Core indicators related to the elimination of hepatitis B and C virus infection in South Korea: A nationwide study

Background/Aims@#To eliminate hepatitis B virus (HBV) and hepatitis C virus (HCV) according to the World Health Organization (WHO) criteria in 2021, this study investigated the national core indicators representing the current status of viral hepatitis B and C in South Korea. @*Methods@#We analyzed the incidence, linkage-to-care, treatment, and mortality rates of HBV and HCV infection using the integrated nationwide big data of South Korea. @*Results@#According to data from 2018–2020, the incidence of acute HBV infection in South Korea was 0.71 cases per 100,000 population; tthe linkage-to-care rate was only 39.4%. Among those who need hepatitis B treatment, the treatment rate was 67.3%, which was less than 80% reported in the WHO program index. The annual liver-related mortality due to HBV was 18.85 cases per 100,000 population, exceeding the WHO target of four; the most frequent cause of death was liver cancer (54.1%). The annual incidence of newly diagnosed HCV infection was 11.9 cases per 100,000 population, which was higher than the WHO impact target of five. Among HCV-infected patients, the linkage-to-care rate was 65.5% while the treatment rate was 56.8%, which were below the targets of 90% and 80%, respectively. The liver-related annual mortality rate due to HCV infection was 2.02 cases per 100,000 population. @*Conclusions@#Many of the current indicators identified in the Korean population did not satisfy the WHO criteria for validation of viral hepatitis elimination. Hence, a comprehensive national strategy should be urgently developed with continuous monitoring of the targets in South Korea.

Ataxia-Telangiectasia Mutated Is Involved in Autolysosome Formation

Ataxia-telangiectasia mutated (ATM), a master kinase of the DNA damage response (DDR), phosphorylates a multitude of substrates to activate signaling pathways after DNA double-strand breaks (DSBs). ATM inhibitors have been evaluated as anticancer drugs to potentiate the cytotoxicity of DNA damage-based cancer therapy. ATM is also involved in autophagy, a conserved cellular process that maintains homeostasis by degrading unnecessary proteins and dysfunctional organelles. In this study, we report that ATM inhibitors (KU-55933 and KU-60019) provoked accumulation of autophagosomes and p62 and restrained autolysosome formation. Under autophagy-inducing conditions, the ATM inhibitors caused excessive autophagosome accumulation and cell death. This new function of ATM in autophagy was also observed in numerous cell lines. Repression of ATM expression using an siRNA inhibited autophagic flux at the autolysosome formation step and induced cell death under autophagy-inducing conditions.Taken together, our results suggest that ATM is involved in autolysosome formation and that the use of ATM inhibitors in cancer therapy may be expanded.

Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group

Molecular biomarker testing is the standard of care for non–small cell lung cancer (NSCLC) patients. In 2017, the Korean Cardiopulmonary Pathology Study Group and the Korean Molecular Pathology Study Group co-published a molecular testing guideline which contained almost all known genetic changes that aid in treatment decisions or predict prognosis in patients with NSCLC. Since then there have been significant changes in targeted therapies as well as molecular testing including newly approved targeted drugs and liquid biopsy. In order to reflect these changes, the Korean Cardiopulmonary Pathology Study Group developed a consensus statement on molecular biomarker testing. This consensus statement was crafted to provide guidance on what genes should be tested, as well as methodology, samples, patient selection, reporting and quality control.

Current status and future perspectives of liquid biopsy in non-small cell lung cancer

With advances in target therapy, molecular analysis of tumors is routinely required for treatment decisions in patients with advanced non-small cell lung cancer (NSCLC). Liquid biopsy refers to the sampling and analysis of circulating cell-free tumor DNA (ctDNA) in various body fluids, primarily blood. Because the technique is minimally invasive, liquid biopsies are the future in cancer management. Epidermal growth factor receptor (EGFR) ctDNA tests have been performed in routine clinical practice in advanced NSCLC patients to guide tyrosine kinase inhibitor treatment. In the near future, liquid biopsy will be a crucial prognostic, predictive, and diagnostic method in NSCLC. Here we present the current status and future perspectives of liquid biopsy in NSCLC.

