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Background: Myhre syndrome is a rare connective tissue disorder caused by heterozygous pathogenic variants in the SMAD4 gene. Although recognizing Myhre syndrome in early childhood is challenging, it is important to manage airway stenosis in patients with Myhre syndrome. Case Presentation: We report the case of a 2-month-old boy who initially presented with severe multilevel airway stenosis, dysmorphic face, and multiple abnormalities. Lung fibrosis and mild aortic valve stenosis were additionally observed on follow-up examinations. A heterozygous missense variant, c.1499T>C (p.Ile500Thr), in SMAD4 was identified through exome sequencing. Tracheostomy was performed, and the patient has maintained stable respiration through a customized tracheostomy tube with a home ventilator. Conclusions: Patients who have dysmorphic face, airway stenosis, and cardiovascular anomalies that do not fit the diagnosis of common syndromes should be evaluated for rare diseases, including Myhre syndrome. Since respiratory complications can be life threatening, early diagnosis and suitable intervention are necessary.

Introduction The single most common cause of miscarriage is genetic abnormality. Objective We conducted a prospective cohort study to compare the performance of conventional karyotyping and chromosomal microarray analysis (CMA) using array comparative genomic hybridization (array-CGH) and single nucleotide polymorphism array (SNP-array) to identify genetic abnormalities in miscarriage specimens. Methods A total of 63 miscarriage specimens were included. Conventional karyotyping, array-CGH, and SNP-array were performed and the results compared. Results Genetic abnormalities were detected in 31 cases (49.2%) by at least one testing modality. Single autosomal trisomy was the most common defect (71.0%), followed by polyploidy (16.1%), multiple aneuploidy (9.7%), and monosomy X (3.2%). Mosaicisms were identified in four cases and confirmed by fluorescence in situ hybridization (FISH) using appropriate probes. SNP-array had a higher detection rate of genetic abnormalities than array-CGH (93.5 vs. 77.4%), and conventional karyotyping had the lowest detection rate (76.0%). SNP-array enabled the detection of all types of genetic abnormalities, including polyploidy. Conclusions Although conventional karyotyping and FISH are still needed, SNP-array represents the first choice for miscarriage because the technique showed excellent performance in the detection of genetic abnormalities and minimized the probability of testing failure as well as time, costs, and labor. Supplementary Information The online version contains supplementary material available at 10.1007/s40291-021-00523-9.

Rationale: Osteopathia striata with cranial sclerosis is characterized by linear striations in the metaphysis of the long bones and pelvis with cranial sclerosis. It is an X-linked dominant sclerosing bone dysplasia and affected males show fetal or neonatal lethality. Mutations in the gene encoding Wilms tumor on the X chromosome (WTX) was identified as the cause of X-linked osteopathia striata with cranial sclerosis. About 30 pathogenic mutations in WTX have been reported recently. We have identified a novel nonsense mutation in the family diagnosed as osteopathia striata with cranial sclerosis. Patient concerns The proband came to our attention at age 9 for the evaluation of toe-out gait and planovalgus deformity. Clinically, the proband showed coarse facial features including frontal bossing, ocular hypertelorism, wide depressed nasal bridge, dental malocclusion, mild macrocephaly and low set ears. Radiologically, sclerotic linear striations were seen in the X-rays of the pelvis and the metaphyseal region of femur and tibia and the cranial sclerosis was observed. The proband's mother presented similar facial features and the X-rays of the pelvis, femur, and tibia revealed same sclerotic linear striations as the proband's. Diagnoses Osteopathia striata with cranial sclerosis. Interventions A genetic analysis was conducted on genomic DNA isolated from peripheral blood leukocytes of the proband and the mother for confirming the clinical suspicion of osteopathia striata with cranial sclerosis. WTX on Xq11.2 gene was analyzed in direct sequencing for coding exons including intron-exon boundaries. Outcomes One novel nonsense mutation (c.1003C>T, p.Gln335∗) and known single nucleotide variant were observed in a heterozygous form. Lessons We found a novel nonsense mutation in a family diagnosed as osteopathia striata with cranial sclerosis. The relationship between various clinical features and genetic mutations can be clarified by accumulation of genetic database.

