Diagnostic Pitfall and Clinical Characteristics of Variant Versus Wild-Type Transthyretin Amyloid Cardiomyopathy in Asian Population: The Korean Nationwide Cohort Study

Background@#Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) with clinical phenotypes that vary across regions and genotypes.We sought to characterize the clinical characteristics of ATTR-CM in Asia. @*Methods@#Data from a nationwide cohort of patients with ATTR-CM from six major tertiary centres in South Korea were analysed between 2010 and 2021. All patients underwent clinical evaluation, biochemical laboratory tests, echocardiography, and transthyretin (TTR) genotyping at the time of diagnosis. The study population comprised 105 Asian ATTR-CM patients (mean age: 69 years; male: 65.7%, wild-type ATTR-CM: 41.9%). @*Results@#Among our cohort, 18% of the patients had a mean left ventricular (LV) wall thickness < 12 mm. The diagnosis of ATTR-CM increased notably during the study period (8 [7.6%] during 2010–2013 vs. 22 [21.0%] during 2014–2017 vs. 75 [71.4%] during 2018–2021).Although the duration between symptom onset and diagnosis did not differ, the proportion of patients with HF presenting mild symptoms increased during the study period (25% NYHA class I/II between 2010–2013 to 77% between 2018–2021). In contrast to other international registry data, male predominance was less prominent in wild-type ATTR-CM (68.2%). The distribution of TTR variants was also different from Western countries and from Japan.Asp38Ala was the most common mutation. @*Conclusion@#A nationwide cohort of ATTR-CM exhibited less male predominance, a proportion of patients without increased LV wall thickness, and distinct characteristics of genetic mutations, compared to cohorts in other parts of the world. Our results highlight the ethnic variation in ATTR-CM and may contribute to improving the screening process for ATTR-CM in the Asian population.

Cremastranone-Derived Homoisoflavanes Suppress the Growth of Breast Cancer Cells via Cell Cycle Arrest and Caspase-Independent Cell Death

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

Knowledge, Attitudes and Nursing Stress Related to Life-Sustaining Treatment among Oncology Nurses / 한국호스피스완화의료학회지

Purpose@#This study investigated knowledge, attitudes, and nursing stress related to lifesustaining treatment among oncology nurses. @*Methods@#A descriptive study design was used. Data were collected through a survey from April 1 to May 31, 2022. The participants were 132 nurses working in the oncology ward of a tertiary hospital in Seoul. Data were analyzed using the SPSS 25.0 program with descriptive statics, the independent t-test, analysis of variance, and Pearson correlation coefficients. @*Results@#The average scores for knowledge, attitudes, and nursing stress related to life-sustaining treatment were 14.42, 3.29, and 3.96, respectively. Significant differences in knowledge about life-sustaining treatment were observed based on clinical experience (P=0.029) and education about life-sustaining treatment (P=0.044). Attitudes toward life-sustaining treatment varied significantly with education about life-sustaining treatment (P=0.014), while stress levels differed significantly across working units (P=0.004). A positive correlation was found between the dilemma of extending or stopping life-sustaining treatment (a subdomain of nursing stress) and attitudes toward life-sustaining treatment (r=0.260, P=0.003). @*Conclusion@#There was no significant correlation between the nursing stress experienced by oncology nurses and their knowledge and attitudes toward life-sustaining treatment. However, a more positive experience with life-sustaining treatment education was associated with higher stress levels related to the dilemma of extending or stopping life-sustaining treatment. Therefore, it is crucial to develop strategies to manage this dilemma and reduce stress in the field.

Analysis on Validity and Academic Competency of Mock Test for Korean Medicine National Licensing Examination Using Item Response Theory / 계명의대학술지

The national licensing examination is used to evaluate the medical competency at the time of graduation, however no study has been performed on the validity of traditional Korean medicine license examination yet. The purpose of this study was to develop learning analytics using item response theory (IRT) to examine the validity and academic competency of the mock test of the national licensing exam. Classical test theory and IRT were used to evaluate the validity of test items, and IRT was used for test validity and competency analysis. The correlation between competency score of 12 subjects was analyzed using Pearson’s correlation. The distribution of students’ latent competencies was examined by gender and administrative group using a Kernel density map, Latent Profile Analysis, and χ2. The guessing parameter of 340 items was relatively high, and the information level of 12 subjects were relatively low. Significant correlations (r = 0.49–0.83, p < 0.05) were observed between the competency scores of total and 12 subjects. Two (high and low) latent academic competency groups were identified based on the competency score of 12 subjects. The low academic competency group requiring intensive management has a significantly higher frequency of male students with the experience of academic fail in the seven-year course. This study presented the quantitative learning analytics for the national licensing exam of traditional Korean medicine. The multifaceted item and test validities of the mock license test were provided, and an evidence-based approach to competency-based student management and national licensing exam of traditional Korean medicine was suggested.

