Clinical and Radiological Features of Korean Patients With Anti-HMGCR Myopathy

Background@#and Purpose To understand the characteristics of Korean patients with anti-3-hydroxy-3-methylglutaryl-coenxyme A reductase (HMGCR) myopathy, we measured antiHMGCR antibodies and analyzed the clinical, radiological, and pathological features of patients with anti-HMGCR myopathy. @*Methods@#We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy, 36 patients with genetic myopathy, and 63 healthy subjects using an enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. @*Results@#Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years.Ten (59%) of the patients with anti-HMGCR positivity had taken statins. The titer of antiHMGCR antibodies was significantly higher in the statin-naïve group (median=230 U/mL, interquartile range=170–443 U/mL) than in the statin-exposed group (median=178 U/mL, interquartile range=105–210 U/mL, p=0.045). The most common symptom was proximal muscle weakness in 15 patients (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/mL. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p=0.027). @*Conclusions@#Our study was the first to measure anti-HMGCR antibodies in inflammatory myopathy. It has provided new findings, including the suggestion of the coexistence of other MSAs in Korean patients.

Outcomes of Endoscopic Resection for Early Gastric Cancer in Very Elderly Patients: A Nationwide Population-Based Study

Background/Aims@#Few studies have investigated the long-term outcomes of endoscopic resection for early gastric cancer (EGC) in very elderly patients. The aim of this study was to determine the appropriate treatment strategy and identify the risk factors for mortality in these patients. @*Methods@#Patients with EGC who underwent endoscopic resection from 2006 to 2017 were iden-tified using National Health Insurance Data and divided into three age groups: very elderly (≥85 years), elderly (65 to 84 years), and non-elderly (≤64 years). Their long- and short-term outcomes were compared in the three age groups, and the survival in the groups was compared with that in the control group, matched by age and sex. We also evaluated the risk factors for long- and short-term outcomes. @*Results@#A total of 8,426 patients were included in our study: 118 very elderly, 4,583 elderly, and 3,725 non-elderly. The overall survival and cancer-specific survival rates were significantly lower in the very elderly group than in the elderly and the non-elderly groups. Congestive heart failure was negatively associated with cancer-specific survival. A significantly decreased risk for mortality was observed in all groups (p<0.001). The very elderly group had significantly higher readmission and mortality rates within 3 months of endoscopic resection than the non-elderly and elderly groups. Furthermore, the cerebrovascular disease was associated with mortality within 3 months after endoscopic resection. @*Conclusions@#Endoscopic resection for EGC can be helpful for very elderly patients, and it may play a role in achieving overall survival comparable to that of the control group.

Rechallenge with Anti-PD-1 Inhibitors in Patients with Recurrent Gynecologic Malignancies

Purpose@#We investigated the treatment outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with recurrent gynecologic cancers. @*Materials and Methods@#We retrospectively reviewed the medical records of 20 patients who underwent rechallenge with PD-1 inhibitors for recurrent gynecologic cancers at two tertiary centers between January 2018 and September 2022. @*Results@#The median age of the patients was 56 years (range, 35–79). Seven (35%), 1 (5%), 11 (55%), and 1 (5%) patients presented with cervical, vulvar, ovarian, and endometrial cancers, respectively. Sixteen (80%) patients received pembrolizumab and 4 (20%) received nivolumab at first treatment. Eight (40%) and 12 (60%) patients received pembrolizumab and nivolumab, respectively, at second treatment. At initial ICI treatment, 1 (5%) and 4 (20%) cases of a complete response (CR) and a partial response (PR) were observed, respectively, with a median progression-free survival (PFS) of 2.8 months (range, 1.4–49.6). Reasons for first ICI discontinuation were disease progression (n=16), severe adverse events (AEs) (n=2), and treatment withdrawal (n=2). During second ICI treatment, 1 (5%) patient achieved CR, 2 (10%) showed PR, and 5 (25%) experienced stable disease. The median PFS to second ICI was 1.8 months (range, 0.4–10.4). The median overall survival was 21.3 months (range, 10.1–52.7). Neither patient who discontinued ICI treatment due to AEs experienced AE relapse during second ICI treatment. @*Conclusion@#These results suggest that responses to ICI rechallenge are not as intolerable as responses to previous ICI. Clinicians should carefully consider rechallenge with PD-1 inhibitors outside of clinical trials until there are sufficient data to routinely support this practice.

