7 % and 6.2 %, respectively. The rate of HSOS development was not statistically different between HR/DF + and SR group (p = 0.237). HSOS prophylaxis (defibrotide) was significantly decreased HSOS-related mortality (p = 0.004). The incidence of HSOS was found similar to literature in this large Turkish cohort. Defibrotide prophylaxis appears to be associated with low incidence of HSOS development and reduced HSOS-related mortality. Although these results are promising, future studies are needed to support the efficacy of defibrotide prophylaxis in patients with risk of HSOS. © 2020 Elsevier Ltd, We thank to Raika Durusoy for statistical analysis and data interpretation.

WOS: 000448137100007, PubMed ID: 29486663, Objectives: This report presents final results (24 months of follow-up) from the first prospective, national study of frontline nilotinib in chronic myeloid leukemia (CML) patients in Turkey. Methods: Patients with newly diagnosed Philadelphia chromosome-positive CML in chronic phase (CML-CP; N = 112) received nilotinib 300 mg twice daily. The primary endpoint, which was the cumulative rate of major molecular response (MMR; BCR-ABL1, Novartis Pharmaceuticals CorporationNovartis, This work was supported by the Novartis Pharmaceuticals Corporation.

Objective: The purpose of this study was to investigate whether functional variants of Catechol-O-Methyltrans-ferase (COMT) (rs4680) and Cannabinoid Receptor 2 (CNR2) (rs2501432) genes play a role in tobacco use disor-der (TUD) or tobacco use disorder and schizophrenia (TUDSch) comorbidity. Methods: This study consisted of 163 participants with TUD, 60 participants with TUDSch, and 106 gender-, age- and ethnicity-matched non-smoker con-trols (HNC). While the TUD and TUDSch were diagnosed according to the DSM-5, the severity of TUD was rated according to the Fagerstrom Test for Nicotine Dependence. Genotyping of COMT and CNR2 genes was determined using the polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Results: Distributions of genotypes and allele frequencies were compared among the groups. Patients with TUDSch had higher frequency of COMT Val/Val genotype compared to the TUD and HNC groups (p=0.001, p=0.034, respect-tively). Patients with TUD had higher frequency of Val/Met genotype than TUDSch and HNC groups (p=0.001, p=0.033, respectively). The frequency of the Val allele was higher in TUDSch than the HNC group, whereas the frequency of the Met allele was higher in TUD than in the TUDSch group (p=0.047, p=0.001, respectively). Addi-tionally, patients with TUD had higher frequency of TT CNR2 genotype than the HNC group (p=0.019). Conclusion: While the Val/Val genotype of the COMT gene is associated with an increased risk for TUDSch, the Val/Met geno-type is associated with an increased risk for TUD. Additionally, the TT CNR2 genotype was associated with in-creased risk for TUD in the Turkish population.

Background: We analyzed the relationship between matrix metalloproteinase (MMP)-2, -7, and -13 gene expression and polymorphisms and disease susceptibility and prognosis in patients who had undergone surgery for nonesmall-cell lung cancers. Materials and methods: The study group consisted of 132 patients who had undergone radical surgery for nonesmall-cell lung cancers. The control group consisted of 80 healthy volunteers. We isolated deoxyribonuclease samples for use in analyzing gene polymorphisms from pathology blocks for the patient group and from blood samples for the control group. We identified MMP gene polymorphisms with polymerase chain reaction and restriction fragment length polymorphisms. Results were compared with those of the control group to evaluate disease susceptibility, correlation with other clinical parameters, and with survival and prognosis by using appropriate statistical methods. Results: When we compared polymorphisms pertaining to MMP genes in healthy controls and lung tumor DNA, we observed a decrease in the MMP-2 (� 735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes (P ¼ 0.008, P ¼ 0.047, and P ¼ 0.047, respectively). For the MMP-7 (� 181) polymorphism, the genotype did not differ significantly for disease susceptibility. Median overall survival time was 25.5 mo in the MMP-13 AA/AG genotypes and 9.3 mo in the GG genotype. Conclusions: Decreases in the MMP-2 (� 735) polymorphism GG genotype and increases in the MMP-13 (A77G) polymorphism AG and GG genotypes increase the risk for lung cancer. Furthermore, the presence of the MMP-13 (A77G) polymorphism GG genotype is an unfavorable prognostic factor.

