Browsing by Author "Aydin K."
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Item Influence of the selective oestrogen receptor modulator (raloxifene hydrochloride) on IL-6, TNFα, TGF-β1 and bone turnover markers in the treatment of postmenopausal osteoporosis(2007) Özmen B.; Kirmaz C.; Aydin K.; Kafesciler S.O.; Guclu F.; Hekimsoy Z.Background. Osteoporosis that is encountered frequently in postmenopausal women, may cause an increased incidence of vertebral and iliac fractures that are associated with excess morbidity. Raloxifene hydrochloride, a selective oestrogen receptor modulator, has been shown to increase bone mineral density and decrease biochemical markers of bone turnover in postmenopausal women, without stimulatory effects on breast or uterus. Levels of proinflammatory cytokines, including IL-6, and TNF-α and TGF-β1 which are important cytokines involved in remodeling, have been evaluated previously in in vitro studies of osteoporosis. However, there seems to be a paucity of in vivo research concerned with changes in these cytokines in osteoporosis. Objective. In this study, we evaluated the effects of raloxifene (Evista®; Lilly Pharmaceutical Co. USA, 60 mg/day) on biochemical bone turnover markers, serum parathyroid hormone, and 25-OH vitamin D, as well as the serum levels of IL-6, TNF-α and TGF-β1, in 22 postmenopausal, osteoporotic women before and after 12 weeks of raloxifene treatment. Methods. Well-matched, postmenopausal, non-osteoporotic control subjects were also enrolled in the study. Serum levels of all the parameters were measured in postmenopausal, osteoporotic women at baseline and end of the study. Results. It was found that serum osteocalcin and parathyroid hormone, and urine deoxypyridinoline levels decreased to normal levels with treatment. Serum 25-OH vitamin D levels after treatment in the patient group were higher than those in the control group. Serum IL-6, TNF-α and TGF-β1 levels did not change significantly with treatment. However, serum levels of IL-6 and TGF-β1 in the patient group after treatment, decreased to levels lower than those found in the control group. Serum TNF-α levels in the patient group before and after treatment, were lower than those in the control group. Conclusion. Raloxifene treatment reduces bone turnover biochemical markers, parathyroid hormone and induces 25-OH vitamin D in postmenopausal women. Moreover, it also affects some serum cytokine levels in the postmenopausal period.Item Prognostic factors of patients who received chemotherapy after cranial irradiation for non-small cell lung cancer with brain metastases: A retrospective analysis of multicenter study (Anatolian Society of Medical Oncology)(Wolters Kluwer Medknow Publications, 2018) Inal A.; Kodaz H.; Odabas H.; Duran A.; Seker M.; Inanc M.; Elkiran E.; Gunaydin Y.; Menekse S.; Topcu T.; Urakci Z.; Tastekin D.; Bilici M.; Cihan S.; Geredeli C.; Sezer E.; Uncu D.; Arpaci E.; Ozturk B.; Bal O.; Uysal M.; Tanriverdi O.; Gumus M.; Oven Ustaalioglu B.; Suner A.; Cokmert S.; Hacibekiroglu I.; Aydin K.; Isikdogan A.Purpose: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. Methods: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). Results: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options. © 2017 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow.Item Shared Biological Pathways and Processes in Patients with Intellectual Disability: A Multicenter Study(Georg Thieme Verlag, 2022) Günay Ç.; Aykol D.; Özsoy Ö.; Sönmezler E.; Hanci Y.S.; Kara B.; Akkoyunlu Sünnetçi D.; Cine N.; Deniz A.; Özer T.; Ölçülü C.B.; Yilmaz Ö.; Kanmaz S.; Yilmaz S.; Tekgül H.; Yildiz N.; Acar Arslan E.; Cansu