Selective Fascicular Involvement of the Median Nerve Trunk Causing Pseudo-Anterior Interosseous Nerve Syndrome: Ultrasound and MR Imaging Features

Fascicular involvement of the median nerve trunk in the upper arm is uncommon in cases of peripheral neuropathy, and its symptoms are consistent with those of anterior interosseous nerve (AIN) syndrome. We report three cases of focal anterior interosseous fascicular involvement in the median nerve trunk presenting as AIN palsy. Our report emphasizes the unique ultrasonographic and magnetic resonance imaging (MRI) features of swelling, hourglass-like constriction and torsion, and entwinement of the nerve fascicle of the dorsal region of the median nerve, which were confirmed surgically. On MRI, all patients showed denervation changes in the AIN territory, as well as in the median nerve territory, without compressing structures.

A Rare Case of Tracheal Leiomyoma: Role of Digital Tomosynthesis in Diagnosis and Treatment

Tracheal leiomyoma is a rare benign tumor, which is composed of transformed cells of mesenchymal origin. We describe a case in which digital tomosynthesis was useful to evaluate a tracheal tumor that was overlooked on initial chest radiographs.

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Treatment Outcome and Renal Safety of 3-Year Tenofovir Disoproxil Fumarate Therapy in Chronic Hepatitis B Patients with Preserved Glomerular Filtration Rate

BACKGROUND/AIMS: To investigate the treatment efficacy and renal safety of long-term tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients with preserved renal function. METHODS: The medical records of 919 CHB patients who were treated with TDF therapy were reviewed. All patients had preserved renal function with an estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2. RESULTS: A total of 426 patients (184 treatment-naïve and 242 treatment-experienced) were included for analysis. A virologic response (VR) was defined as achieving an undetectable serum hepatitis B virus (HBV) DNA level, and the overall VR was 74.9%, 86.7%, and 89.4% at the 1, 2, and 3-year follow-ups, respectively. Achieving a VR was not influenced by previous treatment experience, TDF combination therapy, or antiviral resistance. In a multivariate analysis, being hepatitis B e antigen positive at baseline and having a serum HBV DNA level ≥2,000 IU/mL at 12 months were associated with lower VR rates during the long-term TDF therapy. The overall renal impairment was 2.9%, 1.8%, and 1.7% at the 1, 2, and 3-year follow-ups, respectively. With regard to renal safety, underlying diabetes mellitus (DM) and an initial eGFR of 60 to 89 mL/min/1.73 m2 were significant independent predictors of renal impairment. CONCLUSIONS: TDF therapy appears to be an effective treatment option for CHB patients with a preserved GFR. However, patients with underlying DM and initial mild renal dysfunction (eGFR, 60 to 89 mL/min/1.73 m2) have an increased risk of renal impairment.

Gender Differences in Aggression-related Responses on EEG and ECG

Gender differences in aggression viewed from an evolutionary and sociocultural perspective have traditionally explained why men engage in more direct and physical aggression, and women engage in more indirect and relational aggression. However, psychological and behavioral studies offer inconsistent support for this theory due to personal or social factors, and little is known about the gender-based neurobiological mechanisms of aggression. This study investigates gender differences in aggression through an analysis of electroencephalography (EEG) and electrocardiography (ECG) based neurobiological responses to commonly encountered stimuli, as well as psychological approaches in healthy Korean youth. Our results from self-reports indicate that overall aggression indices, including physical and reactive/overt aggression, were stronger in men. This agrees with the results of previous studies. Furthermore, our study reveals prominent gender-related patterns in γ signals from the right ventrolateral frontal cortex and changes in heart rate through stimulation by aggressive videos. In particular, gender differences in EEG and ECG responses were observed in response to different scenes, as simple aversion and situation-dependent aggression, respectively. In addition, we discovered decisive gender-distinct EEG signals during stimulation of the situation-dependent aggression regions within the right ventromedial prefrontal and ventrolateral frontal regions. Our findings provide evidence of a psychological propensity for aggression and neurobiological mechanisms of oscillation underlying gender differences in aggression. Further studies of oscillatory responses to aggression and provocation will expand the objective understanding of the different emotional worlds between men and women.

