Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study.

BACKGROUND: Isavuconazole is a relatively new antifungal agent indicated for the management of various invasive fungal diseases (IFDs), including invasive aspergillosis. Information on real-world experience with isavuconazole is scarce. This retrospective observational study aimed to describe the usage of isavuconazole in clinical practice with an in-depth evaluation of individual isavuconazole exposure. METHODS: Patients treated with isavuconazole were evaluated based on retrospective data, including therapeutic drug monitoring (TDM) data and efficacy and safety data. Additionally, we calculated the individual isavuconazole exposure described by the average AUC24 over the first 7 days of treatment by means of non-linear mixed-effects modelling and compared this with the currently desired lower target AUC of 60 mg·h/L. RESULTS: Ninety-nine patients treated with isavuconazole were evaluated. In our real-life cohort, isavuconazole was often deployed off-label in patients with non-classical host factors and infections with non-Aspergillus and non-Mucorales species. Isavuconazole was most often chosen for its safety profile, even after prior triazole treatment with manifestations of toxicity. TDM and subsequent dosage adjustments were frequently performed. The individual average AUC24 over 7 days was above 60 mg·h/L in 29 out of 77 (37.7%) patients. CONCLUSIONS: This overview provides practical insights that can aid clinicians in the management of their patients with IFD. Our study shows that isavuconazole was used in a diverse patient population and was well tolerated overall. Individual isavuconazole exposure reflected by the average AUC24 over the first 7 days of treatment was generally low and variable. Dosage adjustments following TDM were frequently performed. Our experience shows that isavuconazole is a feasible alternative after prior azole treatment.

Cytomegalovirus Matching in Deceased Donor Kidney Allocation: Results From a U.S. National Simulation Model.

Background: Cytomegalovirus (CMV) infects >60% of adults and can pose an independent risk factor for allograft loss and mortality in solid organ transplant recipients. The purpose of this study is to evaluate the impact of a nationwide implementation of CMV seromatching (donor/recipient: D-/R- and D+/R+) in the U.S. deceased donor kidney allocation system (KAS). Methods: Adult candidates on the U.S. kidney-only transplant waiting list and deceased donor kidneys offered to the U.S. transplant centers were considered. A discrete-event simulation model, simulating the pre-COVID-19 period from January 1, 2015, to January 1, 2018, was used to compare the performances of currently employed KAS-250 policy (without CMV matching) to various simulated CMV matching policies parameterized by calculated panel reactive antibody exception threshold. Outcomes included CMV serodistribution, waiting time, access to transplantation among various groups, transplant rate, graft survival, kidney discard rate, and antigen-mismatch distribution, stratified by CMV serostatus. Results: CMV matching policy with a calculated panel reactive antibody exception threshold of 50% (namely, the CMV">50%" policy) strikes a better balance between benefits and drawbacks of CMV matching. Compared with KAS-250, CMV">50%" reduced CMV high-risk (D+/R-) transplants (6.1% versus 18.1%) and increased CMV low-risk (D-/R-) transplants (27.2% versus 13.1%); increased transplant rate for CMV R- patients (11.54 versus 12.57) but decreased for R+ patients (10.68 versus 10.48), yielding an increase in aggregate (11.09 versus 10.94); and reduced mean time to transplantation (by 6 wk); and reduced kidney discard rate (25.7% versus 26.2%). Conclusions: Our findings underscore the feasibility and potential advantages of a nationwide CMV seromatching policy in kidney transplantation.

Modeling Xanthan Gum Foam's Material Properties Using Machine Learning Methods.

Xanthan gum is commonly used in the pharmaceutical, cosmetic, and food industries. However, there have been no studies on utilizing this natural biopolymer as a foam material in the insulation and packaging sectors, which are large markets, or modeling it using an artificial neural network. In this study, foam material production was carried out in an oven using different ratios of cellulose fiber and xanthan gum in a 5% citric acid medium. As a result of the physical and mechanical experiments conducted, it was determined that xanthan gum had a greater impact on the properties of the foam material than cellulose. The densities of the produced foam materials ranged from 49.42 kg/m3 to 172.2 kg/m3. In addition, the compressive and flexural moduli were found to vary between 235.25 KPa and 1257.52 KPa and between 1939.76 KPa and 12,736.39 KPa, respectively. Five machine-learning-based methods (multiple linear regression, support vector machines, artificial neural networks, least squares methods, and generalized regression neural networks) were utilized to analyze the effects of the components used in the foam formulation. These models yielded accurate results without time, material, or cost losses, making the process more efficient. The models predicted the best results for density, compression modulus, and flexural modulus achieved in the experimental tests. The generalized regression neural network model yielded impressive results, with R2 values above 0.97, enabling the acquisition of more quantitative data with fewer experimental results.

