Soo Yeon Kim

Fine-needle aspiration versus core needle biopsy for diagnosis of thyroid malignancy and neoplasm: a matched cohort study

AbstractObjectivesTo compare the diagnostic performances of fine-needle aspiration (FNA) and core needle biopsy (CNB) in the diagnosis of thyroid malignancy and neoplasm in patients who underwent surgery for thyroid nodules.MethodsThis retrospective study was approved by the institutional review board, and the need to obtain informed consent was waived. 3192 patients who underwent FNA (n = 3048) or CNB (n = 144) for diagnosis of thyroid nodules and then proceeded with surgery were included. Surgical pathologic diagnosis was the reference standard. Diagnostic performances of FNA and CNB to predict malignancy and neoplasm were compared. Propensity score matching was used to match patients with FNA with those with CNB because there were significant differences in the number of nodules and nodule characteristics between the FNA and CNB groups.ResultsBefore matching, the sensitivity and accuracy of FNA were significantly higher or comparable with those of CNB, and the specificity, negative predictive value and positive predictive value were comparable. After matching, the diagnostic performances were similar, with the exception of specificity for predicting neoplasm being higher with CNB than with FNA.ConclusionFNA showed comparable diagnostic performance to CNB; therefore, there may be no benefit in performing CNB to diagnose papillary thyroid carcinoma and neoplasm.Key Points• Diagnostic performances of FNA and CNB for thyroid malignancy and neoplasm were compared. • FNA showed comparable performances to CNB both before and after statistical matching. • There may be no benefit in performing CNB, given the comparable performances.

Tofacitinib relieves symptoms of stimulator of interferon genes (STING)–associated vasculopathy with onset in infancy caused by 2 de novo variants in TMEM173

4. Kukkonen AK, Pelkonen AS, M€akinen-Kiljunen S, Voutilainen H, M€akel€a MJ. Ara h 2 and Ara 6 are the best predictors of severe peanut allergy: a double-blind placebo-controlled study. Allergy 2015;11:1239-45. 5. Nozawa A, Okamoto Y, Mov erare R, Borres MP, Kurihara K. Monitoring Ara h 1, 2 and 3-sIgE and sIgG4 antibodies in peanut allergic children receiving oral rush immunotherapy. Pediatr Allergy Immunol 2014;25:323-8. 6. Vickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, et al. Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol 2014;133:468-75. 7. Krause S, Reese G, Randow S, Zennaro D, Quaratino D, Palazzo P, et al. Lipid transfer protein (Ara h 9) as a new peanut allergen relevant for a Mediterranean allergic population. J Allergy Clin Immunol 2009;124:771-8.e5. 8. Glaumann S, Nilsson C, Asarnoj A, Mov erare R, Johansson SG, Borres MP, et al. IgG4 antibodies and peanut challenge outcome in children IgE-sensitized to peanut. Pediatr Allergy Immunol 2015;26:386-9. 9. Santos AF, James LK, Bahnson HT, Shamji MH, Couto-Francisco NC, Islam S, et al. IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens. J Allergy Clin Immunol 2015;135:1249-56.

Breast Cancer Detected at Screening US: Survival Rates and Clinical-Pathologic and Imaging Factors Associated with Recurrence

Purpose To determine the survival rates and clinical-pathologic and imaging factors associated with recurrence in women with breast cancer detected at screening ultrasonography (US). Materials and Methods This study was approved by the institutional review board, and the requirement to obtain informed consent was waived. A retrospective review of the databases of four institutions identified 501 women (median age, 47 years; range, 27-74 years) with breast cancer (425 invasive cancers and 76 ductal carcinoma in situ) detected at screening US between January 2004 and March 2011. Five-year overall survival (OS) and recurrence-free survival (RFS) rates were estimated, and the clinical-pathologic and imaging data were collected. Multivariate analysis was performed by using Cox proportional hazard regression to determine factors associated with recurrence. Results At a median follow-up of 7.0 years (range, 5.0-12.1 years), 15 (3.0%) recurrences were detected: five in ipsilateral breast and 10 in contralateral breast. The 5-year OS and RFS rates were 100% and 98.0% (95% confidence interval [CI]: 96.8%, 99.2%), respectively. In patients with invasive cancers, age younger than 40 years (hazard ratio: 3.632 [95% CI: 1.099, 11.998]; P = .032), the triple-negative subtype (hazard ratio: 7.498 [95% CI: 2.266, 24.816]; P = .001), and Breast Imaging Reporting and Data System (BI-RADS) category 4A lesions (hazard ratio: 5.113 [95% CI: 1.532, 17.195]; P = .008) were associated with recurrence. Conclusion Women with breast cancers detected at screening US have excellent outcomes, with a 5-year RFS rate of 98.0%. However, in patients with invasive breast cancer, age younger than 40 years, the triple-negative subtype, and BI-RADS category 4A lesions were associated with recurrence.

Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations

Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole‐exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole‐exome sequencing for diagnosis of ultra‐rare diseases.

Precision and trueness of dental models manufactured with different 3-dimensional printing techniques

Introduction: In this study, we assessed the precision and trueness of dental models printed with 3‐dimensional (3D) printers via different printing techniques. Methods: Digital reference models were printed 5 times using stereolithography apparatus (SLA), digital light processing (DLP), fused filament fabrication (FFF), and the PolyJet technique. The 3D printed models were scanned and evaluated for tooth, arch, and occlusion measurements. Precision and trueness were analyzed with root mean squares (RMS) for the differences in each measurement. Differences in measurement variables among the 3D printing techniques were analyzed by 1‐way analysis of variance (&agr; = 0.05). Results: Except in trueness of occlusion measurements, there were significant differences in all measurements among the 4 techniques (P <0.001). For overall tooth measurements, the DLP (76 ± 14 &mgr;m) and PolyJet (68 ± 9 &mgr;m) techniques exhibited significantly different mean RMS values of precision than the SLA (88 ± 14 &mgr;m) and FFF (99 ± 14 &mgr;m) techniques (P <0.05). For overall arch measurements, the SLA (176 ± 73 &mgr;m) had significantly different RMS values than the DLP (74 ± 34 &mgr;m), FFF (89 ± 34 &mgr;m), and PolyJet (69 ± 18 &mgr;m) techniques (P <0.05). For overall occlusion measurements, the FFF (170 ± 55 &mgr;m) exhibited significantly different RMS values than the SLA (94 ± 33 &mgr;m), DLP (120 ± 28 &mgr;m), and PolyJet (96 ± 33 &mgr;m) techniques (P <0.05). There were significant differences in mean RMS values of trueness of overall tooth measurements among all 4 techniques: SLA (107 ± 11 &mgr;m), DLP (143 ± 8 &mgr;m), FFF (188 ± 14 &mgr;m), and PolyJet (78 ± 9 &mgr;m) (P <0.05). For overall arch measurements, the SLA (141 ± 35 &mgr;m) and PolyJet (86 ± 17 &mgr;m) techniques exhibited significantly different mean RMS values of trueness than DLP (469 ± 49 &mgr;m) and FFF (409 ± 36 &mgr;m) (P <0.05). Conclusions: The 3D printing techniques showed significant differences in precision of all measurements and in trueness of tooth and arch measurements. The PolyJet and DLP techniques were more precise than the FFF and SLA techniques, with the PolyJet technique having the highest accuracy. HighlightsThe PolyJet technique provides the greatest trueness and precision.Accuracy of 3‐dimensional printers differs in the sizes of print outcomes.Three‐dimensional printing techniques may be used for orthodontic purposes.

Ultrasound texture analysis: Association with lymph node metastasis of papillary thyroid microcarcinoma

This retrospective study aimed to evaluate whether ultrasound texture analysis is useful to predict lymph node metastasis in patients with papillary thyroid microcarcinoma (PTMC). This study was approved by the Institutional Review Board, and the need to obtain informed consent was waived. Between May and July 2013, 361 patients (mean age, 43.8 ± 11.3 years; range, 16–72 years) who underwent staging ultrasound (US) and subsequent thyroidectomy for conventional PTMC ≤ 10 mm between May and July 2013 were included. Each PTMC was manually segmented and its histogram parameters (Mean, Standard deviation, Skewness, Kurtosis, and Entropy) were extracted with Matlab software. The mean values of histogram parameters and clinical and US features were compared according to lymph node metastasis using the independent t-test and Chi-square test. Multivariate logistic regression analysis was performed to identify the independent factors associated with lymph node metastasis. Tumors with lymph node metastasis (n = 117) had significantly higher entropy compared to those without lymph node metastasis (n = 244) (mean±standard deviation, 6.268±0.407 vs. 6.171±.0.405; P = .035). No additional histogram parameters showed differences in mean values according to lymph node metastasis. Entropy was not independently associated with lymph node metastasis on multivariate logistic regression analysis (Odds ratio, 0.977 [95% confidence interval (CI), 0.482–1.980]; P = .949). Younger age (Odds ratio, 0.962 [95% CI, 0.940–0.984]; P = .001) and lymph node metastasis on US (Odds ratio, 7.325 [95% CI, 3.573–15.020]; P < .001) were independently associated with lymph node metastasis. Texture analysis was not useful in predicting lymph node metastasis in patients with PTMC.

Consecutive analysis of mutation spectrum in the dystrophin gene of 507 Korean boys with Duchenne/Becker muscular dystrophy in a single center.

Duchenne and Becker muscular dystrophies (DMD and BMD) are allelic X‐linked recessive muscle diseases caused by mutations in the large and complex dystrophin gene.