Incidence and Seasonal Variation of Distal Radius Fractures in Korea: a Population-based Study

BACKGROUND: The present study aimed to investigate the incidence and seasonal variation of distal radius fractures (DRFs) in Korea. METHODS: We analyzed a nationwide database acquired from the Korean Health Insurance Review and Assessment Service from 2011 to 2015. We used International Classification of Diseases, 10th revision codes and procedure codes to identify patients of all ages with newly diagnosed DRFs. RESULTS: An average of about 130,000 DRFs occurred annually in Korea. The incidence of DRF, by age group, was highest in the 10 to 14-year-old age group for males and the highest in the 70s age group for females, with a rapid increase of incidence after 50 years. The peak incidence of DRF occurred during winter; however, the incidence greatly varied annually when compared with that of other seasons. The incidence of DRFs during the winter season was correlated with the average temperature. CONCLUSION: The annual incidence of DRF was 130,000 in Korea. The incidence increased under an intense cold surge during winter. Active preventive measures are recommended especially in women exceeding 50 years considering the higher incidence in this age group.

The Epidemiology of Dupuytren's Disease in Korea: a Nationwide Population-based Study

BACKGROUND: To date, there have been few reports on the nationwide population-based epidemiology of Dupuytren's disease (DD). We investigated the prevalence and incidence of DD in Korea using the large dataset provided by the Korean Health Insurance Review and Assessment Service. This study is the second nationwide epidemiological study of DD after the study in Taiwan. METHODS: Records of patients diagnosed with DD between 2007 and 2014 were extracted from the large dataset by diagnostic code searching (International Classification of Disease 10th revision code M72.0) and were included in the study. We calculated the prevalence and incidence of DD based on the total population of Korea provided by the Korean Statistical Information Service. Diseases associated with DD and the trends in surgery for DD were also analyzed. RESULTS: A total 16,630 patients were diagnosed with DD during the study period. The mean annual prevalence was 32.2 per 100,000 population (41.8 per 100,000 for men; 22.5 per 100,000 for women). The mean annual incidence was 1.09 per 100,000 population (1.80 per 100,000 for men; 0.38 per 100,000 for women). The common diseases associated with DD were hypertension (30.5%), diabetes mellitus (26.7%), hyperlipidemia (20.4%), ischemic heart disease (7.9%), and cerebrovascular disease (4.6%). The mean annual proportion of the patients who had surgery for DD was 5.24% of all DD patients. CONCLUSION: The prevalence and incidence of DD in Korea were 100–1,000 times lower than those in western countries; however, it was slightly larger than that in Taiwan.

Occupational Accident Experience by Working Life Cycle of Korean Workers / 산업간호학회지

PURPOSE: In this study, we attempted to analyze the occupational accident experience rate by working life cycle of Korean workers considering entrance and turnover in their jobs. The specific goal of this study was to calculate the accident experience rate according to workers' turnover history and previous accident experience. METHODS: We constructed a cumulative data set of 90,338 cases of workers' accident experiences in their jobs from the Fourth Korean Working Conditions Survey. The accident experience rates according to workers' turnover and previous accident experiences were analyzed using descriptive statistics and analysis of variance. RESULTS: In this study, the cumulative accident experience rate of Korean workers was found to be 5.2%. It was confirmed that the accident experience rate of workers increased as the turnover frequencies increased. In addition, we analyzed only the data of the workers who had experienced turnover and found that the accident experience rate after turnover increased about 7.5 times when workers had experienced accidents in the past. CONCLUSION: To prevent occupational accidents in workers, safety strategies should consider a worker's previous job history and injury experiences. It will also be necessary to focus preventive efforts on new and young workers through ongoing monitoring and on-the-job training.

