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Publication Open Access Recommendations for clinical decision-making in children with type 1 diabetes and celiac disease: type 1 diabetes and celiac disease joint working group report(Galenos Yayınevi, 2022) Dalgıç, B.; Gökşen, D.; Aydoğdu, S.; Savaş, Erdeve Ş.; Kuloğu, Z.; Doğan, Y.; Aycan, Z.; Keser, A.; Beşer, Ö.F.; Özbek, M.N.; Bideci, A.; Ertem, D.; Evliyaoğlu, O.; Eliüz Tipici, B.; Gökçe, T.; Muradoğlu, S.; Koca, T.; Tütüncüler, F.; Baş, F.; Darendeliler, F.; Selimoğlu, M.A.; Hatun, Şükrü; Yeşiltepe Mutlu, Rahime Gül; Kızılkan, Nuray Uslu; Taşkın, Orhun Çığ; Faculty Member; Faculty Member; Faculty Member; School of Medicine; Koç University Hospital; 153504; 153511; 221274; 166686It is well-known that in children with type 1 diabetes (T1D), the frequency of Celiac disease (CD) is increased due to mechanisms which are not fully elucidated but include autoimmune injury as well as shared genetic predisposition. Although histopathologic examination is the gold standard for diagnosis, avoiding unnecessary endoscopy is crucial. Therefore, for both clinicians and patients’ families, the diagnosis of CD remains challenging. In light of this, a joint working group, the Type 1 Diabetes and Celiac Disease Joint Working Group, was convened, with the aim of reporting institutional data and reviewing current international guidelines, in order to provide a framework for clinicians. Several controversial issues were discussed: For CD screening in children with T1D, regardless of age, it is recommended to measure tissue transglutaminase-immunoglobulin A (tTG-IgA) and/or endomysial-IgA antibody due to their high sensitivity and specificity. However, the decision-making process based on tTG-IgA titer in children with T1D is still debated, since tTG-IgA titers may fluctuate in children with T1D. Moreover, seronegativity may occur spontaneously. The authors’ own data showed that most of the cases who have biopsy-proven CD had tTG-IgA levels 7-10 times above the upper limit. The decision for endoscopy based solely on tTG-IgA levels should be avoided, except in cases where tTG-IgA levels are seven times and above the upper limit. A closer collaboration should be built between divisions of pediatric endocrinology and gastroenterology in terms of screening, diagnosis and follow-up of children with T1D and suspicious CD.Publication Open Access Mutations in AR or SRD5A2 genes: clinical findings, endocrine pitfalls, and genetic features of children with 46,XY DSD(Galenos Yayınevi, 2022) Akcan, Neşe; Uyguner, Oya; Baş, Firdevs; Toksoy, Güven; Karaman, Birsen; Abalı, Zehra Yavaş; Poyrazoğlu, Şükran; Aghayev, Agharza; Karaman, Volkan; Bundak, Ruveyde; Basaran, Seher; Darendeliler, Feyza; Altunoğlu, Umut; Avcı, Şahin; Faculty Member; Faculty Member; School of Medicine; 126174; N/AObjective: androgen insensivity syndrome (AIS) and 5 alpha-reductase deficiency (5 alpha-RD) present with indistinguishable phenotypes among the 46,XY disorders of sexual development (DSD) that usually necessitate molecular analyses for the definitive diagnosis in the prepubertal period. The aim was to evaluate the clinical, hormonal and genetic findings of 46,XY DSD patients who were diagnosed as AIS or 5 alpha-RD. Methods: patients diagnosed as AIS or 5 alpha-RD according to clinical and hormonal evaluations were investigated. Sequence variants of steroid 5-alpha-reductase type 2 were analyzed in cases with testosterone/dihydrotestosterone (T/DHT) ratio of >= 20, whereas the androgen receptor (AR) gene was screened when the ratio was <20. Stepwise analysis of other associated genes were screened in cases with no causative variant found in initial analysis. For statistical comparisons, the group was divided into three main groups and subgroups according to their genetic diagnosis and T/DHT ratios. Results: a total of 128 DSD patients from 125 non-related families were enrolled. Birth weight SDS and gestational weeks were significantly higher in 5 alpha-RD group than in AIS and undiagnosed groups. Completely female phenotype was higher in all subgroups of both AIS and 5 alpha-RD patients than in the undiagnosed subgroups. In those patients with stimulated T/DHT <20 in the prepubertal period, stimulated T/DHT ratio was significantly lower in AIS than in the undiagnosed group, and higher in 5 alpha-RD. Phenotype associated variants were detected in 24% (n=18 AIS, n=14 5 alpha-RD) of the patients, revealing four novel AR variants (c.94G>T, p.Glu32*, c.330G>C, p.Leu110=; c.2084C>T, p.Pro695Leu, c.2585_2592delAGCTCCTG, p.