Wos Açık Erişimli Yayınlar
Permanent URI for this collectionhttps://hdl.handle.net/11727/10754
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Item Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study(2022) Ferrandiz-Pulido, C.; Gomez-Tomas, A.; Llombart, B.; Mendoza, D.; Marcoval, J.; Piaserico, S.; Baykal, C.; Bouwes-Bavinck, J.N.; Racz, E.; Kanitakis, J.; Harwood, C.A.; Cetkovska, P.; Geusau, A.; Del Marmol, V; Masferrer, E.; Cano, C.Orte; Ricar, J.; de Oliveira, W.R.; Salido-Vallejo, R.; Ducroux, E.; Gkini, M.A.; Lopez-Guerrero, J.A.; Kutzner, H.; Kempf, W.; Seckin, D.; 35607918Background The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. Objective To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. Methods Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. Results A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. Limitations Retrospective design and heterogeneity of SOTR cohort. Conclusions MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.Item Prognostic Value of Pretreatment Systemic Immune-Inflammation Index in Glioblastoma Multiforme Patients Undergoing Postneurosurgical Radiotherapy Plus Concurrent and Adjuvant Temozolomide(2020) Topkan, Erkan; Besen, Ali Ayberk; Ozdemir, Yurday; Kucuk, Ahmet; Mertsoylu, Huseyin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0002-2218-2074; 0000-0001-8120-7123; 0000-0002-7862-0192; 32565725; M-9530-2014; AAG-5629-2021; AAG-2213-2021; AAD-6910-2021Objectives. To evaluate the potential prognostic utility of pretreatment systemic immune-inflammation index (SII) in newly diagnosed glioblastoma multiforme (GBM) patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide. Methods. The retrospective data of GBM patients who underwent postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide were analyzed. For each patient, SII was calculated using the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SII=plateletsxneutrophils/lymphocytes. The receiver operating characteristic (ROC) curve analysis was utilized for the evaluation of optimal cut-off values for SII those linked with the outcomes. Primary and secondary endpoints constituted the overall (OS) and progression-free survival (PFS) per conveyance SII group. Results. A total of 167 patients were included. The ROC curve analysis identified the optimum SII cut-off at a rounded 565 value that significantly interacted with the PFS and OS and stratified patients into two groups: low-SII (SII<565; n=71) and high-SII (SII >= 565; n=96), respectively. Comparative survival analyses exhibited that the high-SII cohort had significantly shorter median PFS (6.0 versus 16.6 months; P<0.001) and OS (11.1 versus 22.9 months; P<0.001) than the low-SII cohort. The relationship between the high-SII and poorer PFS (P<0.001) and OS (P<0.001) further retained its independent significance in multivariate analysis, as well. Conclusions. The outcomes displayed here qualified the pretreatment SII as a novel independent prognostic index for predicting survival outcomes of newly diagnosed GBM patients undergoing postneurosurgical radiotherapy and concurrent plus adjuvant temozolomide.Item Platelet/lymphocyte ratio is an independent predictor for osteoporosis(2019) Eroglu, Semra; Karatas, Gulsah; 30957129; AAD-8353-2020Objectives: To investigate the intercourse between the platelet/lymphocyte (P/L) and neutrophil/lymphocyte ratio (N/L), and vitamin D (Vit-D) levels in low bone mineral density (BMD) of women. Methods: Two hundred fifty-two postmenopausal female outpatients who were admitted to the obstetrics and gynecology and physical therapy clinics between July 2016 and December 2017 were retrospectively analyzed. The patients were grouped in relation to their T-score (normal [n=92], osteopenia [n=112], and PMO [n=48]). The serum levels of P/L, N/L, Vit-D, BMD and complete blood count of the patients were retrospectively examined. Results: The median P/L was significantly higher and Vit-D levels were significantly lower in the PMO group (130.75 [52.89-385] versus 123.05 [54-232.5], p=0.02 and 15.4 [4-34] versus 20.1 [4-47], p=0.003). While BMD and P/L were negatively correlated, a positive correlation between BMD and Vit-D was found. Vitamin D levels were negatively correlated with P/L (p<0.001) and N/L (p=0.04). Older age (>= 65 years), Vit-D deficiency and P/L values >125.06 were found as independent prognostic factors for PMO in regression analysis. Conclusion: Higher P/L seems to be a quite simple marker to help predict postmenopausal PMO. As seen in our study, having low levels of Vit-D is crucial for PMO.Item Plasma fetuin-A levels are reduced in patients with hypothyroidism(2014) Bakiner, Okan; Bozkirli, Emre; Ertugrul, Derun; Sezgin, Nurzen; Ertorer, EdaObjective: To determine plasma fetuin-A levels in hypothyroid patients before and after treatment with L-thyroxine (T-4) and to determine the relation between plasma fetuin-A levels with cardiovascular risk factors. Design: A prospective, controlled, single-blind study. Methods: Forty-four treatment-naive female patients diagnosed with hypothyroidism and 39 age-and sex-matched control subjects were enrolled. Anthropometric measurements, blood pressure, plasma TSH, fetuin-A, free T-4, LDL-cholesterol, triglyceride, C-reactive protein, fibrinogen levels, and brachial artery flow-mediated dilatation were measured. All measurements were repeated after 3 months in the control group and 3 months after the attainment of euthyroidism with (L)-T4 replacement in the hypothyroid group. Baseline data were compared between the two groups. Posttreatment plasma fetuin-A levels of hypothyroid patients were compared