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Arıkan, Çiğdem

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Çiğdem

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Arıkan

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Arıkan, Çiğdem

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2019 - 201922020 - 202321

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    SERPINB11 variant-related liver injury in STEC-HUS: case reports and literature review
    (Springer, 2022) Umman, Nazlı; Petmezci, Mey Talip; Altuntaş, Cansu; Ertürk, Biray; Dursun, Hasan; Arıkan, Çiğdem; Faculty Member; School of Medicine; 240198
    Background Liver damage is uncommon in Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS). Herein, we present two cases with a diagnosis of STEC-HUS that progressed to liver damage, with findings presumably related to the SERPINB11 gene c.268G > T (p.Glu90Ter) variant. Case-diagnosis/treatment Two boys aged 3 and 2 years, respectively, were referred to our clinic with a preliminary diagnosis of STEC-HUS. The patients had low hemoglobin, thrombocyte, and haptoglobin levels but high levels of lactic dehydrogenase, urea, creatinine, and schistocytes in peripheral smears. Escherichia coli O157:H7 was detected in their stool samples. The patients underwent hemodialysis, plasma exchange, and supportive treatments. Meanwhile, cholestasis developed in the patients, resulting in elevated total bilirubin levels. During the follow-up period, kidney function recovered completely; however, liver function did not improve, and one patient developed chronic liver damage. Gene mutations that may cause liver damage were investigated, and c.268G > T (p.Glu90Ter) homozygous and heterozygous variants were detected in exon 9 of the SERPINB11 gene in the patients. Conclusions Our patients presented with kidney impairment and liver malfunction. Hepatic involvement in STEC-HUS may result from ischemia, hemolysis, and endothelial damage in the hepatic vessels. Liver injury in STEC-HUS cases may be associated with the homozygous SERPINB11 gene c.268G > T (p.Glu90Ter) variant.
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    Telemedicine in monitoring pediatric LT patients before and during COVID-19 pandemic
    (Wiley, 2022) N/A; N/A; Musaoğlu, Miraç Nur; Yüksel, Muhammed; Mizikoğlu, Özlem; Arıkan, Çiğdem; PhD Student; Researcher; Other; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Graduate School of Health Sciences; N/A; School of Medicine; School of Medicine; N/A; N/A; N/A; 240198
    Background: the delivery of healthcare services by telemedicine decreases costs of traveling for patients, is less time-consuming, and most importantly permits the connection between highly skilled specialists and patients. However, whether the use of telemedicine (text messaging) for LT patients was affected by the COVID-19 pandemic is unknown. Methods: We collected data (following consent from patients and parents) from 57 patients (33 male/24 female) with a median age of 47 (IQR: 9-91) months, whom we followed up with text messaging between September 2019 and September 2020, spanning the 6 months prior to COVID-19 and during this period. Results: in total, 723 text message mediated consultations occurred during this period, henceforth simply referred to as "messages." Three hundred and twenty-eight (45%) messages occurred during the 6 months up to the start of the pandemic. Following the COVID-19 outbreak, the number of messages increased to 395 (55%). the three most common reasons of messaging were post-liver-LT follow-up messages (n = 215/723, 29.7%), consultations for drug use (n = 157/723, 21.7%), and medication prescriptions (n = 113/723, 15.6%). Protocol biopsy discussions (n = 33/723, 4.6%) and fever (n = 27/723, 3.7%) were among others (vaccination, rash, diarrhea, cough, fatigue, Acne). During the COVID-19 outbreak, only post-LT follow-up messages increased significantly to 132/395 (33%) from 83/328 (25%) (p-value: .02). Conclusions: We found that the pandemic resulted in an increase in the total number of text message mediated consultations and specifically for the use of post-LT follow-up. Messaging was effective for post-LT follow-ups and all patients were at least satisfied.
