Fakülteler / Faculties
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Item Disease Burden And Management Of Crigler-Najjar Syndrome: Report Of A World Registry(2022) Aronson, Sem J.; Junge, Norman; Trabelsi, Mediha; Kelmemi, Wided; Hubert, Aurelie; Brigatti, Karlla W.; Fox, Michael D.; de Knegt, Robert J.; Escher, Johanna C.; Ginocchio, Virginia M.; Iorio, Raffaele; Zhu, Yan; Ozcay, Figen; Rahim, Fakher; El-Shabrawi, Mortada H. F.; Shteyer, Eyal; Di Giorgio, Angelo; D'Antiga, Lorenzo; Mingozzi, Federico; Brunetti-Pierri, Nicola; Strauss, Kevin A.; Labrune, Philippe; Mrad, Ridha; Baumann, Ulrich; Beuers, Ulrich; Bosma, Piter J.; 35274801Item Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease(2021) Ozen, Ahmet; Kasap, Nurhan; Vujkovic-Cvijin, Ivan; Apps, Richard; Cheung, Foo; Karakoc-Aydiner, Elif; Akkelle, Bilge; Sari, Sinan; Tutar, Engin; Uygun, Dilara Kocacik; Islek, Ali; Akgun, Gamze; Selcuk, Merve; Sezer, Oya Balci; Ozcay, Figen; Zhang, Yu; Kutluk, Gunsel; Topal, Erdem; Sayar, Ersin; Celikel, Cigdem; Houwen, Roderick H.J.; Bingol, Aysen; Ogulur, Ismail; Eltan, Sevgi Bilgic; Snow, Andrew L.; Lake, Camille; Fantoni, Giovanna; Alba, Camille; Sellers, Brian; Chauvin, Samuel D.; Dalgard, Clifton L.; Harari, Olivier; Ni, Yan G.; Wang, Ming-Dauh; Devalaraja-Narashimha, Kishor; Subramanian, Poorani; Ergelen, Rabia; Artan, Reha; Guner, Sukru Nail; Dalgic, Buket; Tsang, John; Belkaid, Yasmine; Ertem, Deniz; Baris, Safa; Lenardo, Michael J.; https://orcid.org/0000-0002-8402-8208; https://orcid.org/0000-0002-5214-516X; 33398182; AAI-9346-2021; ABG-5684-2020CHAPLE disease is a lethal syndrome caused by genetic loss of the complement regulatory protein CD55. Lenardo, Ozen and their colleagues report that blockade of C5 complement activation in a small cohort of pediatric patients with CHAPLE disease reduced gastrointestinal pathology and restored their immunity and growth. Complement hyperactivation, angiopathic thrombosis and protein-losing enteropathy (CHAPLE disease) is a lethal disease caused by genetic loss of the complement regulatory protein CD55, leading to overactivation of complement and innate immunity together with immunodeficiency due to immunoglobulin wasting in the intestine. We report in vivo human data accumulated using the complement C5 inhibitor eculizumab for the medical treatment of patients with CHAPLE disease. We observed cessation of gastrointestinal pathology together with restoration of normal immunity and metabolism. We found that patients rapidly renormalized immunoglobulin concentrations and other serum proteins as revealed by aptamer profiling, re-established a healthy gut microbiome, discontinued immunoglobulin replacement and other treatments and exhibited catch-up growth. Thus, we show that blockade of C5 by eculizumab effectively re-establishes regulation of the innate immune complement system to substantially reduce the pathophysiological manifestations of CD55 deficiency in humans.Item Fecal calprotectin levels in Helicobacter pylori gastritis in children(2020) Aksoy, Ozlem Yuksel; Canan, Oguz; Hosnut, Ferda Ozbay; Akcay, EdaYilmaz; Ozcay, Figen; 0000-0003-0614-4497; 0000-0002-5214-516X; 33372437; AAI-9386-2021; ABG-5684-2020Background. Fecal calprotectin is an important inflammatory marker in intestinal diseases and is not routinely used in the upper gastrointestinal system disorders. The aim of this study was to show whether there is a relationship between fecal calprotectin levels and Helicobacter pylori (H pylori) gastritis in children and to determine the association of fecal calprotectin levels with gastric biopsy results in terms of chronic inflammation and neutrophil activity. Methods. Patients with the complaints of the upper gastrointestinal system (epigastric pain, heartburn, nausea and vomiting) who were planned to undergo endoscopy were enrolled prospectively. The presence of H pylori was defined according to the gastric antrum biopsy results. Fecal calprotectin level was tested in the stool sample of the patients. The fecal calprotectin levels, upper gastrointestinal endoscopy and gastric biopsy results of 89 patients were evaluated. Results. H pylori was found to be positive in the gastric biopsies of 51 (57.3%) patients. In the H pylori positive group mean fecal calprotectin level was 74.8 +/- 67 mu g/g, and in the H pylori negative group mean fecal calprotectin level was 52.7 +/- 46 mu g/g and the difference was significant (p= 0.039). We also found a significant relationship between fecal calprotectin levels and gastric neutrophil activity grades (p= 0.034). Conclusions. Mean fecal calprotectin levels were found to be higher in H pylori positive subjects in our study. Fecal calprotectin levels were correlated with gastric neutrophil activity grades. Fecal calprotectin represents gastric neutrophilic inflammation. When interpreting a high fecal calprotectin level, H pylori infection should be kept in mind.Item The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease(2019) Ozcay, Figen; Canan, Oguz; 