A.; Olgaç Dündar N.; Kusgoz F.; Didinmez E.; Gençpinar P.; Aksu Uzunhan T.; Ertürk B.; Gezdirici A.; Ayaz A.; Ölmez A.; Ayanoǧlu M.; Tosun A.; Topçu Y.; Kiliç B.; Aydin K.; Çaǧlar E.; Ersoy Kosvali Ö.; Okuyaz Ç.; Besen Ş.; Tekin Orgun L.; Erol İ.; Yüksel D.; Sezer A.; Atasoy E.; Toprak Ü.; Güngör S.; Ozgor B.; Karadaǧ M.; Dilber C.; Şahinoǧlu B.; Uyur Yalçin E.; Eldes Hacifazlioglu N.; Yaramiś A.; Edem P.; Gezici Tekin H.; Yilmaz Ü.; Ünalp A.; Turay S.; Biçer D.; Gül Mert G.; Dokurel Çetin İ.; Kirik S.; Öztürk G.; Karal Y.; Sanri A.; Aksoy A.; Polat M.; Özgün N.; Soydemir D.; Sarikaya Uzan G.; Ülker Üstebay D.; Gök A.; Yeśilmen M.C.; Yiś U.; Karakülah G.; Bursali A.; Oktay Y.; Hiz Kurul S.Background Although the underlying genetic causes of intellectual disability (ID) continue to be rapidly identified, the biological pathways and processes that could be targets for a potential molecular therapy are not yet known. This study aimed to identify ID-related shared pathways and processes utilizing enrichment analyses. Methods In this multicenter study, causative genes of patients with ID were used as input for Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Results Genetic test results of 720 patients from 27 centers were obtained. Patients with chromosomal deletion/duplication, non-ID genes, novel genes, and results with changes in more than one gene were excluded. A total of 558 patients with 341 different causative genes were included in the study. Pathway-based enrichment analysis of the ID-related genes via ClusterProfiler revealed 18 shared pathways, with lysine degradation and nicotine addiction being the most common. The most common of the 25 overrepresented DO terms was ID. The most frequently overrepresented GO biological process, cellular component, and molecular function terms were regulation of membrane potential, ion channel complex, and voltage-gated ion channel activity/voltage-gated channel activity, respectively. Conclusion Lysine degradation, nicotine addiction, and thyroid hormone signaling pathways are well-suited to be research areas for the discovery of new targeted therapies in ID patients. © 2022 Hippokrates Verlag GmbH. All rights reserved.Item Assesment of attainment of recommended TSH levels and levothyroxine compliance in differentiated thyroid cancer patients(John Wiley and Sons Inc, 2022) Yavuz D.G.; Yazan C.D.; Hekimsoy Z.; Aydin K.; Gokkaya N.; Ersoy C.; Akalın A.; Topaloglu O.; Aydogan B.I.; Dilekci E.N.A.; Alphan Uc Z.; Cansu G.B.; Ozsari L.; Iyidir O.T.; Olgun M.E.; Keskin L.; Mert M.; Can B.; Gungor K.; Galip T.; Cantürk Z.; Elbuken G.; Pekkolay Z.; Kutbay N.O.; Yorulmaz G.; Kalkan A.T.; Unsal Y.A.; Yay A.; Karagun B.; Bozkur E.Objective: Thyroid-stimulating hormone (TSH) suppression treatment can induce signs and symptoms of hyperthyroidism and hypothyroidism due to inappropriate treatment or poor compliance to the treatment. The current study aimed to investigate TSH levels, frequency of being on target TSH, adherence to levothyroxine (LT4) suppression treatment in differentiated thyroid cancer (DTC) patients after surgery in a multicentric setting. Design and Patients: This multicentric cross-sectional study was conducted at 21 medical centres from 12 cities in Turkey. DTC patients followed at least one year in the same center included in the study. Clinical data, serum TSH, free thyroxine (FT4), thyroglobulin (Tg) and anti-Tg levels were recorded during the most recent visit. Body mass index, systolic and diastolic blood pressures, pulse rate were measured. LT4 doses were recorded and doses per kilogram of bodyweight were calculated. Pill ingestion habits recorded and adherence to