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    Posterior reversible encephalopathy syndrome in a five-year-old child: a case report
    (Elsevier, 2019) Acar, Şencan; Kavlak, Mustafa Emre; Özkan, Perihan; Polat, Kamil Yalçın; Akyıldız, Murat; N/A; N/A; Demir, Barış; Arıkan, Çiğdem; Doctor; Faculty Member; School of Medicine; School of Medicine; Koç University Hospital; N/A; 240198
    Posterior reversible encephalopathy syndrome (PRES) is a neuroradiologic syndrome. The etiology of PRES is still unclear. Some factors were described. We present a case of a pediatric patient with liver transplant who developed PRES following blood transfusion while receiving tacrolimus therapy. A 51/2-year-old boy who underwent living donor liver transplantation, and PRES developed on the sixth day post transplant under tacrolimus treatment after 6 hours of red blood transfusion. PRES is a rare condition; it should be kept in mind about patients who have received organ transplants and develop sudden neurologic symptoms.
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    Gastrointestinal perforations and associated risk factors in children after liver transplantation
    (Wiley, 2021) Aslan, Serdar; Akis Yildiz, Zeliha; Yazar, Serafettin; Kargi, Ahmet; Donmez, Ramazan; Selimoglu, Ayse; Arikan, Cigdem; Kavlak, Emre; Polat, Kamil Yalcin; Arıkan, Çiğdem; Faculty Member; School of Medicine; 240198
    In this study, possible risk factors of gastrointestinal perforations (GIP) that increase mortality after liver transplantation in children were investigated. One hundred and thirty-one pediatric patients who underwent 139 liver transplants between January 2016 and February 2020 were evaluated retrospectively based on preoperative and surgical data. Furthermore, cases with biliary atresia, which constitute 26.7% (35) of the patients, were compared within themselves and with other groups. It was found that the cases that developed perforations were younger, lower in weight, and had higher number of surgeries than those who did not, while the mortality and morbidity rates were higher in these patients. When cases with biliary atresia were analyzed within themselves, no significant difference was found between perforated biliary atresia and non-perforated cases in terms of age, weight, and previous surgery. When biliary atresia and other etiologies were compared, biliary atresia cases were found to be transplanted at a younger age, at a lower weight, and this group had a higher risk for perforation. Early laparotomy should be performed in order to reduce mortality in GIPs. Patients that are younger, underweight, previously operated, and using mesh must be closely monitored.
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    Liver involvement is rare during COVID-19 infection in children
    (Elsevier, 2021) Polat, Esra; Güven, Şirin; N/A; N/A; N/A; Arıkan, Çiğdem; Aktürk, Hacer; Khalilova, Fidan; Faculty Member; Faculty Member; Doctor; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; N/A; Koç University Hospital; 240198; 162936; N/A
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    Eosinophilic GI disorders after transplantation are a unique transient entity reply
    (Lippincott Williams and Wilkins (LWW), 2021) N/A; N/A; Arıkan, Çiğdem; N/A; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; N/A; 240198
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    Standard immunosuppressive treatment reduces regulatory B cells in children with autoimmune liver disease