0000-0002-5214-516X; 30540705; ABG-5684-2020Objectives: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. Methods: Patients (aged 3 months-18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D(<0.02), intermediate (0.02-0.37) or normal (>0.37). Asecond dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. Results: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (<1%). LAL activity was normal in 634 (78%) and intermediate in 174 (21%) patients. LAL-D was identified in 2 siblings aged 15 and 6 years born to unrelated parents. Dyslipidemia, liver steatosis, and mild increase in aminotransferases were common features in these patients. Moreover, the 15-year-old patient showed growth failure and microvesicular steatosis, portal inflammation, and bridging fibrosis in the liver biopsy. Based on 795 families, 2 siblings in the same family were identified as LAL-D cases, making the prevalence of LAL-D in this study population, 0.1% (0.125%-0.606%). In the repeated measurement (76/174), LAL activity remained at the intermediate level in 38 patients. Conclusions: Overall, the frequency of LAL-D patients in this study (0.1%) suggests that LAL-D seems to be rare even in the selected high-risk population.Item Severe Adenovirus Infection Associated with Hemophagocytic Lymphohistiocytosis(2014) Hosnut, Ferda Ozbay; Ozcay, Figen; Malbora, Baris; Hizli, Samil; Ozbek, Namik; 24764742Item The safety and efficacy of ERCP in the pediatric population with standard scopes: Does size really matter?(2016) Yildirim, Abdullah Emre; Altun, Reskan; Ocal, Serkan; Kormaz, Murat; Ozcay, Figen; Selcuk, Haldun; 26933627Experience with endoscopic retrograde cholangiopancreatography in the pediatric population is limited. The aim of this study was to evaluate the outcomes of ERCP in the pediatric population performed by adult gastroenterologists with standard duodenoscopes. This study is a structured retrospective review of endoscopic reports, computerized and paper medical records, and radiographic images of patients under the age of 18 who underwent ERCP for any indication at a tertiary referral centre. Data regarding demographic characteristics and medical history of patients, indications, technical success rate, final clinical diagnosis, and complications were analyzed. Forty-eight children with a mean age of 13 years (range 2-17) underwent a total of 65 ERCPs. The indications of ERCP were as follows; suspected choledocholithiasis (55 %), post-liver transplantation anastomotic biliary strictures (21 %), post-surgical bile duct injury (10 %), choledochal cyst (2 %), recurrent or chronic pancreatitis (10 %), and trauma (2 %). The cannulation success rate in the overall procedure was 93.8 %. Therapeutic interventions were performed in 70.7 % of patients. Post ERCP pancreatitis was the most common complication occurring in 9.2 % of patients, and no procedure related mortality occurred. When performed by well-trained adult gastroenterologists, the use of endoscopic retrograde cholangiopancreatography with standard duodenoscopes is safe in pediatric population.Item Can platelet count/spleen diameter ratio be used for cirrhotic children to predict esophageal varices?(2016) Sezer, Oya Balci; Celik, Deniz; Tutar, Nihal; Ozcay, Figen; 27957245AIM To determine the laboratory and radiologic parameters, including the platelet count (PC)-to-spleen diameter (SD) ratio as a non-invasive marker that may predict the presence of esophageal varices (EV) in children with cirrhosis. METHODS Eighty-nine patients with cirrhosis, but without a history of variceal bleeding were prospectively included. The children were grouped into 6-12 and 12-18 years of age groups. These groups were also divided into 2 subgroups (presence and absence of EV). All of the patients underwent a complete biochemical and radiologic evaluation. The PC (n/mm(3))-to-SD (mm) ratio was calculated for each patient. RESULTS Sixty-nine of 98 (70.4%) patients had EV. The presence of ascites in all age groups was significantly associated with the presence of EV. There were no differences in serum albumin levels, PC, SD and the PC-to-SD ratio between the presence and absence of EV groups in both age groups (P > 0.05). CONCLUSION Laboratory and radiologic parameters, including the PC-to-SD ratio as a non-invasive marker (except for the presence of ascites), was inappropriate for detecting EV in children with cirrhosis.Item Intestinal Failure and Aberrant Lipid Metabolism in Patients With DGAT1 Deficiency(2018) Ozcay, Figen; Baris, Zeren; van Rijn, Jorik M.; Ardy, Rico Chandra; Kuloglu, Zarife; Haerter, Bettina; van Haaften-Visser, Desiree Y.; van der Doef, Hubert P. J.; van Hoesel, Marliek; Kansu, Aydan; van Vugt, Anke H. M.; Thian, Marini; Kokke, Freddy T. M.; Krolo, Ana; Basaran, Meryem Keceli; Kaya, Neslihan Gurcan; Aksu, Aysel Unlusoy; Dalgic, Buket; Kain, Renate; Stigter, Edwin C. A.; Lichtenbelt, Klaske D.; Massink, Maarten P. G.; Duran, Karen