COSAP: Comparative Sequencing Analysis Platform.

BACKGROUND: Recent improvements in sequencing technologies enabled detailed profiling of genomic features. These technologies mostly rely on short reads which are merged and compared to reference genome for variant identification. These operations should be done with computers due to the size and complexity of the data. The need for analysis software resulted in many programs for mapping, variant calling and annotation steps. Currently, most programs are either expensive enterprise software with proprietary code which makes access and verification very difficult or open-access programs that are mostly based on command-line operations without user interfaces and extensive documentation. Moreover, a high level of disagreement is observed among popular mapping and variant calling algorithms in multiple studies, which makes relying on a single algorithm unreliable. User-friendly open-source software tools that offer comparative analysis are an important need considering the growth of sequencing technologies. RESULTS: Here, we propose Comparative Sequencing Analysis Platform (COSAP), an open-source platform that provides popular sequencing algorithms for SNV, indel, structural variant calling, copy number variation, microsatellite instability and fusion analysis and their annotations. COSAP is packed with a fully functional user-friendly web interface and a backend server which allows full independent deployment for both individual and institutional scales. COSAP is developed as a workflow management system and designed to enhance cooperation among scientists with different backgrounds. It is publicly available at https://cosap.bio and https://github.com/MBaysanLab/cosap/ . The source code of the frontend and backend services can be found at https://github.com/MBaysanLab/cosap-webapi/ and https://github.com/MBaysanLab/cosap_frontend/ respectively. All services are packed as Docker containers as well. Pipelines that combine algorithms can be customized and new algorithms can be added with minimal coding through modular structure. CONCLUSIONS: COSAP simplifies and speeds up the process of DNA sequencing analyses providing commonly used algorithms for SNV, indel, structural variant calling, copy number variation, microsatellite instability and fusion analysis as well as their annotations. COSAP is packed with a fully functional user-friendly web interface and a backend server which allows full independent deployment for both individual and institutional scales. Standardized implementations of popular algorithms in a modular platform make comparisons much easier to assess the impact of alternative pipelines which is crucial in establishing reproducibility of sequencing analyses.

Improving somatic exome sequencing performance by biological replicates.

BACKGROUND: Next-generation sequencing (NGS) technologies offer fast and inexpensive identification of DNA sequences. Somatic sequencing is among the primary applications of NGS, where acquired (non-inherited) variants are based on comparing diseased and healthy tissues from the same individual. Somatic mutations in genetic diseases such as cancer are tightly associated with genomic instability. Genomic instability increases heterogenity, complicating sequencing efforts further, a task already challenged by the presence of short reads and repetitions in human DNA. This leads to low concordance among studies and limits reproducibility. This limitation is a significant problem since identified mutations in somatic sequencing are major biomarkers for diagnosis and the primary input of targeted therapies. Benchmarking studies were conducted to assess the error rates and increase reproducibility. Unfortunately, the number of somatic benchmarking sets is very limited due to difficulties in validating true somatic variants. Moreover, most NGS benchmarking studies are based on relatively simpler germline (inherited) sequencing. Recently, a comprehensive somatic sequencing benchmarking set was published by Sequencing Quality Control Phase 2 (SEQC2). We chose this dataset for our experiments because it is a well-validated, cancer-focused dataset that includes many tumor/normal biological replicates. Our study has two primary goals. First goal is to determine how replicate-based consensus approaches can improve the accuracy of somatic variant detection systems. Second goal is to develop highly predictive machine learning (ML) models by employing replicate-based consensus variants as labels during the training phase. RESULTS: Ensemble approaches that combine alternative algorithms are relatively common; here, as an alternative, we study the performance enhancement potential of biological replicates. We first developed replicate-based consensus approaches that utilize the biological replicates available in this study to improve variant calling performance. Subsequently, we trained ML models using these biological replicates and achieved performance comparable to optimal ML models, those trained using high-confidence variants identified in advance. CONCLUSIONS: Our replicate-based consensus approach can be used to improve variant calling performance and develop efficient ML models. Given the relative ease of obtaining biological replicates, this strategy allows for the development of efficient ML models tailored to specific datasets or scenarios.