    (Frontiers, 2023) Polat, Esra; N/A; Yüksel, Muhammed; Nazmi, Farinaz; Alwardat, Dima; Akgül, Sebahat Usta; Akyıldız, Murat; Arıkan, Çiğdem; Researcher; PhD Student; Researcher; Doctor; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); Koç University Transplant Immunology Research Centre of Excellence (TIREX) Inaugurated; N/A; Graduate School of Health Sciences; N/A; N/A; School of Medicine; School of Medicine; Koç University Hospital; Koç University Hospital; N/A; Koç University Hospital; Koç University Hospital; Koç University Hospital; N/A; N/A; N/A; N/A; 123080; 240198
    Introduction: Autoimmune hepatitis (AIH) is a chronic liver disease caused by a perturbed immune system. The scarcity of short- and long-term immune monitoring of AIH hampered us to comprehend the interaction between immunosuppressive medication and immune homeostasis. Methods and Patients: We recruited children with AIH at the time of diagnosis and at the 1st, 3rd, 6th, 12th, 18th, and 24th months of immunosuppression (IS). We also enrolled children with AIH being on IS for >2 years. Children with drug-induced liver injury (DILI), and those receiving tacrolimus after liver transplantation (LT), were enrolled as disease/IS control subjects. Healthy children (HC) were also recruited. Peripheral blood mononuclear cells (PBMCs) were isolated from all participants. Healthy liver tissue from adult donors and from livers without inflammation were obtained from children with hepatoblastoma. By using flow cytometry, we performed multi-parametric immune profiling of PBMCs and intrahepatic lymphocytes. Additionally, after IS with prednisolone, tacrolimus, rapamycin, or 6-mercaptopurine, we carried out an in vitro cytokine stimulation assay. Finally, a Lifecodes SSO typing kit was used to type HLA-DRB1 and Luminex was used to analyze the results. Results: Untreated AIH patients had lower total CD8 T-cell frequencies than HC, but these cells were more naïve. While the percentage of naïve regulatory T cells (Tregs) (CD4+FOXP3lowCD45RA+) and regulatory B cells (Bregs, CD20+CD24+CD38+) was similar, AIH patients had fewer activated Tregs (CD4+FOXP3highCD45RA-) compared to HC. Mucosal-associated-invariant-T-cells (MAIT) were also lower in these patients. Following the initiation of IS, the immune profiles demonstrated fluctuations. Bregs frequency decreased substantially at 1 month and did not recover anymore. Additionally, the frequency of intrahepatic Bregs in treated AIH patients was lower, compared to control livers, DILI, and LT patients. Following in vitro IS drugs incubation, only the frequency of IL-10-producing total B-cells increased with tacrolimus and 6MP. Lastly, 70% of AIH patients possessed HLA-DR11, whereas HLA-DR03/DR07/DR13 was present in only some patients. Conclusion: HLA-DR11 was prominent in our AIH cohort. Activated Tregs and MAIT cell frequencies were lower before IS. Importantly, we discovered a previously unrecognized and long-lasting Bregs scarcity in AIH patients after IS. Tacrolimus and 6MP increased IL-10+ B-cells in vitro.
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    Genotype-phenotype relationships of truncating mutations, p.E297G and p.D482G in bile salt export pump deficiency
