Fakülteler / Faculties
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Item A Partial Epithelial-Mesenchymal Transition Signature For Highly Aggressive Colorectal Cancer Cells That Survive Under Nutrient Restriction(JOURNAL OF PATHOLOGY, 2024-01-24) Pastorino, Gil A.; Sheraj, Ilir; Oral, Goksu; Gulec Taskiran, Aliye Ezgi; Palmisano, Ralph; Schneider-Stock, ReginePartial epithelial-mesenchymal transition (p-EMT) has recently been identified as a hybrid state consisting of cells with both epithelial and mesenchymal characteristics and is associated with the migration, metastasis, and chemoresistance of cancer cells. Here, we describe the induction of p-EMT in starved colorectal cancer (CRC) cells and identify a p-EMT gene signature that can predict prognosis. Functional characterisation of starvation-induced p-EMT in HCT116, DLD1, and HT29 cells showed changes in proliferation, morphology, and drug sensitivity, supported by in vivo studies using the chorioallantoic membrane model. An EMT-specific quantitative polymerase chain reaction (qPCR) array was used to screen for deregulated genes, leading to the establishment of an in silico gene signature that was correlated with poor disease-free survival in CRC patients along with the CRC consensus molecular subtype CMS4. Among the significantly deregulated p-EMT genes, a triple-gene signature consisting of SERPINE1, SOX10, and epidermal growth factor receptor (EGFR) was identified. Starvation-induced p-EMT was characterised by increased migratory potential and chemoresistance, as well as E-cadherin processing and internalisation. Both gene signature and E-cadherin alterations could be reversed by the proteasomal inhibitor MG132. Spatially resolving EGFR expression with high-resolution immunofluorescence imaging identified a proliferation stop in starved CRC cells caused by EGFR internalisation. In conclusion, we have gained insight into a previously undiscovered EMT mechanism that may become relevant when tumour cells are under nutrient stress, as seen in early stages of metastasis. Targeting this process of tumour cell dissemination might help to prevent EMT and overcome drug resistance. (c) 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.Item Health Literacy In Older Adults Receiving Hemodialysis In Turkey: A Cross-Sectional Study(THERAPEUTIC APHERESIS AND DIALYSIS, 2024-01-10) Ugurlu, Ziyafet; Kav, Sultan; Eler, Cigdem Ozdemir; Kaya, Semiha; Korkmaz, YaseminIntroductionThis study aimed to determine the health literacy level and related factors of older adults receiving hemodialysis treatment.MethodsA cross-sectional study was conducted at the five dialysis centers, using the information form and Turkish Health Literacy Survey-32 (THLS-32). A total of 336 older adults receiving hemodialysis treatment participated.ResultsThe general health literacy score was found to be 25.69 +/- 14.47. Based on the health literacy assessment scores, 62.5% of the participants were in the category of inadequate and limited level of health literacy. The lower level of education, perceived health status, income, and getting help in reading and writing were statistically significant predictors of the health literacy score.ConclusionThe health literacy of older adults receiving hemodialysis treatment was inadequate and limited. Findings of this study emphasize the importance of integrating health literacy assessment in clinical care settings and supporting the health literacy of older adults receiving hemodialysis treatment.Item Subcortical Auditory Processing and Speech Perception in Noise Among Individuals With and Without Extended High-Frequency Hearing Loss(JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH, 2024-05-16) Colak, Hasan; Aydemir, Berfin Eylul; Sakarya, Merve Deniz; Cakmak, Eda; Alniacik, Asuman; Turkyilmaz, Meral DidemPurpose: The significance of extended high -frequency (EHF) hearing (> 8 kHz) is not well understood so far. In this study, we aimed to understand the relationship between EHF hearing loss (EHFHL) and speech perception in noise (SPIN) and the associated physiological signatures using the speech-evoked frequency-following response (sFFR). Method: Sixteen young adults with EHFHL and 16 age- and sex-matched individuals with normal hearing participated in the study. SPIN performance in right speech-right noise, left speech-left noise, and binaural listening conditions was evaluated using the Turkish Matrix Test. Additionally, subcortical auditory processing was