Use of cutting-edge RNA-sequencing technology to identify biomarkers and potential therapeutic targets in canine and feline cancers and other diseases

With the growing interest in companion animals and the rapidly expanding animal healthcare and pharmaceuticals market worldwide. With the advancements in RNAsequencing (RNA-seq) technology, it has become a valuable tool for understanding biological processes in companion animals and has multiple applications in animal healthcare.Historically, veterinary diagnoses and treatments relied solely on clinical symptoms and drugs used in human diseases. However, RNA-seq has emerged as an effective technology for studying companion animals, providing insights into their genetic information. The sequencing technology has revealed that not only messenger RNAs (mRNAs) but also noncoding RNAs (ncRNAs) such as long ncRNAs and microRNAs can serve as biomarkers. Based on the examination of RNA-seq applications in veterinary medicine, particularly in dogs and cats, this review concludes that RNA-seq has significant potential as a diagnostic and research tool. It has enabled the identification of potential biomarkers for cancer and other diseases in companion animals. Further research and development are required to maximize the utilization of RNA-seq for improved disease diagnosis and therapeutic targeting in companion animals.

Dentists’ Recognition of Child Abuse and Neglect and Mandatory Attitude to Report / 대한소아치과학회지

In this study, the recognition of child abuse and neglect (CAN) and reporting attitudes of general dentists and pediatric dentists in Korea were estimated. A survey was conducted among dentists working at clinics or university hospitals, including interns and residents at dental hospital training institutions. The questionnaire, consisting of 32 questions and detailed questions, subdivided into ‘general characteristics of respondents’, ‘CAN’, ‘CAN report’, ‘laws to CAN’, ‘countermeasures against CAN’. The survey was conducted using a messenger, and 176 respondents’ answers were analyzed. The recognition of CAN showed high scores in the order of physical abuse, neglect, and emotional abuse. The positive attitude toward reporting CAN had a higher score than the negative attitude. Of the total respondents, 19 said they reported child abuse, and 18 said they were suspected of child abuse but hesitated to report it. Among the laws related to CAN, the protection measures for CAN reporters and the protocol for CAN showed low awareness. Since then, they have wanted to know how to find abused children and how to deal with them in education. This study is expected to be used as data to improve dentists’ awareness and consciousness of CAN in the future.

Incidence, Disability, and Mortality in Patients With Guillain-Barré Syndrome in Korea:A Nationwide Population-Based Study

Background@#and Purpose This study aimed to identify the epidemiological features of Guillain-Barré syndrome (GBS) in the Korean population. @*Methods@#Patients with GBS were defined as those who were hospitalized with a primary diagnostic code of G61.0 on the Korean Classification of Disease in a department of neurology, rehabilitation medicine, or pediatrics. We evaluated the incidence and prevalence of GBS as well as physical disability, mortality, and cause of death in patients with GBS from 2002 to 2018 in the Korean population using the Korean National Health Insurance Service database. @*Results@#We identified 11,146 patients with GBS. The ratio of males to females was 1.48. The age-adjusted incidence rate per 100,000 persons increased steadily from 0.84 in 2002 to 1.68 in 2018, as did the age-adjusted prevalence rate per 100,000 persons, from 0.77 to 15.62. The incidence and prevalence of GBS increased with age, peaking at 70–79 years. Among 10,114 patients without physical disability at the time of GBS being diagnosed, 502 (5.0%) patients had moderate disability and 526 (5.2%) had severe disability by the end of the study period.A total of 1,221 (11.0%) patients with GBS died during the mean follow-up period of 17 years (2002–2019). There were 144 (1.3%) in-hospital deaths. @*Conclusions@#This was the first nationwide epidemiological study of patients with GBS covering the entire population including patients of all ages in the Republic of Korea. We have revealed the seasonality of admissions, disability, and long-term mortality rates in patients with GBS.

