Qualitative and Quantitative Magnetic Resonance Imaging Phenotypes May Predict CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase-Mutant Astrocytomas:A Multicenter Study

Objective@#Cyclin-dependent kinase inhibitor (CDKN)2A/B homozygous deletion is a key molecular marker of isocitrate dehydrogenase (IDH)-mutant astrocytomas in the 2021 World Health Organization. We aimed to investigate whether qualitative and quantitative MRI parameters can predict CDKN2A/B homozygous deletion status in IDH-mutant astrocytomas. @*Materials and Methods@#Preoperative MRI data of 88 patients (mean age ± standard deviation, 42.0 ± 11.9 years; 40 females and 48 males) with IDH-mutant astrocytomas (76 without and 12 with CDKN2A/B homozygous deletion) from two institutions were included. A qualitative imaging assessment was performed. Mean apparent diffusion coefficient (ADC), 5th percentile of ADC, mean normalized cerebral blood volume (nCBV), and 95th percentile of nCBV were assessed via automatic tumor segmentation.Logistic regression was performed to determine the factors associated with CDKN2A/B homozygous deletion in all 88 patients and a subgroup of 47 patients with histological grades 3 and 4. The discrimination performance of the logistic regression models was evaluated using the area under the receiver operating characteristic curve (AUC). @*Results@#In multivariable analysis of all patients, infiltrative pattern (odds ratio [OR] = 4.25, p = 0.034), maximal diameter (OR = 1.07, p = 0.013), and 95th percentile of nCBV (OR = 1.34, p = 0.049) were independent predictors of CDKN2A/B homozygous deletion. The AUC, accuracy, sensitivity, and specificity of the corresponding model were 0.83 (95% confidence interval [CI], 0.72–0.91), 90.4%, 83.3%, and 75.0%, respectively. On multivariable analysis of the subgroup with histological grades 3 and 4, infiltrative pattern (OR = 10.39, p = 0.012) and 95th percentile of nCBV (OR = 1.24, p = 0.047) were independent predictors of CDKN2A/B homozygous deletion, with an AUC accuracy, sensitivity, and specificity of the corresponding model of 0.76 (95% CI, 0.60–0.88), 87.8%, 80.0%, and 58.1%, respectively. @*Conclusion@#The presence of an infiltrative pattern, larger maximal diameter, and higher 95th percentile of the nCBV may be useful MRI biomarkers for CDKN2A/B homozygous deletion in IDH-mutant astrocytomas.

A New Integrated Newborn Screening Workflow Can Provide a Shortcut to Differential Diagnosis and Confirmation of Inherited Metabolic Diseases

PURPOSE: We developed a new workflow design which included results from both biochemical and targeted gene sequencing analysis interpreted comprehensively. We then conducted a pilot study to evaluate the benefit of this new approach in newborn screening (NBS) and demonstrated the efficiency of this workflow in detecting causative genetic variants. MATERIALS AND METHODS: Ten patients in Group 1 were diagnosed clinically using biochemical assays only, and 10 newborns in Group 2 were diagnosed with suspected inherited metabolic disease (IMD) in NBS. We applied NewbornDiscovery (SD Genomics), an integrated workflow design that encompasses analyte-phenotype-gene, single nucleotide variant/small insertion and deletion/copy number variation analyses along with clinical interpretation of genetic variants related to each participant's condition. RESULTS: A molecular genetic diagnosis was established in 95% (19/20) of individuals. In Group 1, 13 and 7 of 20 alleles were classified as pathogenic and likely pathogenic, respectively. In Group 2, 11 and 6 of 17 alleles with identified causative variants were pathogenic and likely pathogenic, respectively. There were no variants of uncertain significance. For each individual, the NewbornDiscovery and biochemical analysis results reached 100% concordance, since the single newborn testing negative for causative genetic variant in Group 2 showed a benign clinical course. CONCLUSION: This integrated diagnostic workflow resulted in a high yield. This approach not only enabled early confirmation of specific IMD, but also detected conditions not included in the current NBS.

Prevalence of Attention-Deficit/Hyperactivity Disorder and its Comorbidity among Korean Children in a Community Population

The aim of this study was to determine the prevalence of attention deficit hyperactivity disorders (ADHD) in children according to socio-demographic factors and the distribution of ADHD subtypes in a community in Korea. A screening survey using the Korean version of ADHD Rating Scale (K-ARS) was conducted between 2007 and 2008, and clinical interviews by a pediatric psychiatrist were performed for selected children between 2009 and 2010. A total of 49,573 elementary school students, between ages of 7 and 12, constituted the target population, among which 38,365 students (77.2%) and respective parents gave consent to participate. Of the participants, 200 screened children were clinically examined to confirm the diagnosis of ADHD. We estimated the prevalence of ADHD and its comorbidity in the population, after adjusting for nonresponse and nonparticipation. The prevalence of ADHD was 11.7% in boys and 5.2% in girls, with an overall prevalence of 8.5%. The combined type of inattentive and hyperactive was the most frequent at 4.7% of the whole population. Children were more likely to have ADHD if their parents were separated and had less education. Most commonly combined comorbidity was autism spectrum disorder (ASD) (10.1%). The prevalence of ADHD in the school-aged population is an essential information for improving the quality of public health mental services for evaluation and treatment of ADHD.