the therapy were evaluated using the Morisky Medication Adherence Scale and categorized as good, moderate or poor compliant based on their scores. Risk stratification forpredicting the disease persistance and/or reccurence was assessed using the American Joint Committee on Cancer-7th edition thyroid cancer staging calculator. TSH serum concentrations were classified as severe suppression (TSH < 0.01 mU/L), moderate suppression (TSH: 0.01–0.1 mU/L), mild suppression (TSHL 0.1–0.5 mU/L), euthyroid (TSH: 0.5–4 mU/L) and hypothyroid (TSH > 4 mU/L). TSH levels can also be classified as on being on target, under the target, or beyond over the target, according to the American Thyroid Association recommendations. Results: A group of 1125 patients (F/M: 941/184, 50.7 ± 11.7 years) were included in the study. The mean LT4 daily dosage was 132.4 ± 39.6 mcg/day. TSH levels showed severe suppression in 99 (%8.8) patients, moderate suppression in 277 (%24.6) patients and mild suppression in 315 (%28) patients and euthyroid range in 332 (%29.5) patients and hypothyroid range in 97 (8.6%). TSH levels were in target in 29.2% of the patients 20.4% of the patients were undertreated, 50.4% overtreated. The daily LT4 dose and LT4 dose/kg were significantly higher in the severe suppression group (p <.001, p <.001). According to the Morisky scale, 564 patients (50.1%) were good compliant, 368 patients (32.7%) were moderate compliant, and 193 patients (17.1%) were noncompliant. Patients with poor compliance need a higher dose of LT4 compared to the good compliance group (p <.001). TSH levels of patients with good compliance were 0.67 ± 1.96 mU/L and TSH with poor compliance was 2.74 ± 7.47 mU/L (p <.001). TSH levels were similar in patients on fixed and alternating dosages. Conclusion: In 29.2% of the DTC patients, serum TSH levels were at target levels. Remaining of the study group have TSH levels under or over treatment range, exposing the patient to medication side effects. Majorty of the study group 82.8% have good or moderate adherence to LT4 therapy. Reaching TSH targets requires simplified and applicable guidelines and following the guideline recommendations. © 2022 John Wiley & Sons Ltd.Item The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?(Georg Thieme Verlag, 2022) Ciftci S.; Soyluk O.; Selek A.; Erol S.; Hekimsoy Z.; Esen A.; Dursun H.; Sahin S.; Oruk G.; Mert M.; Soylu H.; Yurekli B.S.; Ertorer M.E.; Omma T.; Evran M.; Adas M.; Tanrikulu S.; Aydin K.; Pekkolay Z.; Can B.; Karakilic E.; Karaca Z.; Bilen H.; Canturk Z.; Cetinarslan B.; Kadioglu P.; Yarman S.The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels.In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels.The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone.This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation. © 2022 ASTM International. All rights reserved.Item The effect of heat treatment on laser-welding performance of additive manufactured Ti6Al4V sheets(Springer Science and Business Media Deutschland GmbH, 2023) Aydin K.; Karamolla M.; Karaağaç İ.; Kaçal A.; Doğan H.In this study, the laser weldability of Ti6Al4V materials produced by the selective laser melting (SLM) method, which is an additive manufacturing method, and the effects of heat treatment applied to the welded material on the welding performance were investigated experimentally. Stress relief and heat treatment were applied to the materials joined by laser welding at 800 °C (below the α phase transformation temperature), 950 °C (between α and β phase transformation temperature), and 1080 °C (above the β phase transformation temperature). In addition, transverse and longitudinal