Epithelial-Mesenchymal Transition-Inducing Factors Involved in the Progression of Lung Cancers

Although there have been advances in cancer therapy and surgical improvement, lung cancer has the lowest survival rate (19%) at all stages. This is because most patients are diagnosed with concurrent metastasis, which occurs due to numerous related reasons. Especially, lung cancer is one of the most common and malignant cancers in the world. Although there are advanced therapeutic strategies, lung cancer remains one of the main causes of cancer death. Recent work has proposed that epithelialmesenchymal transition (EMT) is the main cause of metastasis in most cases of human cancers including lung cancer. EMT involves the conversion of epithelial cells, wherein the cells lose their epithelial abilities and become mesenchymal cells involved in embryonic development, such as gastrulation and neural crest formation. In addition, recent research has indicated that EMT contributes to altering the cancer cells into cancer stem cells (CSCs). Although EMT is important in the developmental stages, this process also activates lung cancer progression, including complicated and diverse signaling pathways. Despite the numerous investigations on signaling pathways involved in the progression of lung cancer, this malignancy is considered critical for treatment. EMT in lung cancer involves many transcription factors and inducers, for example, Snail, TWIST, and ZEB are the master regulators of EMT. EMT-related factors and signaling pathways are involved in the progression of lung cancer, proposing new approaches to lung cancer therapy. In the current review, we highlight the signaling pathways implicated in lung cancer and elucidate the correlation of these pathways, indicating new insights to treat lung cancer and other malignancies.

Gallic Acid Hindered Lung Cancer Progression by Inducing Cell Cycle Arrest and Apoptosis in A549 Lung Cancer Cells via PI3K/Akt Pathway

This study elucidates the anti-cancer potential of gallic acid (GA) as a promising therapeutic agent that exerts its effect by regulating the PI3K/Akt pathway. To prove our research rationale, we used diverse experimental methods such as cell viability assay, colony formation assay, tumor spheroid formation assay, cell cycle analysis, TUNEL assay, Western blot analysis, xenograft mouse model and histological analysis. Treatment with GA inhibited cell proliferation in dose-dependent manner as measured by cell viability assay at 48 h. GA and cisplatin (CDDP) also inhibited colony formation and tumor spheroid formation. In addition, GA and CDDP induced apoptosis, as determined by the distribution of early and late apoptotic cells and DNA fragmentation. Western blot analysis revealed that inhibition of the PI3K/Akt pathway induced upregulation of p53 (tumor suppressor protein), which in turn regulated cell cycle related proteins such as p21, p27, Cyclin D1 and E1, and intrinsic apoptotic proteins such as Bax, Bcl-2 and cleaved caspase-3. The anti-cancer effect of GA was further confirmed in an in vivo mouse model. Intraperitoneal injection with GA for 4 weeks in an A549-derived tumor xenograft model reduced the size of tumor mass. Injection of them downregulated the expression of proliferating cell nuclear antigen and p-Akt, but upregulated the expression of cleaved caspase-3 in tumor tissues. Taken together, these results indicated that GA hindered lung cancer progression by inducing cell cycle arrest and apoptosis, suggesting that GA would be a potential therapeutic agent against non-small cell lung cancer.