assessed by recording sFFRs elicited by 40 -ms /da/ stimuli. Results: Individuals with EHFHL demonstrated poorer SPIN performances in all listening conditions (p < .01). Longer latencies were observed in the V (onset) and O (offset) peaks in these individuals (p <= .01). However, only the V/A peak amplitude was found to be significantly reduced in individuals with EHFHL (p < .01). Conclusions: Our findings highlight the importance of EHF hearing and suggest that EHF hearing should be considered among the key elements in SPIN. Individuals with EHFHL show a tendency toward weaker subcortical auditory processing, which likely contributes to their poorer SPIN performance. Thus, routine assessment of EHF hearing should be implemented in clinical settings, alongside the evaluation of standard audiometric frequencies (0.25-8 kHz).Item Working Memory, Attention Skills, and Language Proficiency in Children with Unilateral and Bilateral Cochlear Implants(JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY, 2024) Dikderi, Cagla; Atak, Hilal B. Ozkan; Yucel, EsraBackground Previous studies observed that children with cochlear implants (CIs) have poor language, working memory, and attention skills. The ability to perform cognitive tasks, such as attention and memory, plays a crucial role in the academic achievement and everyday life of children with hearing impairment. Purpose This study aimed to evaluate and compare the effects of age at the time of implantation and bilateral hearing on cognitive skills, such as language development, working memory, and selective attention, among children with CIs. Research Design Language skills were assessed using the Test of Language Development-Primary: Fourth Edition (TOLD-P:4), working memory using the Visual-Aural Digit Span Test-Revised Form (VADS-R), and selective attention skills using the Stroop Test TBAG Form. Study Sample A total of 58 participants, comprised of 21 children with early unilateral CIs (before 2 years), 18 children with late unilateral CIs (after 2 years), and 19 children with bilateral CIs, between the ages of 6 and 9 years, were included in the study. Data Collection and Analysis According to the age at the time of implantation and whether or not the participant was unilaterally or bilaterally implanted, the mean scores, percentage values, and resultant scores of the participants were calculated using the Mann-Whitney U test. The number of repeated backward digit spans for the VADS-R test, completion times, number of errors and corrections for the Stroop test, raw scores, scaled scores corresponding to raw scores at the relevant age, descriptive terms for the TOLD-P:4 test, and within-group comparisons for all tests were examined. Results There were significant differences in language, working memory, and attention skills between individuals with early and late unilateral cochlear implantation, whereas there were no significant differences in many subtests between individuals with early unilateral and bilateral cochlear implantation. Conclusion These findings demonstrate the importance of early cochlear implantation and bilateral hearing on the development of cognitive processes, such as language development, selective attention, and memory skills, which are important factors that may contribute to children's academic performance and overall success.Item The Effect of Forced-Air Warming in the Cesarean Section on Maternal Hypothermia, Shivering, and Thermal Comfort: A Randomized Controlled Trial(HEALTH CARE FOR WOMEN INTERNATIONAL, 2024)This trial was carried out to investigate the effect of forced air warming in various body areas of women on hypothermia during cesarean delivery. The patients in the study groups (n = 76) were assigned to the full-body warming group, upper-extremity warming group, lower-extremity warming group, and control groups. The intervention groups received forced-air warming 30 min before the surgery and continued until 30 min after surgery. The incidence of hypothermia was significantly higher in the control group than in the other groups at the 60th minute of the operation (p < 0.01). The intervention and control groups showed significant differences in the frequency of shivering at the entrance to the PACU (p = 0.001). Thermal comfort scores have significant difference between the control group and all of the intervention groups (p<.001). It is said that the full-body forced-air warming technique prevents hypothermia, shivering, and thermal