Occupational Accident Experience by Working Life Cycle of Korean Workers / 한국직업건강간호학회지

PURPOSE@#In this study, we attempted to analyze the occupational accident experience rate by working life cycle of Korean workers considering entrance and turnover in their jobs. The specific goal of this study was to calculate the accident experience rate according to workers' turnover history and previous accident experience.@*METHODS@#We constructed a cumulative data set of 90,338 cases of workers' accident experiences in their jobs from the Fourth Korean Working Conditions Survey. The accident experience rates according to workers' turnover and previous accident experiences were analyzed using descriptive statistics and analysis of variance.@*RESULTS@#In this study, the cumulative accident experience rate of Korean workers was found to be 5.2%. It was confirmed that the accident experience rate of workers increased as the turnover frequencies increased. In addition, we analyzed only the data of the workers who had experienced turnover and found that the accident experience rate after turnover increased about 7.5 times when workers had experienced accidents in the past.@*CONCLUSION@#To prevent occupational accidents in workers, safety strategies should consider a worker's previous job history and injury experiences. It will also be necessary to focus preventive efforts on new and young workers through ongoing monitoring and on-the-job training.

A Simple Outline of Methods for Protein Isolation and Purification

At the summer workshop of the Korean Endocrine Society held in 2016, some examples of protein experiments were discussed in the session entitled “All about working with proteins.” In contrast to what the title suggested, it was unrealistic to comprehensively discuss all protein analytical methods. Therefore, the goal was to outline protein experimental techniques that are useful in research or in bench work. In conversations with clinicians, however, I have always felt that researchers who do not engage in bench science have different demands than those who do. Protein research tools that are useful in bench science may not be very useful or effective in the diagnostic field. In this paper, I provide a general summary of the protein analytical methods that are used in basic scientific research, and describe how they can be applied in the diagnostic field.

Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been determined in breast cancers. Interferons can affect T-cell activity through direct and indirect mechanisms. Myxovirus resistance A (MxA) is an excellent marker of interferon activity. Here,we evaluated TILs and MxA expression in human epidermal growth factor receptor 2 (HER2)–positive breast cancers. MATERIALS AND METHODS: Ninety cases of hormone receptor (HR)+/HER2+ tumors and 78 cases of HR–/HER2+ tumors were included. The TILs level was assessed using hematoxylin and eosin–stained full face sections, and MxA expressionwas evaluated by immunohistochemistrywith a tissue microarray. RESULTS: MxA protein expression was significantly higher in tumors with high histologic grade (p=0.023) and high levels of TILs (p=0.002). High levels of TILs were correlated with high histological grade (p=0.001), negative lymphovascular invasion (p=0.007), negative lymph node metastasis (p=0.007), absence of HR expression (p < 0.001), abundant tertiary lymphoid structures (TLSs) around ductal carcinoma in situ (p=0.018), and abundant TLSs around the invasive component (p < 0.001). High levels of TILs were also associated with improved disease-free survival, particularly in HR–/HER2+ breast cancers. However, MxA was not a prognostic factor. CONCLUSION: High expression of MxA in tumor cells was associated with high levels of TILs in HER2-positive breast cancers. Additionally, a high level of TILs was a prognostic factor for breast cancer, whereas the level of MxA expression had no prognostic value.

National Surgical Trends for Distal Radius Fractures in Korea

The objective of this study was to investigate national surgical trends for distal radius fractures (DRFs) in Korea and analyze healthcare institution type-specific surgical trends. We analyzed a nationwide database acquired from the Korean Health Insurance Review and Assessment Service (HIRA) from 2011 to 2015. International Classification of Diseases, 10th revision (ICD-10) codes and procedure codes were used to identify patients aged ≥ 20 years with newly diagnosed DRFs. A total of 459,388 DRFs occurred from 2011 to 2015. The proportion of DRF cases treated by surgery tended to increase over time, from 32.6% in 2011 to 38.3% in 2015 (P < 0.001). Open reduction with internal fixation (ORIF) using a plate steadily gained in popularity each year, increasing from 39.2% of overall surgeries in 2011 to 60.9% in 2015. The type of surgery for DRFs differed depending on the type of healthcare institution. ORIF (91%) was the most popular procedure in tertiary hospitals, whereas percutaneous pinning (58%) was most popular in clinics. In addition, general hospitals and hospitals with 30–100 beds used external fixation more frequently than tertiary hospitals and clinics did. Overall, our findings indicate that surgical treatment of DRF, particularly ORIF, continues to increase, and that the component ratio of operation codes differed according to the healthcare institution type.