To evaluate a relationship between preeclampsia and prolidase enzyme activity.A prospective cohort study of 41 pregnant women diagnosed with preeclampsia and 31 healthy pregnant women as control group was selected at Harran University Hospital Department of Obstetrics and Gynecology. The prolidase enzyme activity was analyzed in maternal and umbilical cord plasma, amniotic fluid and placental and umbilical cord tissues by Chinard method in addition to maternal serum levels of lactate dehydrogenase (LDH), serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT).A significant relationship was found between plasma prolidase activity (635 ± 83 U/L) (p = 0.007), umbilical cord plasma prolidase activity (610 ± 90 U/L) (p = 0.013), amniotic fluid prolidase activity (558 ± 100 U/L) (p = 0.001), umbilical cord tissue prolidase activity (4248 ± 1675 U/gr protein) (p = 0.013) and placental tissue prolidase activity (2116 ± 601 U/gr protein) (p = 0.001) in preeclamptic group when compared to healthy pregnant women.There is a strong correlation between prolidase enzyme activity and preeclampsia. Prolidase enzyme activity may play a role in preeclampsia.

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis. Keywords

European Biotechnology Congress -- APR 26-28, 2018 -- Athens, GREECE WOS: 000454825900063 Ankylosing spondylitis (AS) is a chronic inflammatory disorder. Micro RNAs (miRNAs), small noncoding RNA molecules, can function as either oncogenes or tumor suppressor genes. Altered miRNA expression has been implicated in the pathogenesis of several diseases. Therefore, we aimed to explore the effects of miR-196a2 T/C (rs11614913) variant profile on susceptibility to AS in a Turkish population. Blood samples were collected from 78 AS patients and 79 controls.

This study examined the diagnostic accuracy of nine indices to discriminate between patients with mild-to-moderate (haemoglobin 8.5 − 11 g/dl) or moderate-to-severe (haemoglobin < 8.5 g/dl) iron deficiency anaemia (IDA) from those with β-thalassaemia (β-TT) ( n = 100 per group). Indices examined were red blood cell (RBC) count, RBC distribution width (RDW), Mentzer index (MI), Shine and Lal index (S&L), England and Fraser index (E&F), Srivastava index (S), Green and King index (G&K), RDW index (RDWI), and Ricerca index (R). Index sensitivity, specificity, and positive and negative prognostic values were examined. Youden's indices were calculated and showed: S&L > G&K > E&F > RBC = RDWI > MI > S > R > RDW to differentiate between β-TT and mild-to-moderate IDA; and S&L > G&K > E&F = RDWI > RBC > R > MI > S > RDW to differentiate between β-TT or moderate-to-severe IDA. For both groups, S&L and G&K offered the best discrimination and RDW the worst. S&L showed the highest Youden index for β-TT and IDA discrimination, but sensitivity and specificity were not 100%. In both mild and severe IDA, the S&L index may be used to differentiate cases of β-TT from IDA cases, but large clinical trials are needed to explore this further.

PubMed ID: 27501474, Objective: Nilotinib is a BCR-ABL1 tyrosine kinase inhibitor approved for the treatment of patients with chronic myeloid leukemia in chronic phase (CML-CP). This study was the first prospective evaluation of the efficacy and safety of nilotinib in Turkish patients with newly diagnosed CML-CP. The primary endpoint of the study was the rate of major molecular response (MMR; BCR-ABL1 ? 0.1% on the International Scale [BCR-ABL1IS]) by 12 months. Methods: Patients with newly diagnosed CML-CP were treated with nilotinib 300 mg twice daily. This analysis was based on the first 12 months of follow-up in a 24-month study. Results and Conclusions: Of 112 patients enrolled, 66.1% (80% CI, 59.7–72.0%) achieved MMR and 22.3% achieved a deep molecular response of MR4.5 (BCR-ABL1IS ? 0.0032%) by 12 months. During the first year of treatment, 1 patient progressed to blast crisis and 2 patients died. Safety results were consistent with previous studies. Most adverse events (AEs) were grade 1/2. Most frequently reported nonhematologic AEs of any grade were elevations in bilirubin, alanine aminotransferase, and triglycerides. These results support the use of nilotinib 300 mg twice daily as a standard-of-care treatment option for patients with newly diagnosed CML-CP. © 2016 Informa UK Limited, trading as Taylor & Francis Group., Novartis Pharmaceuticals Corporation, This study was funded by Novartis Pharmaceuticals Corporation.

