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Publication Open Access A case of Burkitt’s lymphoma mimicking peritonitis carcinomatosa(Galenos Yayınevi, 2020) Örnek, Serdar; Tecimer Tülay; Ferhanoğlu, Ahmet Burhan; Büyüktaş, Deram; Faculty Member; Faculty Member; School of Medicine; 18320; N/APublication Open Access A multi-center study on the efficacy of eltrombopag in management of refractory chronic immune thrombocytopenia: a real-life experience(Galenos Yayınevi, 2019) Çekdemir, Demet; Güvenç, Serkan; Özdemirkıran, Füsun; Eser, Ali; Toptaş, Tayfur; Özkocaman, Vildan; Haydaroğlu Şahin, Handan; Ermiş Turak, Esra; Esen, Ramazan; Cömert, Melda; Sadri, Sevil; Aslaner, Müzeyyen; Uncu Ulu, Bahar; Karakuş, Abdullah; Selim Bapur, Derya; Alacacıoğlu, İnci; Aydın, Demet; Tekinalp, Atakan; Namdaroğlu, Sinem; Ceran, Funda; Tarkun, Pınar; Kiper, Demet; Çetiner, Mustafa; Yenerel, Mustafa; Demir, Ahmet Muzaffer; Yılmaz, Güven; Terzi, Hatice; Atilla, Erden; Malkan, Ümit Yavuz; Acar, Kadir; Öztürk, Erman; Tombak, Anıl; Sunu, Cenk; Salim, Ozan; Alayvaz, Nevin; Sayan, Özkan; Ozan, Ülkü; Ayer, Mesut; Gökgöz, Zafer; Andıç, Neslihan; Kızılkılıç, Ebru; Noyan, Figen; Özen, Mehmet; Pepedil Tanrıkulu, Funda; Alanoğlu, Güçhan; Özkan, Hasan Atilla; Aslan, Vahap; Çetin, Güven; Akyol Erikçi, Alev; Deveci, Burak; Ersoy Dursun, Fadime; Dermenci, Hasan; Aytan, Pelin; Gündüz, Mehmet; Karakuş, Volkan; Özlü, Can; Demircioğlu, Sinan; Akay Yanar, Olga Meltem; Özatlı, Düzgün; Ündar, Levent; Tiftik, Eyüp Naci; Türköz Sucak, Ayhan Gülsan; Haznedaroğlu, İbrahim; Özcan, Muhit; Şencan, Mehmet; Tombuloğlu, Murat; Özet, Gülsüm; Bilgir, Oktay; Turgut, Burhan; Özcan, Mehmet Ali; Bahriye Payzın, Kadriye; Sönmez, Mehmet; Ayyıldız, Orhan; Dal, Mehmet Sinan; Ertop, Şehmus; Turgut, Mehmet; Soysal, Teoman; Kaya, Emin; Ünal, Ali; Pehlivan, Mustafa; Atagündüz, Işık; Tuğlular Fıratlı, Tülin; Saydam, Güray; Diz Küçükkaya, Reyhan; N/A; Çetiner, Mustafa; Öztürk, Erman; Faculty Member; Doctor; School of MedicineObjective: 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. / Amaç: bu çalışmanın amacı kronik immün trombositopeni (ITP) hastalarında bir oral trombopoietin reseptör agonisti olan eltrombopagın etkinlik ve güvenirliliğini değerlendirmektir. Gereç ve Yöntemler: elli beş merkezde izlem altındaki toplam 285 kronik ITP hastası (187 kadın, %65,6) bu geriye dönük küme çalışmasına alınmıştır. Tedaviye yanıt trombosit sayısına göre değerlendirilmiş ve tam yanıt (>100.000/mm3), kısmi yanıt (30.000-100.000/mm3 veya tedaviden sonra trombosit sayısının bir kat artmış olması) ve yanıtsızlık (<30.000/mm3) olarak tanımlanmıştır. Hastaların klinik bulguları, tanımlayıcı özellikleri, tedaviye yanıt ve yan etki bilgileri toplanmış ve aralarındaki ilişki incelenmiştir. Bulgular: tanı anında yaş ortalaması 43,9±20,6 (3-95) yıl olan hastalar ortalama 18,0±6,4 (6-28,2) ay izlenmiştir. Tam ve kısmi yanıtı içeren toplam yanıt %86,7 (n=247) bulundu. Sırasıyla 182 (%63,8) ve 65 (%22,8) hastada tam ve parsiyel tedavi yanıtları gözlenmiştir. Otuz sekiz hasta (%13,4) eltrombopag tedavisine yanıt vermemiştir. Altmış yaş üzerindeki hastalarda (n=68) toplam yanıt %89,7 (n=61) bulunurken, bu oran 80 yaş üzerindeki (n=12) hastalarda %83 (n=10) olmuştur. Tedavi öncesi trombosit sayısı göz önüne alındığında, eltrombopag, tedavinin 1., 2., 3., 4. ve 8. haftalarında trombosit sayısını anlamlı şekilde artırmıştır. Kısmi veya tam cevap için gereken süre arttıkça, tedaviye cevap önemli ölçüde azaldığı saptanmıştır. Eltrombopag tedavisinden sonra maksimum trombosit sayısı ne kadar yüksekse, yan etkilerin oluşabilme ihtimalinin o kadar yüksek olabildiği dikkati çekmiştir. En sık görülen yan etkiler baş ağrısı (%21,6), güçsüzlük (%13,7) ve hepatotoksisite (%11,8) ve trombozdur (%5,9). Sonuç: Mevcut çalışmanın sonuçları, eltrombopag tedavisinin kronik ITP’de, yaşlı hastalar dahil olmak üzere, etkili bir tedavi seçeneği olduğunu göstermektedir. Bununla birlikte, hastalar tedavi sırasında yanıt ve yan etkiler açısından yakından izlenmelidir. Hem cevap hem de yan