Aldehyde dehydrogenase is used by cancer cells for energy metabolism

We found that non-small-cell lung cancer (NSCLC) cells express high levels of multiple aldehyde dehydrogenase (ALDH) isoforms via an informatics analysis of metabolic enzymes in NSCLC and immunohistochemical staining of NSCLC clinical tumor samples. Using a multiple reaction-monitoring mass spectrometry analysis, we found that multiple ALDH isozymes were generally abundant in NSCLC cells compared with their levels in normal IMR-90 human lung cells. As a result of the catalytic reaction mediated by ALDH, NADH is produced as a by-product from the conversion of aldehyde to carboxylic acid. We hypothesized that the NADH produced by ALDH may be a reliable energy source for ATP production in NSCLC. This study revealed that NADH production by ALDH contributes significantly to ATP production in NSCLC. Furthermore, gossypol, a pan-ALDH inhibitor, markedly reduced the level of ATP. Gossypol combined with phenformin synergistically reduced the ATP levels, which efficiently induced cell death following cell cycle arrest.

Disease Progression in Chronic Hepatitis B Patients under Long-Term Antiviral Therapy

BACKGROUND/AIMS: We investigated factors associated with the disease progression and development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients during long-term oral nucleos(t)ide analog (NA) therapy. METHODS: This retrospective study included 524 naive CHB patients who received oral NA therapy for more than 48 weeks between January 2003 and December 2007. The primary outcome was 5-year cumulative probability of disease progression and HCC development. Disease progression was defined as cirrhosis development, cirrhotic complications, HCC or liver-related mortality. RESULTS: For the 524 patients, the cumulative probabilities of disease progression and HCC development at 1, 2, 3, 4 and 5 years were 1.1%, 6.3%, 9.0%, 11.6%, and 16.2% and 0.2%, 1.8%, 3.6%, 5.8%, and 9.3%, respectively. In multivariate analysis, age >50 years (hazard ratio [HR], 1.05) and cirrhosis (HR, 2.95) were significant factors for disease progression. Similarly, age >50 years (HR, 1.05), family history of HCC (HR, 5.48), and cirrhosis (HR, 17.16) were significant factors for HCC development. Importantly, longer duration (>12 months) of maintained virological response (<20 IU/mL) reduced the risks of disease progression (HR, 0.19) and HCC development (HR, 0.09). CONCLUSIONS: Longer duration of maintained virological response significantly reduces the risk of disease progression or HCC development in CHB patients undergoing long-term oral NA therapy.

Clinical Characteristics and Prognostic Impact of Bacterial Infection in Hospitalized Patients with Alcoholic Liver Disease

Bacterial infection is an important cause of death in patients with liver cirrhosis. The aim of this study was to investigate the clinical characteristics and prognostic impact of bacterial infection in hospitalized patients with alcoholic liver disease (ALD). We retrospectively analyzed data from 409 patients consecutively admitted to a tertiary referral center with ALD diagnosis. Of a total of 544 admissions, 133 (24.4%) cases presented with bacterial infection, of which 116 were community-acquired whereas 17 were hospital-acquired. The common types of infection were pneumonia (38%), biliary tract infection (17%), soft tissue infection (12%), and spontaneous bacterial peritonitis (9%). Diabetes, serum Na or =20 mg/L, systemic inflammatory response syndrome (SIRS) positivity were independently associated with bacterial infection in patients with ALD. Overall 30-day and 90-day mortalities in patients with bacterial infection were significantly (P or =32 (HR, 2.3; 95% CI, 1.036-5.222, P = 0.041), and hemoglobin <12 g/dL (HR, 2.4; 95% CI, 1.081-5.450, P = 0.032) were independent predictors of short-term mortality. In conclusion, bacterial infection and SIRS positivity predicted short-term prognosis in hospitalized patients with ALD. A thorough evaluation at admission or on clinical deterioration is required to detect possible infection with prompt management.