discomfort in women Cesarean Section (CS).Item Comparison of Visual Performance and Quality of Life with A New Nondiffractive EDOF Intraocular Lens and A Trifocal Intraocular Lens(2023) Asena, Leyla; Dogan, Irem Kirci; Oto, Sibel; Altinors, Dilek Dursun; 0000-0003-0171-4200; 0000-0002-6848-203X; 0000-0002-5574-7318; 36700928; AAJ-4668-2021; E-5914-2016Purpose: To compare visual performance and quality of life (QoL) following bilateral implantation of a new nondiffractive extended depth-of-focus (EDOF) intraocular lens (IOL) and a trifocal IOL. Setting: Department of Ophthalmology, Baskent University Faculty of Medicine, Ankara, Turkey. Design: Prospective comparative interventional case series. Methods: 104 eyes of 52 patients with cataract, bilaterally implanted with a nondiffractive EDOF IOL or a trifocal IOL, were included. Outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), distance corrected intermediate visual acuity and distance corrected near visual acuity, defocus curves, QoL (Visual Function Index 14), quality of vision (Quality of Vision [QoV] index), contrast sensitivity (Pelli-Robson chart), and binocular reading speed. Results: Twenty-six patients were included in each group. The UDVA and CDVA were better in the EDOF group (0.05 +/- 0.04 and 0.01 +/- 0.04) than the trifocal group (0.13 +/- 0.06 and 0.11 +/- 0.07) (P=.02 and .01). Defocus curves showed that visual acuity was better with the EDOF IOL for vergences at 0.00, -0.50, and -1.00 and better with the trifocal IOL for vergences at -2.50, -3.00, -3.50, and -4.00. Contrast sensitivity scores were similar with both IOLs (P=.12). The overall mean QoL scores were lower in the EDOF group, indicating a better QoL (P=.04). The QoV was better in the EDOF group with significantly less glare, halos, and blurry vision (P<.01). Conclusions: The EDOF IOL performed better at distance, and the trifocal IOL performed better at near. Overall QoL and quality of vision were better with the EDOF IOL. Copyright (c) 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRSItem The Impact of CoronaVac Vaccination on 28-day Mortality Rate of Critically Ill Patients with COVID-19 in Turkiye(2023) Sahinturk, Helin; 37867428Background: Vaccines against coronavirus disease-19 (COVID-19) have been effective in preventing symptomatic diseases, hospitalizations, and intensive care unit (ICU) admissions. However, data regarding the effectiveness of COVID-19 vaccines in reducing mortality among critically ill patients with COVID-19 remains unclear.Aims: To determine the vaccination status and investigate the impact of the COVID-19 vaccine on the 28-day mortality in critically ill patients with COVID-19.Study Design: Multicenter prospective observational clinical study.Methods: This study was conducted in 60 hospitals with ICUs managing critically ill patients with COVID-19. Patients aged >= 18 years with confirmed COVID-19 who were admitted to the ICU were included. The present study had two phases. The first phase was designed as a one-day point prevalence study, and demographic and clinical findings were evaluated. In the second phase, the 28-day mortality was evaluated.Results: As of August 11, 2021, 921 patients were enrolled in the study. The mean age of the patients was 65.42 +/- 16.74 years, and 48.6% (n = 448) were female. Among the critically ill patients with COVID-19, 52.6% (n = 484) were unvaccinated, 7.7% (n = 71) were incompletely vaccinated, and 39.8% (n = 366) were fully vaccinated. A subgroup analysis of 817 patients who were unvaccinated (n = 484) or who had received two doses of the CoronaVac vaccine (n = 333) was performed. The 28-day mortality rate was 56.8% (n = 275) and 57.4% (n = 191) in the unvaccinated and two-dose CoronaVac groups, respectively. The 28-day mortality was associated with age, hypertension, the number of comorbidities, type of respiratory support, and APACHE II and sequential organ failure assessment scores (p < 0.05). The odds ratio for the 28-day mortality among those who had received two doses of CoronaVac was 0.591 (95% confidence interval: 0.413-0.848) (p = 0.004).Conclusion: Vaccination with at least two doses of CoronaVac within six months significantly decreased mortality in vaccinated patients than in unvaccinated patients.Item First-Line Cemiplimab Monotherapy and Continued Cemiplimab Beyond Progression Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 50% Or More (EMPOWER-Lung 1): 35-Month Follow-Up From A Multicentre, Open-Label, Randomised, Phase 