J.; Verheij, Joke B. G. M.; Lugtenberg, Dorien; Nikkels, Peter G. J.; Brouwer, Henricus G. F.; Verkade, Henkjan J.; Scheenstra, Rene; Spee, Bart; Nieuwenhuis, Edward E. S.; Coffer, Paul J.; Janecke, Andreas R.; van Haaften, Gijs; Houwen, Roderick H. J.; Mueller, Thomas; Middendorp, Sabine; Boztug, KaanBACKGROUND & AIMS: Congenital diarrheal disorders are rare inherited intestinal disorders characterized by intractable, sometimes life-threatening, diarrhea and nutrient malabsorption; some have been associated with mutations in diacylglycerol-acyltransferase 1 (DGAT1), which catalyzes formation of triacylglycerol from diacylglycerol and acyl-CoA. We investigated the mechanisms by which DGAT1 deficiency contributes to intestinal failure using patient-derived organoids. METHODS: We collected blood samples from 10 patients, from 6 unrelated pedigrees, who presented with early-onset severe diarrhea and/or vomiting, hypoalbuminemia, and/or (fatal) protein-losing enteropathy with intestinal failure; we performed next-generation sequencing analysis of DNA from 8 patients. Organoids were generated from duodenal biopsies from 3 patients and 3 healthy individuals (controls). Caco-2 cells and patient-derived dermal fibroblasts were transfected or transduced with vectors that express full-length or mutant forms of DGAT1 or full-length DGAT2. We performed CRISPR/Cas9-guided disruption of DGAT1 in control intestinal organoids. Cells and organoids were analyzed by immunoblot, immunofluorescence, flow cytometry, chromatography, quantitative real-time polymerase chain reaction, and for the activity of caspases 3 and 7. RESULTS: In the 10 patients, we identified 5 bi-allelic loss-of-function mutations in DGAT1. In patient-derived fibroblasts and organoids, the mutations reduced expression of DGAT1 protein and altered triacylglycerol metabolism, resulting in decreased lipid droplet formation after oleic acid addition. Expression of full-length DGAT2 in patient-derived fibroblasts restored formation of lipid droplets. Organoids derived from patients with DGAT1 mutations were more susceptible to lipid-induced cell death than control organoids. CONCLUSIONS: We identified a large cohort of patients with congenital diarrheal disorders with mutations in DGAT1 that reduced expression of its product; dermal fibroblasts and intestinal organoids derived from these patients had altered lipid metabolism and were susceptible to lipid-induced cell death. Expression of full-length wildtype DGAT1 or DGAT2 restored normal lipid metabolism in these cells. These findings indicate the importance of DGAT1 in fat metabolism and lipotoxicity in the intestinal epithelium. A fat-free diet might serve as the first line of therapy for patients with reduced DGAT1 expression. It is important to identify genetic variants associated with congenital diarrheal disorders for proper diagnosis and selection of treatment strategies.Item A single-center experience of post-transplant lymphoproliferative disorder (PTLD) cases after pediatric liver transplantation: Incidence, outcomes, and association with food allergy(2018) Haberal, Mehmet; Haberal, Nihan; Baris, Zeren; Ozcay, Figen; Ozbek, Ozlem Yilmaz; Sarialioglu, Faik; 29755021; AAB-4153-2020Background/Aims: We evaluated our 16-year single-center experience of pediatric post-transplant lymphoproliferative disorder (PTLD) cases who underwent liver transplantation between 2001 and 2017. Materials and Methods: Of the 236 pediatric patients who underwent liver transplantation between 2001 and 2017, the clinical and laboratory data of eight patients diagnosed with PTLD were reviewed. The pre-transplant Epstein-Barr virus (EBV) status of 172 patients was also recorded. Results: The total incidence of PTLD was 3.4%. The incidence of PTLD was 10% in pre-transplant EBV immunoglobulin G (IgG)-seronegative patients and 0.8% in pre-transplant EBV IgG-seropositive patients. The mean age of the patients at liver transplantation was 2.71 +/- 3.21 years, and four patients were aged below 1 year at the time of transplantation. PTLD was diagnosed at 21.81 +/- 18.1 months after transplantation. The primary site of involvement was variable among patients: peripheral and mediastinal lymph nodes, stomach and intestine, transplanted graft, bone marrow, and nasopharynx. The eosinophil count varied greatly among patients, with a mean value of 524.62 +/- 679/mm3. Three patients had a food allergy and were administered an elimination diet at the time of PTLD diagnosis. Six patients had PTLD of B-cell origin. One patient died due to neutropenic sepsis during chemotherapy, whereas seven patients were followed up in full remission for 7.75 +/- 4 years. Conclusion: PTLD is a life-threatening complication of solid-organ transplantation with a heterogeneous clinical spectrum. Food allergy had a close association with PTLD. A close follow-up of patients with risk factors and an early diagnosis with appropriate treatment may lead to a better outcome.