(Lys862Argfs*16), of these c.330G>C with silent status remained undefined in terms of its causative effects. Conclusion: T/DHT ratio is an important hormonal criterion, but in some cases, T/DHT ratio may lead to diagnostic confusion. Molecular is for the robust of 46,XY DSD Four novel AR variants were identified in our study.Publication Open Access Effects of antenatal magnesium exposure on intestinal blood flow and outcome in Preterm Neonates(Thieme Medical Publishers, 2015) İmamoğlu, Ebru Yalın; Ovalı, Fahri; Karatekin, Güner; N/A; Gürsoy, Tuğba; Faculty Member; School of Medicine; 214691Objective This study aims to investigate the effects of antenatal magnesium sulfate on intestinal blood flow in preterm neonates. Study Design In this prospective case-match study, 25 preterm neonates exposed to magnesium sulfate antenatally were included (study group). Overall, 25 gestational age-matched neonates who had no exposure to magnesium constituted the control group. Serial daily Doppler flow measurements of superior mesenteric artery (SMA) were performed. The time to reach full feeds, first meconium passage were assessed. Presence of feeding intolerance or necrotizing enterocolitis was recorded. Results Blood flow velocities of SMA were not different between the groups during the first five postnatal days. However, SMA blood flow showed an increasing trend in the control group unlike the study group (control group, p < 0.001; study group, p = 0.29). There was no significant difference between the two groups regarding the time to reach full feeds or first meconium passage and presence of feeding intolerance. No case of necrotizing enterocolitis was seen. Conclusion Antenatal magnesium does not significantly affect intestinal blood flow, but it seems to attenuate the increasing trend of the intestinal blood flow in the early postnatal days. However, this study failed to show any impact of this finding on clinical outcomes.Publication Open Access The prevalence and diagnostic criteria of health-care associated infections in neonatal intensive care units in Turkey: a multicenter point- prevalence study(Elsevier, 2021) Demirdağ, Tuğba Bedir; Koç¸ Esin; Tezer, Hasan; Oğuz, Suna; Satar, Mehmet; Sağlam, Özge; Uygun, Saime Sündüz; Önal, Esra; Hırfanoğlu, İbrahim Murat; Tekgündüz, Kadir; Oygür, Nihal; Bülbül, Ali; Zübarioğlu, Umut; Üstün, Nuran; Ünal, Sezin; Aygün, Canan; Karagöl, Belma Saygılı; Zenciroğlu, Ayşegül; Öncel, M. Yekta; Sağlık, Adviye Çakıl; Okulu, Emel; Terek, Demet; Narlı, Nejat; Aliefendioğlu, Didem; Ünal, Sevim; Türkmen, Münevver Kaynak; Narter, Fatma Kaya; Çiftdemir, Nükhet Aladağ; Beken, Serdar; Çakır, Salih Çağrı; Yiğit, Şule; Çoban, Asuman; Ecevit, Ayşe; Çelik, Yalçın; Kulalı, Ferit; Gürsoy, Tuğba; Faculty Member; School of Medicine; 214691Background: healthcare-acquired infections (HAIs) in the neonatal period cause substantial morbidity, mortality, and healthcare costs. Our purpose was to determine the prevalence of HAIs, antimicrobial susceptibility of causative agents, and the adaptivity of the Centres for Disease Control and Prevention (CDC) criteria in neonatal HAI diagnosis. Methods: a HAI point prevalence survey was conducted in the neonatal intensive care units (NICUs) of 31 hospitals from different geographic regions in Turkey. Results: the Point HAI prevalence was 7.6%. Ventilator-associated pneumonia (VAP) and central line-associated bloodstream infections (CLABSI) and late onset sepsis were predominant. The point prevalence of VAP was 2.1%, and the point prevalence of CLABSI was 1.2% in our study. The most common causative agents in HAIs were Gram-negative rods (43.0%), and the most common agent was Klebsiella spp (24.6%); 81.2% of these species were extended spectrum beta-lactamase (ESBL) (+). Blood culture