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The article presents a study that compared the functional outcomes of two different ligament reattachment techniques using suture anchors. Topics include ligament reattachment techniques for the modified Brostrom procedure, the cost-effectiveness of the suture bridge technique, and the need to address proper indication and clinical usefulness of suture bridge technique for chronic ankle instability.

Autosomal dominant non-syndromic hearing loss (AD-NSHL) is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES) and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP) chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A) in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15) described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3rd alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL. [ABSTRACT FROM AUTHOR]

Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. Bacteriophages that prey on V. cholerae may be employed as phage therapy against cholera. However, the influence of the chemical environment on the infectivity of vibriophages has been unexplored. Here, we discovered that a common metabolite produced by gut microbes─linear enterobactin (LinEnt), represses vibriophage proliferation. We found that the antiphage effect by LinEnt is due to iron sequestration and that multiple forms of iron sequestration can protect V. cholerae from phage predation. This discovery emphasizes the significance that the chemical environment can have on natural phage infectivity and phage-based interventions.

Background: Accurate nomenclature of variants is an essential element for genetic diagnosis and patient care., Objective: To investigate annotation differences of clinical variants between annotation tools., Methods: We analyzed 218,156 clinical variants from the Human Gene Mutation Database. Multiple nomenclatures based on RefSeq transcripts were provided using ANNOVAR and snpEff., Results: The concordance rate between ANNOVAR and snpEff was approximately 85%. Based on the Human Genome Variation Society (HGVS) nomenclature, snpEff was more accurate than ANNOVAR (coding variants, 99.3% vs 84.9%; protein variants, 94.3% vs 79.8%). When annotating each variant with ANNOVAR and snpEff, the accuracy of nomenclature was 99.5%., Conclusions: There were substantial differences between ANNOVAR and snpEff annotations. The findings of this study suggest that simultaneous use of multiple annotation tools could decrease nomenclature errors and contribute to providing standardized clinical reporting., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To investigate the interpretation differences of germline-shared somatic variants., Methods: A total of 123,302 COSMIC variants associated with hematologic malignant neoplasms were used. The pathogenicity and actionability of shared variants were analyzed based on the standardized guidelines., Results: The overall frequency of variants shared in ClinVar/HGMD and COSMIC was 10%. The pathogenicity of 54 shared variants was pathogenic/likely pathogenic (P/LP; n = 30), variants of unknown significance (n = 3), and benign/likely benign (n = 21). In total, 30 P/LP variants were reclassified to tier I/tier II (83%) and tier III (17%) variants., Conclusions: This is the first study about different clinical interpretations of shared variants based on the current standard guidelines. This study takes a meaningful step in bridging the interpretation gap between the somatic and germline variants., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Three new neolignan glycosides ( 1 - 3 ), a new phenolic glycoside ( 15 ), and a new cyanoglycoside ( 16 ) were isolated and characterized from the twigs of Aleurites fordii together with 14 known analogues ( 4 - 14 and 17 - 19 ). The structural elucidation of the new compounds was performed through the analysis of their NMR, HRMS, and ECD spectra and by chemical methods. All isolated compounds were tested for their antineuroinflammatory and neuroprotective activities., (Copyright © 2021, Park et al.)