The frequency and clinical significance of antibodies to soluble liver antigen/liver pancreas in autoimmune hepatitis: a prospective single-center study.

BACKGROUND AND AIMS: Soluble liver antigen/liver pancreas antibodies (anti-SLA/LP) are specific markers for autoimmune hepatitis (AIH) that have been associated with a distinct clinical phenotype and a more aggressive form of AIH. We prospectively evaluated the frequency and clinical significance of anti-SLA/LP in Turkish patients with AIH. MATERIAL AND METHODS: We prospectively included patients diagnosed with AIH between January 2018 and May 2023. Autoantibodies were detected using by immunofluorescence and immunoblot. RESULTS: We included 61 (80%, female) AIH patients with a median age of 31 years (15-78) at the time of diagnosis. Anti-SLA/LP was detected in 20% ( n  = 12) of the patients. Baseline characteristics, treatment responses and outcomes were similar among anti-SLA/LP-positive and anti-SLA/LP-negative AIH patients. Anti-SLA/LP-positive patients had significantly higher biochemical response rates after 4 weeks (100 vs. 67%, P  = 0.027), 3 months (100 vs. 39%, P  < 0.001), 6 months (100 vs. 69%, P  = 0.041) of therapy but not after 12 months (100 vs. 76%, P  = 0.103) and at the end of follow-up (100 vs. 91%, P  = 0.328). Relapse rates following treatment response were similar in patients with and without anti-SLA/LP (22 vs. 23%, P  = 0.956). Second-line therapies (tacrolimus and mycophenolate mofetil) were given to seven (11%) patients, all were anti-SLA/LP-negative. Two of these progressed into end-stage liver disease and both underwent liver transplantation. CONCLUSION: Our study results suggest that anti-SLA/LP positivity does not entail clinically distinct or severe features in AIH. In our cohort, anti-SLA/LP-positive patients showed a quicker response to immunosuppressive therapy.

The interrelation between the high expression level of MIR34a and the trisomic abortion materials.

AIMS: The underlying mechanism and constitution of spontaneous abortions are complicated and heterogeneous. Many factors, including epigenetic scenarios like micro-ribonucleic acids (miRNAs, MIRs), can additively affect the progression of pregnancy losses. This study aimed to evaluate whether the expression levels of placental inhibitor and/or activator miRNAs had a difference between the numerically abnormal and normal karyotyped spontaneous abortions. METHODS: The case-control study included 100 spontaneous abortion materials consisting of trophoblastic tissues with 42 disomies (controls), 43 aneuploidies (including trisomy 16, 21, 22, and monosomy X), and 15 triploidies. Disomic abortion materials with XX normal karyotypes were omitted from the study to exclude possible maternal decidual cell contamination. Total RNA isolation was performed with TRIzol™ reagent directly from frozen trophoblastic tissues, and the mature miRNAs were obtained by reverse transcription via quantitative real-time polymerase chain reaction (qRT-PCR). Then, the expression levels of placental activators MIR378a-5p, MIR376c, MIR195, and inhibitors MIR34a and MIR210 were relatively evaluated using MIR130 as a reference. RESULTS: The expression level of placental inhibitor MIR34a was detected to be high in trisomic abortion materials (trisomy 16 and 21) when compared to the disomic ones (p = 0.0324). MIR195 (p = 0.0484) and MIR34a (p = 0.0346) expression levels were increased in numerically abnormal cases with advanced maternal age compared to the disomic ones within all maternal ages. CONCLUSIONS: It seems likely that the high expression level of MIR34a and the coexistence of trisomic abortion materials are quite interrelated with the additive effect of advanced maternal age.

Analysis of Turkish Breast Cancer Patients With ATM-Heterozygous Germline Mutation According to Clinicopathological Features.