positivity was seen in 33.3% of samples taken from the umbilical venous catheter, whereas 0.9% of samples of peripherally inserted central catheters (PICCs) were positive. In our study, 60% of patients who had culture positivity in endotracheal aspirate or who had purulent endotracheal secretions did not have any daily FiO2 change (p = 0.67) and also 80% did not have any increase in positive end-expiratory pressure (PEEP) (p = 0.7). On the other hand, 18.1% of patients who had clinical deterioration compatible with VAP did not have endotracheal culture positivity (p = 0.005). Conclusions: neonatal HAIs are frequent adverse events in district and regional hospitals. This at-risk population should be prioritized for HAI surveillance and prevention programs through improved infection prevention practices, and hand hygiene compliance should be conducted. CDC diagnostic criteria are not sufficient for NICUs. Future studies are warranted for the diagnosis of HAIs in NICUs.Publication Open Access Effects of Saccharomyces boulardii on neonatal hyperbilirubinemia: a randomized controlled trial(Thieme Medical Publishers, 2015) Ovalı, Fahri; Karatekin, Güner; N/A; Gürsoy, Tuğba; Faculty Member; School of Medicine; 214691Since probiotics modulate intestinal functions and enterohepatic circulation; they might have an effect on neonatal hyperbilirubinemia treatment. The objective of this study was to investigate the efficacy of Saccharomyces boulardii supplementation on hyperbilirubinemia. Study Design A prospective, double-blind, placebo controlled trial was performed on 35 to 42 gestational weeks' neonates. They were randomized either to receive feeding supplementation with S. boulardii 125 mg every 12 hours or placebo during phototherapy. Serum bilirubin levels were measured at 0, 24th, 48th, 72nd, and 96th hour of phototherapy. Results A total of 119 infants (61 in the control group and 58 in the study group) were enrolled. The duration of phototherapy (2 [1-3] vs. 2 [1-3], p: 0.22) was not different between groups. The levels of bilirubin during phototherapy ([24th hour; 14.1 {12.8-15.7} vs. 13.5 {12.4-14.9}, p: 0.085]; [48th hour; 14.1 {12-15.3} vs. 13.4 {12.4-14.5}, p: 0.41]; [72nd hour; 13.9 {12.2-15.6} vs. 13.5 {12.5-14.5}, p: 0.41]; [96th hour; 14.7 {11.4-15.5} vs. 13.4{10.7-14.1}, p: 0.24]) or the duration of rebound phototherapy (1 [1-1] vs. 1.5 [1-2], p: 0.40) were lower in the study group than in the controls, but none of the values were statistically significant. Conclusion S. boulardii did not influence the clinical course of hyperbilirubinemia significantly.Publication Open Access Vitamin D status across age groups in Turkey: results of 108,742 samples from a single laboratory(Galenos Yayınevi, 2020) Bereket, Abdullah; Hatun, Şükrü; Yeşiltepe Mutlu, Rahime Gül; Aksu, Ekin Deniz; Faculty Member; School of Medicine; 153504; 153511; N/AObjective: the aim was to determine vitamin D status in the general population in Turkey between 2011 and 2016, and to evaluate the effectiveness of the national vitamin D supplementation programme. Methods: serum 25-hydroxyvitamin D (25-OHD) measurement data were retrieved from an internationally accredited laboratory, operating nationwide. A total of 108,742 measurements of 25-OHD were analyzed using the cut-off values of 0-11 ng/mL, 12-19 ng/mL, 20-49 ng/mL, 50-70 ng/mL and >70 ng/mL for vitamin D deficiency, insufficiency, sufficiency, possibly harmful and excess respectively. Results: the mean±standard deviation 25-OHD level was 21.6±13.3 ng/mL. Mean 25-OHD concentrations by age groups were: 37.3 ng/mL, 30.1 ng/mL and 23.7 ng/mL for <1, 1-10 and 11-18 year old groups, respectively. Mean 25-OHD levels of children <1 year and 1-3 years of age were significantly higher than those found in other age groups. The prevalence of vitamin D deficiency (<12 ng/mL) was lowest in children at 1-3 years of age (5%). In subjects older than 18 years of age, mean 25-OHD levels were 18.2 ng/mL, 20.1 ng/ mL, 21.9 ng/mL and 21.1 ng/mL for age groups 19-30, 31-50, 51-70 and >70 years, respectively. Conclusion: successful implementation of the national vitamin D supplementation programme, appears to have nearly