etkiler, takip süresi boyunca değişken olabileceğinden, hastalar özellikle tromboz risk faktörleri açısından dinamik olarak değerlendirilmelidir.Publication Open Access Blood storage alters mechanical stress responses of erythrocytes(IOS Press, 2017) N/A; Uğurel, Elif; Küçüksümer, Zeynep; Eğlenen, Buse; Yalçın, Özlem; Researcher; Graduate School of Health Sciences; School of Medicine; N/A; N/A; N/A; 218440BACKGROUND: Erythrocytes undergo irreversible morphological and biochemical changes during storage. Reduced levels of deformability have been reported for stored erythrocytes. Erythrocyte deformability is essential for healthy microcirculation. OBJECTIVE: The aim of this study is to evaluate shear stress (SS) induced improvements of erythrocyte deformability in stored blood. METHODS: Deformability changes were evaluated by applying physiological levels of SS (5 and 10 Pa) in metabolically depleted blood for 48 hours and stored blood for 35 days with citrate phosphate dextrose adenine-1 (CPDA-1). Laser diffractometry was used to measure erythrocyte deformability before and after application of SS. RESULTS: Erythrocyte deformability, as a response to continuous SS, was significantly improved in metabolically depleted blood, whereas it was significantly impaired in the blood stored for 35 days with CPDA-1 (p <= 0.05). The SS-induced improvements of deformability were deteriorated due to storage and relatively impaired according to the storage time. However, deformability of stored blood after exposure to mechanical stress tends to increase at low levels of shear while decreasing at high SS levels. CONCLUSION: Impairment of erythrocyte deformability after storage may contribute to impairments in the recipient's microcirculation after blood transfusion. The period of the storage should be considered to prevent microcirculatory problems and insufficient oxygen delivery to the tissues.Publication Open Access Cases of secondary hemophagocytic lymphohistiocytosis: a single center experience(Ferrata Storti Foundation, 2015) Karaman, Serap; Yıldız, İsmail; Nisli, Kemal; Aktürk, Hacer; Citak, Agop; Anak, Sema; Unuvar, Ayşegül; Öztürk, Gülyüz; Karakaş, Zeynep; Devecioğlu, Ömer; N/A; Demirkol, Demet; Bilge, İlmay; Faculty Member; Faculty Member; School of Medicine; N/A; 198907Publication Open Access Comparative hemorheology(IOS Press, 2013) Meiselman, Herbert J.; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; 2389Comparative data on blood composition and blood flow properties indicate different levels of interspecies variation for several parameters. Hematocrit and hemoglobin levels have relatively low variability among mammals, while mean cell volume and red blood cell (RBC) count are more variable. There is also a difference of variability between high and low shear rate blood viscosity in mammals, with low shear rate viscosity having a higher degree of interspecies variation. This observation parallels the diversity of RBC aggregation among mammalian species. Allometric relations for blood rheology parameters indicate highly significant correlations of low shear rate blood viscosity and RBC aggregation with body weight, especially if species belonging to the order Artiodactyla are excluded. These allometric relations can be used to formulate various hypotheses about the evolutionary histories of circulatory functions, as well as hypotheses related to the role of RBC aggregation in the mammalian circulatory system. Such comparative studies and analytical reasoning based on comparative data may contribute to answering the “why” questions, and accordingly may improve our understanding of circulatory functions and hence may have possible clinical importance. During the last several decades, similar approaches to various medical concepts have yielded a new approach to medicine that is now known as Evolutionary Medicine.Publication Open Access Data reduction methods for ektacytometry in clinical hemorheology(IOS Press, 2013) Meiselman, Herbert J.; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; 