A Familial Case with Phenotypic Differences in a CAV3 Pathogenic Variant / 대한신경근육질환학회지

We reported an age 32 male with progressive proximal muscle weakness. The serum creatine kinase was 1,908 IU/L. The muscle biopsy from biceps brachii muscle showed nonspecific myopathic changes. The whole exome sequencing identified a heterozygous variant (c.296A>C) in CAV3. It was previously reported as a likely pathogenic variant. It was also detected in the male’s mother and brother. However, his mother and brother had only hyperCKemia without muscle weakness. Our case showed phenotypic heterogeneity in a family, with the same variant in CAV3.

Validation of the Individualized Neuromuscular Quality of Life Questionnaire in Korean Patients With Genetic Neuromuscular Diseases

Background@#and Purpose The Individualized Neuromuscular Quality of Life questionnaire (INQoL) is a widely used measure of the quality of life in patients with neuromuscular diseases. The purpose of this study was to translate and validate the Korean version of INQoL in Korean patients with neuromuscular diseases. @*Methods@#We translated the original INQoL version into Korean while applying appropriate language adaptations. The internal consistency, known-group validity, and test-retest reliability were also assessed. Construct validity was measured using the modified Rankin Scale (mRS) score and the manual muscle testing (MMT)-sum score based on the Medical Research Council scale, and concurrent validity was measured using the 36-item Short Form Survey (SF-36) questionnaire. @*Results@#This study enrolled 193 patients. The coefficients for internal consistency (Cronbach’s α=0.805 to 0.987) and test-retest reliability (Spearman’s ρ=0.453 to 0.886) were adequately high for all subscales except in the ‘treatment effects’ dimension. INQoL subscales other than those for locking, droopy eyelids, double vision, and swallowing difficulties were significantly associated with their relevant SF-36 domains (Spearman’s ρ=-0.274 to -0.833). Functional status and muscle strength were most strongly associated with independence (Spearman’s ρ=0.753 and p<0.001 for mRS score, Spearman’s ρ=-0.741 and p<0.001 for MMT-sum score). @*Conclusions@#The Korean INQoL is a reliable and validated measurement tool for Korean patients with neuromuscular diseases.

Comparisons of survival outcomes between bevacizumab and olaparib in BRCA-mutated, platinum-sensitive relapsed ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG 3052) / 부인종양

Objective@#To compare survival outcomes between bevacizumab (BEV) and olaparib (OLA) maintenance therapy in BRCA-mutated, platinum-sensitive relapsed (PSR) high-grade serous ovarian carcinoma (HGSOC). @*Methods@#From 10 institutions, we identified HGSOC patients with germline and/or somatic BRCA1/2 mutations, who experienced platinum-sensitive recurrence between 2013 and 2019, and received second-line platinum-based chemotherapy. Patients were divided into BEV (n=29), OLA (n=83), and non-BEVon-OLA users (n=36). The OLA and non-BEVon-OLA users were grouped as the OLA intent group. We conducted 1:2 nearest neighbor-matching between the BEV and OLA intent groups, setting the proportion of OLA users in the OLA intent group from 65% to 100% at 5% intervals, and compared survival outcomes among the matched groups. @*Results@#Overall, OLA users showed significantly better progression-free survival (PFS) than BEV users (median, 23.8 vs. 17.4 months; p=0.004). Before matching, PFS improved in the OLA intent group but marginal statistical significance (p=0.057). After matching, multivariate analyses adjusting confounders identified intention-to-treat OLA as an independent favorable prognostic factor for PFS in the OLA 65P (adjusted hazard ratio [aHR]=0.505; 95% confidence interval [CI]=0.280−0.911; p=0.023) to OLA 100P (aHR=0.348; 95% CI=0.184−0.658; p=0.001) datasets. The aHR of intention-to-treat OLA for recurrence decreased with increasing proportions of OLA users. No differences in overall survival were observed between the BEV and OLA intent groups, and between the BEV and OLA users. @*Conclusion@#Compared to BEV, intention-to-treat OLA and actual use of OLA maintenance therapy were significantly associated with decreased disease recurrence risk in patients with BRCA-mutated, PSR HGSOC.

