Person: YÜCEL, SELÇUK
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YÜCEL
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SELÇUK
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Publication Open Access The association of urinary BDNF, ATP, and MMP-2 with bladder compliance in children with myelodysplasia(2023-01-01) ŞEKERCİ, ÇAĞRI AKIN; KÜTÜKOĞLU, MEHMET UMUT; YÜCEL, SELÇUK; TARCAN, TUFAN; ŞEKERCİ Ç. A., KÜTÜKOĞLU M. U., Basok B. I., Fidan M., ÇAM S., YÜCEL S., TARCAN T.Aim: The purpose of our study was to evaluate the relationship of urinary brain-derived neurotrophic factor (BDNF), adenosine triphosphate (ATP), matrix metallopreteinase-2 (MMP-2) with urodynamic findings and upper urinary tract deterioration (UUTD) in children with myelodysplasia. Materials and Methods: Children with myelodysplasia evaluated in outpatient clinic between 2022 and 2023 were included. All patients underwent urinary ultrasonography, voiding cystourethrography, urodynamics, and DMSA scintigraphy. Urine samples were collected before urodynamics. Control urine was collected from 10 healthy children. Urinary biomarker values of patients and controls were compared, and subgroup analysis was performed. Results: The median age of 40 children (26 girls) included in the study was 108 (8–216) months, and the control group (six girls) was 120 (60–154) (p = 0.981). Urinary BDNF, MMP-2, and ATP were found to be significantly higher in children with myelodysplasia compared to the control (p = 0.007, p = 0.027, p = 0.014, respectively). The three biomarker values were similar in children with bladder compliance below or above 10 cmH2O/mL (p = 0.750, p = 0.844, p = 0.575). No difference was found in terms of UUTD in all three biomarkers (p = 0.387, p = 0.892, p = 0.705). A negative correlation was found between urinary ATP and compliance (p < 0.05). Conclusion: In this study, all three biomarkers were found to be higher in children with myelodysplasia than in controls. There was a negative correlation between urinary ATP and compliance. Urinary biomarkers may contribute the follow-up of children with neurogenic lower urinary tract deterioration in future with their noninvasive features. However, the lack of standardization and the inability to reliably predict risky groups are important shortcomings of urinary biomarkers.Publication Metadata only The value of urinary BDNF, ATP And MMP-2 in children with myelodysplasia(2023-09-27) ŞEKERCİ, ÇAĞRI AKIN; KÜTÜKOĞLU, MEHMET UMUT; YÜCEL, SELÇUK; TARCAN, TUFAN; Şekerci Ç. A., Kütükoğlu M. U., İşbilen Başok B., Fidan M., Yücel S., Tarcan T.HYPOTHESIS / AIMS OF STUDYStudies on the effects of various urinary biomarkers in children with neurogenic or non-neurogenic lower urinary tract dysfunction (LUTD) have been published in recent years. Three of them are Brain Derived Neurotrophic Factor (BDNF), Adenosine Triphosphate (ATP), Matrix Metallopreteinase-2 (MMP-2), and various positive effects in diagnosis and follow-up have been reported in different patient groups. In this study, it was aimed to evaluate the relationship of these urinary biomarkers with urodynamic findings and upper urinary tract deterioration (UTTD) in children with myelodysplasia.STUDY DESIGN, MATERIALS AND METHODSChildren with myelodysplasia evaluated in the pediatric urology outpatient clinic between 2022 and 2023 were included in the study. All patients underwent urinary ultrasonography, voiding cystourethrography, urodynamic studies, and DMSA renal scintigraphy. Children with missing data were excluded from the study. Urine samples were collected into sterile urine collection tubes before urodynamics. After each urine sample