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Öğe Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database(American Society of Hematology, 2024) Mohsenian, S.; Palla, R.; Menegatti, M.; Cairo, A.; Lecchi, A.; Casini, A.; Neerman-Arbez M.Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB, and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory, and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade 3 based on their bleeding severity. In addition, FGA, FGB, and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, and 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of the cases. The rates of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%, respectively) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. Eighty-six patients received treatment (69 on-demand and/or 17 on prophylaxis), with fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory, and genetic history of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects. © 2024 by The American Society of Hematology.Öğe Hematological predictors of silent new cerebral ischemic lesions in carotid artery stenting: A retrospective study(Churchill Livingstone, 2024) Altunova, M.; Demir, Y.; Gulmez, R.; Evsen, A.; Aktemur, T.; Anil, Sahin, A.; Arslan E.Background: Silent new cerebral ischemic lesions (sNCIL) are a common complication of carotid artery stenting (CAS) that can lead to an increase in morbidity and mortality. We aimed to evaluate the impact of hematological parameters on sNCIL in patients undergoing CAS. Methods: We retrospectively evaluated 103 patients who underwent CAS, with a mean age of 70.5 ± 6.7 years, and 31 (20.1 %) of whom were female. Stents were placed for internal carotid artery revascularization. The presence of new hyperintense lesions on diffusion-weighted imaging (DWI) without neurological symptoms was considered as sNCIL in cases without apparent neurological findings. Patients were categorized into two groups based on DWI results: positive (29) and negative (74). Results: In the study population, sNCIL was observed in 29 patients (28.2 %). The DWI-positive group exhibited significantly higher Plateletcrit (PCT) levels, advanced age, and a lack of embolic protection device usage compared to the DWI-negative group. The Receiver Operating Characteristic (ROC) analysis identified a PCT value of 0.26 as the optimal threshold, detecting the development of sNCIL with a sensitivity of 75.9 % and specificity of 59.1 % (AUC: 0.700; 95 % CI: 0.594–0.806, p = 0.002). Conclusion: To be determined by a simple blood parameter, PCT can predict the risk of sNCIL before CAS and holds clinical value in the treatment of patients with carotid artery stenosis. © 2024 Elsevier LtdÖğe Implication of transcription factor FOXD2 dysfunction in syndromic congenital anomalies of the kidney and urinary tract (CAKUT)(Elsevier B.V., 2024) Riedhammer, K.M.; Nguyen, T.-M.T.; Koşukcu, C.; Calzada-Wack, J.; Li, Y.; Assia, Batzir, N.; Saygılı S.Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause for chronic kidney disease below age 30 years. Many monogenic forms have been discovered due to comprehensive genetic testing like exome sequencing. However, disease-causing variants in known disease-associated genes only explain a proportion of cases. Here, we aim to unravel underlying molecular mechanisms of syndromic CAKUT in three unrelated multiplex families with presumed autosomal recessive inheritance. Exome sequencing in the index individuals revealed three different rare homozygous variants in FOXD2, encoding a transcription factor not previously implicated in CAKUT in humans: a frameshift in the Arabic and a missense variant each in the Turkish and the Israeli family with segregation patterns consistent with autosomal recessive inheritance. CRISPR/Cas9-derived Foxd2 knockout mice presented with a bilateral dilated kidney pelvis accompanied by atrophy of the kidney papilla and mandibular, ophthalmologic, and behavioral anomalies, recapitulating the human phenotype. In a complementary approach to study pathomechanisms of FOXD2-dysfunction–mediated developmental kidney defects, we generated CRISPR/Cas9-mediated knockout of Foxd2 in ureteric bud–induced mouse metanephric mesenchyme cells. Transcriptomic analyses revealed enrichment of numerous differentially expressed genes important for kidney/urogenital development, including Pax2 and Wnt4 as well as gene expression changes indicating a shift toward a stromal