Autologous peripheral blood stem cells transplantation (PBSCT) is a therapeutic option which can be used in various hematological neoplastic disorders; and it can prolong disease free survival and total survival and at times it may be curative. In this study, we investigated variables influencing PBSCT in 91 patients who had undergone PBSCT between 1998 and 2002 in our center, retrospectively. PBSC collection was performed after mobilization with G-CSF or chemotherapy plus growth factor. Only high dose chemotherapy was used for conditioning regimes. The median number of CD34+ was 11.5 x 10(6)/kg. Posttransplant neutrophil engraftment (>500/microL) was requiring a median of 10 days, it was 13 days for platelet engraftment (>20,000/microL). For neutrophil and platelet engraftment, we investigated; sex, age, diagnosis and CD34+ cells, the time interval between diagnosis and transplantation, number of apheresis, conditioning regime, growth factor initiation day as independent variables. In univariate analysis CD34+ cell number (>10 x 10(6)/kg), time interval more than one year between diagnosis and transplantation and BEAM conditioning was found to be significant for neutrophil engraftment. But in multivariate analysis none of them was found to be significant. For platelet engraftment in univariate analysis CD34+ cell number (>7 x 10(6)/kg), primary diagnosis of multiple myeloma initiation day of growth factor (>2 day) was found to be significant. In multivariate analyses only CD34+ cell count was found to be significant (p=0.005). In conclusion, as in previous studies we found that the only predictor of engraftment kinetics was CD34+ cell count.

This study aimed to investigate fungal agents in febrile neutropenic patients with hematological malignancies. Direct microscopy and cultures were performed on clinical samples collected from febrile neutropenic episodes. The galactomannan (GM) antigen was tested using enzyme-linked immunosorbent assays, and Aspergillus fumigatus and Candida albicans deoxyribonucleic acid (DNA) assessed using real-time polymerase chain reaction (PCR) in consecutive serum samples. Of the 199 episodes investigated, 1.5% were classified as definite invasive aspergillosis (IA), 4.0% as IA with high probability, and 4.0% as IA with low probability. Additionally, candidaemia was detected in eight episodes (4.1%). The GM antigen was found negative for 86.4% of episodes, as one positive for 7.0% of episodes, as two or more consecutive positives for 5.5% of episodes, and as positive in any two serum samples in 1.0% of episodes. While no C. albicans DNA was detected in 98.5% of 199 episodes, one positive result was obtained in 1.0% of episodes, and two or more consecutive positives in 0.5% of episodes. A. fumigatus PCR results were found negative in 81.9% of episodes, as one positive in 16.1% of episodes, as positive in any two serum samples in 1.0% of episodes, and consecutively positive in 1.0% of episodes. GM antigen tests were found consecutively positive in all three patients diagnosed as having definite IA. These findings indicate that conventional, serological, and molecular methods should be used in combination to detect fungal agents in febrile neutropenic patients.

Leptin is a regulator of fat metabolism that is synthesized in adipocytes and released into circulation. The serum levels of leptin are, therefore, correlated with body fat mass and show a wide variation in healthy individuals. Leptin may have an additional indirect effect on leukemic hematopoesis. We investigated serum leptin levels with enzyme-linked immunosorbent assays in 14 acute myeloblastic leukemia (AML) patients before and after chemotherapy and compared the results with that of the levels determined 14 healthy controls. We found no significant difference between leptin levels before and after chemotherapy and control group. Therefore, serum leptin level should not be used as a diagnostic marker in acute leukemia patients. However, the possibility of regional leptin production by leukemia blasts in bone marrow stroma creates a high local concentration of leptin within bone marrow microenvironment and systemic leptin level in combination with local leptin production may affect leukemic he...

Imatinib mesylate, a the thyrosine kinase inhibitor (trade name Glivec or Gleevec) is an important therapy in the management of chronic myeloid leukemia (CML). A complete cytogenetic response was a...

WOS: 000331341700002, PubMed ID: 24385824, 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.

