Clinical applications of next-generation sequencing in the diagnosis of genetic disorders in Korea: a narrative review

Next-generation sequencing (NGS) technologies have revolutionized genetic testing and enabled efficient screening of various genetic conditions in clinical settings. However, the clinical application of genetic test results presents numerous significant challenges. This review aims to provide a comprehensive overview of key concepts for the clinical application of NGS, including (1) technical aspects and limitations, (2) variant classification, (3) clinical interpretation, (4) familial testing and genetic counseling, and (5) ethical considerations.Current Concepts: In short-read-based NGS, several limitations exist in detecting genomic variations, including repetitive sequences or complex structural variations. The variant classification process can be influenced by suspected genomic conditions and the accessibility of genomic databases. Therefore, the final genetic diagnosis depends on the physician’s discretion, which relies on the genotype-phenotype correlations and reverse phenotyping through additional evaluations. Familial testing can help trace the origin of variants and allele segregation and aid in variant interpretation, risk assessment, disease prevention, and family planning. In addition to addressing the clinical impact of genetic results, genetic counselors should also consider potential consequences related to ethical, legal, and social issues, including family dynamics.Discussion and Conclusion: NGS-based genetic testing is a promising diagnostic tool for genetic disorders, but proper variant interpretation and clinical evaluation are crucial for optimal clinical practice. Notably, ethical considerations and regulatory measures are required to prepare for the next era of genomic medicine.

Practical Examples of the Comprehensive Strategy of Japanese Dementia Policy: Kumamoto Model by Kumamoto Province / 보건행정학회지

The purpose of this research is to introduce the best practice of the Japanese national dementia strategy and explore implications to the Korean national dementia strategy. Interview was conducted among professions those who is in charge of Kumamoto dementia care practice in Kumamoto province, upon review of related literature and public documents. The Kumamoto model is implemented by the department of neuropsychiatry in public university hospitals, which can offer dementia-specialized medical services. Medical centers for dementia in public university hospitals play a leading role for managing practice and training local dementia centers specialist, coordinating medical services among medical institutions and community welfare facilities. In reference to the Kumamoto model, the Korean national dementia strategy can find implications in the direction of current system, specifically its approaches toward policy governance.

Patient-Centeredness during In-Depth Consultation in the Outpatient Clinic of a Tertiary Hospital in Korea: Paradigm Shift from Disease to Patient

BACKGROUND: Patient-centered care (PCC) and integrative care approach are widely advocated. However, their implementation usually requires an extended consultation time. Despite significant advances in medical diagnosis and treatment, no studies have examined consultation time and patient centeredness in Korea. METHODS: We conducted a “15-Minute Consultation” for first-time patients in outpatient clinics of 13 departments. A control group was selected from the same physicians' first-time patients, adjusting for age and gender. A total of 275 patients were selected for receiving in-depth consultation and 141 control patients were selected for regular consultation. Data were collected from patients using a questionnaire comprising a patient-centeredness scale and items on potential predictors such as socio-demographic and clinical factors. We also investigated the participating physician's professionalism. RESULTS: As compared to the control group, the in-depth consultation group scored higher on 5 variables associated with PCC, including (patients' perception of) medical professionals, wait and consultation times, treatment, patient advocacy, and patient satisfaction. While 92.4% of patients in the in-depth consultation group reported that the consultation time was sufficient, only 69.0% of those in the control group reported the same (P < 0.01). In the in-depth consultation group, scores on satisfaction level were the highest for the department of internal medicine, followed by departments of surgery and pediatrics. Participating physicians' improved satisfaction following the intervention proved that in-depth consultation facilitated building a rapport with patients. CONCLUSION: This study illustrated that the provision of sufficiently long consultation for serious and rare diseases could improve PCC and physicians' professionalism. Health authorities should reshuffle the healthcare delivery system and provide sufficient consultation time to ensure PCC and medical professionalism.