cell identity. Histology of Foxd2 knockout mouse kidneys confirmed increased fibrosis. Further, genome-wide association studies suggest that FOXD2 could play a role for maintenance of podocyte integrity during adulthood. Thus, our studies help in genetic diagnostics of monogenic CAKUT and in understanding of monogenic and multifactorial kidney diseases. © 2023 International Society of NephrologyÖğe Short-term azithromycin use is associated with QTc interval prolongation in children with cystic fibrosis(Elsevier Masson s.r.l., 2024) Enhoş, A.; Doğuş, Kus, H.; Yozgat, C.Y.; Cakır, E.; Yazan, H.; Erol, A.B.; Erenberk U.Background: Azithromycin is used for children with cystic fibrosis (CF) for its immunomodulatory and anti-inflammatory action. This study investigated the short-term alterations in QTc interval associated with azithromycin prophylaxis in pediatric patients with CF. Methods: This study included 121 patients with mild CF, of whom 76 received azithromycin (patient group) and 45 did not receive azithromycin (control group). The patient and control groups were categorized according to age as under 12 years of age and over 12 years of age. The first presentation measured all the patient and control groups at basic QTc time intervals. The QTc intervals of all patients were then remeasured systemically at 1, 3, and 6 months. Age categories and QTc intervals that were calculated at each month in the patient and control groups were compared statistically. Results: A statistically significant difference was detected in the patient group between the initial QTc interval time and the electrocardiogram (ECG) findings in the first and third months after prophylaxis treatment (p < 0.001; p = 0.01). However, no statistically significant difference was detected in the sixth month (p > 0.05) in all groups. Almost all of the children's QTc intervals were within normal range and within the safety zone (under 0.44 s). No statistically significant difference was detected in the control group between the initial ECG and the QTc intervals measured at 1, 3, and 6 months. Conclusion: Short-term use of azithromycin prophylaxis in pediatric patients with mild CF slightly increased the QTc interval in the first and third months of follow-up. Nevertheless, all QTc interval changes fell within the safety zone. Notably, 1 month of follow-up treatment should be performed to check for any alteration in the QTc interval. If increased QTc interval duration is not detected in the first month, azithromycin prophylaxis can be safely prescribed. © 2024 French Society of PediatricsÖğe Concomitant amyloidosis is the primary cause of endothelial and coronary microvascular dysfunction in carpal tunnel syndrome(Elsevier Inc., 2024) İrgi, T.; Baycan, Ö.F.; Güvenç, T.S.; Özcan, F.B.; Atıcı, A.; Yılmaz, Y.; Çalişkan M.Study objectives: Patients with carpal tunnel syndrome (CTS) show manifestations of arterial abnormalities, including carotid intimal thickening and increased vascular stiffness. As carpal tunnel syndrome is associated with amyloidosis, we hypothesized that previously observed abnormalities can largely be related with concomitant amyloidosis rather than CTS itself. Design: Prospective observational study. Setting: Medeniyet University Goztepe Hospital Participants: 61 patients with CTS (of whom 32 had biopsy-proven amyloidosis) and 36 healthy controls. Interventions: Subjects underwent ultrasound examinations for the measurement of coronary flow velocity reserve (CFVR), flow-mediated vasodilatation (FMD) and carotid intimal-media thickness (CIMT). Main outcome measures: Comparison of CFVR, FMD and CIMT in CTS patients with or without amyloidosis. Results: Patients with either CTS or CTS with concomitant amyloidosis (CTS-A) had significantly lower FMD (9.7 % ± 4.0 % in CTS and 10.3 % ± 4.6 % in CTS-A groups, p < 0.05 for both) and CFVR (2.4 (2.1–2.8) in CTS and 1.8 (1.6–2.1) in CTS-A groups, p < 0.001 for both) as compared to controls, while CIMT was only increased in CTS-A group (0.70 (0.60–0.80), p < 0.001). The reduction in CFVR was solely related to an increased basal flow velocity in CTS patients while there was also a reduced hyperemic flow velocity in patients with CTS-A. Conclusion: Most arterial phenomena in CTS patients could be attributable to concomitant amyloidosis, although endothelial dysfunction was present even in patients with CTS without amyloidosis. © 2024 The Author(s)Öğe Can biomarkers predict myocardial iron overload in children with thalassemia major?