Dear Editor, Glucose meters are increasingly used in hospitals and home settings. These handheld devices provide instant readings and are therefore, beneficial for glucose-level monitoring in patients with diabetes [1]. Nonetheless, there have been concerns regarding the measurement accuracy of glucose meters. Some substances, such as vitamin C and maltose, are considered responsible for errors in glucose measurements using point-of-care testing glucose meters [1,2,3]. Vitamin C is widely used in the treatment of cancer, viral infections, severe burns, and chronic fatigue syndrome because of the antioxidant effects [4]. Maltose can be upregulated in patients undergoing peritoneal dialysis involving icodextrin as an osmotic agent [3]. High concentrations of vitamin C and maltose in blood can lead to false increase in glucose meter readings, resulting in misdiagnosis of hypoglycemia and potential fatalities [1]. Therefore, there is an urgent need for interference-resistant glucose meters [5]. We evaluated the interference of vitamin C and maltose with glucose readings obtained using the following three meters: Accuchek Inform (Roche Diagnostics, Indianapolis, IN, USA), Starstrip (Nova Biomedical, Waltham, MA, USA), and Barozen H plus (i-SENS Inc., Seoul, Korea). These three models are based on the glucose dehydrogenase-pyrroloquinoline quinone (GDH-PQQ), modified glucose oxidase (GOD), and GDH-flavin adenine dinucleotide (FAD) assays, respectively [5,6]. After prior depletion of glucose by overnight storage at room temperature, we prepared three pooled blood specimens [4] from EDTA-treated whole blood samples and added glucose (CAS 50-99-7, Duksan Pure Chemicals Co., Ansan, Korea) at final concentrations of 60, 126, or 300 mg/dL. To study the effect of various concentrations of vitamin C (0, 3, 15, or 30 mg/dL) [7] or maltose (0, 10, 40, 200, or 500 mg/dL) [8], we added 0.15 mL of the vitamin C or maltose stock solutions (control: normal saline) to 3 mL of pooled blood specimens. The stock solutions were prepared from L-ascorbic acid (CAS 50-81-7, Sigma-Aldrich, St. Louis, MO, USA) and D (+) -maltose monohydrate (CAS 6363-53-7, Junsei Chemical Co., Tokyo, Japan). Then, we compared the whole blood glucose readings of the specimens, with and without an interfering substance, using three glucose meters. We also measured the plasma glucose levels in each sample with Hitachi 7600 chemistry analyzer (Hitachi, Tokyo, Japan) for a benchmark comparison. Each sample was tested in duplicate. Assessment of interference and accuracy for each glucose meter was performed according to the criteria of the International Organization for Standardization (ISO) 15197:2013(E) [9]. Accuchek Inform glucose level readings at all concentrations were subject to significant positive interference (>10% deviation from control sample levels) from vitamin C presence at concentrations of 15 and 30 mg/dL, whereas no significant positive interference was observed for Barozen H plus and Starstrip models (Fig. 1). However, Starstrip failed to produce readings in two out of three measurements in specimens, which contained 30 mg/dL vitamin C (Fig. 1). In contrast to the effect of vitamin C, no significant interference at any maltose concentration was noted for all the three models tested (Fig. 1). Owing to interference from high concentrations of vitamin C (15 and 30 mg/dL), Accuchek Inform showed unacceptable accuracy levels (>15% difference from the value obtained by the chemistry analyzer; Table 1). Starstrip generally showed lower readings than those determined by the chemistry analyzer, especially at higher glucose concentrations: a negative bias >15% was detected in four out of nine measurements (Table 1). Fig. 1 Glucose level measurements in different concentrations of interferents. Glucose was added to blood at various concentrations: low (60 mg/dL), medium (126 mg/dL), and high (300 mg/dL). The X-axis represents the level of interferent, and the Y-axis represents ... Table 1 Accuracy of whole-blood glucose concentration readings using three glucose meter models compared with the measurements obtained by using a chemistry analyzer Vitamin C is a strong antioxidant that inactivates free radicals and can be oxidized at the surface of electrochemical strips producing electrons and increasing the current [1]. Icodextrin, an osmotic agent used in peritoneal dialysis, is metabolized in the systemic circulation into various glucose polymers, mainly maltose [10]. It can interfere with readings obtained using GDH-PQQ-based method, because GDH-PQQ catalyzes the oxidation of not only glucose but also other sugars [1]. Thus, vitamin C and maltose can cause positive interference resulting in misdiagnosis of true glucose levels. However, GDH currently used in Accuchek Inform was modified by the manufacturer to increase enzyme specificity for glucose and to diminish probability of incorrect high glucose readings [8]. In this study, all three glucose meters showed reliable results in presence of maltose. However, at higher vitamin C concentrations, Accuchek Inform showed a positive bias, while Starstrip occasionally malfunctioned. In conclusion, high concentrations of vitamin C may affect blood glucose measurements depending on the glucose meter used. Therefore, caution is required while monitoring the glucose level, using a glucose meter, of patients receiving high dose of vitamin C. There is a need for continuous technical improvement and further studies for possible interferents of glucose meters.