Prevalence of Possible Depression and Post-traumatic Stress Disorder among Community Dwelling Adult Refugees and Refugee Applicants in South Korea

BACKGROUND: Because there has been a recent increase in refugee applications in Korea, the mental health of these refugees merits greater study. METHODS: We surveyed 129 refugees (including those in process of refugee application) and 121 migrant workers living in urban communities, using: the Patient Health Questionnaire-9 for depressive symptoms, the Impact Event Scale-Revised for post-traumatic stress disorder (PTSD) symptoms, and the health questionnaires used in 2016 Korean National Health and Nutrition Examination Survey (KNHANES). The majority of refugee subjects were from sub-Saharan Africa and Middle East. We compared the prevalence of possible depression and possible PTSD between refugees and migrant workers and refugees and age-gender matched samples from the KNHANES 2016. RESULTS: Frequency of suicidal planning during the last year was higher in the refugee group than Korean nationals, but frequency of suicidal attempt was not. High risk drinking was found in 0.8% of refugees, 6.6% of migrant workers and 27.2% of Korean nationals. Possible depression was present in 42.9% of refugee subjects, 33.3% of migrant workers, and 4.2% of Korean controls. Possible PTSD was present in 38.9% of refugees compared to 12.5% of migrant workers. Only major risk factor for depression among refugees was a traumatic event before entering Korea. CONCLUSION: Possible depression and PTSD are significantly more prevalent in refugees, compared to both migrant workers and Korean nationals. Prevalence rates are commensurate with refugee studies worldwide. Appropriate early screening and intervention schemes need to be developed for refugees entering Korea.

A qualitative study of satisfaction with the Community-based Primary Care Project among primary care patients and its efficacy

This study aimed to characterize patients experiences as service recipients, and to examine their satisfaction with the Community-based Primary Care Project and its efficacy. To achieve these aims, qualitative data were collected from 13 patients through a semi-structured in-depth interview. Four trained researchers extracted each theme separately and discussed them, at which point they were subjected to thematic analysis. Patient satisfaction was found to be associated with the doctor-patient relationship, comprehensive chronic disease care, face-to-face education, standardized education material, and computer-based education modules. Education allowed patients to strengthen their knowledge and establish their motivations, which brought about behavioral change and improved health conditions. In addition to these effects, patients also reported improved perceptions of the quality of primary care based on experiences with clinical team coordination. The findings of this study emphasize that community-based primary care services should be considered to be an effective chronic disease management strategy.

What is the Safe Training to Educate the Laparoscopic Cholecystectomy for Surgical Residents in Early Learning Curve?

PURPOSE: This study was conducted to investigate the safety of laparoscopic cholecystectomy (LC) performed by surgical residents. METHODS: We reviewed the records of patients who underwent LC for chronic cholecystitis and gallbladder polyps between February 2010 and July 2012. All diagnoses were confirmed by biopsy. All procedures performed by surgical residents were conducted under the close supervision of an experienced laparoscopic surgeon. A standard four-port method was used, and we achieved the critical view of safety in almost all patients. RESULTS: Of 219 LC procedures, 136 were performed by an experienced laparoscopic surgeon, and 83 by surgical residents. There was no significant difference in postoperative hospital stay (1.1 vs. 1.2 days, p=0.337) or complication rates (3.7% vs. 2.4%, p=0.712) between groups. However, the patients operated on by surgical residents had significantly longer operation times (40.7 vs. 63.7 min, p<0.05). CONCLUSION: LC performed by inexperienced surgical residents under the supervision of an experienced surgeon is safe and feasible for chronic cholecystitis and gallbladder polyps. Major bile duct injury is strongly correlated with having performed fewer than 20 LC procedures, so surgical residents must secure the critical view of safety, and the supervising surgeon must confirm it before the cystic duct and cystic artery are ligated.

Positive immunostaining of Sal-like protein 4 is associated with poor patient survival outcome in the large and undifferentiated Korean hepatocellular carcinoma

PURPOSE: Previous studies have shown the role of Sal-like protein 4 (SALL4) as a biomarker in hepatocellular carcinoma (HCC), and some studies have shown the relationship between SALL4 and prognosis. Given the debates in study groups differences in terms of etiologic causes between Western and Asian HCC and detection methods, we attempted to verify the features of SALL4 immunoreactivity and its clinical correlation in Korean HCC patients. METHODS: Immunohistochemical staining of SALL4 of tissue microarrays (TMAs) consisting of 213 surgically resected HCC patients' tissue were scored in a semiquantitative scoring system with immunoreactive score and the results analyzed with clinical outcome, in addition to general demographics and clinical characteristics. RESULTS: SALL4 immunoreactivity was expressed in 50 cases. Relevance between SALL4 and α-FP correlated significantly (P = 0.002). Also, the SALL4-positive patients had considerably higher tumor grade (P < 0.001). The survival analysis showed negative correlation with SALL4 immunoreactivity in all HCC patient groups, but SALL4 immunoreactivity in T3 and T4 HCC correlated with poor prognosis. CONCLUSION: Here, we found that positive immunostaining of SALL4 is correlated with poor patient survival outcome in large and undifferentiated Korean HCC. SALL4 expression showed close relationship with clinical outcomes of HCCs in Korean patients.