(Cambridge Univ Press, 2023) Karakaş, Hasan; Eroğlu, Ayşe Güler; Akyel, Nazlı Gülsüm; Çiğ, Gülnaz; Adaletli, İbrahim; Özdemir, Gül Nihal; Türkkan, Emine; Celkan, Tülin TirajeAim:Beta-thalassemia major requires regular blood transfusions throughout life, which in turn leads to iron accumulation in the body. While cardiac T2* MRI is the gold standard in determining cardiac iron accumulation, it is not always feasible, which has led to the search for new biomarkers. Herein, the value of growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide in predicting cardiac iron accumulation is investigated in asymptomatic children with beta-thalassemia major. Materials and method:Forty-one patients aged 11-21 years and 41 age-, gender-, body mass index-matched healthy controls were included. Serum growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were compared between the patients and controls. Additionally, the relations of these biomarkers with cardiac and liver T2 * MRI were investigated in the patients. Results:In the patients, growth differentiation factor-15, galectin-3, and N-terminal pro-B-type natriuretic peptide levels were higher than healthy controls (p < 0.001, p = 0.025, p < 0.001, respectively). There were no significant correlations of growth differentiation factor-15 and N-terminal pro-B-type natriuretic peptide levels with both cardiac and liver T2 * MRI measurements. While there was no significant correlation of serum galectin-3 with cardiac T2 * MRI measurements, a negative correlation was found with liver T2 * MRI measurements (p = 0.040, rho = -0.325). Conclusion:All three biomarkers investigated in this study failed to predict myocardial iron accumulation in asymptomatic children with beta-thalassemia major. However, a weak relation between serum galectin-3 level and hepatic iron accumulation was demonstrated.Öğe Pre-transplantation vitamin D deficiency increases acute graft-versus-host disease after hematopoietic stem cell transplantation in thalassemia major patients(WILEY, 2022) Daloğlu, Hayriye; Uygun, Vedat; Öztürkmen, Seda; Yalçın, Koray; Karasu, Gülsü; Yeşilipek, AkifBackground: Although there are many studies on the role of vitamin D deficiency (VDD) in hematopoetic stem cell transplantation (HSCT), outcomes have often reported conflicting results because of the heterogeneity of the patients in the studies. Methods: We investigated the association between VDD prior to HSCT and outcomes after HSCT in a relatively homogenous group of patients with thalassemia major (TM) who received identical treatment for TM before transplantation, and the same conditioning regimen and GVHD prophylaxis during and after transplantation. All patients, including the patients with normal vitamin D3 levels received 400 to 800 IU per day of vitamin D for the first 6 months after HSCT. Results: Pre-HSCT VDD increased the frequency of aGVHD after transplantation, particularly in HSCTs performed with PBSC for the stem cell source. Pre-transplant low vitamin D3 levels had no association with transplant outcomes such as engraftment, viral infections, alloimmunization, chronic GvHD, total days of hospitalization, and success in terms of transfusion independence. Conclusions: Low vitamin D3 levels before HSCT carry a significant risk for aGVHD. All patients with TM should be screened for VDD before HSCT, and every effort should be made to supplement vitamin D before the transplant in VDD patientsÖğe Enhancing effect of nicotine on electrical field stimulation elicited contractile responses in isolated rabbit bladder straight muscle; the role of cannabinoid and vanilloid receptors(Turkiye Klinikleri, 2022) İlhan, Sevil Özger; Fincan, Gökçe Sevim Öztürk; Okçay, Yağmur; Koç, Derya Sebile; Aşkin, Celil İlker; Kibar, Ayşe Kübra; Vural, İsmail Mert; Sarıoğlu, YusufBackground/aim: Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system. Materials and methods: The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs–Henseleit solution. After obtaining EFS-induced contractile responses, 10–4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10–6 M), AM630 (a cannabinoid CB2R antagonist, 10–6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10–6 M). Results: Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines’ effect. Conclusion: These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines’ effect. © TÜBİTAK.