Objective: Discordant variant classifications among public databases is one of the well-documented limitations when interpreting the pathogenicity of variants. The aim of this study is to investigate the level of germline variant misannotation from the Human Gene Mutation Database (HGMD) and the annotation concordance between databases., Methods: We used a total of 188,106 classified variants (disease-causing mutations [n = 179,454] and polymorphisms [n = 8652]) in 6466 genes from the HGMD. All variants were reanalyzed based on the American College of Medical Genetics and Genomics (ACMG) guidelines and compared to ClinVar database variants., Results: When variants were classified based on the ACMG guidelines, misclassification was observed in 3.47% (2289/65,896) of variants. The overall concordance between HGMD and ClinVar was 97.62% (52,499/53,780) of variants studied., Conclusion: Variants in databases must be used with caution when variant pathogenicity is interpreted. This study reveals the frequency of misannotation of the HGMD variants and annotation concordance between databases in depth., (© American Society for Clinical Pathology 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoblasts and osteoclasts play a pivotal role in maintaining bone homeostasis, of which excessive bone resorption by osteoclasts can cause osteoporosis and various bone diseases. However, current osteoporosis treatments have many side effects, and research on new treatments that can replace these treatments is ongoing. Therefore, in this study, the roles of ligustroside (LGS) and oleoside dimethylester (ODE), a natural product-derived compound isolated from Syringa oblata subsp. dilatata as a novel, natural product-derived osteoporosis treatments were investigated. In the results of this study, LGS and ODE inhibited the differentiation of receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced RAW264.7 cells into osteoclasts without cytotoxicity, and down-regulated the activity of TRAP, a specific biomarker of osteoclasts. In addition, it inhibited bone resorption and actin ring formation, which are important functions and features of osteoclasts. Also, the effects of LGS and ODE on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and phosphoinositide 3-kinases (PI3K)/ protein kinase B (Akt)/mechanistic target of rapamycin (mTOR) signaling pathways that play important roles in osteoclast differentiation were evaluated. In the results, LGS and ODE downregulated the phosphorylation of RANKL-induced MAPK and PI3K/Akt/mTOR proteins in a concentration-dependent manner, translocation of NF-κB into the nucleus was inhibited. As a result, the compounds LGS and ODE isolated from S. oblate subsp. dilatata effectively regulated the differentiation of RANKL-induced osteoclasts and inhibited the phosphorylation of signaling pathways that play a pivotal role in osteoclast differentiation. Therefore, these results suggest the possibility of LGS and ODE as new natural product treatments for bone diseases caused by excessive osteoclasts.

Background: To evaluate the demographics, clinical and radiographic features of calcific tendinitis of the shoulder in the Korean population, specifically focusing on the incidence of coexisting rotator cuff tear., Methods: Between October 2014 and January 2015, we performed a prospective multicenter study with 506 patients from 11 training hospitals in Korea. We collected data of demographics and radiographic analysis based on simple radiographs, clinical assessments based on visual analog scale (VAS) and the American Shoulder Elbow Surgeons (ASES) score, and treatment modalities that are used currently. We also evaluated coexisting rotator cuff tear by ultrasonography (US) or magnetic resonance imaging (MRI) images., Results: There were 402 female patients (79%) with mean age of 55 years (range, 31-87 years). Mean duration of symptoms was 16 months. Mean size of calcific materials was 11.4 mm (range, 0-35 mm). Mean value of VAS and ASES scores were 6.5 (range, 1-10) and 47 (range, 8-95), respectively. Of 383 patients (76%), 59 (15%) had rotator cuff tear including 15 full-thickness tears on US or MRI. Patients with rotator cuff tears were significantly associated with older age, recurrent symptoms, menstrual disorders in females, and having undergone calcification removal surgery and rotator cuff repair (all p<0.05)., Conclusions: This study reported demographic, radiographic, and clinical features of calcific tendinitis of the shoulder in Korean population, which were not different from those of Western population. Coexisting rotator cuff tear was found with 15% incidence in this large series, suggesting that further radiographic study to evaluate rotator cuff tear might be needed in some calcific tendinitis patients of older age and presenting with recurrent symptoms.