Positive immunostaining of Sal-like protein 4 is associated with poor patient survival outcome in the large and undifferentiated Korean hepatocellular carcinoma

PURPOSE: Previous studies have shown the role of Sal-like protein 4 (SALL4) as a biomarker in hepatocellular carcinoma (HCC), and some studies have shown the relationship between SALL4 and prognosis. Given the debates in study groups differences in terms of etiologic causes between Western and Asian HCC and detection methods, we attempted to verify the features of SALL4 immunoreactivity and its clinical correlation in Korean HCC patients. METHODS: Immunohistochemical staining of SALL4 of tissue microarrays (TMAs) consisting of 213 surgically resected HCC patients' tissue were scored in a semiquantitative scoring system with immunoreactive score and the results analyzed with clinical outcome, in addition to general demographics and clinical characteristics. RESULTS: SALL4 immunoreactivity was expressed in 50 cases. Relevance between SALL4 and α-FP correlated significantly (P = 0.002). Also, the SALL4-positive patients had considerably higher tumor grade (P < 0.001). The survival analysis showed negative correlation with SALL4 immunoreactivity in all HCC patient groups, but SALL4 immunoreactivity in T3 and T4 HCC correlated with poor prognosis. CONCLUSION: Here, we found that positive immunostaining of SALL4 is correlated with poor patient survival outcome in large and undifferentiated Korean HCC. SALL4 expression showed close relationship with clinical outcomes of HCCs in Korean patients.

Clinical implications of advances in liver regeneration

Remarkable advances have been made recently in the area of liver regeneration. Even though liver regeneration after liver resection has been widely researched, new clinical applications have provided a better understanding of the process. Hepatic damage induces a process of regeneration that rarely occurs in normal undamaged liver. Many studies have concentrated on the mechanism of hepatocyte regeneration following liver damage. High mortality is usual in patients with terminal liver failure. Patients die when the regenerative process is unable to balance loss due to liver damage. During disease progression, cellular adaptations take place and the organ microenvironment changes. Portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy are relatively recent techniques exploiting the remarkable progress in understanding liver regeneration. Living donor liver transplantation is one of the most significant clinical outcomes of research on liver regeneration. Another major clinical field involving liver regeneration is cell therapy using adult stem cells. The aim of this article is to provide an outline of the clinical approaches being undertaken to examine regeneration in liver diseases.

A Case of ANCA-Negative Generalized Wegener's Granulomatosis / 영남의대학술지

Wegener's granulomatosis is a very rare systemic vasculitis characterized by necrotizing granulomatosis. The detection of antineutrophil cytoplasm antibody (ANCA) is a valuable finding in diagnosing Wegener's granulomatosis because ANCA is positive in approximately 90 percent of patients with active, generalized Wegener's granulomatosis. But ANCA is not necessarily positive to make a diagnosis. A 59-year-old man was transferred to our hospital. He was diagnosed with lung abscess and treated with antibiotics at previous hospital. Initially, the ANCA was negative in immunofluorescence assay but we suspected Wegener's granulomatosis because of systemic inflammatory symptoms. Clinical symptoms deteriorated rapidly so we did bronchoscopic biopsy early. Wegener's granulomatosis was diagnosed according to pathologic finding that reported necrotizing granulomatous inflammation associated with vasculitis. Thus we treated with steroid then clinical symptoms and laboratory findings were improved.

Benefits of Nutrition Consultation for Preventing Diabetes According to HbA1c Levels in Overweight and Obese Women

HbA1c was recently adopted as a reliable indicator for screening diabetes. This study investigated the ability of nutrition consultation to prevent diabetes in overweight women (BMI 23 kg/m2 or more) using HbA1c as an indicator. Twenty overweight and obese women (with HbA1c> or =5.7%) completed the 12-week nutritional study, with individual and personalized nutrition counseling performed every 2 weeks. The main study guidelines involved the following: 1) reducing the intake of high fat foods and alcohol, 2) consuming a large amount of vegetables, 3) reducing the intake of simple sugars and empty-calorie foods, and 4) increasing physical activity to > or =30 min/day. Anthropometric (height, weight, BMI, body muscle (kg), body fat (%), waist and hip circumference, blood pressure) and biochemical parameters (fasting blood sugar (FBS), HbA1c, lipid profiles, hs-CRP) were measured before and after the nutrition consultation. After 12 weeks, the HbA1c or =5.7% group, HbA1c, TC, LDL, NON-HDL, hs-CRP and dietary intake of energy, carbohydrate, lipid, protein, and cholesterol significantly decreased (P<0.05). These results suggest that nutrition consultation effectively helps to prevent diabetes in overweight and obese women after applying HbA1c standards. Overall, the improvement in all markers measured suggest that HbA1c is a good indicator for blood glucose regulation, helping to prevent diabetes.