Major clinical research advances in gynecologic cancer in 2020 / 부인종양

In 2020 series, we summarized the major clinical research advances in gynecologic oncology with providing representative figures of the most influential study for 1 of each 3 gynecologic cancers: cervix, ovary, and uterine corpus. Review for cervical cancer covered targeted agents and immune checkpoint inhibitors, adjuvant radiation therapy or concurrent/sequential chemoradiation therapy after radical hysterectomy in early cervical cancer, radical surgery in early cervical cancer; and prevention and screening. Ovarian cancer research included studies of various combinations of poly (ADP-ribose) polymerase inhibitors with chemotherapy, immune checkpoint inhibitors, and/or vascular endothelial growth factor inhibitors according to the clinical setting. For uterine corpus cancer, molecular classification upon which the decision of adjuvant treatments might be based, World Health Organization recommendation of 2-tier grading system (low grade vs. high grade), sentinel lymph node assessment and ovarian preservation in clinically early-stage endometrial cancer were reviewed. Molecular targeted agents including immune checkpoint inhibitors which showed promising anti-tumor activities in advanced/recurrent endometrial cancer were also included in this review.

Hyperthermic intraperitoneal chemotherapy as consolidation treatment of advanced stage ovarian cancer

Objective@#To investigate the therapeutic efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) as consolidation treatment after completing first-line treatment in patients with advanced ovarian cancer. @*Methods@#A retrospective chart review was conducted on patients treated at the Comprehensive Gynecologic Cancer Center between January 2014 and 2019. Based on the inclusion criteria, 24 eligible patients who received HIPEC (paclitaxel 175 mg/m2, for 90 minutes, at 42°C) (HIPEC group) as consolidation treatment after terminating the adjuvant chemotherapy were identified. Another 24 patients who met the inclusion criteria and did not receive HIPEC were matched, representing the non-HIPEC group. Disease-free survival (DFS) and overall survival (OS) were examined between the two groups. @*Results@#The median DFS was 28.7 and 24.2 months in the HIPEC and non-HIPEC groups, respectively (P=0.688). The 3-year DFS rates in the HIPEC and non-HPEC groups were 39.5% and 32.6%, respectively. However, the median OS was not determined. The 5-year OS rates in the HIPEC and non-HIPEC groups were 86.2% and 81.3%, respectively (P=0.850). One patient developed grade 3 neutropenia. Other patients experienced mild adverse events after HIPEC. @*Conclusion@#This study suggests that consolidation HIPEC could not support the survival benefit after completing the first-line treatment for patients with advanced ovarian cancer, although no severe specific safety issues were found. Therefore, randomized trials evaluating consolidation HIPEC for the management of ovarian cancer are warranted.

Multicenter Targeted Population Screening of Late Onset Pompe Disease in Unspecified Myopathy Patients in Korea

Background@#Pompe disease is a rare autosomal recessive disorder caused by the deficiency of a lysosomal enzyme, acid alpha-glucosidase (GAA). Early diagnosis and initiation of treatment with enzyme replacement therapy have remarkable effects on the prognosis of Pompe disease. We performed the expanded screening for late onset Pompe disease (LOPD) at eight centers in Korea. @*Methods@#From September 1, 2015, GAA activity were measured from both dried blood spot (DBS) and mixed leukocyte for 188 available patients. For 12 patients with low GAA activity, we performed Sanger sequencing of GAA gene. @*Results@#Among 188 patients, 115 were males. The mean of age of symptom onset and diagnosis were 34.3 years and 41.6 years. Among 12 patients with decreased GAA activity, two patients were confirmed to have LOPD with genetic test (c.1316T>A [p.M439K] + c.2015G>A [p.R672Q], c.1857C>G [p.S619R] + c.546G>C [leaky splicing]). Other two patients had homozygous G576S and E689K mutation, known as pseudodeficiency allele. @*Conclusions@#This study is expanded study of LOPD screening for targeted Korean population. We found two patients with LOPD, and the detection rate of LOPD is 1.06%. With application of modified GAA cutoff value (0.4), which was previously reported, there were no false positive results of GAA activity test using DBS. Therefore, it could be an appropriate screening test for LOPD in especially East-Asian population, in which pseudodeficiency allele is frequent.