Obesity causes a wide range of metabolic diseases including diabetes, cardiovascular disease, and kidney disease. Thus, plenty of studies have attempted to discover naturally derived compounds displaying anti-obesity effects. In this study, we evaluated the inhibitory effects of morolic acid 3- O -caffeate (MAOC), extracted from Betula schmidtii , on adipogenesis. Treatment of 3T3-L1 cells with MAOC during adipogenesis significantly reduced lipid accumulation and decreased the expression of adiponectin, a marker of mature adipocytes. Moreover, the treatment with MAOC only during the early phase (day 0-2) sufficiently inhibited adipogenesis, comparable with the inhibitory effects observed following MAOC treatment during the whole processes of adipogenesis. In the early phase of adipogenesis, the expression level of Wnt6, which inhibits adipogenesis, increased by MAOC treatment in 3T3-L1 cells. To identify the gene regulatory mechanism, we assessed alterations in histone modifications upon MAOC treatment. Both global and local levels on the Wnt6 promoter region of histone H3 lysine 4 trimethylation, an active transcriptional histone marker, increased markedly by MAOC treatment in 3T3-L1 cells. Our findings identified an epigenetic event associated with inhibition of adipocyte generation by MAOC, suggesting its potential as an efficient therapeutic compound to cure obesity and metabolic diseases.

Eleven new labdane-type diterpenoid glycosides, koraiensides A-K ( 1 - 11 ), together with two known analogues were isolated from the twigs of Pinus koraiensis . Their structures were elucidated via NMR, HRMS, and ECD data, DP4+ statistical analysis, and hydrolysis. The metabolites were tested for induction of nerve growth factor in C6 glioma cells to evaluate their potential neuroprotective activity. The compounds were measured for production of nitric oxide levels in lipopolysaccharide (LPS)-activated murine microglia BV2 cells to assess their antineuroinflammatory activity. Compounds 10 and 13 showed NGF secretion inducing effects from C6 glioma cells (162.3 ± 13.9% and 162.7 ± 6.9%, respectively). Compound 6 showed an IC 50 value of 24.1 μM, implying significant inhibition of NO production.

Genomic studies have illuminated the alterations in pathways underlying T-cell acute lymphoblastic leukemia (T-ALL) pathogenesis, but detailed mutation data by next-generation sequencing have not been reported in Korean patients. We aimed to investigate mutation frequency, spectrum, and pattern in the Korean patients with T-ALL. We designed a multigene panel targeting 101 genes and validated it using 10 reference materials. The mutation analysis was done in a total of 10 patients with T-ALL. Clinical data and laboratory tests including immunophenotyping, cytogenetics, and molecular genetic tests were also investigated. All of the 10 patients harbored at least one mutation (range 1-6 per patient). A total of 34 clinically significant mutations including 15 novel mutations were identified in 23 genes. The median of variant allelic frequencies (VAFs) and blasts were counted upto 33% (range 5-91%) and 79% (range 38-90%), respectively. Recurrent mutations were involved in epigenetic regulators (60%), NOTCH1 signaling (40%), PI3K-AKT (40%), JAK-STAT (30%), and transcription factors (30%). We found that both NOTCH signaling and JAK-STAT signaling were positively associated with epigenetic regulators, while showed mutually exclusive patterns with PI3K-AKT pathway. This study showed that the frequency of mutations in epigenetic regulators in Korean patients was significantly higher than expected. Distribution of VAF as well as mutation spectrum is considerably heterogeneous in Korean patients with T-ALL. Although from a limited number of patients, this study provides the first detailed mutational portrait of T-ALL of Korean patients, and gives additional insight into molecular pathogenesis of the disease.