Two Cases of Lipedematous Scalp in Korean Patients / 대한피부과학회지

No abstract available.

A scientific treatment approach for acute mast cell leukemia: using a strategy based on next-generation sequencing data

BACKGROUND: Mast cell leukemia (MCL) is the most aggressive form of systemic mastocytosis disorders. Owing to its rarity, neither pathogenesis nor standard treatment is established for this orphan disease. Hence, we tried to treat a patient with MCL based on the exome and transcriptome sequencing results of the patient's own DNA and RNA. METHODS: First, tumor DNA and RNA were extracted from bone marrow at the time of diagnosis. Germline DNA was extracted from the patient's saliva 45 days after induction chemotherapy and used as a control. Then, we performed whole-exome sequencing (WES) using the DNA and whole transcriptome sequencing (WTS) using the RNA. Single nucleotide variants (SNVs) were called using MuTect and GATK. Samtools, FusionMap, and Gene Set Enrichment Analysis were utilized to analyze WTS results. RESULTS: WES and WTS results revealed mutation in KIT S476I. Fusion analysis was performed using WTS data, which suggested a possible RARα-B2M fusion. When RNA expression analysis was performed using WTS data, upregulation of PIK3/AKT pathway, downstream of KIT and mTOR, was observed. Based on our WES and WTS results, we first administered all-trans retinoic acid, then dasatinib, and finally, an mTOR inhibitor. CONCLUSION: We present a case of orphan disease where we used a targeted approach using WES and WTS data of the patient. Even though our treatment was not successful, use of our approach warrants further validation.

Female Hairline Preference among Various Segments of the Korean Population

No abstract available.

A Case of Isolated Collagenoma of the Scalp Resembling Cutis Verticis Gyrata / 대한피부과학회지

No abstract available.

Two Cases of Malignant Proliferating Trichilemmal Tumors: Large Tumors on the Scalp without Metastasis / 대한피부과학회지

Proliferating trichilemmal tumor (PTT) is an uncommon neoplasm originated from the outer root sheath of a hair follicle. Malignant transformation occurs occasionally in proliferating trichilemmal tumors, which can be manifested by sudden rapid growths. Histologically, the malignant proliferating trichilemmal tumors (MPTTs) have shown severe nuclear atypia, marked cellular pleomorphism with atypical mitoses, dyskeratotic cells and infiltrating margins. Squamous cell carcinoma (SCC) should be differentiated with MPTT which indicates characteristic trichilemmal keratinization. Large tumor is considered as a risk factor of metastasis in SCC, but the relationship between tumor size and metastasis in the MPTT is not yet clarified. In this report, two patients have large erythematous nodules with focal ulceration and necrosis on their scalps and were diagnosed as MPTT. Despite the large sizes of the tumors, there were no evidences of metastases. Herein, we report 2 cases of the large MPTT which are presented without metastasis.

Sensitization rates to inhalant allergens in children and adolescents of Incheon and Asan area and the relationship between polysensitization and prevalence of allergic diseases

PURPOSE: Sensitization to allergens is considered as major mechanism of allergy and related to the development of allergic diseases. The objective of this study was to evaluate overall sensitization rates of inhalant allergens and the relationship between polysensitization and prevalence of allergic diseases in children and adolescents. METHODS: A cross-sectional pilot study of 122 elementary school students, 114 middle school students, and 115 high school students from Incheon and Asan was conducted by using the International Study of Asthma and Allergies in Childhood (ISSAC) questionnaire. The skin prick tests were performed with 14 common inhalant allergens on 339 students. RESULTS: The inhalant allergen that has a significantly different sensitization rate according to age was Dermatophagoides farinae. And the inhalant allergen that has significantly different sensitization rate according to region was Japanese hop. In addition, girls have higher sensitization rate to any mold allergens than boys. In case of having sensitization more than two allergens, the risks of diagnosis of asthma and allergic rhinitis on questionnaire were increased. Asthma is related to sensitization of dog or cat and allergic rhinitis is related to sensitization of house dust mites. However, atopic dermatitis is not related to sensitization of any inhalant allergens. CONCLUSION: The sensitization rates of inhalant allergens may differ among age, gender, and region in children and adolescents of Incheon and Asan area. The polysensitized children and adolescents with inhalant allergens showed higher prevalences of allergic diseases such as asthma and allergic rhinitis on questionnaire than monosensitized group.

Peptide Mimotopes of Neisseria meningitidis Group B Capsular Polysaccharide

The antigenic similarity between Neisseria meningitidis group B (NMGB) capsular polysaccharide (PS) and human polysialic acid (PSA) has hampered the development of a NMGB PS-based vaccine. But the possibility of a safe vaccine based on NMGB PS has been demonstrated by the existence of the NMGB PS-associated nonautoreactive epitope, which is distinct from those present on human PSA. To obtain peptide mimotopes of NMGB PS, we used HmenB3, a protective and nonautoreactive monoclonal antibody, to screen a phage library with 12 amino acids. We obtained 23 phage clones that bound to HmenB3 but not in the presence of E. coli K1 PS [which is alpha (2-8) -linked PSA like NMGB PS]. The clones contained 3 mimotopes and differed from previously described NMGB PS mimotopes. Immunization with a synthetic peptide of one mimotope elicited anti-NMGB antibodies in BALB/c mice. These mimotopes may be useful in the development of group B meningococcal vaccines.