WOS: 000313165500093, PubMed ID: 23076533, The aim of this work was to report two cases of hypereosinophilic syndrome (HES). FIP1L1-PDGFRA fusion was assessed with two protocols at RNA level. The fusion transcript was found positive at the RNA level with both PCR methods in two cases. In this study, the efficiency of imatinib treatment and a dramatic response in two HES cases with multisystemic involvement showing the characteristics of a chronic myeloproliferative disease were presented. Both cases showed complete responses confirming that imatinib mesylate treatment could be successful even in patients with advanced HES having myeloproliferative disease.

WOS: 000306389200002, We report our experience in 41 patients with chronic phase (CF)-chronic myeloid leukemia (CML) who had discontinued imatinib switched to dasatinib, retrospectively. The CF-CML patients received dasatinib at starting dose of 100 once daily. Dose adjustment were observed in 11 patients, respectively. In case of other circumstances, treatment has been continued with a lower dose if needed. The median dose of dasatinib was 100 mg daily (range: 50 to 140 mg). We conclude that even low-dose dasatinib therapy is an effective and safe in second line treatment of CML patients patients.

A 45-year-old male patient was admitted to our emergency department complaining of fatigue, headache, mild confusion, nausea, and vomiting. He had had Type 2 diabetes mellitus for 10 years that was managed with insulin injections. Two days before the onset of symptoms, he had consumed the natural herb Chenopodium polyspermum to regulate his blood glucose levels. Upon examination, he was found to be experiencing tenderness in the upper left abdominal area, icteric sclera, and pallor conjunctivas. Laboratory tests revealed that he was anemic and had increased levels of indirect bilirubin, lactic dehydrogenase, and creatinine in blood. Direct and indirect Coombs tests were negative, and fragmented erythrocytes were observed in peripheral blood smears. The best supportive care was provided, and therapeutic plasma exchange (TPE) treatments were administered. TPE was performed five times and hemolytic findings improved. The patient then developed chronic renal failure and was transferred to the dialysis program and discharged. In this article, we present a case with hemolytic and renal toxicity induced by the ingestion of Chenopodium polyspermum that was managed with TPE and hemodialysis. J. Clin. Apheresis 27:278–281, 2012. © 2012 Wiley Periodicals, Inc.

Previous studies have suggested that DNA repair enzyme polymorphisms may bear prognostic value in metastatic colorectal carcinoma (MCRC).We prospectively treated 43 MCRC patients with irinotecan-based regimens (XELIRI or IFL). Allelic variants of the XRCC1 gene at codon 399 and XPD gene at codon 751 were analyzed in lymphocyte DNA by PCR-RFLP. Clinical outcome variables: overall survival (OAS), progression-free survival (PFS) and the occurrence of grade 3 or 4 hematological and gastrointestinal (GIS) toxicities were evaluated.In the univariate analysis for OAS (n = 43) only XPD and XRCC1 polymorphisms were significant (P = 0.05 and P = 0.04, respectively). After adjustment for performance status (ECOG = 0, 1 vs. 2) and disease extent (single vs. multiple metastatic site), XRCC1 genotype and performance status retained significance (HR = 2.85, P = 0.04, and HR = 3.19, P = 0.02, respectively). Gln/Gln genotype was associated with the greatest risk of death. Type of presentation (metastatic vs. local disease at first presentation) was the only significant predictor of PFS in the univariate analysis (n = 40, P = 0.003). After adjustment for performance status and disease extent, type of presentation retained its significance (HR = 4.35, P = 0.003). None of the toxicities was associated with these genotypes.XRCC1 genotype independently predicted overall survival in metastatic colorectal carcinoma patients treated with irinotecan-based chemotherapy.

To identify the outcomes of prognostic factors of solitary plasmacytoma mainly treated with local radiotherapy (RT). The data were collected from 80 patients with solitary plasmacytoma (SP). Forty patients (50.0%) received radiotherapy (RT) alone while 38 of them (47.5%) were treated with surgery (S) and RT. The median radiation dose was 46 Gy (range 30-64). The median follow up was 2.41 years (range 0.33-12.33). Ten-year overall survival (OS) and local relapse-free survival (LRFS) were 73% and 94%, respectively. The median progression-free survival (PFS) and multiple myeloma-free survival (MMFS) were 3.5 years and 4.8 years, respectively. On multivariate analyses, the favorable factors were radiotherapy dose of > or =50 Gy and RT + S for PFS and younger age for MMFS. For the patients with medullary plasmacytoma, the favorable factor was younger age for MMFS. RT at > or =50 Gy and RT + S may be favorable prognostic factors on PFS. Younger patients, especially with head-neck lesion and without pre-RT macroscopic tumor, seem to have the best outcome when treated with RT +/- S. Progression to MM remains as the main problem especially for older patients.

