Background: Genetic studies are clinically recommended in some cases of inherited arrhythmia syndromes. Nextgeneration sequencing (NGS) would be helpful because of its high analytical throughput and relative speed. This study aimed to assess the mutation-detection yield obtained by NGS compared with conventional Sanger sequencing method. Methods: Patients with aborted sudden cardiac death and their families who underwent gene sequencing tests for inherited arrhythmia syndromes were retrospectively and enrolled in this study from 2017 to 2022 at Chonnam National University Hospital. We evaluated NGS study results of 17 patients (NGS group) and Sanger study results of 19 patients (Sanger group). Results: 64.7% of NGS and 94.7% of Sanger group were probands. Type 1 Brugada pattern ECG was more frequent in NGS group (64.7% vs. 21.1%; p = 0.007). BrS was the most common disorder in NGS group (76.5%), and idiopathic ventricular fibrillation was the most common one in Sanger group (63.2%). Mutations with uncertain significance were the most common ones in NGS group (89.5%), and pathogenic or likely pathogenic mutations were the most common ones in Sanger group (45.7%). When positive yield was defined as the ratio of pathogenic or likely pathogenic mutations that were detected by sequencing, the yields were 10.5% and 45.7% in NGS and Sanger groups, respectively. The NGS arrhythmia panel did not cover two inherited arrhythmia-related mutations (RYR1, APOA5) that were detected by the Sanger method. The extended NGS arrhythmia panel was able to detect 84.8% of inherited arrhythmia-related mutations that were detected in Sanger group. Conclusions NGS study has some limitations in obtaining the full genetic data of probands. Well-designed NGS panels are needed to increase the efficiency of the NGS study. With the well-designed panels, large-scale gene sequencing can efficiently and rapidly be applied in real clinical practices, especially in inherited fatal arrhythmia syndromes that have a high detection yield in genetic analyses.

Background: Cardiac rehabilitation (CR) after acute myocardial infarction (AMI) is recommended as a mandatory intervention in several national clinical practice guidelines published in America, Europe, and Korea to reduce recurrence and mortality. However, underutilization of CR is an established worldwide issue. In Korea, the promotion of CR is expected due to coverage by National Health Insurance. Nevertheless, the national status of CR use has not been reported. This retrospective cohort study aimed to investigate the current status of CR use in patients with AMI using nationwide data from the National Health Insurance Service of Korea. Methods: Patients with AMI admitted with the diagnosis of ‘I21’ code (from International Classification of Diseases, 10th revision, Clinical Modification) from July 1st, 2017 to June 30th, 2018 were included. CR use was defined as CR treatment or evaluation being performed during an outpatient follow-up period within 6 months after discharge. Participation rate and density were calculated nationally and by administrative division. Logistic regression analysis was performed to identify the influencing factors of CR participation. Results: Nationally, 1.5% of AMI patients (960/64,982) underwent CR during outpatient treatment after discharge. CR density was approximately 10. Logistic regression analysis revealed that influencing factors included old age, female sex, rural residence, and low Charlson comorbidity index. Conclusion Hospital-based CR after AMI is underutilized despite its coverage by the National Health Insurance. More CR facilities have to be installed according to the needs of CR in various regions.

PURPOSE: To investigate the correlation between the tenosynovitis pattern on two-phase bone scintigraphy (2P-BS) and clinical manifestation in patients with suspected rheumatoid arthritis (RA).METHOD: 2P-BS including technetium-99m-methylene diphosphonate blood pool and bone phase imaging in 402 consecutive patients with clinically suspected RAwere retrospectively reviewed. According to 2010 RA Classification Criteria, patients were grouped as RA and non-RA. Visual assessment of all fingers, toes, wrists, and ankles on 2P-BS was performed. Clinical suspected tenosynovitis was evaluated on physical examination. Rheumatoid factor, anti-cyclic citrullinated protein antibody, C-reactive protein, and estimated sedimentation rate were obtained. Radiographic findings were also used to define early and established arthritis.RESULTS: Tenosynovitis pattern was detected in 12.7%(51/402 patients) on 2P-BS.A total of 94.1%(48/51) were diagnosed as RA vs. 5.9% (3/51) as non-RA. Of the 48 RA patients with positive 2P-BS finding, 85.4% (41/48) had early arthritis and 14.6% (7/48) had established arthritis. On physical examination, tenosynovitis was suspected in 21.9% (88/402). A total of 56.8% (50/88) belonged to the RA group and 43.2% (38/88) to the non-RA group. The tenosynovitis pattern of 2P-BS and physical examination showed statistical difference and moderate agreement. The positive tenosynovitis pattern on 2P-BS represented up to 26.408 of odds ratio which was highest among the RA-associated factors.CONCLUSION: Tenosynovitis pattern on 2P-BS was more commonly detected in the RA group and was more frequently associated with early arthritis pattern. Therefore, 2P-BS could give additional information for the detection of subclinical tenosynovitis in early or preclinical RA patients.
Ankle ; Arthritis ; Arthritis, Rheumatoid ; C-Reactive Protein ; Classification ; Fingers ; Humans ; Methods ; Odds Ratio ; Physical Examination ; Radionuclide Imaging ; Retrospective Studies ; Rheumatoid Factor ; Tenosynovitis ; Toes ; Wrist