Six undescribed phenolic derivatives along with thirty two known compounds were isolated from the twigs of Betula schmidtii. The chemical structures were characterized through extensive spectroscopic analysis and chemical methods. All known compounds were first isolated in this plant. The anti-inflammatory effect of the isolates was tested by measuring nitric oxide production in lipopolysaccharide-activated BV-2 cells. Isotachioside, 4-allyl-2-hydrophenyl 1-O-β-D-apiosyl-(1 → 6)-β-D-glucopyranoside, genistein 5-O-β-D-glucoside, and prunetinoside showed a slight potency to lower the NO production against LPS-activated microglia with IC 50 values of 23.9, 25.3, 28.8, and 34.0 μM, respectively., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To compare inferior capsular redundancy by using magnetic resonance arthrography (MRA) images in patients with multidirectional instability (MDI) of the shoulder and control subjects without instability and thereby develop a screening method to identify the presence of shoulder MDI., Materials and Methods: The MRA images of patients with MDI of the shoulder (n = 65, 57 men, 8 women; mean age, 24.5 years; age range, 18-42 years) treated over an eight-year period were retrospectively reviewed; a control group (n = 65, 57 men, 8 women; mean age, 27.4 years; age range, 18-45 years) without instability was also selected. The inferior capsular redundancy was measured using a new method we named the glenocapsular (GC) ratio method. MRA images of both groups were randomly mixed together, and two orthopedic surgeon reviewers measured the cross-sectional areas (CSAs) and sagittal capsule-head ratios on oblique sagittal images, as well as the axial capsule-head ratios on axial images and GC ratios on oblique coronal images., Results: The CSAs and GC ratios were significantly higher in patients than in controls (both, p < 0.001); however, the sagittal capsule-head ratios and axial capsule-head ratios were not significantly different ( p = 0.317, p = 0.053, respectively). In addition, GC ratios determined the presence of MDI more sensitively and specifically than did CSAs. A GC ratio of > 1.42 was found to be most suggestive of MDI of the shoulder, owing to its high sensitivity (92.3%) and specificity (89.2%)., Conclusion: GC ratio can be easily measured and used to accurately screen for MDI of the shoulder., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Background: Krebs von den Lungen 6 (KL-6) is a sensitive marker for diagnosing, monitoring, and predicting the prognoses of interstitial lung diseases (ILDs). This study aimed to evaluate the performance of the Nanopia KL-6 assay (Sekisui Medical, Tokyo, Japan) and to test the relationship between KL-6 concentrations and clinical results., Methods: In total, 230 patients diagnosed as having ILDs were enrolled. All underwent high-resolution computed tomography (HRCT) followed by the pulmonary function test (PFT). We also enrolled 116 disease controls and 200 healthy controls. Evaluation of the Nanopia KL-6 assay involved determination of precision, linearity, and limit of quantification (LOQ). Results from the Nanopia KL-6 assay were compared with those from ELISA and correlated with the HRCT and PFT results., Results: The within-laboratory precisions were <2% of CV, and linearity was acceptable between 52.2 and 4,966.5 U/mL. The LOQ was 45.2 U/mL. Nanopia and ELISA results were strongly correlated ( r =0.979). The average concentration of KL-6 was greater in ILD patients (711.5 U/mL) than in the disease (168.4 U/mL) and healthy (209.4 U/mL) controls. Serum KL-6 concentrations were strongly and moderately correlated with the extent of lung involvement and presence of typical HRCT abnormalities, respectively, and moderately correlated with PFT parameters., Conclusions: The overall analytical and clinical performance of the Nanopia KL-6 assay was acceptable. Our study is the first to compare assay platforms and show correlations between KL-6 concentrations and HRCT or PFT results in Korean ILD patients., Competing Interests: The authors declare that there are no conflicts of interest., (© The Korean Society for Laboratory Medicine.)

The protein lysine methyltransferase G9a, which controls gene expression by epigenetic regulation of H3K9 methylation, is related to various human diseases, including cancer, drug addiction, and mental retardation. In recent years, genetic, biological, and physiological evidence has established G9a inhibitors as potential chemotherapeutic agents for cancer treatment. In this study, we identified protoberberine alkaloid pseudodehydrocorydaline (CT13) as a novel G9a inhibitor, by structure-based virtual screening of in-house library containing natural product compounds. The activity of CT13 was determined by biophysical analyses involving MALDI-TOF mass spectrometry and western blot analysis. CT13 showed selective inhibitory activity against G9a and suppressed the level of H3K9me2 in MCF7 human breast cancer cells. Molecular docking analysis suggested the binding mode of CT13 which occupies the binding site of histone H3 substrate. CT13 provides a novel scaffold for further development of analogous synthetic G9a inhibitors.