Clinical Scales for the Evaluation of Myopathy Patients

With the rapid increase in the number of clinical trials in myopathy over the past decade, there is an increasing need for clinical scales to reflect patient’s clinical status. This article outlines the process of identifying possible measures. Detailed consideration has been given to key measures of muscle strength, function, and disability. As well as the usual assessment of the validity and reliability of the measures, three key characteristics were identified as necessary to the assessment of clinical scales used in health care: 1) the type of scale; 2) the clinical significance of the property being measured; and 3) the mathematical properties of the data. Consideration of such aspects facilitates the choice of clinical scales and the interpretation of data.

Is Job Insecurity Worse for Mental Health Than Having a Part-time Job in Canada? / 예방의학회지

Objectives@#A growing number of people depend on flexible employment, characterized by outsider employment status and perceived job insecurity. This study investigated whether there was a synergistic effect of employment status (full-time vs. part-time) and perceived job insecurity on major depressive disorder. @*Methods@#Data were derived from the 2012 Canadian Community Health Survey-Mental Health of 12 640 of Canada’s labor force population, aged 20 to 74. By combining employment status with perceived job insecurity, we formed four employment categories: fulltime secure, full-time insecure, part-time secure, and part-time insecure. @*Results@#Results showed no synergistic health effect between employment status and perceived job insecurity. Regardless of employment status (full-time vs. part-time), insecure employment was significantly associated with a high risk of major depressive disorder. Analysis of the interaction between gender and four flexible employment status showed a gender-contingent effect on this link in only full-time insecure category. Men workers with full-time insecure jobs were more likely to experience major depressive disorders than their women counterparts. @*Conclusions@#This study’s findings imply that perceived job insecurity may be a critical factor for developing major depressive disorder, in both men and women workers.

Discrepancy between Cytology and Histology in Cervical Cancer Screening:a Multicenter Retrospective Study (KGOG 1040)

Background@#Cervical cancer is the fourth common cancer in women worldwide. The Papanicolau test is the primary screening procedure to detect abnormal cervical cells.Colposcopy is the main procedure for discriminating high-grade cervical lesions. The study aimed at clarifying the discrepancy between cervical cytology and colposcopic biopsy histology as well as confounding factors. @*Methods@#Eligible patients visited thirteen tertiary hospitals for colposcopic biopsy following cervical cytology and human papillomavirus (HPV) genotypes between January and December 2018. Baseline characteristics including age, body mass index (BMI), and parity were collected. @*Results@#In our study, 3,798 eligible patients were included. Mean age of patients was 42.7(19–88) years and mean BMI was 22.5 (16.9–34.1) kg/m2 . The referred cervical cytologic findings consisted of 495 normal, 1,390 atypical squamous cells of undetermined significance, 380 atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion, 792 low-grade squamous intraepithelial lesion, 593 high-grade squamous intraepithelial lesion, 79 atypical glandular cells, 46 squamous cell carcinoma, and 23 adenocarcinoma. HPV-positive findings were found in 3,008 (79.2%) patients and were not detected in 914 (24.1%) cases. The risk of unexpected low-grade lesions from histology was higher in patients > 45 years (odds ratio [OR], 2.137; 95% confidence intervals [CIs], 1.475–3.096). In contrast, the risk of unexpected high-grade lesions from colposcopic biopsy was lower in patients ≥ 45 years (OR, 0.530; 95% CI, 0.367–0.747) and HPV 16/18 infection was higher than other HPV (OR, 1.848; 95% CI, 1.385–2.469). @*Conclusion@#Age and HPV genotypes were responsible for the discrepancies between cytology and histology. Precautions should be taken for women over the age of 45 in triage for colposcopy in order to avoid unnecessary testing.