3 Trial(2023) Ozguroglu, Mustafa; Kilickap, Saadettin; Sezer, Ahmet; Gumus, Mahmut; Bondarenko, Igor; Gogishvili, Miranda; Nechaeva, Marina; Schenker, Michael; Cicin, Irfan; Ho, Gwo Fuang; Kulyaba, Yaroslav; Zyuhal, Kasimova; Scheusan, Roxana-Ioana; Garassino, Marina Chiara; He, Xuanyao; Kaul, Manika; Okoye, Emmanuel; Li, Yuntong; Li, Siyu; Pouliot, Jean-Francois; Seebach, Frank; Lowy, Israel; Gullo, Giuseppe; Rietschel, Petra; 37591293Background: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.Item Graft-Versus-Host Disease and Relapse/Rejection-Free Survival After Allogeneic Transplantation for Idiopathic Severe Aplastic Anemia: A Comprehensive Analysis from the SAAWP of the EBMT(2023) Devillier, Raynier; Eikema, Dirk-Jan; Dufour, Carlo; Aljurf, Mahmoud; Wu, Depei; Maschan, Alexei; Kulagin, Alexander; Halkes, Constantijn J. M.; Collin, Matthew; Snowden, John; Renard, Cecile; Ganser, Arnold; Sykora, Karl-Walter; Gibson, Brenda E.; Maertens, Johan; Itala-Remes, Maija; Corti, Paola; Cornelissen, Jan; Bornhaeuser, Martin; Colorado Araujo, Mercedes; Ozdogu, Hakan; Risitano, Antonio; Socie, Gerard; de latour, Regis Peffault; 36951165Survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for severe idiopathic aplastic anemia (SAA) has improved in recent years, approaching 75% at 5 years. However, an SAA-adapted composite endpoint, graft-versus-host disease (GvHD) and relapse/rejection-free survival (GRFS), may more accurately assess patient outcomes beyond survival. We analyzed GRFS to identify risk factors and specific causes of GRFS failure. Our retrospective analysis from the Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation included 479 patients with idiopathic SAA who underwent allo-HSCT in two conventional situations: i) upfront allo-HSCT from a matched related donor (MRD) (upfront cohort), and ii) allo-HSCT for relapsed or refractory SAA (rel/ref cohort). Relevant events for GRFS calculation included graft failure, grade 3-4 acute GvHD, extensive chronic GvHD, and death. In the upfront cohort (n=209), 5-year GRFS was 77%. Late allo-HSCT (i.e., >6 months after SAA diagnosis) was the main poor prognostic factor, specifically increasing the risk of death as the cause of GRFS failure (hazard ratio [HR]=4.08; 95% confidence interval [CI]: 1.41-11.83; P=0.010). In the rel/ref cohort (n=270), 5-year GRFS was 61%. Age was the main factor significantly increasing the risk of death (HR=1.04; 95% CI: 1.02-1.06; P<0.001), acute GvHD (HR=1.03; 95% CI: 1.00-1.07; P=0.041), and chronic GvHD (HR=1.04; 95% CI: 1.01-1.08; P=0.032) as the cause of GRFS failure. GRFS after upfront MRD allo-HSCT was very good, notably with early allo-HSCT, confirming that younger patients with an MRD should be transplanted immediately. GRFS was worse in cases of salvage allo-HSCT, most notably in older patients, questioning the utility of allo-HSCT earlier in the disease course.Item Asymptomatic Lower Pole Small Renal Stones: Shock Wave Lithotripsy, Flexible Ureteroscopy, or Observation? A Prospective Randomized Trial(2015) Sener, Nevzat Can; Bas, Okan; Sener, Emine; Zengin, Kursad; Ozturk, Ufuk; Altunkol, Adem; Evliyaoglu, Yalcin; 25440816; HKN-9151-2023OBJECTIVE To present the outcomes of flexible ureteroscopy (F-URS), shock wave lithotripsy (SWL), and observation in the management of asymptomatic lower calyceal stones. METHODS A total of 150 patients with asymptomatic lower calyceal stones were randomized into F-URS (group 1), SWL (group 2), and observation (group 3) groups. The main criteria for patient enrollment were having asymptomatic single lower pole stones <1 cm. RESULTS In F-URS, the mean stone-free rate was 92% (46 of 50). The mean number of sessions for the SWL group was 1.48 +/- 0.65. Stone-free rate was 90% (45 of 50). In the observation group, patients were followed up for a mean of 21.02 +/- 3.65 months. Three stones passed spontaneously without any symptoms. Pain developed in 3 patients during follow-up, and 2 of them passed a stone and responded to analgesics without further treatment. Complication rates for groups 1 and 2 were similar, but group 2 had higher Clavien grades. CONCLUSION For asymptomatic small-sized lower calyceal stones, SWL and F-URS are established treatment modalities. However, with low auxiliary treatment rates, observation may be an option for the management of nonsymptomatic small-sized lower pole kidney stones. (C) 2015 Elsevier Inc.
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