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Evaluation of Intervention Policies for the COVID-19Epidemic in the Seoul/Gyeonggi Region through a Model Simulation

Purpose@#To evaluate the efficacy of intervention policies on coronavirus disease-19 (COVID-19) dissemination. @*Materials and Methods@#An age-structured compartmental model for the COVID-19 outbreak was proposed to predict the impact of control measures in the Seoul/Gyeonggi region. The model was calibrated based on actual data and realistic situations, including daily vaccine doses, proportion of delta variant cases, and confirmed cases by age. We simulated different scenarios for non-pharmaceutical interventions by varying social distancing and school attendance strategies. @*Results@#Two-step mitigation of social distancing without in-person classes would result in a rapid increase in confirmed cases up to 10000 but would keep severe cases within the manageable range of the health care system. The overall impact of taking down the distancing level by one step with twice the increase in contacts at school was comparable to the above scenario. Implementation of two-step mitigation of social distancing along with a two-fold increase in contacts among the school-age group would dramatically increase confirmed and severe cases by over 80000 and 100, respectively, as early as the beginning of December. This policy would cause the situation to spiral out of control, considering the scale of the response and time to prepare. On the other hand, the burden on the current healthcare system caused by two-step mitigation of social distancing and 40% increased contacts in the school-age group was manageable if prepared. @*Conclusion@#A compromise between social distancing and school attendance policy and timely preparations for the spread of COVID-19 are required.

Fibrinolysis with Lower Dose Urokinase in Patients with Complicated Parapneumonic Effusion / 결핵및호흡기질환

Background@#Intrapleural urokinase is one of the most widely used fibrinolytic agents in the treatment of complicated parapneumonic effusion (CPPE). However, little research has been performed on the optimal urokinase dosage. The aim of this study was to evaluate the treatment efficacy of half dose urokinase compared with conventional dose urokinase. @*Methods@#We retrospectively enrolled 92 patients with CPPE or empyema who underwent intrapleural urokinase treatment at two tertiary hospitals. Patients received antibiotics, chest tube drainage, and other treatments as part of routine care. The primary outcome was the treatment success rate in the half dose urokinase group (50,000 IU daily for maximal 6 days) and the conventional dose urokinase group (100,000 IU daily). Treatment success was defined as clinical and radiological improvements without surgical treatment or re-admission within one month. @*Results@#Forty-four patients received half dose urokinase, whereas 48 patients were treated with conventional dose urokinase. Both groups were relatively well matched at baseline, excluding higher serum white blood cell count and higher empyema prevalence in the half dose urokinase group. The treatment success rate was not different between the two groups (p=0.048). There were no differences in the rate of in-hospital death and surgical treatment, hospitalization duration, and indwelling catheter duration. In the multivariate analysis, urokinase dose was not a predictor of treatment success. @*Conclusion@#Half dose intrapleural urokinase is equally effective conventional dose urokinase in treating patients with CPPE or empyema.

Deep Learning in MR Motion Correction:a Brief Review and a New Motion Simulation Tool (view2Dmotion)

With the development of deep-learning techniques, the application of deep learning in MR imaging processing seems to be growing. Accordingly, deep learning has also been introduced in motion correction and seemed to work as well as do conventional motion-compensation methods. In this article, we review the motion-correction methods based on deep learning, focusing especially on the motion-simulation methods adopted. We then propose a new motion-simulation tool, which we call view2Dmotion.

Deep Learning in MR Motion Correction:a Brief Review and a New Motion Simulation Tool (view2Dmotion)

With the development of deep-learning techniques, the application of deep learning in MR imaging processing seems to be growing. Accordingly, deep learning has also been introduced in motion correction and seemed to work as well as do conventional motion-compensation methods. In this article, we review the motion-correction methods based on deep learning, focusing especially on the motion-simulation methods adopted. We then propose a new motion-simulation tool, which we call view2Dmotion.