Chromosomal Microarray With Clinical Diagnostic Utility in Children With Developmental Delay or Intellectual Disability

Background Chromosomal microarray (CMA) testing is a first-tier test for patients with developmental delay, autism, or congenital anomalies. It increases diagnostic yield for patients with developmental delay or intellectual disability. In some countries, including Korea, CMA testing is not yet implemented in clinical practice. We assessed the diagnostic utility of CMA testing in a large cohort of patients with developmental delay or intellectual disability in Korea. Methods We conducted a genome-wide microarray analysis of 649 consecutive patients with developmental delay or intellectual disability at the Seoul National University Childrens Hospital. Medical records were reviewed retrospectively. Pathogenicity of detected copy number variations (CNVs) was evaluated by referencing previous reports or parental testing using FISH or quantitative PCR. Results We found 110 patients to have pathogenic CNVs, which included 100 deletions and 31 duplications of 270 kb to 30 Mb. The diagnostic yield was 16.9%, demonstrating the diagnostic utility of CMA testing in clinic. Parental testing was performed in 66 patients, 86.4% of which carried de novo CNVs. In eight patients, pathogenic CNVs were inherited from healthy parents with a balanced translocation, and genetic counseling was provided to these families. We verified five rarely reported deletions on 2p21p16.3, 3p21.31, 10p11.22, 14q24.2, and 21q22.13. Conclusions This study demonstrated the clinical utility of CMA testing in the genetic diagnosis of patients with developmental delay or intellectual disability. CMA testing should be included as a clinical diagnostic test for all children with developmental delay or intellectual disability.

Correlation between electrical conductivity and apparent diffusion coefficient in breast cancer: effect of necrosis on magnetic resonance imaging

ObjectivesTo investigate the correlation between conductivity and ADC in invasive ductal carcinoma according to the presence of necrosis on MRI.MethodsEighty-one women with invasive ductal carcinoma ≥1 cm on T2-weighted fast spin echo sequence of preoperative MRI were included. Phase-based MR electric properties tomography was used to reconstruct conductivity. Mean ADC was measured. Necrosis was defined as an area with very high T2 signal intensity. The relationship between conductivity and ADC was examined using Spearman’s correlation coefficient (r). Multiple linear regression analysis was performed to identify factors associated with conductivity or ADC.ResultsIn the total group, conductivity showed negative correlation with ADC (r = –0.357, p = 0.001). This correlation was maintained in the subgroup without necrosis (n = 53, r = –0.455, p = 0.001), but not in the subgroup with necrosis (n = 28, r = –0.080, p = 0.687). The correlation between the two parameters was different according to necrosis (r = -0.455 vs -0.080, p = 0.047). HER2 enriched subtype was independently associated with conductivity (p = 0.029). Necrosis on MRI was independently associated with ADC (p = 0.027).ConclusionsConductivity shows negative correlation with ADC that is abolished by the presence of necrosis on MRI.Key Points• Electric conductivity showed negative correlation with ADC• However, the correlation was abolished by the presence of necrosis on MRI• HER2-enriched subtype was independently associated with conductivity• Necrosis on MRI was independently associated with ADC

Surgical outcome and predictive factors of epilepsy surgery in pediatric isolated focal cortical dysplasia

OBJECTIVE Focal cortical dysplasia (FCD) is a common cause of medically intractable epilepsy in children. Epilepsy surgery has been a valuable treatment option to achieve seizure freedom in these intractable epilepsy patients. We aimed to present long-term surgical outcome, in relation to pathological severity, and to assess predictive factors of epilepsy surgery in pediatric isolated FCD. METHODS We retrospectively analyzed the data of 58 children and adolescents, with FCD International League Against Epilepsy (ILAE) task force classification types I and II, who underwent resective epilepsy surgery and were followed for at least 2 years after surgery. RESULTS The mean age at epilepsy onset was 4.3 years (0-14.2 years), and mean age at epilepsy surgery was 9.4 years (0.4-17.5 years). The mean duration of postoperative follow-up was 5.1±2.6 years (2-12.4 years). Of 58 patients, 62% of patients achieved Engel class I at 2 years postoperatively, 58% at 5 years postoperatively, and 53% at the last follow up. Forty eight percent of our cohort successfully discontinued antiepileptic medication. Of 30 patients with seizure recurrence, 83% of seizures recurred within 2 years after surgery. We observed that FCD type IIb was significantly associated with a better surgical outcome. At fifth postoperative year, 88% of FCD IIb patients were seizure free compared with 21% of type I and 57% of type IIa patients (P=0.043). By multivariate analysis, lesion on MRI (P=0.02) and complete resection (P<0.01) were the most important predictive factors for a seizure-free outcome. SIGNIFICANCE Epilepsy surgery is highly effective; more than half of medically intractable epilepsy patients achieved seizure freedom after surgery. In addition, we found significant difference in surgical outcomes according to the ILAE task force classification. Lesion on MRI and complete resection were the most important predictive factors for favorable seizure outcome in isolated FCD patients.