Öğe Anti-amoebic activity of a series of benzofuran/benzothiophene derivatives against acanthamoeba castellanii belonging to the T4 genotype(2022) Akbar, Noor; El-Gamal, Mohammed, I; Zaraei, Seyed-Omar; Saeed, Balsam Qubais; Khan, Naveed Ahmed; Siddiqui, RuqaiyyahAims: To determine the anti-amoebic activity of benzofuran/benzothiophene-possessing compounds against Acanthamoeba castellanii of the T4 genotype. Method and results: A series of benzofuran/benzothiophene-possessing compounds were tested for their anti-amoebic activities, in particular, to block encystation and excystation processes in amoebae. Cytotoxicity of the compounds were evaluated using lactate dehydrogenase (LDH) assays. The amoebicidal assay results revealed significant anti-amoebic effects against A. castellanii. Compounds 1p and 1e showed the highest amoebicidal activity, eliminating 68% and 64% of the amoebae, respectively. These compounds remarkably repressed both the encystation and excystation processes in A. castellanii. Furthermore, the selected compounds presented minimal cytotoxic properties against human cells, as well as considerably abridged amoeba-mediated cytopathogenicity when compared to the amoebae alone. Conclusions: Our findings show that benzofuran/benzothiophene derivatives depict potent anti-amoebic activities; thus these compounds should be used as promising and novel agents in the rationale development of therapeutic strategies against Acanthamoeba infections.Öğe Quality of Life assessment with EORTC QLQ in patients with hodgkin lymphoma: multicenter study(Tr dizin, 2022) Gemici, Ali Ihsan; Serin, İstemi; Erol, Vedat Buğra; Doğu, Mehmet Hilmi; Karakuş, VolkanAim: The aim of our study is to obtain data on the quality of life (QoL) in Hodgkin lymphoma (HL) patients in a representative sample of the general population of Turkey with the help of the EORTC QLQ-C30 and QLQ-HL27 questionnaires. Material and Methods: A total of 68 patients from seven different centers diagnosed with HL between 2018-2020 were included in the study. The questionnaires were answered cross-sectionally by the patient under the control of a physician in the centers participating in the study. Results: Out of 68 patients, 42.6% (n=29) were female and 57.4% (n=39) were male. The ages of the patients ranged from 18 to 74 years, with a mean of 42.10±16.62 and with a median value of 40 years. There was no significant difference between age subgroups in terms of QLQ-C30 global health status/ QoL, functional or symptom scales and HL27 SB, PC, EI and WF scores (p>0.05, for all). It was determined that the constipation scores of females were higher than the scores of males (p=0.041). No statistically significant difference was found in terms of HL27 SB, PC, EI and WF sub-dimension scores according to gender (p>0.05). Conclusions: There was only a statistically significant difference in terms of QLQ-C30 constipation sub-dimension scores according to gender. The constipation scores of females were higher than the scores of men. More detailed and large population studies are needed to reveal the effectiveness of QoL assessment in HL patients.Öğe The effect of cord blood vitamin d level on bronchopulmonary dysplasia and other meonatal morbidities in preterm infants(GORM, 2022) Elif,Koç; Bolat, Fatih; Cihan, Meriç KaymakOBJECTIVES: We aimed to investigate the relationship between cord 25-hydroxyvitamin D level and bronchopulmonary dysplasia and other neonatal morbidities (sepsis, necrotizing enterocolitis, intraventricular hemorrhage, patent ductus arteriosus, respiratory distress syndrome, retinopathy of prematurity) in preterm neonates. STUDY DESIGN: Infants aged <32 gestational weeks who were admitted to the neonatal intensive care unit between March 2014 and November 2014 were enrolled in this prospective study. Cord blood samples were obtained during delivery. 