Investigation of the MeOH extract of Betula schmidtii twigs resulted in the isolation and identification of three new triterpenoids (1-3), along with ten known ones (4-13). The structures of new compounds (1-3) were elucidated by spectroscopic methods, including 1D, 2D NMR ( 1 H and 13 C NMR, COSY, HSQC, HMBC, and NOESY), HR-MS, and chemical methods. All the isolated compounds were evaluated for their cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines. Compound 11 exhibited potent cytotoxic activities against four cell lines, and compounds 5 and 13 significantly induced nerve growth factor secretion in a C6 rat glioma cell line. Their anti-inflammatory effects were also assessed by measuring nitric oxide production in lipopolysaccharide-activated BV-2 cells. Compounds 7 and 12 displayed potent inhibition of nitric oxide production, without significant cell toxicity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.

Purpose: To verify the clinical features and the risk factors of rapid progressive osteonecrosis of the humeral head after arthroscopic rotator cuff surgery (ARCS)., Methods: Data and medical records of 24 patients who had rapid progressive collapse of the humeral head after ARCS performed from October 2012 to March 2016 were retrospectively analyzed. Among them, 8 patients demonstrated no evidence of osteonecrosis of the humeral head preoperatively yet developed rapid progressive collapse of the humeral head within 12 months after ARCS., Results: All patients were women with a mean age of 64.0 years (range, 52-74 years), and all of them had surgery on their dominant side. Sudden pain developed at a mean 4 months (range, 0-6 months) after index surgery. The rapid progressive collapse of the humeral head occurred within 12 months after index surgery. No clear risk factor or evidence supporting an association between ARCS and humeral head osteonecrosis was found., Conclusions: Although the cause of the rapid progressive humeral head osteonecrosis after ARCS still needs to be established, surgeons should be aware of the possible development of humeral head osteonecrosis after ARCS, especially in older women with dominant arm involvement., Level of Evidence: Level IV, prognostic case series., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

A new pregnane-type steroidal glycoside (1), two new spirostane-type steroidal glycosides (2, 3), and two new furostane-type steroidal glycosides (4, 5), named allimacrosides A-E, together with four known compounds (6-9) were isolated from a 80% MeOH extract of Allium macrostemon Bunge. The identification and structural elucidation of these compounds were based on their 1D- and 2D-NMR spectra, and HR-FAB-MS data analysis. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To compare the capsular dimension as measured on magnetic resonance arthrography (MRA) between patients with multidirectional instability (MDI) of the shoulder and control subjects without instability. Ultimately, we aimed to develop an easy and reliable new screening method to assess MDI of the shoulder using MRA., Materials and Methods: MRA images of patients with MDI of the shoulder (n = 25) during a 6-year period (February 2010 to May 2015) were retrospectively reviewed. A control group (n = 26) without instability was also identified. The capsular area was measured using a new screening method we termed labro-capsular (LC) distance. MRA images of the two groups were randomly mixed, and two orthopedic surgeon reviewers recorded anterior, posterior, and inferior LC distance measurements on axial and coronal images using a mid-glenoid cut., Results: The inferior LC distance increased significantly in the patient group versus control group (P < 0.001), but there were no statistically significant differences in the anterior (P = 0.1165) and posterior (P = 0.5229) LC distances. An inferior LC distance >16.88 mm is most suggestive of MDI of the shoulder because of its high sensitivity (76 %) and specificity (96 %)., Conclusion: The inferior LC distance can be easily and quickly measured and used as an effective clinical screening method for atraumatic MDI of the shoulder.

A phytochemical investigation of Allium tuberosum Rottler afforded two new phenylpropane glycosides, named tuberonoid A (1) and B (2), along with four known flavonoids, kaempferol 3-O-β-sophoroside (3), 3-O-β-D-(2-O-feruloyl)-glucosyl-7,4'-di-O-β-D-glucosylkaempferol (4), 3-O-β-sophorosyl-7-O-β-D-(2-O-feruloyl)glucosyl kaempferol (5), kaempferol 3,4'-di-O-β-D-glucoside (6). The identification and structural elucidation of the new compounds were carried out based on spectral data analyses ((1)H and (13)C NMR, (1)H-(1)H COSY, HMQC) and HR-MS.