Evaluation of skeletal maturity in the cervical vertebrae and hand-wrist in relation to vertical facial types / 대한치과교정학회지

OBJECTIVE@#To evaluate differences in skeletal maturity in relation to vertical facial types and to compare differences in the skeletal maturity of the cervical vertebrae and hand-wrist in females.@*METHODS@#This study included 59 females aged 7 to 9 years with skeletal Class I malocclusion. The participants were categorized into three groups (low, normal, and high) according to the mandibular plane angle. Skeletal maturity was measured using skeletal maturity indicators (SMIs) and the Tanner–Whitehouse III (TW3) method on hand-wrist radiographs and by using cervical vertebrae maturation indicators (CVMIs) on lateral cephalometric radiographs.@*RESULTS@#The SMI was higher in the high-angle group than in the low-angle group (p = 0.014). The median TW3 bone age was 11.4 months higher in the high-angle group than in the low-angle group (p = 0.032). There was no significant difference in CVMI among the three groups. Skeletal maturity showed a weakly positive correlation with the mandibular plane angle (SMI, r = 0.391; TW3, r = 0.333; CVMI, r = 0.259).@*CONCLUSIONS@#The skeletal maturity of the hand-wrist in females with a high mandibular plane angle was higher than that in females with a low mandibular plane angle. Obtaining additional hand-wrist radiographs may facilitate evaluation of skeletal maturity of females. In females with a high mandibular angle, the time to commence orthodontic treatment may be earlier than that in females with a low mandibular angle.

Relationships between the diabetes awareness and clinical indices/nutrient intakes in Korean adults: Based on the 2012–2013 Korea National Health and Nutrition Examination Survey Data

BACKGROUND/OBJECTIVES: Diabetes is diagnosed after an average of 10–12 years of diabetic development. Strict glycemic control in diabetic patients promotes the normalization of blood glucose and reduces cardiovascular diseases (CVDs) and diabetic complications. Therefore, early diagnosis in non-aware individuals is very important. SUBJECTS/METHODS: Clinical indices and nutrient intakes in Korean diabetic adults aged 19–64 years were examined according to the awareness of diabetes, using 2012 and 2013 Korea National Health and Nutrition Examination Survey (KNHANES) data. The aware group was defined as individuals who were aware of having diabetes from diagnosis by physician before the survey and the non-aware group as individuals who were not aware of having diabetes. RESULTS: The average age was higher in the aware group compared to the non-aware group in both men (P = 0.002) and women (P = 0.004). The prevalences of hypertension and dyslipidemia were not different between the two groups, but the diagnosis rate was significantly lower in the non-aware group. In the non-aware group, total and LDL-cholesterol were significantly higher (P < 0.001), the risk for total cholesterol over 240 mg/dL was 3.4 times (95% CI: 1.58–7.52) higher (P = 0.002) and the risk for LDL-cholesterol over 160 mg/dL was 4.59 times (95% CI: 2.07–10.17) higher (P < 0.001). The calorie intake of the female non-aware group was significantly higher compared to the female aware group (P = 0.033). CONCLUSION: The results suggested that the recommendation of screening test is necessary even for young adults. Studies on the methodology for early diagnosis of diabetes are also needed.

Characterization of hidden rules linking symptoms and selection of acupoint using an artificial neural network model / 医学前沿

Comprehension of the medical diagnoses of doctors and treatment of diseases is important to understand the underlying principle in selecting appropriate acupoints. The pattern recognition process that pertains to symptoms and diseases and informs acupuncture treatment in a clinical setting was explored. A total of 232 clinical records were collected using a Charting Language program. The relationship between symptom information and selected acupoints was trained using an artificial neural network (ANN). A total of 11 hidden nodes with the highest average precision score were selected through a tenfold cross-validation. Our ANN model could predict the selected acupoints based on symptom and disease information with an average precision score of 0.865 (precision, 0.911; recall, 0.811). This model is a useful tool for diagnostic classification or pattern recognition and for the prediction and modeling of acupuncture treatment based on clinical data obtained in a real-world setting. The relationship between symptoms and selected acupoints could be systematically characterized through knowledge discovery processes, such as pattern identification.

