Jak 2 v617f mutasyonunun miyeloproliferatif hastalik gurubundaki sıklığı, tanısal değeri ve prognoz üzerine etkisinin araştırılması

Janus kinaz 2 (JAK2) geni eritropoetin, trombopoetin ve granülosit-makrofaj koloni stimüle edici faktörün sinyallerini iletmeye yarayan reseptörlerin sentezinde rol alır. Ayrıca diğer sitoplazmik proteinlerin de sinyal iletiminde rol alan bu reseptörler için tirozin kinaz görevi yapar. JAK2 geni 9. kromozom üzerinde olup mutasyonu BCR-ABL negatif miyeloproliferatif hastalıklarda (MPH) ilk olarak 2005’te tarif edilmiştir. Yapılan çalışmalar sonucunda polisitemia vera (PV) hastalarının ortalama % 97’sinde, esansiyel trombositoz (ET) hastalarının % 57’sinde, idiopatik miyelofibrozis (IMF) hastaların % 50 sinde bu mutasyon saptanmıştır. Bazı çalışmalarda JAK2 mutasyonuna sahip olan kişilerde diğerlerine göre daha yüksek hemoglobin (Hb), lökosit düzeyleri ve daha fazla artmış kemik iliği sellüleritesi olduğu bulunmuş ve nötrofil aktivasyonu, nötrofil-trombosit komplekslerinin artışının MPH’da trombozla ilişkili olduğu gösterilmiştir. Ayrıca PV hastalarında JAK2 homozigot mutant olan hastalarda daha yüksek Hb, nötrofil değerleri olup bu hastaların kaşıntıya, kemik iliğinde fibrozise daha fazla eğilimli oldukları rapor edilmiştir. Son yapılan çalışmalardan birinde ise mutasyonun şiddetinin artışı ile tromboz riskinin artışı kadar lökositozda ve splenomegali sıklığında da artış olduğu bulunmuştur. Biz bu çalışmada hastanemizde PV, ET ve IMF tanısı almış hasta populasyonunda JAK2 V617F mutasyon sıklığını, hastalıklara göre dağılımını ve klinikle olan ilişkisini araştırmayı planladık. Çalışmaya PV, ET ve IMF tanısı ile takip edilen ve yeni tanı alan 65 hasta alındı. Hastaların 28’inde (% 43,1) PV, 29’unda (% 44,6) ET, ve 8’inde (% 12,3) IMF vardı. Hastaların 41’i (% 63) kadın, 24’ü (% 37) erkek olup ortalama yaşları 64.02±12.42 idi. Mutasyonun sıklığı ET tanılı hastalarda % 62.1, PV tanılı hastalarda % 89,3, IMF tanılı hastalarda % 25 bulundu. Yirmi sekiz PV hastasından JAK2 mutasyonu olan ve olmayanlar cinsiyet, tromboz varlığı, konstitüsyonel semptomlar, kaşıntı, hemoraji, splenomegali, kemik iliği fibrozisi, kemik iliği sellüleritesi ve sitoredüktif tedavi ihtiyacı açısından incelendi. JAK2 mutasyonu olan ve olmayanlar arasında bu özellikler yönünden fark bulunamadı. PV hastaları tanı sırasındaki hemoglobin düzeyi, hematokrit yüzdesi, lökosit sayısı, laktat dehidrogenaz (LDH), eritropoetin (EPO), ürik asit ve ferritin düzeyi açısından incelendiğinde JAK2 mutasyonu olan ve olmayanlar arasında anlamlı fark bulunamadı. PV hastalarında JAK2 mutasyonu olanlarda olmayanlara göre arteriyel ve venöz tromboz sıklığı benzerdi. Bu hastalardan JAK2 mutasyonu homozigot ve heterozigot olanlar cinsiyet, tromboz varlığı, konstitüsyonel semptomlar, kaşıntı, hemoraji, splenomegali, kemik iliği fibrozisi, kemik iliği sellüleritesi ve sitoredüktif tedavi ihtiyacı açısından