Scapular fractures are uncommon and among them acromial fractures are even more uncommon. Because the vast majority of acromial fractures are either non-displaced or minimally displaced, symptomatic and nonoperative management was performed. We describe a case of avulsion fracture of the acromial physis displaced by acromioclavicular ligament treated with open reduction and internal fixation, and include a review of the literature.

The present prospective study was conducted to evaluate the clinical outcomes of the new ligament reattachment procedure for chronic lateral ankle instability in high-demand athletes. A total of 24 athletes <30 years old were followed for >2 years after undergoing the modified Brostrom procedure using the suture bridge technique. The clinical evaluation included the Karlsson score, the Sefton grading system, and the period to return to exercise. As an evaluation of mechanical stability, the talar tilt angle and anterior talar translation were measured on stress radiographs. The Karlsson score had improved significantly from a preoperative average of 43.5 points to 92.2 points. Using the Sefton grading system, 22 (91.7%) patients achieved satisfactory results. The period to return to exercise was as follows: a mean of 8.4 weeks for jogging, 12.5 weeks for spurt running, 10.5 weeks for jumping, 9.2 weeks for 1 leg standing for >1 minute, 10.6 weeks for walking on uneven ground, and 11.2 weeks for going downstairs. The talar tilt angle and anterior talar translation had improved significantly from the preoperative average of 15.4° and 13.3 mm to 3.8° and 4.2 mm at 2 months postoperatively and 4.9° and 4.8 mm at the final follow-up visit, respectively. The modified Brostrom procedure using the suture bridge technique resulted in satisfactory clinical outcomes comparable to those with conventional ligament reattachment techniques. The suture bridge technique appears to be an effective treatment option for chronic ankle instability in high-demand athletes., (Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

This article describes a minimally invasive plate osteosynthesis technique for midshaft fractures of clavicles using intramedullary indirect reduction and prebent plates with 3D printing models. This technique allows for easy reduction of fractures with accurate prebent plates and minimal soft tissue injury around the fracture site.

Background: Humeral avulsion of the glenohumeral ligaments (HAGL) has become a recognized cause of recurrent shoulder instability; however, it is unknown whether small and large HAGL lesions have similarly destabilizing effects and if large lesion repair results in restoration of stability., Questions/purposes: In a cadaver model, we evaluated the effect of small and large HAGL lesions and large HAGL lesion repair on glenohumeral ROM, translation, and kinematics., Methods: We measured rotational ROM, humeral head translation under load, and humeral head apex position in eight cadaveric shoulders. Each specimen was tested in 60° glenohumeral abduction in the scapular and coronal planes under four conditions: intact, small HAGL lesion (mean ± SD length, 18 ± 1.8 mm), large HAGL lesion (36.8 ± 3.6 mm), and after large HAGL lesion repair. For each condition, we measured maximum internal and external rotation with 1.5 Nm of torque; glenohumeral translation in 90° external rotation with 15- and 20-N force applied in the anterior, posterior, superior, and inferior directions; and humeral head apex position throughout ROM. Repeated-measures ANOVA was used for statistical analysis., Results: Small HAGL lesions did not change ROM, translation, or kinematics from the normal shoulder; however, these parameters changed with large HAGL lesions. Maximum external rotation and total ROM increased in the scapular (13.8° ± 9.4°, p < 0.001; 19.0° ± 16.5°, p < 0.001) and coronal (21.4° ± 10.6°, p < 0.001; 29.1° ± 22.1°, p < 0.001) planes. With anterior force, anterior-inferior translation increased in both planes (mean increase for both loads and planes: anterior: 9.1 ± 9.5 mm, p < 0.01; inferior, 5.7 ± 6.6 mm, p < 0.03). In the coronal plane, posterior and inferior translation also increased (4.9 ± 5.4 mm, p < 0.01; 7.1 ± 9.9 mm, p < 0.03; averaged for both loads). The humeral head apex shifted 3.7 ± 4.9 mm anterior (p = 0.04) and 2.8 ± 2.6 mm lateral (p = 0.004) in the scapular plane and 3.7 ± 3.4 mm superior (p = 0.006) and 4.1 ± 2.6 mm lateral (p < 0.001) in the coronal plane. HAGL lesion repair decreased ROM and translation in both planes and restored humeral head position in maximum external rotation., Conclusions: Anterior large HAGL lesions increase ROM and glenohumeral translation. After large HAGL lesion repair, stability of the shoulder can be restored., Clinical Relevance: Surgeons should be aware of the possibility of HAGL lesions in patients with shoulder instability, and if large HAGL lesions are diagnosed, surgeons should consider repairing the lesions.