PubMed ID: 15635269, Carbohydrate antigen-125 (CA-125) is a tumor marker that has been used for differential diagnosis of peritoneal malignancies. The aim of the present study was to evaluate the diagnostic usefulness of simultaneous quantification of CA-125 in peritoneal fluid and serum for abdominal cancer cases and noncancer diseases. Noncancer disease group included cirrhotic patients (n = 28) and spontaneous bacterial peritonitis (SBP) patients (n = 11). Abdominal cancer group was composed of histologically diagnosed various malignancies (n = 10), such as gastric cancer. CA-125 levels were quantified by chemiluminescent enzyme immuno-assay. Diagnostic usefulness tests and receiver operating characteristics (ROC) curve analysis were performed for the levels of peritoneal fluid CA-125 (pCA-125) and serum CA-125 (sCA-125), and the ratio of pCA-125 to sCA-125 (p/sCA-125). The sCA-125 levels were significantly higher in noncancer patients than those in the cancer patients, while the pCA-125 levels showed no significant difference between the two groups. Notably, the p/sCA-125 ratio was significantly lower in the noncancer patients than that in the cancer patients. Area under the ROC curve was 0.267 for sCA-125, 0.542 for pCA-125 and 0.831 for p/sCA-125. The accepted cutoff values were the combination of values that gave the greatest diagnostic sensitivity plus specificity. Either sCA-125 or pCA-125 value gave lower diagnostic accuracy, whereas p/sCA-125 value demonstrated a significantly higher diagnostic accuracy (sensitivity-specificity pairs: 0.40-0.33 for sCA-125, 0.60-0.54 for pCA-125, and 0.80-0.72 for p/sCA-125, respectively). Hence, determination of p/sCA-125 improves the biochemical discrimination of abdominal cancerous cases from noncancerous diseases. © 2005 Tohoku University Medical Press.

This study investigated the frequency of allelic imbalance (AI) in particular loci in conventional renal cell carcinoma tissue and premalignant lesions of the kidney. DNA from the tumor tissue, premalignant lesions and normal kidney tissue of radical nephrectomy specimens from 33 patients was obtained. It was amplified with a set of eight microsatellite markers, which are located on chromosomes 2, 3, 5, 8, 9, 11, 16, 17. AI in DNA samples was determined by analysis of the alteration in (CA)n repeats. The rates of AI in tumor tissue were found to be between 22.2% and 53.3% and in premalignant lesions between 11.1% and 40.0%. Premalignant lesions and tumor tissues in conventional renal cell carcinoma have the same genotypic changes in 50.0-87.8% (informative cases). These results suggest that the progressive accumulation of AI in areas of premalignant lesions may contribute to the development of renal cell carcinoma, representing an important molecular event in the multistep renal carcinogenesis cascade.

WOS: 000187184800027, PubMed ID: 14675333, Acute leukemias tend to affect a younger population and are much more common in pregnant patients than chronic leukemias are. We report a case of acute lymphoblastic leukemia diagnosed during the third trimester presenting with organomegaly and thrombocytopenia. Delivery of the fetus by cesarean section was decided because of the fulminant nature of the acute leukemia within days of admission. Bone marrow biopsy revealed acute lymphocytic leukemia, French American-British L-2 subtype B cell immunotype. A left ovarian mass was identified during the cesarean section which later proved to be lymphoblastic infiltration. The patient was started on induction chemotherapy consisting of vincristine, daunorubicin, prednisolone, and L-asparaginase immediately after the diagnosis. The patient died of Acinetobacter septicemia 18 days after the first admission.