OBJECTIVE: The ATM gene is one of the most common breast cancer (BC) susceptibility genes after BRCA1/2 and has been shown to be a moderate BC susceptibility gene. The association between ATM germline mutation and clinical features of BC is now unknown. In this article, clinicopathological features of BC patients with ATM germline heterozygous mutation were investigated. MATERIALS AND METHODS: Patients admitted to the Medical Genetics department of a tertiary hospital between January 2020 and December 2022 were examined. Only invasive BC patients with pathogenic mutation, likely pathogenic mutation, or variants of uncertain significance (VUS) were included in the study. RESULTS: In all, 121 patients were included in the study. The median age at the first cancer diagnosis of the patients was 44 years. Of the total number of patients, 75.2% (91) had the histological subtype of infiltrating ductal carcinoma, and 43% (52) had Luminal B molecular subtype features. At a median follow-up of 16 months, 5.8% (7) of patients developed cancer in the contralateral breast. In addition, 7.4% (9) of the patients developed a second primary cancer during follow-up. When the patients were compared according to ATM variant classification, the localization, histologic types, and molecular subtypes of the BC were not different between all groups (respectively; p=0.68, p=0.65, p=0.32). CONCLUSIONS: To the best of our knowledge, this is the first publication that evaluates the clinical and pathological characteristics of BC patients with germline heterozygous ATM mutations in the Turkish population. When patients were compared according to variant classifications of ATM mutation, patients' histological and molecular subtypes were similar.

Athletic performance, sports experience, and exercise addiction: an association study on ANKK1 gene polymorphism rs1800497.

Introduction: Exercise addiction is a phenomenon being able to affecting the athletic performance. The gene, ANKK1 and the polymorphism NM_178510.2:c.2137G > A (rs1800497) has been linked to the exercise addiction. However, further studies on diverse populations and sport branches are needed to totally explore the possible association of this polymorphism with the athletic performance. Thus, the present study aims to decipher any possible relations of the rs1800497 polymorphism with the athletic performance/personal best (PB) and sport experience of elite athletes. Methods: Sixty volunteer elite athletes (31 sprint/power and 29 endurance) and 20 control/sedentary participated in the study. The polymorphism was genotyped using whole exome sequencing approach and PB were determined according to the International Association of Athletics Federations (IAAF) score. Results: Our results underlined that there were not any significance differences for both allele and genotype frequencies between the groups in terms of athletic performance, although the frequency of allele G was higher (p > 0.05). Nevertheless, sport experience significantly associated with the rs1800496 polymorphism (p < 0.05). Discussion: In conclusion, genotype G/G could be inferred to be linked to the higher sport experience and athletic performance. Still, further studies with higher number of participants are needed to conclude the association of this polymorphism with athletic parameters.

Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses.

The α-actinin-3 (ACTN3) gene rs1815739 (C/T, R577X) polymorphism is a variant frequently associated with athletic performance among different populations. However, there is limited research on the impact of this variant on athlete status and physical performance in basketball players. Therefore, the aim of this study was twofold: (1) to determine the association of ACTN3 rs1815739 polymorphism with changes in physical performance in response to six weeks of training in elite basketball players using 30 m sprint and Yo-Yo Intermittent Recovery Test Level 2 (IR 2) tests, and (2) to compare ACTN3 genotype and allelic frequencies between elite basketball players and controls. The study included a total of 363 individuals, comprising 101 elite basketball players and 262 sedentary individuals. Genomic DNA was isolated from oral epithelial cells or leukocytes, and genotyping was performed by real-time PCR using KASP genotyping method or by microarray analysis. We found that the frequency of the ACTN3 rs1815739 XX genotype was significantly lower in basketball players compared to controls (10.9 vs. 21.4%, p = 0.023), suggesting that RR/RX genotypes were more favorable for playing basketball. Statistically significant (p = 0.045) changes were observed in Yo-Yo IRT 2 performance measurement tests in basketball players with the RR genotype only. In conclusion, our findings suggest that the carriage of the ACTN3 rs1815739 R allele may confer an advantage in basketball.

Exome-Wide Association Study of Competitive Performance in Elite Athletes.