The present prospective, randomized study was conducted to compare the clinical outcomes of the modified Brostrom procedure using single and double suture anchors for chronic lateral ankle instability. A total of 50 patients were followed up for more than 2 years after undergoing the modified Brostrom procedure. Of the 50 procedures, 25 each were performed using single and double suture anchors by 1 surgeon. The Karlsson scale had improved significantly to 89.8 points and 90.6 points in the single and double anchor groups, respectively. Using the Sefton grading system, 23 cases (92%) in the single anchor group and 22 (88%) in the double anchor group achieved satisfactory results. The talar tilt angle and anterior talar translation on stress radiographs using the Telos device had improved significantly to an average of 5.7° and 4.6 mm in the single anchor group and 4.5° and 4.3 mm in the double anchor group, respectively. The double anchor technique was superior with respect to the postoperative talar tilt. The single and double suture anchor techniques produced similar clinical and functional outcomes, with the exception of talar tilt as a reference of mechanical stability. The modified Brostrom procedure using both single and double suture anchors appears to be an effective treatment method for chronic lateral ankle instability., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Glanzmann thrombasthenia (GT) is an autosomal recessive bleeding disorder caused by defective glycoprotein, αIIb and β3, encoded by ITGA2B and ITGB3 genes, respectively. We herein describe four unrelated Korean patients with genetically confirmed GT. Two patients were homozygous for c.1913+5G>T (IVS11+5G>T) mutation of ITGB3 with a signature of founder effect. The other two patients were compound heterozygous for two mutations of ITGA2B: c.[2333A>C];[2975delA] (p.[Q778P];[E992Gfs*30]) and c.[1750C>T];[2333A>C] (p.[R584X];[Q778P]). The c.2975delA mutation was a novel frameshift mutation of ITGA2B. Although from a limited number of patients, these results suggests c.1913+5G>T of ITGB3 is a recurrent mutation in Korean patients with GT., (Copyright © 2011 Wiley Periodicals, Inc.)

Streptococcus suis infection is an emerging zoonosis in Asia. The most common disease manifestation is meningitis, which is often associated with hearing loss and cochleovestibular signs. S. suis infection in humans mainly occurs among risk groups that have frequent exposure to pigs or raw pork. Here, we report a case of S. suis meningitis in a 67-yr-old pig carcass handler, who presented with dizziness and sensorineural hearing loss followed by headaches. Gram-positive diplococci were isolated from cerebrospinal fluid (CSF) and blood cultures and showed gray-white colonies with α-hemolysis. S. suis was identified from CSF and blood cultures by using a Vitek 2 system (bioMérieux, France), API 20 STREP (bioMérieux), and performing 16S rRNA and tuf gene sequencing. Even after receiving antibiotic treatment, patients with S. suis infection frequently show complications such as hearing impairment and vestibular dysfunction. To the best of our knowledge, this is the first case of S. suis meningitis in Korea. Prevention through public health surveillance is recommended, especially for individuals who have occupational exposures to swine and raw pork.