    (Elsevier, 2023) Felzen, Antonia; van Wessel, Daan B.E.; Gonzales, Emmanuel; Thompson, Richard J.; Jankowska, Irena; Shneider, Benjamin L.; Sokal, Etienne; Grammatikopoulos, Tassos; Kadaristiana, Agustina; Jacquemin, Emmanuel; Spraul, Anne; Lipiński, Patryk; Czubkowski, Piotr; Rock, Nathalie; Shagrani, Mohammad; Broering, Dieter; Nicastro, Emanuele; Kelly, Deirdre; Nebbia, Gabriella; Arnell, Henrik; Fischler, Björn; Hulscher, Jan B.F.; Serranti, Daniele; Polat, Esra; Debray, Dominique; Lacaille, Florence; Goncalves, Cristina; Hierro, Loreto; Muñoz Bartolo, Gema; Mozer-Glassberg, Yael; Azaz, Amer; Brecelj, Jernej; Dezsőfi, Antal; Calvo, Pier Luigi; Grabhorn, Enke; Hartleif, Steffen; van der Woerd, Wendy J.; Kamath, Binita M.; Wang, Jian-She; Li, Liting; Durmaz, Özlem; Kerkar, Nanda; Jørgensen, Marianne Hørby; Fischer, Ryan; Jimenez-Rivera, Carolina; Alam, Seema; Cananzi, Mara; Laverdure, Noemie; Ferreira, Cristina Targa; Guerrero, Felipe Ordoñez; Wang, Heng; Sency, Valerie; Kim, Kyung Mo; Chen, Huey-Ling; de Carvalho, Elisa; Fabre, Alexandre; Bernabeu, Jesus Quintero; Zellos, Aglaia; Alonso, Estella M.; Sokol, Ronald J.; Suchy, Frederick J.; Loomes, Kathleen M.; McKiernan, Patrick J.; Rosenthal, Philip; Turmelle, Yumirle; Horslen, Simon; Schwarz, Kathleen; Bezerra, Jorge A.; Wang, Kasper; Hansen, Bettina E.; Verkade, Henkjan J.; Arıkan, Çiğdem; Faculty Member; School of Medicine; 240198
    Background & Aims: Bile salt export pump (BSEP) deficiency frequently necessitates liver transplantation in childhood. In contrast to two predicted protein truncating mutations (PPTMs), homozygous p.D482G or p.E297G mutations are associated with relatively mild phenotypes, responsive to surgical interruption of the enterohepatic circulation (siEHC). The phenotype of patients with a compound heterozygous genotype of one p.D482G or p.E297G mutation and one PPTM has remained unclear. We aimed to assess their genotype-phenotype relationship. Methods: From the NAPPED database, we selected patients with homozygous p.D482G or p.E297G mutations (BSEP1/1; n = 31), with one p.D482G or p.E297G, and one PPTM (BSEP1/3; n = 30), and with two PPTMs (BSEP3/3; n = 77). We compared clinical presentation, native liver survival (NLS), and the effect of siEHC on NLS. Results: The groups had a similar median age at presentation (0.7-1.3 years). Overall NLS at age 10 years was 21% in BSEP1/3 vs. 75% in BSEP1/1 and 23% in BSEP3/3 (p <0.001). Without siEHC, NLS in the BSEP1/3 group was similar to that in BSEP3/3, but considerably lower than in BSEP1/1 (at age 10 years: 38%, 30%, and 71%, respectively; p = 0.003). After siEHC, BSEP1/3 and BSEP3/3 were associated with similarly low NLS, while NLS was much higher in BSEP1/1 (10 years after siEHC, 27%, 14%, and 92%, respectively; p <0.001). Conclusions: Individuals with BSEP deficiency with one p.E297G or p.D482G mutation and one PPTM have a similarly severe disease course and low responsiveness to siEHC as those with two PPTMs. This identifies a considerable subgroup of patients who are unlikely to benefit from interruption of the enterohepatic circulation by either surgical or ileal bile acid transporter inhibitor treatment. Impact and implications: This manuscript defines the clinical features and prognosis of individuals with BSEP deficiency involving the combination of one relatively mild and one very severe BSEP deficiency mutation. Until now, it had always been assumed that the mild mutation would be enough to ensure a relatively good prognosis. However, our manuscript shows that the prognosis of these patients is just as poor as that of patients with two severe mutations. They do not respond to biliary diversion surgery and will likely not respond to the new IBAT (ileal bile acid transporter) inhibitors, which have recently been approved for use in BSEP deficiency.