25-hydroxyvitamin D level was measured using an automatic biochemical analyzer. Patients were divided into two groups according to their 25-hydroxyvitamin D levels: 25-hydroxyvitamin D <20 ng/mL and 25-hydroxyvitamin D ?20 ng/mL. We used descriptive statistics and multiple regression models to identify risk factors associated with bronchopulmonary dysplasia. RESULTS: Sixty premature infants were analyzed in this study. The mean cord 25-hydroxyvitamin D level was 13,8±6,8 ng/mL (range 3,5-30,7 ng/mL). Eighty percent of the patients (48/60) had 25-hydroxyvitamin D levels <20 ng/mL. Among the infants, 21 (35%) developed bronchopulmonary dysplasia. Infants with bronchopulmonary dysplasia had higher frequencies of 25-hydroxyvitamin D deficiency than the non-bronchopulmonary dysplasia group (p=0.028). Duration of hospitalization was also longer in infants with low levels of cord 25-hydroxyvitamin D. On the other hand, there was no significant difference between infants with and without vitamin D deficiency with respect to respiratory distress syndrome, patent ductus arteriosus, retinopathy of prematurity, necrotizing enterocolitis, sepsis, and intraventricular hemorrhage. CONCLUSION: This study shows the high rate of vitamin D deficiency in pregnant women in the central Anatolian region (Sivas) of Türkiye. Low cord 25-hydroxyvitamin D levels were associated with an increased risk of bronchopulmonary dysplasia and prolonged hospitalization in very preterm infants. These data strengthen the necessity for vitamin D supplementation during pregnancÖğe A case of bartonellosis mimicking systemic lupus erythematosus(SAGE PUBLICATIONS LTD, 2022) Kara, Emine Manolya; Özdemir, Gül Nihal; Taşdemir, Mehmet; Ata, Serap; Karini, Belma; Valiyev, Eldar; Tutkun, İlknur Tuğal; Köse, Gülşen; Özkaya, OzanBackground and aim: Cat-scratch disease (CSD) is a systemic bacterial infection caused by Bartonella henselae. The disease is typically characterized by regional lymphadenopathy developing after scratches from domestic or feral cats. Rarely, systemic involvement may be observed. The co-occurrence with glomerulonephritis and positive antinuclear antibody (ANA) tests have been reported before. In these cases, the disease can be misdiagnosed as systemic lupus erythematosus. Ocular involvement occurs in 5%-10% of the cases with CSD, and neuroretinitis is among the common manifestations. Administration of corticosteroids (CSs) in addition to antibiotics has been shown to improve prognosis in neuroretinitis cases. However, the optimal dose and duration, remain ill-defined. Case report: In this article, we present an 11-year-old girl with CSD and neuroretinitis with a positive ANA test and hematuria, who benefited from high-dose methyl-prednisolone and antibiotics. Conclusion: Further research is warranted in order to determine the dose and duration of CSs in the treatment of Bartonella neuroretinitis.Öğe Vajenden soyutlanan candida türlerinde biyofilm üretiminin iki farklı yöntemle araştırılması(2022) Aydınlı, Aydın; Vural, GürcanVajenden Soyutlanan Candida Türlerinde Biyofilm Üretiminin İki Farklı Yöntemle AraştırılmasıÖğe Hematopoietic stem cell transplantation in serine/threonine kinase 4 (stk4) deficiency: report of two cases and literature review(WILEY, 2022) Uygun, Vedat; Keleş, Sevgi; Daloğlu, Hayriye; Öztürkmen, Seda; Yalçın, Koray; Tezcan Karasu, Gülsün; Yeşilipek, AkifBackground Serine/threonine kinase 4 (STK4) deficiency is a combined immunodeficiency (CID) characterized by early onset recurrent bacterial, viral, and fungal infections. Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for CID; however, little is known about the necessity and benefits of HSCT in patients with STK4 deficiency. Methods We report two siblings with STK4 deficiency transplanted from two unrelated donors with the same conditioning regimen. Results In the conditioning regimen, rituximab was given on Day -11 (375 mg/m(2)), and sirolimus was added on the same day. Busulfan was administered at a myeloablative dose (3.2 mg/kg; Days -7 to -4) with 150 mg/m(2) of fludarabine (Days -7 to -3). They were transplanted with peripheral blood stem cells, and graft-versus-host disease (GVHD) prophylaxis was administered with 10 mg/m(2) methotrexate on Days 1, 3, and 6. In addition, mycophenolate mofetil (MMF) was started on Day 1 with ongoing use of sirolimus. We did not encounter veno-occlusive disease (VOD), high-grade acute GVHD, or significant organ toxicity in either patient. Both patients were well at the end of the first year after HSCT with complete donor chimerism. Conclusions Serine/threonine kinase 4 deficiency is a disease with high mortality post-HSCT; therefore, the conditioning regimen and GVHD prophylaxis strategies are important considerations in these patients. In our opinion, the conditioning regimen, which includes rituximab and busulfan and fludarabine (BU-FLU), GVHD prophylaxis with sirolimus and MMF, and short-term methotrexate, offers favorable outcomes and is well tolerated in our STK4-deficient patients.