karşılaştırıldığında anlamlı fark bulunamadı. Yirmi sekiz ET hastasından JAK2 mutasyonu olan ve olmayanlar cinsiyet, tromboz varlığı, konstitüsyonel semptomlar, kaşıntı, hemoraji, splenomegali, kemik iliği fibrozisi, kemik iliği sellüleritesi ve sitoredüktif tedavi ihtiyacı açısından incelendi. JAK2 mutasyonu olan ve olmayanlar arasında anlamlı bir fark bulunamadı. Bu hastalar tanı sırasındaki hemoglobin düzeyi, hematokrit yüzdesi, lökosit sayısı, LDH, EPO, ürik asit ve ferritin düzeyi açısından incelendiğinde JAK2 mutasyonu olan ve olmayanlar arasında anlamlı fark bulunamadı. ET hastalarında JAK2 mutasyonu olanlarda olmayanlara göre arteriyel ve venöz tromboz sıklığı benzerdi. Bu hastalar JAK2 mutasyonu homozigot ve heterozigot olanlar tromboz varlığı, konstitüsyonel semptomlar, kaşıntı, hemoraji, splenomegali, kemik iliği fibrozisi, kemik iliği sellüleritesi ve sitoredüktif tedavi ihtiyacı açısından karşılaştırıldığında istatistiksel olarak anlamlı fark bulunamadı. Sekiz IMF hastasından JAK2 mutasyonu olan ve olmayanlar cinsiyet, tromboz varlığı, konstitüsyonel semptomlar, kaşıntı, hemoraji, splenomegali, kemik iliği sellüleritesi ve sitoredüktif tedavi ihtiyacı açısından incelendi. JAK2 mutasyonu olan ve olmayanlar arasında bu açılardan fark bulunamadı. Hastalar tanı sırasındaki hemoglobin düzeyi, hematokrit yüzdesi, lökosit sayısı, LDH, eritropoetin, ürik asit ve ferritin düzeyi açısından incelendiğinde JAK2 mutasyonu olan hastaların hematokrit ve lökosit düzeyleri olmayanlara göre anlamlı olarak yüksek bulundu, diğer parametreler açısından anlamlı fark bulunamadı. Bu çalışmada bulunan JAK2 mutasyonunun MPH’daki sıklığı literatürle benzer olup tanısal değeri bir kez daha doğrulanmıştır. JAK2 mutasyonunun MPH’ın laboratuar ve klinik özellikleri ile korelasyonu ve prognostik değeri ile ilgili daha kapsamlı, prospektif çalışmalara ihtiyaç vardır. Janus kinase 2 (JAK2) gene plays a role in syntesis of erytropoetin, thrombopoetin and granulocyte-macrophage colony stimulating factor receptors. In addition, it works as a tyrosine kinase molecule to these receptors which accomplish signal conduction for other cytoplasmic proteins. JAK2 gene is on 9th chromosome and firstly described in 2005 for BCR-ABL negative myeloproliferative diseases (MPD). This mutation was determined 97% of patients with policytemia vera (PV), 57% of patients with essential thrombocytemia (ET), 50% of patients with idiopathic myelofibrosis (IMF). Some studies showed that pateints with JAK2 mutation had higher hemoglobin (Hb), leukocyte counts and more celluler bone marrow. In these studies, increase in neutrophil-platelet complexes was found related with thrombosis in MPH. In addition, PV pateints with homozygous JAK2 mutation were reported to have high Hb, neutrophil counts and more pruritus. In a recent study, there was found that frequency of splenomegaly and leukocytosis increase when mutation severity