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    Disease course and treatment response of eosinophilic gastrointestinal diseases in children with liver transplantation: long-term follow-up
    (Lippincott Williams & Wilkins, 2021) Doğanay, Latife; Can, Demet; N/A; Arıkan, Çiğdem; Faculty Member; Undergraduate Student; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); School of Medicine; School of Medicine; 240198; N/A
    INTRODUCTION: To describe the clinical and laboratory profile, natural course, treatment outcome, and risk factors of posttransplant esophageal and nonesophageal eosinophilic gastrointestinal disorders (EGIDs). METHODS: All children (aged <18 years) who underwent liver transplantation, between 2011 and 2019, in a single transplant center with a follow-up period of 1 year or more posttransplant and with a history of posttransplant endoscopic evaluation were included in this study. RESULTS: During the study period, 89 children met the inclusion criteria. Patients were followed for a median of 8.0 years. A total of 39 (44%) patients were diagnosed with EGID after transplantation. of these, 29 (33%) had eosinophilic esophagitis (EoE), and 10 (11%) had eosinophilic gastritis, gastroenteritis or enterocolitis. In comparison with the non-EGID group, patients with EGID were younger at transplant (P <= 0.0001), transplanted more frequently due to biliary atresia (P <= 0.0001), and had higher rates of pretransplant allergy (P = 0.019). In the posttransplant period, they had higher rates of mammalian Target of Rapamycin inhibitor use (P = 0.006), Epstein-Barr virus viremia (P = 0.03), post-transplant lymphoproliferative disease (P = 0.005), and allergen sensitization (P <= 0.0001). In regression analysis, young age at transplant, age at diagnosis, pretransplant atopic dermatitis, and post-transplant lymphoproliferative disease were associated with an increased risk of EGID or EoE. Laboratory abnormalities such as anemia (P = 0.007), thrombocytosis (P = 0.012), and hypoalbuminemia (P = 0.031) were more commonly observed in the eosinophilic gastritis, gastroenteritis or enterocolitis group than in the EoE group. Following treatment, most patients had symptomatic resolution at 3 months and histologic resolution at 6 months postdiagnosis. Among the patients who had 5 years of follow-up, none recurred. DISCUSSION: EGID is a common posttransplant diagnosis, which seems to affect patients who are transplanted earlier and who have pretransplant atopy. Posttransplant EGID is responsive to treatment, but as histologic remission occurs after symptomatic resolution, the decision to perform control endoscopy should be delayed.
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    Examining the hepatic immune system in children with liver disease with fine needle aspiration
    (Lippincott Williams & Wilkins, 2022) N/A; N/A; N/A; N/A; N/A; N/A; N/A; Yüksel, Muhammed; Demirbaş, Burak; Mizikoğlu, Özlem; Tütüncü, Yıldız; Kanmaz, Turan; Oğuzkurt, Levent; Arıkan, Çiğdem; Researcher; Doctor; Researcher; Faculty Member; Faculty Member; Faculty Member; Faculty Member; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); N/A; N/A; N/A; School of Medicine; School of Medicine; School of Medicine; School of Medicine; Koç University Hospital; N/A; N/A; N/A; 239430; 275799; 13559; 240198
    Objectives: Liver biopsy is the standard in diagnosing liver diseases. Yet, it provides little space to perform comprehensive immune profiling of the liver. Hence, we explored whether fine needle aspirates (FNAs) could be used to elucidate the hepatic immunity in children. Methods: We enrolled 74 children undergoing diagnostic (n = 17) or protocol biopsy (n = 57) following liver transplantation (LT). Matched blood and FNAs were obtained. Additionally, explant liver tissue was collected from children (n = 14) undergoing LT. Immune cells were isolated from peripheral blood, FNAs and explanted livers. Immune-phenotypical profiling was done by flow cytometry. Results: Biopsied patients (58% female) were at a median age of 46 months (interquartile range [IQR]: 12–118) and LT patients (71% female) were 48 months (IQR: 21–134, P = 0.78) old. CD69+, a hallmark of tissue-resident immune cells was expressed in 1.3% of CD3+ T cells from blood being higher in FNA (20%) and tissue (49%, P < 0.001). CD4+ T-cell frequencies in tissue (13%) and FNAs (20%) were lower compared to blood (35%, P < 0.001) whereas CD8+ T cells in tissue (33.5%) and FNA (32%) were higher than in blood (25%, P < 0.01). Mucosal associated invariant T cells were enriched in liver tissue (8.8%) and in the FNA (4.4%) compared to blood (1.7%, P < 0.001). Whereas the percentage of total Tregs (CD4+CD25+FOXP3+CD127low/−) decreased, the proportion of activated Tregs (CD4+CD45RA-FOXP3high) increased in FNA and explant. Breg (CD19+CD20+CD24highCD38high) frequencies were similar in all groups. Conclusion: FNA is a practical method to sample the liver immune system collecting even small cell subsets such as regulatory T/B cells.