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Permanent URI for this collectionhttps://hdl.handle.net/20.500.14288/6
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Publication Open Access Outcome of extended right lobe liver transplants(Wiley, 2021) Lozanovski, Vladimir J.; Unterrainer, Christian; Dohler, Bernd; Mehrabi, Arianeb; Süsal, Caner; Other; School of Medicine; Koç University Hospital; 351800Split-liver transplantation offers a solution to the organ shortage problem. However, the outcomes of extended right lobe liver transplantation (ERLT) and whether it is a suitable alternative to full-size liver transplantation (FSLT) remain controversial. We compared the outcomes of ERLT and FSLT in adult recipients of 43,409 first deceased donor liver transplantations using Cox regression. We also analyzed 612 ERLT and 1224 FSLT 1:2 matched cases to identify factors that affect ERLT outcome. The risk of graft loss was significantly higher following ERLT than following FSLT during the first posttransplantation year in the matched and unmatched collective (hazard ratio [HR], 1.39 and 1.27 and P = 0.01 and 0.006, respectively). Every additional hour of cold ischemia time (CIT) increased the risk of 1-year graft loss by 10% in the ERLT group compared with only 3% in the FSLT group (P = 0.003 and <0.001, respectively). Importantly, the outcome of ERLT and FSLT did not differ significantly if the CIT was below 10 hours (HR, 0.71; P = 0.22). One-year graft and patient survival were lower in high-risk ERLT recipients with a Model for End-Stage Liver Disease (MELD) score of ?20 (HR, 1.88; P = 0.03 and HR, 2.03; P = 0.02). In the male recipient–male donor combination, ERLT recipients had a higher risk of 1-year graft loss than FSLT recipients (HR, 2.44; P = 0.006). This was probably because of the significantly higher MELD score in ERLT recipients (P = 0.004). ERLT in adults is an adequate alternative to FSLT and offers an elegant solution to the problem of organ shortage as long as the cold storage is less than 10 hours and the recipient’s MELD score is <20.Publication Open Access Posttransplant Hemophagocytic Lymphohistiocytosis in pediatric liver transplant recipients(Wiley, 2021) Arıkan, Çiğdem; Erbey, Mehmet Fatih; Akyıldız, Murat; Faculty Member; Undergraduate Student; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; Koç University Hospital; 240198; N/A; N/A; N/APublication Open Access Histopathological tumour response scoring in resected pancreatic cancer following neoadjuvant therapy: international interobserver study (ISGPP-1)(Oxford University Press (OUP), 2022) Janssen, Boris, V; van Roessel, Stijn; van Dieren, Susan; de Boer, Onno; Basturk, Olca; Brosens, Lodewijk; Campbell, Fiona; Chatterjee, Deyali; Chou, Angela; Doglioni, Claudio; Esposito, Irene; Feakins, Roger; Fuchs, Talia L.; Fukushima, Noriyoshi; Gill, Anthony J.; Hong, Seung-Mo; Hruban, Ralph H.; Kaplan, Jeffrey; Krasinkas, Alyssa; Luchini, Claudio; Shi, Chanjuan; Singhi, Aatur; Thompson, Elizabeth; Velthuysen, Marie-Louise F.; Besselink, Marc G.; Verheij, Joanne; Wang, Huamin; Verbeke, Caroline; Farina, Arantza; Adsay, Nazmi Volkan; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; 286248The ISGPP-1 study demonstrated that identifying the effect of neoadjuvant therapy in resected pancreatic cancer proved unreliable. The interobserver agreement for the current tumour response scoring (TRS) systems was suboptimal. A collaborative effort is required to develop an objective TRS system. Background Most tumour response scoring systems for resected pancreatic cancer after neoadjuvant therapy score tumour regression. However, whether treatment-induced changes, including tumour regression, can be identified reliably on haematoxylin and eosin-stained slides remains unclear. Moreover, no large study of the interobserver agreement of current tumour response scoring systems for pancreatic cancer exists. This study aimed to investigate whether gastrointestinal/pancreatic pathologists can reliably identify treatment effect on tumour by histology, and to determine the interobserver agreement for current tumour response scoring systems. Methods Overall, 23 gastrointestinal/pancreatic pathologists reviewed digital haematoxylin and eosin-stained slides of pancreatic cancer or treated tumour bed. The accuracy in identifying the treatment effect was investigated in 60 patients (30 treatment-naive, 30 after neoadjuvant therapy (NAT)). The interobserver agreement for the College of American Pathologists (CAP) and MD Anderson Cancer Center (MDACC) tumour response scoring systems was assessed in 50 patients using intraclass correlation coefficients (ICCs). An ICC value below 0.50 indicated