2389Laser-diffraction ektacytometry is a generally accepted technique for measuring RBC deformability induced by fluid shear stress (SS) and yields paired elongation index-SS data at several levels of stress. Unfortunately, comparison of results is hindered by the lack of simple indices that accurately characterize these data. Several mathematical models have been proposed, including those developed for analysis of enzyme kinetics (Lineweaver-Burk, Eadie-Hofstee) and curve fitting (Streekstra-Bronkhorst). All of these analytical approaches provide a value for cell deformation at infinite stress (EImax) and the shear stress required to achieve one-half of this deformation (SS1/2); the use of non-linear regression is essential when calculating these parameters. While the current models provide equivalent results for normal RBC if used with non-linear regression, EImax and SS1/2 are not always concordant for cells with abnormal mechanical behavior. This technical note examines such differences for three conditions: glutaraldehyde treatment, mechanical stress and non-isotonic media. It was found that none of the models yield completely satisfactory values for EImax and SS1/2, especially if there are large changes of EImax. However, the ratio of SS1/2 to EImax (SS1/2/EImax) is much less affected by these problems, has similar power (i.e., standardized difference) as SS1/2 and EImax and is more robust in reflecting alterations of deformability. We thus conclude that the SS1/2/EImax ratio can be used when reporting and comparing various populations of RBC or cells obtained from subjects having different clinical states.Publication Open Access Erythrocyte aggregation: basic aspects and clinical importance(IOS Press, 2013) Meiselman, Herbert J.; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; 2389Red blood cells (RBC) aggregate to form two- and three-dimensional structures when suspended in aqueous solutions containing large plasma proteins or polymers; this aggregation is reversible and shear dependent (i.e., dispersed at high shear and reformed at low or stasis). The extent of aggregation is the main determinant of low shear blood viscosity, thus predicting an inverse relationship between aggregation and in vivo blood flow. However, the effects of aggregation on hemodynamic mechanisms (e.g., plasma skimming, Fahraeus Effect, microvascular hematocrit) may promote rather than impede vascular blood flow. The impact of enhanced RBC aggregation on endothelial function and hemostatic mechanisms adds further complexity, thereby requiring specific attention to the nature, extent and time course of aggregation when considering its overall influence on tissue perfusion. A detailed understanding of aggregation effects is important from a clinical point of view since it may be enhanced during a variety of pathophysiological processes, including infections, circulatory and metabolic disorders, hematological pathologies and several other disease states. Altered RBC aggregation may be an indicator of disease as well as a factor affecting the course of the clinical condition; the prognostic value of RBC aggregation indices has been demonstrated in various diseases. Currently, RBC aggregation is an easily and accurately measurable parameter, and therefore may be expected to have broader clinical usage in the future.Publication Open Access Evaluation of iron deposition in the adrenal glands of beta thalassemia major patients using 3-Tesla MRI(Kowsar Publishing Corporation, 2016) Güzelbey, Tevfik; Özveren, Olcay; Sarsılmaz, Ayşegül; Karasu, Ebru; N/A; N/A; Gürses, Bengi; Öztürk, Erman; Faculty Member; Doctor; School of MedicineBackground: Beta-thalassemia major (beta-TM) patients need blood transfusions, which result in iron deposition. To regulate chelation therapy, iron load has to be measured. With MRI, the amount of signal loss and T2* decay time shortening are used for iron quantification. Objectives: The aim was to measure adrenal iron load with T2* relaxometry using MRI, and to compare it