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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 Metadata only A structured mechanical risk sensitivity assessment system using red cell deformability and fragmentation parameters(Ios Press, 2021) Yalçın, Özlem; Uğurel, Elif; Göktaş, Polat; Göksel, Evrim; Çilek, Neslihan; Atar, Dila; Faculty Member; Researcher; Researcher; PhD Student; PhD Student; Undergraduate Student; School of Medicine; School of Medicine; School of Medicine; Graduate School of Health Sciences; Graduate School of Health Sciences; School of Medicine; 218440; N/A; N/A; N/A; N/A; N/AN/APublication Metadata only Activation of protein kinase a cascade increases deformability of sickle red blood cells(Ios Press, 2021) Connes, Philippe; Boisson, Camille; Renoux, Celine; Gauthier, Alexandra; Fort, Romain; Nader, Elie; Poutrel, Solene; Göksel, Evrim; Yalçın, Özlem; PhD Student; Faculty Member; School of Medicine; School of Medicine; N/A; 218440Publication Metadata only Adult philadelphia chromosome-positive acute lymphoblastic leukemia in daily practice: a multicenter experience(Elsevier, 2016) Tekgunduz, Emre; Goker, Hakan; Kaynar, Leylagul; Sari, Ismail; Pala, Cigdem; Dogu, Mehmet Hilmi; Turgut, Burhan; Korkmaz, Serdal; Tetik, Aysegul; Buyukasik, Yahya; Hacioglu, Sibel Kabukcu; Bozdag, Sinem Civriz; Ozdemir, Evren; Altuntas, Fevzi; N/A; Öztürk, Erman; Doctor; N/A; Koç University Hospital; N/AIn this retrospective, multicenter study, we evaluated the real-life outcomes of adult Philadelphia-positive acute lymphoblastic leukemia patients. The best results in terms of survival are achieved in patients who were treated with tyrosine kinase inhibitors during induction and received allogeneic hematopoietic cell transplantation as part of consolidation. Background: The prognosis of Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) is generally poor. Currently, allogeneic hematopoietic cell transplantation (allo-HCT) is the only accepted therapy with curative potential. Patients and Methods: Herein, we report our multicenter, retrospective experience with 46 (23 female; 23 male) Ph+ ALL patients, who were treated off-study between 2005 and 2012. Results: The median age of the patients was 46 years (range, 19-73 years). During induction, 30 (65%), 13 (28%), and 3 (7%) patients received tyrosine kinase inhibitors (TKIs) concurrent with chemotherapy (TKIs/chemotherapy), chemotherapy only, and TKIs only, respectively. Following induction, rates of complete remission (CR) of the study population were 85% (n = 39). CR rate in patients receiving TKIs during induction (n = 33) was significantly higher compared with patients who received chemotherapy only (n = 13; P = .011). Taking TKIs during induction significantly reduced induction mortality (3.3% vs. 38%; P = .01). Allo-HCT was performed subsequently in 21 (46%) patients. More patients who received TKIs with or without chemotherapy (19/33; 58%) during induction were able to undergo to allo-HCT compared with patients who received chemotherapy only (2/13; 15%; P = .005). Median overall survival of patients who were treated with TKIs during induction and received allo-HCT (not reached; NR) was significantly prolonged compared with patients who received allo-HCT but without TKIs during induction (23.2 months) and to the rest of the cohort (21.2 months; P = .019). Conclusions: Current state-of-the art management of Ph+ ALL in real-life seems to be incorporation of TKIs to chemotherapy regimens and proceeding to allo-HCT, whenever possible.Publication Metadata only Applications of deep learning to the assessment of red blood cell deformability(IOS Press, 2021) Turgut, Alper; N/A; Yalçın, Özlem; Faculty Member; School of Medicine; 218440BACKGROUND: Measurement of abnormal Red Blood Cell (RBC) deformability is a main indicator of Sickle Cell Anemia (SCA) and requires standardized quantification methods. Ektacytometry is commonly used to estimate the fraction of Sickled Cells (SCs) by measuring the deformability of RBCs from laser diffraction patterns under varying shear stress. In addition to estimations from model comparisons, use of maximum Elongation Index differences (Delta EImax) at different laser intensity levels was recently proposed for the estimation of SC fractions. OBJECTIVE: Implement a convolutional neural network to accurately estimate rigid-cell fraction and RBC concentration from laser diffraction patterns without using a theoretical model and eliminating the ektacytometer dependency for deformability measurements. METHODS: RBCs were collected from control patients. Rigid-cell fraction experiments were performed using varying concentrations of glutaraldehyde. Serial dilutions were used for varying the concentration of RBC. A convolutional neural network was constructed using Python and TensorFlow. RESULTS and CONCLUSIONS: Measurements and model predictions show that a linear relationship between Delta EImax and rigid-cell fraction exists only for rigid-cell fractions less than 0.2. The proposed neural network architecture can be used successfully for both RBC concentration and rigid-cell fraction estimations without a need for a theoretical model.Publication Metadata only Assessment of oxidant susceptibility of red blood cells in various species based on cell deformability(IOS Press, 2011) Simmonds, Michael J.; Meiselman, Herbert J.; Marshall-Gradisnik, Sonya M.; Pyne, Michael; Kakanis, Michael; Keane, James; Brenu, Ekua; Christy, Rhys; Başkurt, Oğuz Kerim; Faculty Member; School of Medicine; N/APublication Metadata only Bringing packed red blood cells to the point of combat injury: are we there yet?