was centrifuged at 3000 g for 10 minutes, the supernatant was separated and stored at -800C until further analysis. In addition, control urine was collected from 10 healthy children. Urinary BDNF, ATP, and MMP-2 were studied by ELISA method. Urinary biomarker values of patients and controls were compared and subgroup analysis was performed in the myelodysplasia group in terms of urodynamic findings and UUTD. The presence of renal scar, vesicoureteral reflux, or hydronephrosis was considered as UUTD. Constipation status was evaluated with the Bristol stool chart.RESULTSThe median age of 40 children (26 girls (65%), 14 boys (35%)) included in the study was 108 (8-216) months, and the healthy control group (6 girls, 4 boys) was 120 (60-154) months (p=0.981). The primary etiology of 35 children was myelomeningocele (87.5%), 2 dermal sinus (5%), 2 tethered cord (5%), and one sacrococcygeal immature teratoma (2.5%). Urinary BDNF, MMP-2, and ATP were found to be significantly higher in children with myelodysplasia compared to the control group (p=0.007, p=0.027, p=0.014, respectively) (Table 1). In the subgroup analysis, the three biomarker values were similar in children with bladder compliance below or above 10 cmH2O/ml (p=0.750, p=0.844, p=0.575). In addition, no difference was found in terms of UUTD in all three biomarkers (p=0.387, p=0.892, p=0.705). However, a negative correlation was found between urinary ATP and bladder compliance in the correlation analysis (p<0.05) (Table 2). Interestingly, a positive correlation was detected among the three biomarkers (p<0.01) (Table 2). There was no significant difference in urinary biomarkers between children with and without constipation.INTERPRETATION OF RESULTSInvasive urodynamic studies are the gold standard method in the evaluation of children with neurogenic LUTD after first-step tests. In recent years, it is tried to define tests that help and support urodynamic studies in the diagnosis and follow-up of these children. Among these, urine biomarkers come to the forefront with their easy-to-measure features. Three biomarkers evaluated in this study were found to be higher in children with myelodysplasia compared to the healthy control group. However, in subgroup analyses, they were not found to be significantly different in children with UUTD. One of these, urinary BDNF, is the most frequently studied biomarker in children with LUTD after NGF. Urinary BDNF has only been studied in one study in children with myelodysplasia, and decreased after the intravesical injection of botulinum toxin (1). Urinary MMP-2 has been previously studied in adults with spina bifida, and ATP in women with overactive bladders, and significant findings on both biomarkers have been reported (2,3). To our knowledge, these two biomarkers have been studied for the first time in children. In particular, we think that the negative relationship between urinary ATP and bladder compliance may be significant in clinical follow-up. The small number of patients seems to be the most important limitation of the study.CONCLUDING MESSAGEUrinary biomarkers seem promising for the future with their non-invasive features in the follow-up of children with neurogenic LUTD. However, the lack of standardization, the inconsistency between the results of the studies, and the inability to reliably predict risky groups are important shortcomings of urinary biomarkers. We consider that urinary biomarkers should only be assessed as a part of well-designed studies and should not be used in the clinical decision-making process of neurogenic LUTD in children.FIGURE 1Table 1. Comparison of urinary BDNF, ATP and MMP-2 values