As a possible marker of oxidative stress, many studies have measured whole blood reduced glutathione (GSH) and oxidized glutathione (GSSG). However, large differences in GSH and GSSG levels reported in different studies, calls for a reliable standardized method. In this study, we validate not only analytical performance of new measurement method for GSH and GSSG, but also the clinical utility of these markers in a mouse model with chronic oxidative stress. Twenty mice were randomized into four treatment groups according to iron burden: 0mg, 5mg, 10mg, or 15 mg of iron were injected into the peritoneum per day over 4 weeks. To prevent artifactual GSH auto-oxidation, we pretreated the sample with N-ethylmaleimide (NEM) immediately after sample collection. After protein precipitation using sulfosalicylic acid, GSSG and GSH-NEM were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The mean GSH/GSSG ratios of the mouse model were 163.1, 31.0, 27.9, and 12.8 for control, 5mg, 10mg, and 15 mg injection groups, respectively, showing a decrease in the GSH/GSSG ratios according to the amount of oxidative stress induced. Inter-assay coefficients of variation were 4.1% for GSH-NEM and 7.3% for GSSG. Recoveries were 98.0-105.9% for GSH-NEM and 98.0-107.3% for GSSG. No ion suppression was observed at the retention time for GSH-NEM and GSSG. This study suggests an accurate method that can be used for glutathione measurement using LC-MS/MS, and showed that GSH/GSSG ratio could provide an assessment of the degree of oxidative stress.

Dear Editor, Ascorbic acid interferes with certain clinical chemistry assays based on peroxidase and redox indicators [1]. Ascorbic acid is reported to interfere with the measurement of glucose, total cholesterol, triglycerides, and uric acid [2,3,4,5]. We recently encountered several cases of interference from ascorbic acid in serum total cholesterol assays based on colorimetric enzymatic reactions. A 48-yr-old-female with recurrent ovarian cancer underwent palliative segmental resection surgery of the small intestine. The patient showed progressive renal impairment following surgery, and total cholesterol level was