A Compound Heterozygous Pathogenic Variant in B4GALNT1 Is Associated With Axonal Charcot-Marie-Tooth Disease

Background@#and PurposePathogenic variants in B4GALNT1 have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-Tooth disease (CMT). @*Methods@#Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line. @*Results@#The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in B4GALNT1 as the causative of the present patient, a 53-year-old male who presented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. B4GALNT1 was critical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of B4GALNT1. @*Conclusions@#This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in B4GALNT1. This finding expands the clinical and genetic spectra of peripheral neuropathy.

Evaluating an In-House Cell-Based Assay for Detecting Antibodies Against Muscle-Specific Tyrosine Kinase in Myasthenia Gravis

Background@#and Purpose Detecting antibodies against muscle-specific tyrosine kinase (MuSK Abs) is essential for diagnosing myasthenia gravis (MG). We applied an in-house cellbased assay (CBA) to detect MuSK Abs. @*Methods@#A stable cell line was generated using a lentiviral vector, which allowed the expression of MuSK tagged with green fluorescent protein in human embryonic kidney 293 (HEK293) cells. Serum and anti-human IgG antibody conjugated with red fluorescence were added. The presence of MuSK Abs was determined based on the fluorescence intensity and their colocalization in fluorescence microscopy. Totals of 218 serum samples collected from 177 patients with MG, 31 with other neuromuscular diseases, and 10 healthy controls were analyzed. The CBA results were compared with those of a radioimmunoprecipitation assay (RIPA) and an enzyme-linked immunosorbent assay (ELISA). @*Results@#The MuSK-HEK293 cell line stably expressed MuSK protein. The CBA detected MuSK Abs in 34 (19.2%) of 177 samples obtained from patients with MG and in none of the participants having other neuromuscular diseases or in the healthy controls. The clinical characteristics of the patients with MuSK MG determined based on the CBA were strongly correlated with known clinical features of MuSK MG. There was an almost perfect agreement between the results of the CBA and those of the RIPA (Cohen’s kappa=0.880, p<0.001) and ELISA (Cohen’s kappa=0.982, p<0.001). @*Conclusions@#The results of the in-house CBA showed excellent agreement with both the RIPA and ELISA. Our in-house CBA can be considered a reliable method for detecting MuSK Abs.

Clinical Features and Brain MRI Findings in Korean Patients with AGel Amyloidosis

Purpose@#AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis. @*Materials and Methods@#We examined 13 patients with AGel amyloidosis from three unrelated families. Brain MRIs were performed in eight patients and eight age- and sex-matched healthy controls. Therein, we analyzed gray and white matter content using voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and FreeSurfer. @*Results@#The median age at examination was 73 (interquartile range: 64–76) years. The median age at onset of cutis laxa was 20 (interquartile range: 15–30) years. All patients over that age of 60 years had dysarthria, cutis laxa, dysphagia, and facial palsy. Two patients in their 30s had only mild cutis laxa. The median age at dysarthria onset was 66 (interquartile range: 63.5–70) years. Ophthalmoparesis was observed in three patients. No patient presented with muscle weakness of the limbs. Axial fluid-attenuated inversion recovery images of the brain showed no significant differences between the patient and control groups. Also, analysis of VBM, TBSS, and FreeSurfer revealed no significant differences in cortical thickness between patients and healthy controls at the corrected significance level. @*Conclusion@#Our study outlines the clinical manifestations of prominent bulbar palsy and early-onset cutis laxa in 13 Korean patients with AGel amyloidosis and confirms that AGel amyloidosis mainly affects the peripheral nervous system rather than the central nervous system.