poor reliability, 0.50 or more and less than 0.75 indicated moderate reliability, 0.75 or more and below 0.90 indicated good reliability, and above 0.90 indicated excellent reliability. Results The sensitivity and specificity for identifying NAT effect were 76.2 and 49.0 per cent respectively. After NAT in 50 patients, ICC values for both tumour response scoring systems were moderate: 0.66 for CAP and 0.71 for MDACC. Conclusion Identification of the effect of NAT in resected pancreatic cancer proved unreliable, and interobserver agreement for the current tumour response scoring systems was suboptimal. These findings support the recently published International Study Group of Pancreatic Pathologists recommendations to score residual tumour burden rather than tumour regression after NAT.Publication Open Access The role of tissue inhibitor of metalloproteinases in the aetiology of inguinal and incisional hernias(Wiley, 2022) Düzköylü, Yiğit; Paşaoğlu, Esra; Aren, Acar; Durukan, Uğur; Ağcaoğlu, Orhan; Özoran, Emre; Karahan, Salih Nafiz; Özata, İbrahim Halil; Faculty Member; Teaching Faculty; Researcher; Graduate School of Health Sciences; School of Medicine; N/A; 175476; 307296; N/A; N/AInguinal and incisional hernias are the two most common types of hernias caused by abdominal wall weakness and defects in connective tissue. The structure of the extracellular matrix, mainly collagen and metalloproteinases (MMPs), and their regulators have been studied extensively and found to play a significant role in the pathophysiology of hernias. One of the regulators of MMPs, tissue inhibitor metalloproteinases (TIMPs), bind to MMPs and inhibit its activity significantly shifting the balance towards collagen synthesis rather than degradation. Due to their importance in collagen metabolism, their metabolism might be significant in the aetiology of hernias. Our study used immunohistochemical techniques to investigate the possible effects of TIMP 1 and 2 on the samples taken from the abdominal walls of patients with inguinal and incisional hernias, compared them with control patients, and reviewed the literature. In this study, samples of 90 patients (30 patients from control, inguinal hernia, and incisional hernia groups) were taken and analysed. These samples were stained with TIMP-1 Ab-2 and TIMP2 Ab-5 (Clone 3A4) antibodies and evaluated under x100 magnification. The degree of staining was classified as (a): No staining (0), (b): Staining less than 10% (I), (c): Staining between 10% and 50% (II), (d): Staining more than 50% (III). Statistical analyses were done. No significant difference was found between groups in terms of patient demographics. Smoking and family history of hernia was not found to be associated with TIMP expression. TIMP1 expression was significantly higher in the incisional and inguinal hernia group than in the control group (P < .05), while the level of TIMP2 was higher in the control group. (P < .05). TIMP1 and TIMP2 levels did not significantly differ between incisional and inguinal hernia groups. We found significantly increased TIMP-1 levels in tissue samples from patients with hernia supporting its suggested role in hernia pathophysiology. Local alterations in MMP and TIMP levels might play a role in the pathogenesis of hernias. Thus detection of TIMP in tissues can be important for clinical use after further validation studies. In the era of molecular medicine, detecting TIMP levels in hernia patients can impact clinical practice.Publication Open Access Neutralizing antibody response against the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants after a third mRNA SARS-CoV-2 vaccine dose in kidney transplant recipients(Wiley, 2022) Benning, Louise; Morath, Christian; Bartenschlager, Marie; Kim, Heeyoung; Reineke, Marvin; Beimler, Jorg; Buylaert, Mirabel; Nusshag, Christian; Kaelble, Florian; Reichel, Paula; Toellner, Maximilian; Schaier, Matthias; Klein, Katrin; Benes, Vladimir; Rausch, Tobias; Rieger, Susanne; Stich, Maximilian; Toenshoff, Burkhard; Weidner, Niklas; Schnitzler, Paul; Zeier, Martin; Tran, Thuong Hien; Bartenschlager, Ralf; Speer, Claudius; Süsal, Caner; Other; School of Medicine; Koç University Hospital; 351800Seroconversion after COVID-19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age-matched healthy controls. In addition, vaccine-induced neutralization of SARS-CoV-2 wild-type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live-virus assay. After a third vaccine dose, anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine-induced cross-neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti-S1 IgG, surrogate neutralizing, and/or anti-RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all).