The effect of tamoxifen therapy on the endometrium and ovarian cyst formation in patients with breast cancer

OBJECTIVE: To evaluate the effect of tamoxifen on female reproductive organs in women with breast cancer. METHODS: We retrospectively reviewed the medical records of 309 women with breast cancer who were currently receiving tamoxifen and undergoing regular gynecological examination. RESULTS: We evaluated 92 pre- and 217 postmenopausal women. The prevalence of endometrial thickening was 12% in the pre- and 10.6% in the postmenopausal group. An endometrial biopsy was performed in 43 women and confirmed endometrial cancer in 1, endometrial polyps in 14, and endometrial hyperplasia in 4 women. Transvaginal ultrasonography showed 25 cases of newly developed ovarian cysts. Most ovarian cysts had disappeared during follow-up. CONCLUSION: Tamoxifen use in women with breast cancer causes few complications and is considered safe for female reproductive organs in case of regular gynecological examination.

Experience of Patients and Families about Flexible Visiting / 중환자간호학회지

PURPOSE: This study aimed to understand the essence of experiences of patients and family members during flexible visiting in an intensive care unit (ICU).METHODS: This is a qualitative study using interviews with open ended questions. We used Colaizzi's method of phenomenological interpretation.RESULTS: Flexible visiting in the ICU impacted the patients and their families in various ways. The following categories were extracted from the patients' experiences with flexible visiting: 1) the opportunity to feel the presence of the family and 2) the burden of unrestricted visiting. The following categories were extracted from the families' experiences with flexible visiting: 1) psychological comfort by convenience 2) being aware of health care professionals and critical care nursing in the intensive care unit, and 3) double trouble.CONCLUSIONS: These results showed that flexible visiting in the ICU affected the patients and their families positively and negatively. Therefore, nursing staff need to design psychological and social interventions that address the needs of patients and their families.

Clinicopathologic significance of tumor microenvironment CD11c, and FOXP3 expression in diffuse large B-cell lymphoma patients receiving rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy

BACKGROUND/AIMS: CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors' microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy. METHODS: The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors' microenvironment were evaluated using an immunohistochemistry (IHC). RESULTS: CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival (p = 0.019) and overall survival (p = 0.039) between the two groups. CONCLUSIONS: We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.

Analysis of factors affecting hemorrhagic diathesis and overall survival in patients with acute promyelocytic leukemia

BACKGROUND/AIMS: This study investigated whether patients with acute promyelocytic leukemia (APL) truly fulfill the diagnostic criteria of overt disseminated intravascular coagulation (DIC), as proposed by the International Society on Thrombosis and Haemostasis (ISTH) and the Korean Society on Thrombosis and Hemostasis (KSTH), and analyzed which component of the criteria most contributes to bleeding diathesis. METHODS: A single-center retrospective analysis was conducted on newly diagnosed APL patients between January 1995 and May 2012. RESULTS: A total of 46 newly diagnosed APL patients were analyzed. Of these, 27 patients (58.7%) showed initial bleeding. The median number of points per patient fulfilling the diagnostic criteria of overt DIC by the ISTH and the KSTH was 5 (range, 1 to 7) and 3 (range, 1 to 4), respectively. At diagnosis of APL, 22 patients (47.8%) fulfilled the overt DIC diagnostic criteria by either the ISTH or KSTH. In multivariate analysis of the ISTH or KSTH diagnostic criteria for overt DIC, the initial fibrinogen level was the only statistically significant factor associated with initial bleeding (p = 0.035), but it was not associated with overall survival (OS). CONCLUSIONS: Initial fibrinogen level is associated with initial presentation of bleeding of APL patients, but does not affect OS.