increases. We planned to investigate frequency and relation with clinical findings of JAK2 V617F mutation in pateints with PV, ET and IMF. We included 65 patients with PV, ET and IMF. There were 28 (43,1 %) patients with PV, 29 (44 %) patients with ET, 8 (12,3 %) patients with IMF. Forty one (63 %) pateints were female and 24 (37 %) pateints were male. Mean age of patients was 64.02±12.42. Frequency of mutation was 62 % in PV pateints, 89,3 % in ET patients and 25 % of IMF patients. We compared JAK2 mutated PV pateints with unmutated PV pateints in points of gender, thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow fibrosis and cytoreductive treatment requirement.We found no difference among these pateints. We compared JAK2 mutated PV pateints with unmutated PV pateints in points of Hb, hematocrit, leukocyte count, lactate dehidrogenase (LDH), erytropoetin (EPO) and ferritin level. We found no difference among these patients. We compared JAK2 mutated PV pateints with unmutated PV pateints in points of frequency of arterial and venous thrombosis and found no difference. We compared homozygous JAK2 mutated PV patients with heterozygous mutated PV pateints in points of gender, thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow 7 fibrosis and cytoreductive treatment requirement. We found no difference among these patients. We compared JAK2 mutated ET patients with unmutated ET patients in points of gender, thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow fibrosis and cytoreductive treatment requirement.We found no difference among these pateints. We investigated these patients in points of Hb, hematocrit, leukocyte count, lactac dehidrogenase (LDH), erytropoetin (EPO) and ferritin level and found no difference. In these patients, frequency of arterial and venous thrombosis were similar. We compared homozygous JAK2 mutated ET patients with heterozygous mutated ET patients in points of gender, thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow fibrosis and cytoreductive treatment requirement. We found no difference among these patients. We compared JAK2 mutated IMF patients with unmutated IMF patients in points of gender, thrombosis, constitutional symptoms, pruritus, hemorrhage, splenomegaly, bone marrow fibrosis and cytoreductive treatment requirement. We found no difference among these patients. When these patients were compared in points of Hb, hematocrit, leukocyte count, lactate dehidrogenase (LDH), erytropoetin (EPO) and ferritin level we found hematocrit percent and Hb were higher in JAK2 mutated patients than unmutated patients and the other parameters were not different. In this study we found frequency of JAK2 mutation in MPH similar with litherature and this study confirmed diagnostic value of mutation. Comprehensive prospective studies are necessary for determining the correlation of mutation with clinical findings and its prognostic value