Introduction Nilotinib, a more potent and selective drug than imatinib, was approved by the FDA and EMA initially for the treatment of chronic and accelerated phase Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia (CML) patients resistant or intolerant to prior therapy including imatinib and subsequently for the treatment of newly-diagnosed Ph+ CML patients in the chronic phase (CML-CP). The aim of the present study was to investigate efficacy and safety profile of nilotinib in a Turkish population of newly-diagnosed Ph+ CML-CP patients and to evaluate the effects of these results on prognosis according to current treatment guidelines. Methods The study was planned as a multicenter, open-label, one-arm phase II clinical trial. All patients were planned to be treated with nilotinib (AMN107, Tasigna®) 300 mg BID for 24 months. Herein, efficacy results of the patients who completed the first year of the study are presented. Results Of the 112 patients included in the study, data for 94 patients who completed 12 months of the study up to April 29, 2013 were analyzed. Of these 94 patients, 16 were excluded within this period and 78 completed the first year of the study within the median 371 days (range, 339-401 days) or median 12.4 months (range, 11.3-13.4 months). General characteristics of the patients are presented in Table 1. Treatment-related characteristics of the patients are presented in Table 2. Data are presented as mean±standard deviation or number (%), where appropriate. MMR (Major molecular rate): BCR-ABL/control gene ratio of ≤%0.1 measured by RQ-PCR as % CCyR (Complete cytogenetic response): Patients with 0% Ph+ metaphases Cumulative MMR rates at 3rd, 6th 9th, and 12th months of the patients are shown in Figure 1. Conclusions According to the results of interim analysis of this first prospective CML study conducted on Turkish population, the cumulative MMR rate by 12th month (primary endpoint) (61.7%) appears to be similar to that of the ENESTnd study. From the 3rd month, rapid and increasing MMR rates were reported and median time to MMR was 6.5 months. At both 6th and 12th month, high CCyR rates (both 90.5%) were also established. At all landmark evaluations, most of the patients rapidly achieved high rates of cytogenetic and molecular responses to nilotinib assessed by both 2009 and 2013 ELN optimal response criteria, and only one patient had disease progression. These results suggest that more rapid and greater efficacy was achieved with nilotinib during the 1st year of the study in comparison to historical data with imatinib and that nilotinib might improve short-term responses when started in the first-line setting. The rate of patients with BCR-ABL ≤10% at 3rd month, which is very important according to the current treatment guidelines, was 86.2%.The results of the present study revealed that efficacy of nilotinib, which is a licensed alternative for the treatment of newly diagnosed Ph+ CML-CP in Turkey, might provide a new standard of treatment. Disclosures: Saydam: Bristol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Novartis Pharmaceuticals Corporation, Turkey: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Haznedaroglu:Novartis Pharmaceuticals Corporation, Turkey: Honoraria, Research Funding. Yavuz:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Ali:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Guvenc:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Sonmez:Novartis Pharmaceuticals Corporation, Turkey: Membership on an entity’s Board of Directors or advisory committees. Akkaynak:Novartis Pharmaceuticals Corporation, Turkey: Employment. Dag:Novartis Pharmaceuticals Corporation, Turkey: Employment.

Background: Oxidative stress induced DNA damage has been assumed to contribute to the etiopathogenesis of schizophrenia (Sch). Smoking prevalence was more common in patients with Sch. The X-ray repair cross-complementation group 4 (XRCC4) gene plays an important role in the repair of DNA double-strand breaks. Objective: The purpose of this study was to investigate whether XRCC4 rs6869366 polymorphism has a relationship both in nicotine dependence (ND) and Sch+ND risk. Methods: One hundred and four patients with Sch+ND, 133 subjects with ND only and 70 healthy controls were enrolled in the study. XRCC4 rs6869366 polymorphism was analyzed using PCR-RFLP assay. Results: The frequency of XRCC4 rs6869366 GG genotype was more common in the ND and Sch+ND group than controls (p = 0.001 and p = 0.001, respectively). XRCC4 rs6869366 TT genotype was lower in both ND and Sch+ND group compared to controls (p = 0.001 and p = 0.001, respectively). Also, XRCC4 rs6869366 G allele was higher in Sch+ND group than controls (p = 0.001) while XRCC4 rs6869366 T allele was lower in ND group than healthy controls (p=0.001). XRCC4 rs6869366 GT genotype was lower in ND group than control group (p = 0.003). Discussion: These results suggested that the XRCC4 rs6869366 polymorphism G related genotype/allele was associated with susceptibility to both ND and Sch+ND in a Turkish population. © 2018, Universidade de Sao Paulo. All rights reserved.