eliminated vitamin D deficiency for children under 1-years of age. However, the positive impact of the vitamin D supplementation diminishes as children get older suggesting that supplementation may be required in the older children and adults. In addition, improved awareness of the benefits and risks of excess vitamin D should prevent unnecessary and excessive use of vitamin D supplements.Publication Open Access An evaluation of glucagon injection anxiety and its association with the fear of hypoglycemia among the parents of children with type 1 diabetes(Galenos Yayınevi, 2021) Muradoğlu, Serra Küpçüoğlu; Gökçe, Tuğba; Can, Ecem; Yeşiltepe Mutlu, Rahime Gül; Hatun, Şükrü; Faculty Member; School of Medicine; Graduate School of Health Sciences; Koç University Hospital; N/A; N/A; N/A; 153511; 153504Objective: Hypoglycemia is a common acute complication of type 1 diabetes (T1D), which may cause seizure, loss of consciousness, and temporary motor or sensory impairment. Glucagon administration is an effective way of treating severe hypoglycemia, especially in a free-living setting. Nonetheless, families have difficulties in managing severe hypoglycemia due to their anxiety and challenges with current glucagon administration techniques. The aim of the current study was to explore the associations between parental fear of hypoglycemia (FoH) and their general anxiety level, and in particular, their attitudes towards and thoughts on glucagon administration. Methods: Parents of children with T1D completed questionnaires assessing background and clinical information, FoH, generalized anxiety disorder (GAD) and parental anxiety for glucagon administration (PAGA). Results: sixty-eight parents participated. Positive correlations were found between parental GAD-7 score and both FoH and the number of night-time blood glucose measurements and there was a negative correlation with the child's age. Parents mean self-evaluation score of their competence in glucagon administration was 6 (standard deviation +/- 2.9) on a scale of 0 to 10. Unsurprisingly, this score was negatively correlated with the PAGA scores. There was no significant difference between children using continuous glucose monitoring system and self-monitoring of blood glucose in terms of parental FoH, anxiety and misconceptions about glucagon administration. Conclusion: the results showed that parents of children with T1D had anxiety and fear connected with hypoglycemia and glucagon administration. Structured and practical training should be implemented to increase parents' self-confidence including annual refresher training for home glucagon administration.Publication Open Access Care and support of children with type 1 diabetes at school: the Turkish experience(Galenos Yayınevi, 2021) Avcı, Özkan; Yardım, Nazan; Aycan, Zehra; Darendeliler, Feyza; Hatun, Şükrü; Yeşiltepe Mutlu, Rahime Gül; Gökçe, Tuğba; Faculty Member; School of Medicine; Koç University Hospital; 153504; 153511; N/ADiabetes care at school has recently appeared on the agenda of international diabetes organizations, the basic principles of which have been newly determined. The aim of this review was to summarize the activities and output of the Diabetes at School Program - a program that has been delivered in Turkey for the last 10 years - and to focus on different aspects of Diabetes Care at School through a national model. Recently, a detailed set of national regulations, including the basic principles proposed by the International Society for Pediatric and Adolescent Diabetes and the experience in Turkey, was prepared and has come into force. The future agenda includes giving priority to socio-economically disadvantaged regions, provision of an Individual Treatment Plan at School for each child with diabetes and ensuring that each school has an action plan for the care of children with diabetes. We believe that if all countries have programs and structured national regulations similar to the Diabetes at School Program, this will enable significant progress in the level of care delivered to children with diabetes.Publication Open Access General movements assessment and Alberta Infant Motor Scale in neurodevelopmental