with liver and cardiac iron and serum ferritin, and to find out whether adrenal iron could be predicted from those parameters. Patients and Methods: Between October 2014 and March 2015, MRI was performed in 21 patients with beta-TM, recieving blood transfusions and chelation therapy. The control group (n = 11) included healthy volunteers with no known history of adrenal, hematologic, chronic disease, and blood transfusion. Results: Among patients, there was no significant correlation between plasma ferritin and adrenal T2*. Significant difference was detected among T2* values of adrenals between the patient and control groups. There was no significant correlation between adrenal gland and liver T2* in beta-TM patients, moderate correlation was detected between adrenal T2* and cardiac T2*. Conclusion: Adrenal iron in beta-TM can be reliably measured in 3 Tesla MRI. The results highlight the absence of correlation between adrenal iron deposition both with serum ferritin and hepatic iron.Publication Open Access Exercise hemorheology: classical data, recent findings and unresolved issues(IOS Press, 2012) Connes, Philippe; Simmonds, Michael J.; Brun, Jean-Frederic; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; 2389The present review focuses on the past and recent knowledge in the field of exercise hemorheology and presents some unresolved issues for opening discussion. Acute exercise is associated with a rise in hematocrit which results in an increase in blood viscosity. Whereas increased blood viscosity was previously viewed as having negative consequences for cardiovascular function and aerobic performance, recent findings suggest dynamic changes in blood viscosity might be useful for vascular function during exercise by increasing nitric oxide production. Other determinants of blood viscosity are altered by exercise (e.g., decreased red blood cell deformability, increased red blood cell aggregation and plasma viscosity) and may, independent of the associated effect on blood viscosity, directly modulate aerobic capacity. However, the data published on the effects of exercise on the hemorheology are not consistent, with some studies showing decreased, unchanged, or increased red blood cell deformability/aggregation when compared with rest. These discrepancies seem to be related to the exercise protocol investigated, the population tested or the methodogy utilized for hemorheological measurements. Finally, this review focuses on the effects of training exercise training (i.e. chronic physical activity) on the hemorheological profile of healthy individuals and patients with cardiovascular and metabolic disorders.Publication Open Access Iatrogenic hyperviscosity and thrombosis(Thieme Publishing, 2012) Meiselman, Herbert J.; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; 2389It is well known that hemostatic-thrombotic mechanisms are influenced by hemodynamic factors, such as shear forces affecting platelets or red blood cell aggregation, in turn affecting flow in stenotic regions. Endothelial cell function is also significantly influenced by shear forces acting on the vessel wall. Further, the distribution of shear forces in the vasculature is complex and closely associated with factors determining the flow properties of blood. Therefore, there is a link among alterations in the rheological properties of blood and its elements and the risk for thrombosis, with this linkage confirmed by numerous clinical studies. After discussing relevant rheological and hemodynamic concepts, this review focuses on selected drug-induced conditions that are known to be associated with both hyperviscosity conditions and increased thrombotic risk: oral contraceptives, diuretics, intravenous immunoglobulin, erythropoiesis-stimulating agents, chemotherapy, and radio-contrast media. Alterations of relationships between blood rheology and thrombotic risk related to artificial circulatory environments and physical exercise are also briefly discussed.
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