PURPOSE: To investigate the correlation between the tenosynovitis pattern on two-phase bone scintigraphy (2P-BS) and clinical manifestation in patients with suspected rheumatoid arthritis (RA).METHOD: 2P-BS including technetium-99m-methylene diphosphonate blood pool and bone phase imaging in 402 consecutive patients with clinically suspected RAwere retrospectively reviewed. According to 2010 RA Classification Criteria, patients were grouped as RA and non-RA. Visual assessment of all fingers, toes, wrists, and ankles on 2P-BS was performed. Clinical suspected tenosynovitis was evaluated on physical examination. Rheumatoid factor, anti-cyclic citrullinated protein antibody, C-reactive protein, and estimated sedimentation rate were obtained. Radiographic findings were also used to define early and established arthritis. RESULTS: Tenosynovitis pattern was detected in 12.7%(51/402 patients) on 2P-BS.A total of 94.1%(48/51) were diagnosed as RA vs. 5.9% (3/51) as non-RA. Of the 48 RA patients with positive 2P-BS finding, 85.4% (41/48) had early arthritis and 14.6% (7/48) had established arthritis. On physical examination, tenosynovitis was suspected in 21.9% (88/402). A total of 56.8% (50/88) belonged to the RA group and 43.2% (38/88) to the non-RA group. The tenosynovitis pattern of 2P-BS and physical examination showed statistical difference and moderate agreement. The positive tenosynovitis pattern on 2P-BS represented up to 26.408 of odds ratio which was highest among the RA-associated factors. CONCLUSION Tenosynovitis pattern on 2P-BS was more commonly detected in the RA group and was more frequently associated with early arthritis pattern. Therefore, 2P-BS could give additional information for the detection of subclinical tenosynovitis in early or preclinical RA patients.

Cell sheets technology is being available for fracture healing. This study was performed to clarify bone healing mechanism of undifferentiated (UCS) and osteogenic (OCS) differentiated mesenchymal stromal cell (MSC) sheets in the fracture model of dogs. UCS and OCS were harvested at 10 days of culture. Transverse fractures at the radius of six beagle dogs were assigned into three groups (n = 4 in each group) i.e. UCS, OCS and control. The fractures were fixed with a 2.7 mm locking plate and six screws. Cell sheets were wrapped around the fracture site. Bones were harvested 8 weeks after operation, then scanned by micro-computed tomography (micro-CT) and analyzed histopathologically. The micro-CT revealed different aspects of bone regeneration among the groups. The percentages of external callus volume out of total bone volume in control, UCS, and OCS groups were 42.1, 13.0 and 4.9% (p < 0.05) respectively. However, the percentages of limbs having connectivity of gaps were 25, 12.5 and 75% respectively. In histopathological assessments, OCS group showed well organized and mature woven bone with peripheral cartilage at the fracture site, whereas control group showed cartilage formation without bone maturation or ossification at the fracture site. Meanwhile, fracture site was only filled with fibrous connective tissue without endochondral ossification and bone formation in UCS group. It was suggested that the MSC sheets reduced the quantity of external callus, and OCS induced the primary bone healing.
Animals ; Bone Regeneration ; Bony Callus ; Cartilage ; Connective Tissue ; Dogs ; Extremities ; Fracture Healing ; Mesenchymal Stromal Cells ; Osteogenesis ; Radius

Remifentanil is commonly used in operating rooms and intensive care units for the purpose of anesthesia and sedation or analgesia. Although remifentanil may significantly affect the bone regeneration process in patients, there have been few studies to date on the effects of remifentanil on bone physiology. The purpose of this study was to investigate the effects of remifentanil on osteoclast differentiation and bone resorption. Bone marrow-derived macrophages (BMMs) were cultured for 4 days in remifentanil concentrations ranging from 0 to 100 ng/ml, macrophage colony-stimulating factor (M-CSF) alone, or in osteoclastogenic medium to induce the production of mature osteoclasts. To determine the degree of osteoclast maturity, tartrate-resistant acid phosphatase (TRAP) staining was performed. RT-PCR and western blotting analyses were used to determine the effect of remifentanil on the signaling pathways involved in osteoclast differentiation and maturation. Bone resorption and migration of BMMs were analyzed to determine the osteoclastic activity. Remifentanil reduced the number and size of osteoclasts and the formation of TRAP-positive multinuclear osteoclasts in a dose-dependent manner. Expression of c-Fos and NFATC1 was most strongly decreased in the presence of RANKL and remifentanil, and the activity of ERK was also inhibited by remifentanil. In the bone resorption assay, remifentanil reduced bone resorption and did not significantly affect cell migration. This study shows that remifentanil inhibits the differentiation and maturation of osteoclasts and reduces bone resorption.
Acid Phosphatase ; Analgesia ; Anesthesia ; Blotting, Western ; Bone Regeneration ; Bone Resorption* ; Cell Movement ; Humans ; Intensive Care Units ; Macrophage Colony-Stimulating Factor ; Macrophages ; Operating Rooms ; Osteoclasts* ; Physiology