Cleft lip and cleft palate: a disease with multiple risk factors in a pregnant woman

Clefts of the lip and/or palate (CLP) are currently the most common craniofacial birth defects that arise as a result of failure of facial embryonic processes to fuse. CLP etiology, which involves both genetic and environmental factors, is highly complex; its molecular basis remains largely unknown. In the current study we present a case report of a woman with prenatal diagnosis of cleft lip and palate, who had multiple risk factors including genetics, advanced age, family history, antiepileptic drug usage, consanguineous marriage and smoking. Her previous child was born with CLP, and this also contributes. Data of our study supports the hypothesis of a multifactorial etiology for CLP

IN VITRO SUSCEPTIBILITY OF METHICILLIN-RESISTANT STAPHYLOCCOCCUS AUREUS TO LINEZOLID BY E-TEST METHOD

SUMMAR

Splenectomy in patients with idiopathic thrombocytopenic purpura: Analysis of 109 cases

Objectives: Splenectomy is performed in order to provide the treatment in the patients with severe idiopathic thrombocytopenic purpura, refractory to medical treatment. In this study, we aimed to investigate the postoperatif and longterm outcomes in the patients who underwent splenectomy with the diagnosis of idiopathic thrombocytopenic purpura.Materials and Methods: Between 2001-2010 at Dicle University Medical Faculty, General Surgery Department, a retrospective review of the 109 patients who had undergone splenectomy for ITP was reviewed. Age, gender, presence of accessory spleens and location, duration of the operation, number of preoperative platelet tranfusion, number of preoperative and postoperative blood transfusion, length of hospital stay, long-term outcomes, morbidity and mortality were recorded.Results: The mean age was 37.10 ± 16.62 (16-72), and there were 88 (80.7%) female and 21 (19.3%) male patients. The mean operation time was 44.87 ± 10:32 (30-120) minutes. The average postoperative blood and preoperative platelet transfusion were 1.63 ± 0.85 (0-3) and 2.01 ± 0.71 (1-3) units, respectively. The accessory spleens were encountered in 20 (18.3%) patients at the ultrasonographic examination. And also the accessory spleens were encountered in 23 (21.1%) patients during operation and confirmed with histopathologic examination. The most common localization of accessory spleens were splenic hilus. The postoperative complications were occurred in 16 patients (14.7%) and the most complication was atelectasia. The mean length of hospital stay was 4:56 ± 2:45 (2-12) days. Patients were followed for an average of 28 (9-48) months. At the follow-up period, 1 (0.9 %) patient had died.Conclusion: Splenectomy can be performed safely in the treatment of the patients with idiopathic thrombocytopenic purpura unresponsive to medical treatment. Long-term good results can be obtained with splenectomy in these patients. The accessory spleens should not be overlooked to prevent recurrences

İmperfore himen operasyonu sonrasında gelişen stenoz ve Z-plasti yöntemi ile düzeltilmesi

İmperfore himen IH , dişi genital sistem anomalilerinden en sık karşılaşılanıdır. Vaka sunumumuzda IH nedeniyle opere edilen ve sonrasında himenal stenoz gelişen bu nedenle Z–plasti yöntemi ile himenoplasti yapılan olgu sunulmuştu

Evaluation of Four Adult Visceral Leishmaniasis Cases

Leishmania infantum is the species responsible for visceral leishmaniasis [(VL), kala-azar], which is observed sporadically mainly in pediatric age groups in the Aegean, Mediterranean and Central Anatolian regions of Türkiye. The aim of this study is to evaluate the diagnosis, clinic, laboratory results and treatments of four adult patients with VL who applied to our hospital. The patients were referred to our hospital to investigate hematological malignancy. In the study, the data of four patients (three men, one woman; age range: 30-40 years) who were diagnosed with VL and treated in the infectious diseases clinic of our hospital between January 2022 and April 2022 were evaluated retrospectively. The diagnosis of VL was made according to appropriate clinical and physical examination findings, biochemical and serological tests (indirect fluorescent antibody test and rK39 rapid antigen test) and polymerase chain reaction (PCR) results, as well as the presence of amastigote forms of the parasite in bone marrow samples. Serology positivity was found in all patients, and bone marrow positivity was found in two patients. According to the results of RT-PCR in all patients, it was determined that the species causing the disease was L. infantum/L. donovani. Initially, the most common symptoms were fever, fatigue, and abdominal distension. None of the patients had an immunosuppressive condition. It was understood that all the patients lived in the rural area of Syria’s Idlib province. Hepatosplenomegaly, increased erythrocyte sedimentation rate, anemia, leukopenia and thrombocytopenia were found in all patients. The patients were treated with liposomal amphotericin-B (L-AMB). One patient did not come for follow-ups, the other three patients were found to have completely recovered in their follow-up. No recurrence was observed in any of the patients. In conclusion, VL should be considered in patients who apply to health institutions with complaints of fever, hepatosplenomegaly, increased erythrocyte sedimentation rate, anemia, leukopenia and thrombocytopenia

Familial Mediterranean fever: Health-related quality of life and associated variables in a national cohort