The aim of the study was to identify genetic variants associated with personal best scores in Turkish track and field athletes and to compare allelic frequencies between sprint/power and endurance athletes and controls using a whole-exome sequencing (WES) approach, followed by replication studies in independent cohorts. The discovery phase involved 60 elite Turkish athletes (31 sprint/power and 29 endurance) and 20 ethnically matched controls. The replication phase involved 1132 individuals (115 elite Russian sprinters, 373 elite Russian endurance athletes (of which 75 athletes were with VO2max measurements), 209 controls, 148 Russian and 287 Finnish individuals with muscle fiber composition and cross-sectional area (CSA) data). None of the single nucleotide polymorphisms (SNPs) reached an exome-wide significance level (p < 2.3 × 10-7) in genotype-phenotype and case-control studies of Turkish athletes. However, of the 53 nominally (p < 0.05) associated SNPs, four functional variants were replicated. The SIRT1 rs41299232 G allele was significantly over-represented in Turkish (p = 0.047) and Russian (p = 0.018) endurance athletes compared to sprint/power athletes and was associated with increased VO2max (p = 0.037) and a greater proportion of slow-twitch muscle fibers (p = 0.035). The NUP210 rs2280084 A allele was significantly over-represented in Turkish (p = 0.044) and Russian (p = 0.012) endurance athletes compared to sprint/power athletes. The TRPM2 rs1785440 G allele was significantly over-represented in Turkish endurance athletes compared to sprint/power athletes (p = 0.034) and was associated with increased VO2max (p = 0.008). The AGRN rs4074992 C allele was significantly over-represented in Turkish sprint/power athletes compared to endurance athletes (p = 0.037) and was associated with a greater CSA of fast-twitch muscle fibers (p = 0.024). In conclusion, we present the first WES study of athletes showing that this approach can be used to identify novel genetic markers associated with exercise- and sport-related phenotypes.

Evaluation of the Association of VDR rs2228570 Polymorphism with Elite Track and Field Athletes' Competitive Performance.

The present study aimed to examine the vitamin D receptor (VDR), rs2228570 polymorphism, and its effect on elite athletes' performance. A total of 60 elite athletes (31 sprint/power and 29 endurance) and 20 control/ physically inactive, aged 18-35, voluntarily participated in the study. The International Association of Athletics Federations (IAAF) score scale was used to determine the performance levels of the athletes' personal best (PB). Whole exome sequencing (WES) was performed by the genomic DNA isolated from the peripheral blood of the participants. Sports type, sex, and competitive performance were chosen as the parameters to compare within and between the groups by linear regression models. The results showed no statistically significant difference between the CC, TC, and TT genotypes within and between the groups (p > 0.05). Additionally, our results underlined that there were no statistically significant differences for the association of rs2228570 polymorphism with PBs within the groups of the (p > 0.05) athletes. The genetic profile in the selected gene was similar in elite endurance, sprint athletes, and in controls, suggesting that rs2228570 polymorphism does not determine competitive performance in the analyzed athlete cohort.

Incidence, risk factors and pre-emptive screening for COVID-19 associated pulmonary aspergillosis in an era of immunomodulant therapy.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment. MATERIALS AND METHODS: A retrospective, observational, multicentre study was performed from September 2020-April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria. RESULTS: CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy. CONCLUSIONS: CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation.

The effect of apoprotein E gene polymorphism on neurocognitive functions of children with CHD.

Studies have demonstrated an association between CHD and neurodevelopmental delay. This delay is associated with many factors like reduced blood flow and oxygen, cardiac catheterisations, and genetic factors. Apo E gene polymorphism is one of these genetic factors. This study aims to show the effect of Apo E gene polymorphism on neurodevelopmental process in children having CHD. A total of 188 children having CHD were admitted to the study. Apo E gene polymorphism of these patients was determined, and psychometric evaluation was performed. The relationship between psychometric test results and gene polymorphism was evaluated. This study shows that, similar to the literature, patients having cyanotic CHD have worse scores than acyanotic patients, and the children with CHD are under risk in terms of neuropsychiatric disorders. Other novel and important findings of this study were the lower verbal scores of ε2 allele carriers than ε4 carriers in Wechsler Intelligence Scale for Children-Revised group and the worse test score of patients having VSD than other acyanotic patients. Besides, some special disorders may be seen in this patient group.

Assessment of key characteristics, methodology, and effect size measures used in meta-analysis of human-health-related animal studies.