We developed a simple, sensitive, and effective ultra-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) method with an electrospray ionization (ESI) interface in multiple reaction monitoring (MRM) and positive ion modes to determine diazepam concentrations in human plasma using voriconazole as an internal standard (IS). Diazepam and IS were detected at transition 285.2→193.1 and 350.2→127.1, respectively. After liquid-liquid extraction (LLE) using 1.2 ml of ethyl acetate:n-hexane (80:20, v/v), diazepam and IS were eluted on a Phenomenex Cadenza CD-C18 column (150 × 3.0 mm, 3 µm) with an isocratic mobile phase (10 mM ammonium acetate in water:methanol [5:95, v/v]) at a flow rate of 0.4 mL/min. The peak retention time was 2.32 min for diazepam and 2.01 min for IS, respectively. The lower limit of quantitation (LLOQ) was 0.5 ng/mL (S/N > 10) using 50 µL of plasma, and no interferences were observed in chromatograms. Our analytical method was fully validated and successfully applied to a bioequivalence study of two formulations of diazepam in healthy Korean volunteers.
Ammonium Compounds ; Diazepam* ; Humans* ; Liquid-Liquid Extraction ; Mass Spectrometry ; Methods* ; Plasma* ; Therapeutic Equivalency* ; Volunteers ; Voriconazole

Dysphagia is a common manifestation of myasthenia gravis (MG), but it has been rarely reported as the only symptom. We report a 46-year-old man who complained of dysphagia without any other symptoms. Based on a videofluoroscopic swallowing study (VFSS), he showed decreased tongue base retraction, premature bolus loss, and incomplete velopharyngeal closure. He also showed impaired laryngeal elevation that caused incomplete laryngeal closure and aspiration with a small amount of thin fluid. Laryngoscopic evaluations, brain magnetic resonance imaging, and repetitive nerve stimulation tests were unremarkable. Since the acetylcholine receptor antibody level was elevated, he was diagnosed with MG. Treatment with pyridostigmine was initiated and the dysphagia symptoms improved completely. MG is one possible cause of unexplained dysphagia. Therefore, neurological examination is required when abnormal findings are observed in VFSS, and evaluations for MG may be important for the final diagnosis.
Acetylcholine ; Brain ; Deglutition ; Deglutition Disorders* ; Diagnosis ; Early Diagnosis ; Fluoroscopy ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Myasthenia Gravis* ; Neurologic Examination ; Pyridostigmine Bromide ; Tongue

BACKGROUND: Androgenetic alopecia (AGA) is a common hair loss disease with genetic predisposition among men and women, and it may commence at any age after puberty. It may significantly affect a variety of psychological and social aspects of one's life and the individual's overall quality of life (QoL). OBJECTIVE: This study aimed to investigate the QoL of AGA patients and discover the factors that can influence the QoL of AGA patients, including previous experience in non-medical hair care, reasons for hospital visits, age, duration, and the severity of AGA. METHODS: A total of 998 male patients with AGA were interviewed, using the Hair Specific Skindex-29 to evaluate the QoL of AGA patients. RESULTS: The results of the Hair Specific Skindex-29 on patients with AGA were as follows: symptom scale: 26.3+/-19.5, function scale: 24.0+/-20.1, emotion scale: 32.1+/-21.8, and global score: 27.3+/-19.1. According to this assessment, QoL was more damaged if the patient had severe alopecia, a longer duration of AGA, younger age, had received previous non-medical hair care, and visited the hospital for AGA treatment. CONCLUSION: This study showed that AGA could harmfully affect the patients' QoL. These findings indicate that dermatologists should address these QoL issues when treating patients with alopecia.
Alopecia ; Female ; Genetic Predisposition to Disease ; Hair ; Humans ; Male ; Prospective Studies ; Puberty ; Quality of Life

Although it is rare, the right atrium can be encroached on by abnormal mediastinal structures, including aortic aneurysms, carcinomas, hepatic cysts and diaphragmatic paralysis. Extrinsic compression of the right atrium causes significant hemodynamic compromise and can lead to fatal outcomes. We describe the case of a 66-year old man with a past history of pulmonary tuberculosis that had undergone right pneumonectomy 40 years previously. He then presented with signs and symptoms of right-sided heart failure. These new signs and symptoms were recognized to be secondary to extrinsic compression of the right atrium, which was due to late-onset postpneumonectomy empyema, and the signs and symptoms were successfully relieved by performing open drainage of the empyema.
Aortic Aneurysm ; Drainage ; Empyema ; Empyema, Pleural ; Fatal Outcome ; Heart ; Heart Atria ; Heart Failure ; Hemodynamics ; Pneumonectomy ; Respiratory Paralysis ; Tuberculosis, Pulmonary