The Correlation between Increased Serum Concentrations of Interleukin-6 Family Cytokines and Disease Activity in Rheumatoid Arthritis Patients

PURPOSE: This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients. MATERIALS AND METHODS: We obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11. CONCLUSION: The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.

A Case of Pulmonary Hemorrhage through Pulmonary Involvement of Henoch-Schonlein Purpura / 대한내과학회지

Henoch-Schonlein purpura (HSP) is an immunologically mediated systemic vasculitis of small blood vessels that primarily involves the skin, gastrointestinal tract, joints, and kidneys. HSP is a relatively common vasculitic syndrome in children, which usually resolves within several weeks, and requires no treatment. The pulmonary parenchymal involvement of HSP is a rare complication that predominantly occurs in adolescents and adults. Mortality following HSP pulmonary presentation is extremely high. Here, we report a case of HSP combined with pulmonary hemorrhage as a presentation of the vasculitic involvement of the lung. Recently, we experienced a case of a 49-year-old male patient with HSP who presented with palpable purpura, enteritis, and glomerulonephritis. Following the diagnosis of HSP, the patient developed sudden pulmonary hemorrhage due to the pulmonary involvement of vasculitis, and recovered following glucocorticoid therapy.

Peroxisome Proliferator-activated Receptor-gamma Agonist Inhibits Pro-inflammatory Gene Expressions and Cellular Proliferation of Fibroblast Like Synoviocytes from Patients with Rheumatoid Arthritis by Down-regulation of NF-kappaB / 대한류마티스학회지

OBJECTIVE: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, on pro-inflammatory gene expressions and cellular proliferation of fibroblast like synoviocyte (FLS) from patients with rheumatoid arthritis (RA), and to determine whether these actions are mediated by nuclear factor-kappaB (NF-B) down-regulation. METHODS: Synovial tissues from patients with RA were obtained during total knee replacement surgery, and FLS were isolated. RA FLS were subsequently treated with 10 micrometer, 50 micrometer and 150 micrometer rosiglitazone with or without TNF-alpha (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 were determined by real-time quantitative RT-PCR. The effects of rosiglitazone on NF-kappaB activation were evaluated using electrophoretic mobility shift assay (EMSA). RESULTS: Rosiglitazone treatment without TNF-alpha induced a dose-dependent reduction in mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-alpha were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose-dependently. But mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7 were increased in 10 micrometer rosiglitazone with TNF-alpha and then decreased as the concentration of rosiglitazone increased. Rosiglitazone treatment also suppressed FLS proliferation in a dose-dependent manner, and EMSA showed decreased NF-kappaB expression with rosiglitazone treatment. CONCLUSION: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-kappaB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-gamma can be a novel therapeutic approach in RA.

A Case of Sacroiliitis Diagnosed with Positron-Emission Tomography with Normal Magnetic Resonance Imaging Finding / 대한류마티스학회지

No abstract available.

A Case of Paget's Disease of Bone on Skull / 대한류마티스학회지

No abstract available.

Treatment of Transverse Patellar Fracture with Cannulated Screws

PURPOSE: To assess the indication and effect of screw fixation in the transverse patellar fractures. MATERIALS AND METHODS: We analysed the results of 14 transverse patellar fractures fixed with screws from January 1991 to May 2005. Mean follow-up period was 47 months (range, 12~143 months). We analysed the radiologic union, operation time, ROM and postoperative Lysholm score. RESULTS: All fractures healed uneventfully. The mean displacement was decreased from 2.2 mm preoperatively to 0.3 mm postoperatively (p=0.001, Wilcoxon signed rank test). The mean operation time was 34 minutes (range, 20 to 60 minutes). Normal range of motion was achieved in 13 knees (92.9%). Average Lysholm score was 95.9 at final follow-up. CONCLUSION: Screw fixation seemed to be useful for treatment of transverse patellar fracture even in comminuted fractures with large fragments. The advantage of this technique was the preservation of extensor mechanism, simplicity, short operation time and good cosmesis.