Öğe The relation of SYNTAX score with carotid plaque morphology in patients who undergoing coronary by-pass surgery(TRDizin, 2021) Aksoy, Süleyman Hilmi; Birdal, Oğuzhan; Yurdaışık, IşılThe Relation of SYNTAX Score with Carotid Plaque Morphology in Patients Who Undergoing Coronary By-pass SurgeryÖğe The anticancer potential of chlorine dioxide in small-cell lung cancer cells(CUREUS INC, 2022) Yıldız, Salih Zeki; Bilir, Cemil; Eskiler, Gamze Güney; Bilir, FilizBackground Chlorine dioxide (ClO2) is an effective disinfectant consisting of oxygen, chloride, and potassium. Because of its high oxidative capacity, ClO2 exerts antimicrobial, antiviral, and antifungal effects. However, its anticancer effects remain to be elucidated. Methodology The anticancer activity of ClO2 was assessed on DMS114 small-cell lung cancer (SCLC) cells and human umbilical vein endothelial cells (HUVEC) as control by WST-1, Annexin V, cell cycle analysis, and acridine orange staining. We for the first time investigated the possible therapeutic effects of long-term stabilized ClO2 solution (LTSCD). Results Our preliminary findings showed that LTSCD significantly inhibited the proliferation of SCLC cells (p < 0.01) with less toxicity in HUVEC cells. Additionally, LTSCD induced apoptotic cell death in SCLC cells through nuclear blehhing and vacuolar formation. However, LTSCD treatment did not induce cell cycle arrest in both cell lines. Conclusions LTSCD can be a therapeutic potential for the treatment of SCLC. However, further investigations are required to assess the LTSCD-induced cell death in SCLC both in vitro and in vivo.Öğe Antiamoebic properties of Methyltrioctylammonium chloride based deep eutectic solvents(Elsevier Ltd., 2022) Siddiqui, Ruqaiyyah; Makhlouf,Zinb; Akbar, Noor; Khamis, Mustafa; Ibrahim, Taleb; Khan, Amir Sada; Khan, Naveed AhmedAntiamoebic properties of Methyltrioctylammonium chloride based deep eutectic solventsÖğe Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor(ELSEVIER, 2022) Aycan, Zehra; Keskin, Melikşah; Lafcı, Naz Güleray; Savaş Erdeve, Şenay; Baş, Firdevs; Poyrazoğlu, Şükran; Öztürk, Pınar; Parlak, Mesut; Ercan, Oya; Güran, Tülay; Hatipoğlu, Nihal; Uçaktürk, Seyit Ahmet; Çatlı, Gönül; Akyürek, Nesibe; Önder, Asan; Kılınç, Suna; Çetinkaya, SemraTesticular adrenal rest tumor (TART) is one of the important complications that can cause infertility in male patients with congenital adrenal hyperplasia (CAH) and should therefore be diagnosed and treated at an early age. The factors that result in TART in CAH have not been completely understood. The aim of this study is to evaluate the genotype-phenotype correlation in CAH patients with TART.Method: Among 230 malepatients with CAH who were followed upwith regular scrotal ultrasonography in 11 different centers in Turkey, 40 patients who developed TARTand whose CAH diagnosis was confirmed by genetic testing were included in this study. Different approaches and methods were used for genotype analysis in this multicenter study. A few centers first screened the patients for the ten most common mutations in CYP21A2 and performed Sanger sequencing for the remaining regions only if these prior results were inconclusive while the majority of the departments adopted Sanger sequencing for the whole coding regions and exon-intron boundaries as the primary molecular diagnostic approach for patients with either CYP21A2 orCYP11B1 deficiency. The age of CAH diagnosis and TART diagnosis, type of CAH, and identified mutations were recorded.Results: TART was detected in 17.4% of the cohort [24 patients with salt-wasting (SW) type, four simple virilizing type, and one with nonclassical type with 21-hydroxylase (CYP21A2) deficiency and 11 patients with 11-beta hydroxylase (CYP11B1) deficiency]. The youngest patients with TART presenting with CYP11B1 and CYP21A2 deficiency were of 2 and 4 years, respectively. Eight different pathogenic variants in CYP21A2were identified. The most common genotypes were c.293-13C>G/c.293-13C>G (31%) followed by c.955C>T/ c.955C>T(27.6%) and c.1069C>T/c.1069C>T (17.2%). Seven different pathogenic variants were identified in CYP11B1. The most common mutation in CYP11B1 in our study was c.896T>C (p.Leu299Pro).Conclusion: We found that 83% TART patients were affected with SW typeCYP21A2 deficiency,and the frequent mutations detected were c.955C>T (p.Gln319Ter), c.293-13C>G in CYP21A2 and c.896T>C (p.Leu299Pro) inCYP11B1. Patients with CYP11B1 deficiency may develop TART at an earlier age. This study that examined the genotype-phenotype correlation in TART may benefit further investigations in larger series.