Distraction osteogenesis is inhibited by cancer radiotherapy with Co 60

Aim: To investigate the effects of radiotherapy on distraction osteogenesis performed on the same bone in an area that has not received radiation. Radiotherapy (Co60) was carried out in a region where tumors may develop, and then, on the assumption that the tumoral region had been removed, distraction osteogenesis was carried out, and the effects were investigated. Method: Thirty New Zealand rabbits were randomized into two groups, a study group (15 rabbits) and a control group (15 rabbits). In the study group, Co60 was administered by teletherapy to the distal half of the left tibia. Rabbits in the control group were kept in the same environment for the same period, but were not subjected to radiotherapy. Four weeks after radiotherapy, osteotomy was performed on the proximal part of the left tibia of all subjects, and distraction was carried out until 10mm. After distraction was completed, the outcomes were evaluated radiologically, scintigraphically, and histopathologically, and the results were compared. Results: New bone formation achieved through distraction osteogenesis in the study group animals was inadequate, while new bone tissue achieved in the control group was superior (P < 0.001). Conclusion: Radiotherapy has a negative effect on distraction osteogenesis, even if performed on a different part of the bone

Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor

Testicular 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

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry

WOS: 000478208700001PubMed ID: 31321910Background Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent. Method Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered. Results The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony-stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (+/- mean standard error) follow-up period was 129.7 +/- 76.3 months, and overall survival was 96.8% (CI, 94.4-99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene. Conclusion In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Turkish Pediatric Hematology AssociationThis study was supported by Scientific and Technological Research Council of Turkey (TUBITAK) and the Turkish Pediatric Hematology Association

TURKISH NATIONAL SEVERE CONGENITAL NEUTROPENIA REGISTRY

WOS: 000440320200028TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Turkish Pediatric Hematology AssociationThis study was supported by TUBITAK and Turkish Pediatric Hematology Association

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention

WOS: 000426572200002PubMed ID: 28404539Objective: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. Materials and Methods: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with beta-thalassemia major (n = 1658, 83.4%) and intermedia (n = 215, 10.8%). Results: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all beta-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. Conclusion: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.Ege Children's Foundation; Novartis Pharmaceuticals CorporationNovartisThe authors thank Caglar Serdar, Aylin Gokduman, and Tolga Turgay of Plexus Information Technologies for their website support. The current study and the work presented here are from an Investigator Initiated Trial, which was sponsored by the Ege Children's Foundation and funded by Novartis Pharmaceuticals Corporation