Objectives The use of iodinated contrast media has grown in popularity in the past two decades, but relatively little attention has been paid to the possible interferential effects of contrast media on laboratory test results. Herein, we investigate medical contrast media interference with routine chemistry results obtained by three automated chemistry analyzers. Methods Ten levels of pooled serum were used in the study. Two types of medical contrast media [Iopamiro (iopamidol) and Omnipaque (iohexol)] were evaluated. To evaluate the dose-dependent effects of the contrast media, iopamidol and iohexol were spiked separately into aliquots of serum for final concentrations of 1.8%, 3.6%, 5.5%, 7.3%, and 9.1%. The 28 analytes included in the routine chemistry panel were measured by using Hitachi 7600, AU5800, and Cobas c702 analyzers. We calculated the delta percentage difference (DPD) between the samples and the control, and examined dose-dependent trends. Results When the mean DPD values were compared with the reference cut-off criteria, the only uniformly interferential effect observed for all analyzers was in total protein with iopamidol. Two additional analytes that showed trends toward interferential effects only in few analyzers and exceeded the limits of the allowable error were the serum iron and the total CO 2 . The other combinations of analyzer and contrast showed no consistent dose-dependent propensity for change in any analyte level. Conclusions Our study suggests that many of the analytes included in routine chemistry results, except total protein and serum iron, are not significantly affected by iopamidol and iohexol. These results suggest that it would be beneficial to apply a flexible medical evaluation process for patients requiring both laboratory tests and imaging studies, minimizing the need for strict regulations for sequential tests.

Background Periodic monitoring of antimicrobial resistance trends of clinically important anaerobic bacteria such as Bacteroides fragilis group organisms is required. We determined the antimicrobial susceptibilities of clinical isolates of B. fragilis group organisms recovered from 2009 to 2012 in a tertiary-care hospital in Korea. Methods A total of 180 nonduplicate clinical isolates of B. fragilis group organisms were collected in a tertiary care hospital. The species were identified by conventional methods: the ATB 32A rapid identification system (bioMérieux, France) and the Vitek MS matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (bioMérieux). Antimicrobial susceptibility was determined by the CLSI agar dilution method. Results Imipenem and meropenem resistance rates were 0-6% for B. fragilis group isolates. The rate of resistance to piperacillin-tazobactam was 2% for B. fragilis and 0% for other Bacteroides species, but 17% for B. thetaiotaomicron isolates. High resistance rates to piperacillin (72% and 69%), cefotetan (89% and 58%), and clindamycin (83% and 69%) were observed for B. thetaiotaomicron and other Bacteroides spp. The moxifloxacin resistance rate was 27% for other Bacteroides spp. The MIC50 and MIC90 of tigecycline were 2-4 µg/mL and 8-16 µg/mL, respectively. No isolates were resistant to chloramphenicol or metronidazole. Conclusions Imipenem, meropenem, chloramphenicol, and metronidazole remain active against B. fragilis group isolates. Moxifloxacin and tigecycline resistance rates are 2-27% and 8-15% for B. fragilis group isolates, respectively.

Background: Trends in the isolation of enteropatho- genic bacteria may differ depending on environmental sanitation. The aims of this study were to determine trends in the isolation and antimicrobial resistance patterns of enteropathogenic bacteria over the last 10 years. Methods: We analyzed stool cultures of Salmonella spp., Shigella spp., Plesiomonas shigelloides, Yersinia spp., Vibrio spp., and Campylobacter spp. collected at Severance Hospital between 2001 and 2010. Anti- microbial susceptibility testing was performed using the disk diffusion method for nontyphoidal Salmonella (NTS) and Campylobacter. Results: The number of specimens for stool culture significantly increased from 13,412 during 1969-1978 to 60,714 over the past 10 years, whereas the ratio of positive specimens significantly decreased from 12.9% (1,732) to 1.1% (648). The proportion of Sal- monella Typhi decreased from 97.2% in 1969-1978 to 0.8% in 2001-2010, whereas the proportion of NTS increased from 2.8% to 99.2%. The proportion of Shigella among all enteric pathogens was over 50% from 1969 to 1983, while only seven strains were isolated from 2001 to 2010, with the exception of one outbreak. Campylobacter is the second most prevalent organism. The rates of susceptibility to am- picillin and cotrimoxazole were 61% and 92%, respe- ctively, for NTS isolated from 2006 to 2010. The ci- profloxacin susceptibility rate was 79.5% for Campy- lobacter between 2006 and 2010. Conclusion: The number of isolates of Salmonella Typhi and Shigella significantly decreased, while the proportion of NTS and Campylobacter increased. Con- tinuous monitoring of ciprofloxacin-resistant Campylo- bacter isolates is necessary. (Ann Clin Microbiol 2013; 16:45-51)