Öğe Confirmation of drug allergy in a general pediatrics outpatient clinic(American College of Allergy, Asthma and Immunology, 2022) Çapanoğlu, Murat; Erkoçoğlu, Mustafa; Kaya, Ayşenur; Dibek Mısırlıoğlu, Emine; Giniş, Tayfur; Toyran, Müge; Civelek, Ersoy; Kocabaş, Can NaciBackground: Studies including diagnostic workups on true drug allergy in children are limited. Objective: To evaluate the frequency of confirmed drug allergy in children with a history of suspected drug allergy who had applied to the general pediatric outpatient clinics of our hospital owing to various health problems. Methods: The history of drug allergy was asked among children who applied to the general pediatric outpatient clinics of our hospital. Allergy tests were performed to confirm drug allergy in children whose history was compatible with drug allergy. Results: In this study, parents of 5553 children aged between 4 months and 17.9 years were asked, “Has your child ever developed an allergy after drug use?” A total of 7% of the parents (n = 389/5553) thought that their child had a drug allergy. When these patients were evaluated by a pediatric allergist, it was suspected that 21.1% (n = 82/389) had a drug allergy. When diagnostic tests were performed for drug allergy, drug allergy was confirmed in only 4.2% (n = 3/72). Consequently, the frequency of drug allergy according to the history was 1.47% (n = 82/5553) in the population we studied, whereas the frequency of confirmed drug allergy was found to be 0.05% (n = 3/5553). Conclusion: The patient or parent statements alone are not sufficient for the diagnosis of drug allergy in children. To confirm or rule out drug allergy, drug allergy tests must be performed so unnecessary drug restrictions can be avoided.Öğe Is microcystic, elongated, and fragmented pattern of myometrial invasion in endometrioid endometrial carcinoma associated with survival?(Turkiye Klinikleri, 2022) Altındağ, Sultan Deniz; Yiğit, Seyran; Şen, SerhatBackground/aim: Microcystic, elongated, and fragmented (MELF) pattern is one of the myometrial invasion patterns in endometrioid endometrial carcinoma (EEC), and it has been associated with poor prognostic parameters, especially lymphovascular space invasion (LVSI) and lymph node metastasis (LNM). This study aims to represent the frequency of MELF pattern in EEC and the relationship between MELF pattern with clinicopathological parameters, overall survival (OS), and disease-free survival (DFS). Materials and methods: In this retrospective cohort study, we examined 233 patients with EEC diagnoses with the result of a total hysterectomy and bilateral salpingo-oophorectomy between 2009 and 2014. The association of MELF pattern with risk factors such as stage, recurrence, and survival was analysed statistically with the comparison of MELF positive and negative cases. Results: MELF pattern was seen in 21.8% of all cases (51/233) and 23% of grade 1-2 cases (50/217). The MELF pattern showed a significant difference among patients when they were compared according to advanced age (?60) (p = 0.022), LVSI (p = 0.021), deep myometrial invasion (p < 0.01), LNM (p = 0.027), and advanced FIGO stage (p = 0.043). MELF pattern was a predictive factor of LNM in univariate logistic regression analysis but did not show significance in multivariate analysis. The Kaplan–Meier survival analysis showed that MELF positive cases had reduced OS (66.7% vs 79.7% p = 0.003) and DFS (66.7% vs 77.5% p = 0.017) rates. In the univariate analyses, MELF pattern was an independent prognostic factor on OS and DFS along with other parameters, while it was not observed to maintain this effect in the multivariate analyses. Conclusion: This study is one of the largest series examining the relationship between MELF pattern of myometrial invasion and survival, and our results represented that the MELF pattern is associated with the worse clinical outcome since it is associated with lymphovascular space invasion, deep myometrial invasion, lymph node metastasis, and reduced overall survival and disease-free survival rates. Although the presence of MELF pattern is not reported in routine practice, it may be used as an indicator that will help predict a worse outcome. © 2022, Turkiye Klinikleri. All rights reserved.