(Galenos Yayınevi, 2018) Unlu, Aytekin; Yilmaz, Soner; Uyanik, Metin; Petrone, Patrizio; Cetinkaya, Riza Aytac; Eker, Ibrahim; Urkan, Murat; Ozgurtas, Taner; Avci, Ismail Yasar; Zeybek, Nazif; Yalçın, Özlem; Aksu, Ali Cenk; Faculty Member; PhD Student; School of Medicine; Graduate School of Health Sciences; 218440; N/AObjective: Hemorrhage is the leading cause of injury-related prehospital mortality. We investigated worst-case scenarios and possible requirements of the Turkish military. As we plan to use blood resources during casualty transport, the impact of transport-related mechanical stress on packed red blood cells (PRBCs) was analyzed. Materials and Methods: The in vitro experiment was performed in the environmental test laboratories of ASELSAN((R)). Operational vibrations of potential casualty transport mediums such as Sikorsky helicopters, Kirpi((R)) armored vehicles, and the NATO vibration standard MIL-STD-810G software program were recorded. The most powerful mechanical stress, which was created by the NATO standard, was applied to 15 units of fresh (<= 7 days) and 10 units of old (>7 days) PRBCs in a blood cooler box. The vibrations were simulated with a TDS v895 Medium-Force Shaker Device. On-site blood samples were analyzed at 0, 6, and 24 h for biochemical and biomechanical analyses. Results: The mean (+/- standard deviation) age of fresh and old PRBCs was 4.9 +/- 2.2 and 32.8 +/- 11.8 days, respectively. Six-hour mechanical damage of fresh PRBCs was demonstrated by increased erythrocyte fragmentation rates (p=0.015), hemolysis rates (p=0.003), and supernatant potassium levels (p=0.003) and decreased hematocrit levels (p=0.015). Old PRBC hemolysis rates (p=0.015), supernatant potassium levels (p=0.015), and supernatant hemoglobin (p=0.015) were increased and hematocrit levels were decreased (p=0.015) within 6 h. Two (13%) units of fresh PRBCs and none of the old PRBCs were eligible for transfusion after 6 h of meehanical stress. Conclusion: When an austere combat environment was simulated for 24 h, fresh and old PRBC hemolysis rates were above the quality criteria. Currently, the technology to overcome this mechanical damage does not seem to exist. In light of the above data, a new national project is being performed. / Amaç: Kan kayıpları, hastane öncesi dönemdeki yaralanmalara bağlı ölümlerin en sık sebebidir. Türk ordusu için en kötü senaryoları ve olası ihtiyaçları araştırdık. Çatışma alanından nakil esnasında kan kaynaklarını kullanmayı planladığımız için nakil işleminden kaynaklı mekanik stresin eritrosit konsantreleri üzerine etkisini analiz edilmiştir. Gereç ve Yöntemler: İn vitro çalışmalar ASELSAN®’ın dış ortam test laboratuvarlarında gerçekleştirildi. Çatışma alanında kan taşıma işleminde kullanılması muhtemel olan Sikorsky helikopteri ve Kirpi® araçlarının operasyonel vibrasyonları ve NATO MIL-STD-810G titreşim standart yazılımı kayıt altına alındı. NATO standardının en güçlü titreşime neden olduğu hesaplandı. Kan saklama çantası içindeki 15 ünite taze (≤7 gün) ve 10 ünite taze olmayan eritrosit konsantresi (>7 gün), NATO standardı olan mekanik strese maruz bırakıldı. Titreşim TDS v895 Medium-Force Shaker cihazı tarafından simüle edildi. Simülasyonun 0., 6. ve 24. saatinde biyokimyasal ve biyomekanik analiz için kan örnekleri alındı. Bulgular: Taze ve taze olmayan eritrosit konsantreleri sırasıyla ortalama 4,9 [standart deviasyon (SD) ±2,2] ve 32,8 (SD ±11,8) günlüktü. Taze eritrosit konsantrelerinde 6. saatte gelişen mekanik hasar; artmış eritrosit fragmentasyonu (p=0,015), hemoliz oranı (p=0,003) ve supernatant potasyum (p=0,015) düzeyleri ile gösterildi. Taze olmayan eritrosit konsantrelerinin 6. saatte hemoliz oranı (p=0,015) ve supernatant potasyum düzeyi (p=0,015) yükselirken, hematokrit değerleri (p=0,015) düştü. İlk 6 saat içerisinde taze eritrosit konsantrelerinin 2’si (%13) transfüze edilebilir kalitede kalırken, taze olmayanların ise hiçbirisi uygun değildi. Sonuç: Taze ve taze olmayan eritrosit konsantrelerinin hemoliz oranları, bu ürünleri muharebe sahasında taşıdığımızda, çoğunun kullanılamaz hale geleceğini göstermektedir. Halihazırda eritrositler üzerinde oluşan mekanik hasarlanmanın önüne geçebilecek bir teknoloji bulunmamaktadır. Yukarıdaki verilerin ışığı altında yeni bir ulusal proje gerçekleştirilmektedir.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 Metadata only Colchicine in renal medicine: new virtues of an ancient friend(Karger Publishers, 2017) Solak, Yalçın; Siriopol, Dimitrie; Yildiz, Abdulmecit; Yilmaz, Mahmut Ilker; Ortiz, Alberto; Covic, Adrian; N/A; Kanbay, Mehmet; Faculty Member; School of Medicine; 110580Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function.