between patients and controlsFIGURE 2Table 2. Correlations for bladder compliance, ATP, BDNF and MMP-2 in patientsREFERENCESSekerci CA, Tanidir Y, Toprak T, Basok BI, Isman F, Simsek F, et al. Value of Urinary Brain-Derived Neurotrophic Factor Levels on the Assessment of Botulinum Toxin Type A Treatment for Neurogenic Detrusor Overactivity in Children with Myelodysplasia. J Urol. 2019;201(1):174-80.Peyronnet B, Richard C, Bendavid C, Naudet F, Hascoet J, Brochard C, Senal N, Jezequel M, Alimi Q, Khene ZE, Corlu A, Clément B, Siproudhis L, Bouguen G, Kerdraon J, Manunta A, Gamé X. Urinary TIMP-2 and MMP-2 are significantly associated with poor bladder compliance in adult patients with spina bifida. Neurourol Urodyn. 2019 Nov;38(8):2151-2158. doi: 10.1002/nau.24163. Epub 2019 Sep 4. PMID: 31486131.Silva-Ramos M, Silva I, Oliveira O, Ferreira S, Reis MJ, Oliveira JC, Correia-de-Sá P. Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome. PLoS One. 2013 May 31;8(5):e64696. doi: 10.1371/journal.pone.0064696. PMID: 23741373; PMCID: PMC3669404.Publication Open Access A survey study on evaluation and management of nocturnal enuresis in pediatricians and family physicians(2023-09-01) ŞEKERCİ, ÇAĞRI AKIN; KÜTÜKOĞLU, MEHMET UMUT; DÖRÜCÜ, DOĞANCAN; TANIDIR, YILÖREN; ÇAM, HAYDAR KAMİL; TARCAN, TUFAN; YÜCEL, SELÇUK; Şekerci Ç. A., Kütükoğlu M. U., Dörücü D., Ergün R., Tanıdır Y., Çam H. K., Tarcan T., Yücel S.Objective:Nocturnal enuresis (NE) is one of the most common disorders in pediatric urology, and patients often turn to family physicians (FP) and pediatricians (P) initially. The aim of this study was to understand the awareness, self-confidence and suggestions of physicians regarding the management of NE.Materials and Methods:In this study, 360 FP and family medicine residents (FMR), as well as 280 P and pediatrics residents (PR), were contacted through a cellular phone texting system. A simple multiple-choice questionnaire (Surveymonkey®) consisting of 10 questions was used to gather data. The survey included questions about their experience, training, evaluation, and management of NE.Results:A total of 119 FPs and Ps (18.5%) filled the questionnaire. Thirty (25.21%) of the participants were P, 27 (22.69%) PR, 3 (2.52%) FP and 59 (49.58%) FMR. The rate of physicians who encounter at least 5 children with NE per month is 31.33%. The mean self-confidence in the management of NE was 4.5 out of 10. The self-confidence of pediatricians was significantly higher than that of PR and FMR (p<0.001, p<0.001). Most (n=78, 65.55%) of the participants stated that they received training on EN during medical faculty and 62 (52.10%) during residency. Psychological problems (89.92%), sleep disorders (78.15%), and excessive fluid intake (75.63%) were the most frequently considered factors in etiology. While most responders (75.63%) considered dietary regulation and behavioral interventions as the first-line treatment, 25.21% consult a pediatric urologist and only 1.6% recommend medical treatment.Conclusion:Although FP and P admit they had training on NE, they mostly felt incompetent to manage NE and exclusively avoided pharmacological treatment.Keywords:Children, enuresis nocturna, pediatric urology, physicians, surveyPublication Open Access Üriner BDNF, ATP ve MMP-2'nin miyelodisplazili çocuklarda değeri(2023-10-04) ŞEKERCİ, ÇAĞRI AKIN; KÜTÜKOĞLU, MEHMET UMUT; TARCAN, TUFAN; YÜCEL, SELÇUK; Şekerci Ç. A., Kütükoğlu M. U., İşbilen Başok B., Fidan M., Çam S., Yücel S., Tarcan T.Publication Metadata only Spot idrarda ölçülen karbonhidrat antijen 19-9/kreatinin düzeyinin 0-16 yaş grubunda hidronefroz ayırıcı tanısı ve böbrek hasarı tespitinde