welded joining techniques were also investigated to determine anisotropy in the produced parts. The mechanical properties in the laser-welded region were examined by hardness and tensile tests, and an optical microscope, scanning electron microscope (SEM), and X-ray diffraction (XRD) examined the changes in the microstructure. Grain growth was observed in the microstructure due to the increase in heat treatment temperature, and the tensile strength increased from 631.2 to 754.2 MPa in transverse bonding, while it increased from 648.1 to 761.9 MPa in longitudinal bonding. High hardness values due to Widmanstatten morphology were determined in the hardness test, especially after heat treatments at 950 and 1080 °C. It has been observed that the heat treatment increases the welding performance of the laser-welded material, and the best welding performance is obtained with a welding efficiency of 83.5% in the heat treatment at 1080 °C. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.Item Therapeutic implications of etiology-specific diagnosis of early-onset developmental and epileptic encephalopathies (EO-DEEs): A nationwide Turkish cohort study(W.B. Saunders Ltd, 2024) Kanmaz S.; Tekgul H.; Kayilioglu H.; Atas Y.; Kart P.O.; Yildiz N.; Gumus H.; Aydin K.; Olculu C.B.; Dogan D.E.T.; Per H.; Canpolat M.; Gulec A.; Yildirim N.; Turk E.; Celik N.; Ozturk S.; Kumandas S.; Kilic B.; Topcu Y.; Ozpinar E.; Coskun A.; Arslan M.; Akkoyunlu D.S.; Cine N.; Uzan G.S.; Gunay C.; Akyol D.; Ersoy O.; Direk M.C.; Komur M.; Kirkgoz H.; Karaoğlu P.; Ibis I.B.P.; Cerci C.; Orak A.; Oktay S.; Ayanoglu M.; Yildirim M.; Bektas O.; Serdaroglu E.; Yilmaz S.B.; Cankurt I.; Hirfanoglu T.; Arhan E.; Gencpinar P.; Dundar N.O.; Teber S.; Serin H.M.; Yilmaz S.; Tosun A.; Polat M.; Yilmaz U.; Unalp A.; Kara B.; Okuyaz C.; Yis U.; Hiz S.; Aktan G.; Gokben S.; Unay B.; Serdaroglu A.; Cansu A.Objective: To evaluate the etiology-specific diagnosis of early-onset developmental epileptic encephalopathies (EO-DEEs) in a nationwide Turkish cohort to determine the implications for therapeutic management. Methods: The cohort comprised 1450 patients who underwent EO-DEE. The utility of genetic testing was assessed with respect to the initial phases of next generation sequencing (NGS) (2005–2013) and the current NGS era (2014–2022). A predefined four-stepwise diagnostic model was evaluated using cost-effectiveness analysis. The diagnostic and potential therapeutic yields of the genetic tests were subsequently determined. Results: Gene-related EO-DEEs were identified in 48.3 % (n = 701) of the cohort: non-structural genetic (62.6 %), metabolic genetic (15.1 %), and structural genetic (14.1 %). The most common nonstructural genetic variants were SCN1A (n = 132, 18.8 %), CDKL5 (n = 30, 4.2 %), STXBP1 (n = 21, 2.9 %), KCNQ2 (n = 21, 2.9 %), and PCDH19 (n = 17, 2.4 %). The rate of ultra-rare variants (< 0.5 %) was higher in the NGS era (52 %) than that in the initial phase (36 %). The potential therapeutic yields with precision therapy and antiseizure drug modification were defined in 34.5 % and 56.2 % in genetic-EO-DEEs, respectively. The diagnostic model provided an etiology-specific diagnosis at a rate of 78.7 %: structural (nongenetic) (31.4 %), genetic (38.5 %), metabolic (6.1 %), and immune-infectious (2.8 %). Based on a cost-effectiveness analysis, the presented diagnostic model indicated the early implementation of whole-exome sequencing for EO-DEEs. Significance: In the present cohort, the higher rate (48.3 %) of gene-related EO-DEE diagnoses in the NGS era provides a potential therapeutic management plan for more patients. © 2024 British Epilepsy Association