Background: Fibrin-related markers (FRM) such as fibrin monomer (FM) and D-dimer (DD) are considered useful biological markers for the diagnosis of disseminated intravascular coagulation (DIC). However, no studies on the diagnostic performance of different FRMs have been published in Korea. The aim of this study was to evaluate the diagnostic performance of FM for DIC in comparison with DD., Methods: The reference limit of FM was determined based on plasma sample data obtained from 210 control individuals. To evaluate diagnostic performance, FM data from the plasma samples of 139 patients with DIC-associated diseases were obtained for DIC scoring. FM was measured by immunoturbidimetry using STA-LIATEST FM (Diagnostica Stago, France). Patients were classified according to the DIC score as non-DIC, non-overt DIC, or overt DIC. ROC curve analyses were performed., Results: The reference limit in the control individuals was determined to be 7.80 µg/mL. Patients with DIC-associated diseases were categorized as non-DIC (N=43), non-overt DIC (N=80), and overt DIC (N=16). ROC curve analyses showed that the diagnostic performance of FM was comparable to DD in both non-overt DIC and overt DIC (P=0.596 and 0.553, respectively). In addition, FM had higher sensitivity, specificity, positive predictive value, and negative predictive value than DD for differentiating overt DIC from non-DIC., Conclusions: This study demonstrated that the diagnostic performance of FM for DIC was comparable to DD. FM might be more sensitive and more specific than DD in the diagnosis of overt DIC, but not non-overt DIC.

Background: Clopidogrel has been widely used to prevent recurrent ischemia in patients with acute coronary syndrome (ACS). However, inter-individual variability in response to clopidogrel has been a problem in the clinical setting. The aim of the present study was to investigate the frequency of clopidogrel resistance and to determine the clinical, pharmacokinetic, and pharmacogenetic factors for clopidogrel resistance in Korean patients with ACS., Methods: Clinical information, such as the underlying diseases and concurrent medications, of 114 patients with ACS who received clopidogrel therapy was studied. The degree of inhibition of platelets was assessed using the VerifyNow assay (Accumetrics, USA). The patients who showed less than 20% inhibition of platelets were defined as non-responders to clopidogrel treatment. Steady state plasma concentrations of clopidogrel were measured using HPLC/tandem mass spectrometry. CYP2C19 genotyping was also performed., Results: A wide inter-individual variability was observed in platelet inhibition (0-76%); 56 patients (49%) showed less than 20% inhibition. There were no differences between the patients' history of diabetes mellitus and concurrent medications as well as the plasma concentrations of clopidogrel of the responders and non-responders. CYP2C19 variants, including CYP2C19*2 and CYP2C19*3, were more commonly observed in the non-responders than in the responders (P value < 0.0001)., Conclusions: The response to clopidogrel was highly variable in Korean patients with ACS. The results of the present study confirmed that the genetic polymorphism of CYP2C19 could be important in clopidogrel response. However, further studies are required to investigate other likely factors involved in clopidogrel resistance.

X-linked liver glycogenosis (XLG) is caused by a mutation in the PHKA2 gene which encodes the alpha subunit of phosphorylase kinase (PHK). Although XLG is not a rare disease, there have been no reports of PHKA2 mutations in Koreans. A 5-year-old boy presented with easy fatigability and hepatomegaly. Liver enzymes were increased and liver histology revealed deposition of glycogen. The PHK activity was markedly decreased compared to control. No amplification was observed at exon 8 of the PHKA2 gene, as a result of the deletion of exon 8. Sequence analysis revealed a hemizygous deletion in the region of exon 8 (c.717+781&#95;864+225del1626). The patient was diagnosed as having XLG I. To the best of our knowledge, this is the first report of XLG I in Koreans.

During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells. However, there is insufficient information as to how the activation of this seemingly unrelated signaling pathway, either by Sonic Hedgehog or purmorphamine, contributes to osteogenesis. Using alkaline phosphatase assays, we screened 125 purmorphamine derivatives from the Korea Chemical Bank for effects on the differentiation of preosteoblast C2C12 cells. Here, we report that two purine derivatives modulate ALP activity as well as the expression of genes whose expression is known or suggested to be involved in osteogenesis.