Reversible Atrioventricular Block after Electrical Injury / 대한내과학회지

Here, we report a case of electrical injury-induced reversible advanced second-degree atrioventricular (AV) block. A 28-year-old male visited the emergency department for palpitations 3 days after receiving an electrical injury from 220 volt alternating current. The initial electrocardiogram (ECG) showed sinus rhythm and first-degree AV block with a prolonged PR interval of 400 ms. There was no structural heart disease or electrolyte imbalance. Follow up ECGs acquired 4-6 days after the electrical injury showed intermittent AV block with a prolonged PR interval of 400-460 ms. Exercise treadmill and atropine provocation tests performed 6 days after electrical injury induced advanced second-degree AV block. His bundle electrogram showed intermittent AH block in a Wenckebach pattern with a prolonged AH interval of 220-360 ms and a normal HV interval. Episodes of AV block decreased remarkably 4 weeks after the electrical injury, and the prolonged PR interval returned to 220 ms after 5 months.

Intraocular lymphoma in Korea: the Consortium for Improving Survival of Lymphoma (CISL) study

BACKGROUND: Intraocular lymphoma (IOL) is a rare malignant lymphoma that most closely resembles a diffuse large B-cell lymphoma, and it is a subtype of primary central nervous system lymphoma (PCNSL). IOL is located inside the eye in the retina, uvea, and/or optic nerve. We retrospectively analyzed IOL patient data to identify treatment patterns and survival rates in Korea. METHODS: Cytological confirmation for a diagnosis of IOL was performed for all patients. The clinical data collected from medical records included Ann Arbor stage, International Prognostic Index, performance status, date of diagnosis, treatment modality and response, date of relapse, and date of last follow-up. RESULTS: Twenty patients who were diagnosed with IOL, between December 2007 and June 2014 at multiple centers in Korea, were included in the analysis. Four patients were diagnosed with IOL alone, not involving the CNS. Two patients with isolated IOL later developed PCNSL. Nine patients developed CNS lesions before the onset of ocular lymphoma. Five patients had simultaneous onset in the eye and CNS. Twelve patients were treated by intravitreal injection of methotrexate for IOL. The median progression-free survival (PFS) for patients was 19.7 months (95% CI, 8.7-30.7 mo). The estimated 3-year overall survival (OS) for all patients was 75.1%. CONCLUSION: Treatment for IOL patients included radiotherapy and intraocular chemotherapy. IOL patients showed favorable PFS and OS. These patients would require long-term follow-up to identify relapse and adverse effects of radiotherapy or intraocular chemotherapy.

Cardiac Arrest due to Recurrent Ventricular Fibrillation Triggered by Unifocal Ventricular Premature Complexes in a Silent Myocardial Infarction / 대한중환자의학회지

A 51-year-old male patient was referred for a sudden out-of-hospital cardiac arrest. Upon arrival, he was conscious and had no chest pain complaints. There was no abnormality in initial electrocardiographic and echocardiographic examinations. However, episodes of recurrent ventricular fibrillation (VF) were documented on rhythm monitoring. Each VF episode was triggered by an isolated monomorphic ventricular premature complex (VPC). Suspecting idiopathic VF, emergency radiofrequency catheter ablation was planned for the VPCs. However, when coronary angiography was performed to exclude silent ischemia, the results showed a total occlusion of the right coronary artery posterolateral branch, which is thought to supply the left ventricular inferior and septal wall. After successful reperfusion, VF episodes and the triggering VPCs disappeared. We are documenting this case to emphasize the potential for silent myocardial infarction to cause out-of-hospital sudden cardiac arrest even in a patient without any symptom or sign of acute coronary syndrome.

Cardiac Arrest due to Recurrent Ventricular Fibrillation Triggered by Unifocal Ventricular Premature Complexes in a Silent Myocardial Infarction / 대한구급학회지

A 51-year-old male patient was referred for a sudden out-of-hospital cardiac arrest. Upon arrival, he was conscious and had no chest pain complaints. There was no abnormality in initial electrocardiographic and echocardiographic examinations. However, episodes of recurrent ventricular fibrillation (VF) were documented on rhythm monitoring. Each VF episode was triggered by an isolated monomorphic ventricular premature complex (VPC). Suspecting idiopathic VF, emergency radiofrequency catheter ablation was planned for the VPCs. However, when coronary angiography was performed to exclude silent ischemia, the results showed a total occlusion of the right coronary artery posterolateral branch, which is thought to supply the left ventricular inferior and septal wall. After successful reperfusion, VF episodes and the triggering VPCs disappeared. We are documenting this case to emphasize the potential for silent myocardial infarction to cause out-of-hospital sudden cardiac arrest even in a patient without any symptom or sign of acute coronary syndrome.