Since the early 1990s the number of systematic reviews (SR) of animal studies has steadily increased. There is, however, little guidance on when and how to conduct a meta-analysis of human-health-related animal studies. To gain insight about the methods that are currently used we created an overview of the key characteristics of published meta-analyses of animal studies, with a focus on the choice of effect size measures. An additional goal was to learn about the rationale behind the meta-analysis methods used by the review authors. We show that important details of the meta-analyses are not fully described, only a fraction of all human-health-related meta-analyses provided rationales for their decision to use specific effect size measures. In addition, our data may suggest that authors make post-hoc decisions to switch to another effect size measure during the course of their meta-analysis, and possibly search for significant effects. Based on analyses in this paper we recommend that review teams: 1) publish a review protocol before starting the conduct of a SR, prespecifying all methodological details (providing special attention to the planned meta-analysis including the effect size measure and the rational behind choosing a specific effect size, prespecifying subgroups and restricting the number of subgroup analyses), 2) always use the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) checklist to report your SR of animal studies, and 3) use the random effects model (REM) in human-health-related meta-analysis of animal studies, unless the assumptions for using the fixed effect model (FEM) are all met.

Optimal breast cancer risk reduction policies tailored to personal risk level.

Depending on personal and hereditary factors, each woman has a different risk of developing breast cancer, one of the leading causes of death for women. For women with a high-risk of breast cancer, their risk can be reduced by two main therapeutic approaches: 1) preventive treatments such as hormonal therapies (i.e., tamoxifen, raloxifene, exemestane); or 2) a risk reduction surgery (i.e., mastectomy). Existing national clinical guidelines either fail to incorporate or have limited use of the personal risk of developing breast cancer in their proposed risk reduction strategies. As a result, they do not provide enough resolution on the benefit-risk trade-off of an intervention policy as personal risk changes. In addressing this problem, we develop a discrete-time, finite-horizon Markov decision process (MDP) model with the objective of maximizing the patient's total expected quality-adjusted life years. We find several useful insights some of which contradict the existing national breast cancer risk reduction recommendations. For example, we find that mastectomy is the optimal choice for the border-line high-risk women who are between ages 22 and 38. Additionally, in contrast to the National Comprehensive Cancer Network recommendations, we find that exemestane is a plausible, in fact, the best, option for high-risk postmenopausal women.

Growth hormone-releasing pituitary microadenoma overshaded by a macroadenoma: a case of double pituitary adenomas and review of the literature.

OBJECTIVES: Double pituitary adenoma is a rare entity that can pose a significant challenge. The incidence of double or multiple pituitary adenomas is ∼1% in autopsy cases and 0.4-1.3% in surgical series. Its definition varies, including 'double adenomas' in the literature in contrast to 'multiple adenomas', which is more specific and suitable. While some authors require separating topographically unique tumours, others have used a looser definition of separate immunohistochemistry. CASE PRESENTATION: We presented the case of a 26-year-old patient with recurrent carpal tunnel syndrome symptoms, with double pituitary adenomas secreting growth hormone (GH) and thyroid-stimulating hormone (TSH). To date, 89 patients have been reported in the literature with symptomatic carpal tunnel syndrome, but only five had GH-TSH secretion. CONCLUSIONS: Double adenoma resection is of great importance for ensuring successful biochemical treatment. To ensure a successful operation, a careful preoperative 3T MRI examination is of great importance.

Identification of copy number variants in children and adolescents with autism spectrum disorder: a study from Turkey.

BACKGROUND: Copy number variants (CNVs) play a key role in the etiology of autism spectrum disorder (ASD). Therefore, recent guidelines recommend chromosomal microarrays (CMAs) as first-tier genetic tests. This study's first aim was to determine the clinical usefulness of CMAs in children diagnosed with ASD in a Turkish population. The second aim was to describe the CNVs and clinical phenotypes of children with ASD. METHODS AND RESULTS: This was a single-center retrospective cross-sectional study. Data were obtained from the medical records of children with ASD followed at Gazi University Hospital, (Ankara, Turkey). The sample consisted of 47 ASD cases (mean age: 60.34 ± 25.60 months; 82.9% boys). The diagnostic yield of the CMAs was 8.5%. Four pathogenic CNVs were identified: 9p24.3p24.2 deletion, 15q11-q13 duplication, 16p11.2 deletion, and 22q13.3 deletion. Also, four variants were found at 2q36.3, 10p11.21, 15q11.2, and Xp11.22, which were classified as variants of uncertain significance (VUS). CONCLUSIONS: The TRAP12 and PARD3 genes in CNVs classified as VUS may be worth investigating for autism. The initial identification of both clinical and biological markers can facilitate monitoring, early intervention, or prevention and advance our understanding of the neurobiology underlying ASD.