with baseline levels of both groups. The relationship between plasma fetuin-A, TSH levels, and other cardiovascular risk factors was evaluated. Results: Plasma fetuin-A levels were similar to 20% lower in hypothyroid female patients compared with the controls (P=0.0001). Fetuin-A levels increased by similar to 20% in hypothyroid patients after achievement of euthyroidism (P=0.0001) and were no longer different compared with controls (P=0.38). There was a negative correlation between plasma TSH and fetuin-A levels (r=-0.79; P=0.001). There was no significant correlation between plasma fetuin-A levels and cardiovascular risk factors within or between groups. The fetuin-A levels were normalized with thyroid hormone treatment. Conclusion: Plasma fetuin-A levels are reduced in female patients with hypothyroidism, which are restored to normal during restoration of euthyroidism. There was no relation with cardiovascular risk factors.Item Single-Nucleotide Polymorphisms on the RYD5 Gene in Nasal Polyposis(2015) Ozdas, Sibel; Izbirak, Afife; Ozdas, Talih; Ozcan, Kursat Murat; Erbek, Selim S.; Koseoglu, Sabri; Dere, Huseyin; 26204469Nasal polyposis (NP) is a chronic inflammatory disease. Several genes play major roles in the pathophysiology of the disease. We analyzed RYD5 gene polymorphisms to determine the effect of these variants or their genetic combinations on NP. We genotyped the RYD5 gene in 434 participants (196 patients with NP and 238 controls). Data were analyzed with SPSS, SNPStats, and multifactor dimensionality reduction (MDR) software. We genotyped 10 single-nucleotide polymorphisms (SNPs) in the RYD5 gene. RYD5 (+152G>T) (p.Gly51Va) has not been reported previously. The PolyPhen and PROVEAN predicted the missense mutation as deleterious, but sorting intolerant from tolerant (SIFT) did not. In the genotype analysis, we found that four SNPs (RYD5 [-264A>G], [-103G>A], [+57-14C>T], and [+66A>G]) were significantly associated with NP. The individuals with combined genotypes of six risk alleles (RYD5-264G, -103A, +13C, +57-14T, +66G, and +279T) had significantly higher risks for NP compared with the ones with one or four risk alleles. Haplotype analysis revealed that the two haplotypes were associated with risk of NP. As indicated by MDR analysis, RYD5 (-264A>G and -103G>A) and RYD5 (-264A>G, -177C>A, and -103G>A) were the best predictive combinations and they had the highest synergistic interaction on NP. In addition, RYD5 (+13C>T) was significantly associated with increased risk of both NP with asthma and NP with allergy and asthma. Some SNPs and their combinations in the RYD5 gene are associated with increased probability for developing NP. We emphasize the importance of genetic factors on NP and NP-related clinical phenotypes.Item Behcet's: A Disease or a Syndrome? Answer from an Expression Profiling Study(2016) Oguz, Ali Kemal; Yilmaz, Seda Tasir; Oygur, Cagdas Sahap; Candar, Tuba; Sayin, Irmak; Kilicoglu, Sibel Serin; Ergun, Ihsan; Ates, Askin; Ozdag, Hilal; Akar, Nejat; 26890122Behcet's disease (BD) is a chronic, relapsing, multisystemic inflammatory disorder with unanswered questions regarding its etiology/pathogenesis and classification. Distinct manifestation based subsets, pronounced geographical variations in expression, and discrepant immunological abnormalities raised the question whether Behcet's is "a disease or a syndrome". To answer the preceding question we aimed to display and compare the molecular mechanisms underlying distinct subsets of BD. For this purpose, the expression data of the gene expression profiling and association study on BD by Xavier et al (2013) was retrieved from GEO database and reanalysed by gene expression data analysis/visualization and bioinformatics enrichment tools. There were 15 BD patients (B) and 14 controls (C). Three subsets of BD patients were generated: MB (isolated mucocutaneous manifestations, n = 7), OB (ocular involvement, n = 4), and VB (large vein thrombosis, n = 4). Class comparison analyses yielded the following numbers of differentially expressed genes (DEGs); B vs C: 4, MB vs C: 5, OB vs C: 151, VB vs C: 274, MB vs OB: 215, MB vs VB: 760, OB vs VB: 984. Venn diagram analysis showed that there were no common DEGs in the intersection "MB vs C" boolean AND "OB vs C" boolean AND "VB vs C". Cluster analyses successfully clustered distinct expressions of BD. During gene ontology term enrichment analyses, categories with relevance to IL-8 production (MB vs C) and immune response to microorganisms (OB vs C) were differentially enriched. Distinct subsets of BD display distinct expression profiles and different disease associated pathways. Based on these clear discrepancies, the designation as "Behcet's syndrome" (BS) should be encouraged and future research should take into consideration the immunogenetic heterogeneity of BS subsets. Four gene groups, namely, negative regulators of inflammation (CD69, CLEC12A, CLEC12B, TNFAIP3), neutrophil granule proteins (LTF, OLFM4, AZU1, MMP8, DEFA4, CAMP), antigen processing and presentation proteins (CTSS, ERAP1), and regulators of immune response (LGALS2, BCL10, ITCH, CEACAM8, CD36, IL8, CCL4, EREG, NFKBIZ, CCR2, CD180, KLRC4, NFAT5) appear to be instrumental in BS immunopathogenesis.Item Comment on "Metformin Decreases Thyroid Volume and Nodule Size in Subjects with Insulin Resistance: A Preliminary Study"(2017) Nar, Asli; Anil, Cuneyd; Kut, Altug; Atesagaoglu, Berna; Tutuncu, Neslihan Bascil; Gursoy, Alptekin; 0000-0002-1816-3903; 0000-0003-0998-8388; 0000-0003-3534-2628; 0000-0003-2730-7144; 0000-0003-3802-9733; 27802445; ABG-5027-2020; AAA-2743-2021; W-2366-2017