Clinical results of Anterior Cruciate Ligament(ACL) Reconstruction: Bone-patellar Tendon-bone Autograft Versus Allograft

PURPOSE: To compare the clinical results of anterior cruciate ligament(ACL) reconstruction between the bone-patellar tendon-bone(BPTB) autograft and the allograft. MATERIALS AND METHODS: The clinical results of thirty-three patients of BPTB autograft and thirty-six patients of BPTB allograft performed between the periods of May 1994 and March 2004 were compared retrospectively in terms of Lysholm score, IKDC knee rating system, Tegner scale, physical examination, and KT-1000 arthrometry. Minimum follow-up period was 2 years(range: 24 to 144 months, average: 51.9 months). RESULTS: The postoperative Lysholm score at final follow-up was 89.4 in autograft group and 90.1 in allograft group on average. The difference between the two groups was not significant statistically in postoperative Lysholm score, IKDC knee rating system, and Tegner scale. Twenty-seven cases(81.8%) of autograft group had a negative Lachman test versus thirty-one cases(86.1%) of allograft goup, postoperatively. There was no significant difference in Lachman test, flexion-rotation-drawer(FRD) test, pivot shift test, and KT-1000 arthrometry between the two groups. CONCLUSION: The clinical results of ACL reconstruction using the BPTB autograft or allograft was equally good without statistically significant difference.

The Thickness of Normal and Repaired Rotator-cuff Measured in MRI

Purpose: To compare the thickness of the repaired full-thickness rotator-cuff tear to that of normal rotator-cuff in young and old persons and evaluate the relationship between the tear size and the repaired thickness in the full-thickness tear using MRI. Materials and Methods: The thickness of the rotator-cuff of the repaired full thickness tear(age: 45~77, mean 63.3 years, 19 patients: group 1) were compared with those of old intact patients (age: 46~69, mean 57.9 years, 23 patients: group 2) and young intact patients (age: 18~30, mean 23.3 years, 22 patients: group 3). The tear length and width was measured in oblique coronal and oblique sagittal view of MRA, respectively, and the thickness was measured in coronal oblique view 15mm anterior to the posterolateral margin of the glenoid. Correlation between the preoperative tear size (the bigger one between the length and the width) and the postoperative thickness in group 1 was also evaluated statistically. Results: The postoperative rotator-cuff thickness in group 1 was 3.0 mm in average, which was inversely proportional to the preoperative tear size (P<0.001). The rotator-cuff thickness was 3.9mm in group 2 and 5.0mm in group 3, and there was statistically significant difference among the three groups(P<0.05). Conclusion: The rotator-cuff thickness decreases with age and the postoperative thickness in the full-thickness tear was inversely proportional to the tear size, smaller than that of the intact rotator-cuff.

Clinical Study of Contralateral Inguinal Hernia Development in Children with Unilateral Inguinal Hernia

Contralateral exploration in children with unilateral inguinal hernia is controversial. This study was done to identify risk factors for the development of contralateral inguinal hernia in patients with unilateral inguinal hernia. The clinical experience of 4,206 inguinal hernias repaired by one pediatric surgeon on 3,358 children at HanYang University Hospital from September 1979 to December 2002 was analyzed. 1,868 (55.6%) hernias occurred on right side, 1,190 (35.4%) on left side, and 300 (8.9%) were bilateral. 2,702 children were boys and 656 were girls (M:F=4.1:1). 170 children of 3,058 children with unilateral hernias (5.6%) developed contralateral inguinal hernia at 1 day to 95 months after herniotomy. 146 children were boys and 24 were girls (M:F=6.1:1). The patients who had had herniotomy before 1 year of age developed contralateral hernia in 17.4%, compared with 5.6% overall average. The earlier the first herniotomy was performed, the more frequently contralateral hernia developed. The occurrence of contralateral inguinal hernia was more frequent in boys (146 of 2,460, 5.9%) than girls (24 of 598, 4.0%) and more frequent after left herniotomy (80 of 1,190, 6.7%) than after right herniotomy (90 of 1,868, 4.8%), but statistically not significant. 52.9% of contralateral inguinal hernia developed within 1 year after hernia repair, and 87.6% developed within 3 years. Routine exploration on contralateral side in children is not necessary.