Objectives: This study aims to evaluate the effectivity of Familial Mediterranean Fever Quality of Life (FMF-QoL) Scale for the measurement of QoL in patients with FMF and to perform correlations between related clinical variables in Turkish patients. Patients and methods: This multicenter prospective study performed between December 2017 and November 2018 included 974 FMF patients (334 males, 640 females; median age: 35; range, 26 to 45 years). Sociodemographic characteristics and clinical features were recorded. All participants were asked to complete the FMF-QoL Scale, Short Form-36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Health Assessment Questionnaire (HAQ), and Functional Assessment of Chronic Illness Therapy (FACIT) Scale. Results: The median FMF-QoL Scale score was 26. Higher FMF-QoL Scale scores were shown to be related to female sex, illiteracy or primary education, monthly low-income (US$20 years), a higher number of attacks per month (>1/month), and severe disease. FMF-QoL Scale scores were correlated negatively with subscales of SF-36, and positively with HADS-anxiety and HADS-depression scores, HAQ and FACIT. Conclusion: Female sex, smoking, lower educational status, more severe disease, fatigue, and functional impairment were associated with poor QoL. FMF-QoL Scale was noted as a valid and simple patient-reported outcome instrument and correlated with the SF-36 scale

Plasma Ischemia-Modified Albumin Levels and Dynamic Thiol/ Disulfide Balance in Sickle Cell Disease: A Case-Control Study

Objective: Sickle cell disease (SCD), described as a group of inherited blood disorders, affects millions of people throughout the world and is particularly common in the southern part of Turkey. We aimed to determine the relationship between ischemia-modified albumin (IMA) and the dynamic thiol/disulfide balance in SCD. Materials and Methods: Fifty-four adult SCD patients and 30 healthy controls were included in the study. The 54 adult patients included 30 (56%) males and 24 (44%) females with a mean age of 28.3±8.4 years (minimum-maximum: 18-46 years). Of the 54 patients, 46 had homozygous sickle cell anemia (HbSS) and 8 had sickle/β-thalassemia (HbS/β+-thalassemia). Fasting blood samples were collected. After centrifugation at 1500×g for 10 min, plasma samples were portioned and stored at -80 °C. IMA levels were determined by albumin cobalt binding test, a colorimetric method. Total and native thiols and disulfide were analyzed with a novel spectrophotometric method. Results: We found significantly lower levels of native thiol (-SH) (284.0±86.3 μmol/L), disulfide levels (14.6±7 μmol/L), and total thiols (-SH + -S-S-) (313.0±89.3 μmol/L) in SCD patients compared to healthy controls (respectively 417.0±54.2, 22.7±11.3, and 462.0±58.7 μmol/L). Plasma albumin levels (34.9±7.9 g/L) were lower and IMA levels (13.6±3.1 g/L) were higher in SCD patients compared to controls (respectively 43.5±3.1 and 8.4±1.6 g/L). Plasma albumin levels were strongly correlated with both plasma native (r=0.853; p=0.0001) and total thiols (r=0.866; p=0.0001). Conclusion: Decreased plasma native and total thiol levels and increased IMA levels are related to increased oxidative stress and provide an indirect and quick reflection of the oxidative damage in SCD patients

Are serum Netrin-4 levels predictive of preeclampsia?

Objective: To investigate the levels of anti-angiogenic factors, namely sFlt-1 and Netrin-4, in patients with preeclampsia (PE). Material and methods: Cord-blood (UC) sFlt-1 and Netrin-4 concentrations were measured in 30 patients with severe PE, 30 patients with PE and 30 control infants and their mothers (MS). Results: Maternal sFlt-1 levels were significantly higher in the severe PE and PE groups than in the control group. There were no statistical differences among the three groups in maternal and fetal Netrin-4 levels. But Netrin-4 levels were found to be the lowest in the control group and higher in the PE and severe PE groups. The correlation analysis revealed a positive correlation between maternal sFlt-1 levels and maternal Netrin-4 levels (p = 0.012, and r = 0.263), maternal sFlt-1 levels and fetal sFlt-1 levels (p = 0.012, and r = 0.263). Conclusions: There was a positive correlation found between maternal sFlt-1 levels and maternal Netrin-4 levels. We are of the opinion that elevation in levels of Netrin-4 might be secondary to placental hypoxia occurring in PE. The present study led to the consideration of anti-angiogenic biomarkers (sFlt-1 and Netrin-4) on automated platforms for clinical use as an aid in establishing the diagnosis and prognosis of PE