biyobelirteç olarak değerlendirilmesi: prospektif çalışma(2023-10-04) KÜTÜKOĞLU, MEHMET UMUT; HAKLAR, GONCAGÜL; TARCAN, TUFAN; ŞEKERCİ, ÇAĞRI AKIN; YÜCEL, SELÇUK; Kütükoğlu M. U., Şekerci Ç. A., Yılmaz S. S., Haklar G., Tarcan T., Yücel S.AMAÇ: Çocuklarda hidronefroz (HN) ile ortaya çıkan üriner sistem hastalıklarının tanısında, tedavi seyrinde ve prognozunu öngörme konusunda idrarda ölçülebilen birçok biyobelirteç mevcuttur. Çalışmamızda çocuk hastalarda spot idrarda karbonhidrat antijeni 19-9 (CA 19-9)/ kreatinin düzeylerinin, HN ayırıcı tanısı ve yapılan görüntüleme tetkikleri ve bunların sonucunda böbrek hasarının tespit edilmesinin değerlendirilmesi amaçlandı. MATERYAL-METOD: Prospektif olarak yapılan çalışmamıza Nisan 2021- Aralık 2022 tarihleri arasında çocuk ürolojisi polikliniğimize başvuran üreteropelvik bileşke darlığı (ÜPBD), vezikoüreteral reflü (VUR), böbrek/üreter taşı, non-nörojenik ve nörojenik (spina bifida) alt üriner sistem disfonksiyonu (AÜSD) tanısı nedeniyle HN’si olanlar hasta grubu, başka nedenlerle başvuran ve görüntülemelerinde HN’si olmayanlar kontrol grubu olarak dahil edildi. Hastaların başvuru sırasında yaş, cinsiyet, glomerül filtrasyon hızları, spot idrarda CA 19-9 (ünite/mililitre) ve kreatinin değerleri, HN etiyolojisi, HN'si olanlarda Society for Fetal Urology (SFU) evresi, dimerkapto süksinik asit (DMSA) sintigrafisinde skar varlığı, merkapto asetil triglisin (MAG-3) sintigrafisinde diüretik yanıtlılık durumları ele alındı. BULGULAR: Çalışmaya hidronefrozu olan 168 (%42,4) çocuk hasta hidronefroz grubu olarak; 229 (%57,6) sağlıklı çocuk ise kontrol grubu olarak dahil edildi. Hidronefroz grubunun 80’i (%47,6) kız, 88’i (%52,4) erkekti ve bunların 132’si (%78) tek taraflı, 36’sı (%22) iki taraflı hidronefroza sahipti. HN’si olan hasta grubunun 41’i (%10,3) VUR, 42’si (%10,6) böbrek/üreter taşı, 52’si (%13,1) ÜPBD, 18’i (%4,5) non-nörojenik AÜSD, 19’u (%4,8) nörojenik AÜSD tanılıydı. HN varlığı risk faktörü alınarak yapılan ROC analizinde %71,4 hassasiyet ve %70,7 özgüllük oranlarında eğri altında kalan alan 0,823 (%95 güven aralığında 0,783-0,864) olup, spot idrar CA 19-9/kreatinin için eşik değer 0,59 Ünite/mililitre kreatinin (Ü/ml kre) olarak elde edildi (p=0,001). Kontrol grubunda başvuru anında spot idrar CA 19- 9/kreatinin 0,48 (0,14-1,80), hasta grubunda 0,82 (0,16-2,60) olarak ölçüldü (p=0,0001). Başvuruda SFU evre 1’de spot idrar CA 19-9/kreatinin 0,75 (0,16-2,60), evre 2’de 0,82 (0,28- 1,72), evre 3’te 0,90 (0,45-2,02), evre 4’te 1,12 Ü/ml kre (0,41-2,43) olarak ölçüldü (p=0,085). Böbrek/üreter taşı olanlarda başvuruda 0,84 Ü/ml kre (0,34-1,80), postoperatif 6.ayda 0,46 Ü/ml kre (0,23-1,52) olarak ölçüldü (p=0,001). ÜPBD olup cerrahi yapılanlarda başvuruda 0,91 Ü/ml kre (0,28-2,43), takip edilenlerde başvuruda 0,80 Ü/ml kre (0,41-2,18) olarak ölçüldü (p=0,770). ÜPBD tanılı ve sintigrafisi diüretik yanıtsızlarda 0,96 Ü/ml kre (0,28-2,43), diüretik yanıtlılarda 0,80 Ü/ml kre (0,41-2,12) olarak ölçüldü (p=0,686). VUR tanılı düşük evreli grupta başvuruda 0,87 Ü/ml kre (0,30-2,60), yüksek evreli grupta 0,80 Ü/ml kre (0,16-1,72) olarak ölçüldü (p=0,709). Böbrek parankiminde skarı olan grupta başvuruda 0,58 Ü/ml kre (0,16- 2,60), böbrek parankimi skarsız grupta oran 0,70 Ü/ml kre (0,14-2,43) olarak ölçüldü (p=0,437), (Tablo-1). SONUÇ: CA 19-9/kreatinin oranında saptanan yüksek değerler hidronefroz varlığını öngörmede, ÜPBD ve taş hastalarında operasyon sonrası gerileyen HN dereceleriyle paralel olarak oranın azalmasıyla; hidronefroz tanısında ve cerrahi yapılan grupta tedavi başarısını öngörmede önemlidir ve klinik uygulamada oldukça faydalı olabilecek potansiyele sahiptir.