outcome of preterm infants(Elsevier, 2022) Yıldırım, C.; Asalıoğlu, A.; Acar, G., Akman, İ.; Coşkun, Yeşim; Koç University HospitalAim: we aimed to compare the General Movement Assessment (GMA) and the Alberta Infant Motor Scale (AIMS) in preterm infants for the prediction of cerebral palsy (CP) and neurodeve-lopmental delay (NDD). Additionally, we aimed to evaluate the diagnostic compatibility of the General Movement Optimality Score (GMOS), the Motor Optimality Score (MOS), and AIMS for detecting CP and NDD.Method: seventy-five preterm infants with gestational age (GA) 24-37 weeks were enrolled. Group 1 was composed of infants with 24-28 GA (n = 22); groups 2 and 3 consisted of infants with 29-32 GA weeks (n = 23) and 33-37 GA (n = 30) weeks, respectively. The infants were assessed during the writhing period, the fidgety period, and at 6-12 months of corrected age with GMOS, MOS, and AIMS, respectively.Results: in the writhing period, a cramped-synchronized pattern was observed in 17 (22%) in-fants, whereas a poor repertoire pattern was observed in 34 (45%) infants. In the fidgety period of the 63 infants, 29 (46%) presented with fidgety movements absent. The MOS and AIMS scores of the infants in group 1 were significantly lower than the other groups, which were statisti-cally significant (p = 0.004, p<0.00 1). High and positive compatibility (Kappa coefficient: 0.709; p = 0.001) was found between AIMS and GMOS scores and between AIMS and MOS scores (Kappa coefficient: 0.804; p < 0.001). In all groups, a statistically significant association was found between total GMOS scores (p = 0.003) and the presence of fidgety movements (p = 0.003). GMOS, MOS, and AIMS were found to be associated with CP and NDD (p < 0.001).Conclusion: GMA is an important tool for the prediction of CP and NDD. The combined use of GMOS, MOS, and AIMS may guide the clinical practice for the valid and reliable diagnosis of CP and NDD.Copyright 2022, Taiwan Pediatric Association.Publication Open Access A novel and simple machine learning algorithm for preoperative diagnosis of acute appendicitis in children(Springer, 2020) Türkmen, İnan Utku; Namlı, Gözde; Özturk, Çiğdem; Esen, Ayşe B.; Eray, Y. Nur; Akova, Fatih; Aydın, Emrah; Eroğlu, Egemen; Faculty Member; faculty Member; School of Medicine; 32059; N/AIntroduction: there is a tendency toward nonoperative management of appendicitis resulting in an increasing need for preoperative diagnosis and classification. For medical purposes, simple conceptual decision-making models that can learn are widely used. Decision trees are reliable and effective techniques which provide high classification accuracy. We tested if we could detect appendicitis and differentiate uncomplicated from complicated cases using machine learning algorithms. Materials and methods: we analyzed all cases admitted between 2010 and 2016 that fell into the following categories: healthy controls (Group 1); sham controls (Group 2); sham disease (Group 3), and acute abdomen (Group 4). The latter group was further divided into four groups: false laparotomy; uncomplicated appendicitis; complicated appendicitis without abscess, and complicated appendicitis with abscess. Patients with comorbidities and whose complete blood count and/or pathology results were lacking were excluded. Data were collected for demographics, preoperative blood analysis, and postoperative diagnosis. Various machine learning algorithms were applied to detect appendicitis patients. Results: there were 7244 patients with a mean age of 6.84 +/- 5.31 years, of whom 82.3% (5960/7244) were male. Most algorithms tested, especially linear methods, provided similar performance measures. We preferred the decision tree model due to its easier interpretability. With this algorithm, we detected appendicitis patients with 93.97% area under the curve (AUC), 94.69% accuracy, 93.55% sensitivity, and 96.55% specificity, and uncomplicated appendicitis with 79.47% AUC, 70.83% accuracy, 66.81% sensitivity, and 81.88% specificity. Conclusions: machine learning is a novel approach to prevent unnecessary operations and decrease the burden of appendicitis both for patients and health systems.