The diagnostic significance of hepatitis C virus antibody levels for chronic hepatitis C virus infection

Background/Aims@#Although anti-hepatitis C virus (HCV) assay is widely used to screen for HCV infection, it has a high false-positive (FP) rate in low-risk populations. We investigated the accuracy of anti-HCV signal-to-cutoff (S/CO) ratio to distinguish true-positive (TP) from FP HCV infection. @*Methods@#We retrospectively analyzed 77,571 patients with anti-HCV results. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of anti-HCV S/CO ratio in anti-HCV positive patients. @*Results@#Overall, 1,126 patients tested anti-HCV positive; 34.7% of patients were FP based on HCV RNA and/or recombinant immunoblot assay (RIBA) results. The age and sex-adjusted anti-HCV prevalence was 1.22%. We identified significant differences in serum aspartate transaminase and alanine transaminase levels, anti-HCV S/CO ratio, and RIBA results between groups (viremia vs. non-viremia, TP vs. FP). Using ROC curves, the optimal cutoff values of anti-HCV S/CO ratio for HCV viremia and TP were 8 and 5, respectively. The area under the ROC curve, sensitivity, specificity, positive and negative predictive values were 0.970 (95% CI, 0.959–0.982, p < 0.001), 99.7%, 87.5%, 87.4%, and 99.7%, respectively, for predicting HCV viremia at an anti-HCV S/CO ratio of 8 and 0.987 (95% CI, 0.980–0.994, p < 0.001), 95.3%, 94.7%, 97.1%, and 91.4%, respectively, for TP HCV infection at an anti-HCV S/CO ratio of 5. No patients with HCV viremia had an anti-HCV S/CO ratio below 5. @*Conclusions@#The anti-HCV S/CO ratio is highly accurate for discriminating TP from FP HCV infection and should be considered when diagnosing HCV infections.

Delayed Migration of Tapered Open-Cell Design Carotid Stent: A Case Report / 신경중재치료의학

We present a case of delayed migration of an open-cell design carotid stent, which is a rare complication following carotid artery stenting (CAS). A 65-year-old patient with carotid artery stenosis underwent CAS with an open-cell stent, initially achieving successful deployment. However, 4 months later, the stent migrated and resulted in restenosis. The patient underwent balloon angioplasty and received an additional stent, leading to improved blood flow. The rarity of stent migration, particularly in the absence of risk factors, highlights the need for clinicians to be vigilant and consider early imaging follow-up for patients at risk of this complication after CAS.

Cardiac Amyloidosis in Autopsy Case of Sudden Unexpected Death / 대한법의학회지

A 78-year-old woman with a medical history of hypertension and diabetes mellitus who underwent surgery for lumbar stenosis died of sudden cardiac arrest two days after the operation. An autopsy was performed; however, the cause of death was not identified macroscopically. Congo red staining detected amyloid deposits in the systemic organs, including the heart, lungs, liver, thyroid, and kidney. Immunohistochemical staining revealed an immunoglobulin lambda light chain, which can cause the primary form of systemic amyloidosis. The prognosis of patients with systemic amyloidosis is directly associated with cardiac involvement. In this case, amyloid formation was noted in the myocardial interstitium and intramyocardial vascular wall, which caused luminal narrowing, subsequently causing arrhythmia and ischemic heart disease in each tissue, respectively. We present a case of primary systemic amyloidosis with severe cardiac involvement that was diagnosed after a comprehensive postmortem examination.

Minimal and Maximal Extent of Band Ligation for Acute Variceal Bleeding during the First Endoscopic Session

Background/aims@#The appropriate number of band ligations during the first endoscopic session for acute variceal bleeding is debatable. We aimed to compare the technical aspects of endoscopic variceal ligation (EVL) in patients with variceal bleeding according to the number of bands placed per session. @*Methods@#We retrospectively reviewed multicenter data from patients who underwent EVL for acute variceal bleeding. Patients were classified into minimal EVL (targeting only the foci with active bleeding or stigmata of recent bleeding) and maximal EVL (targeting potential bleeding sources in addition to the aforementioned targets) groups. The primary endpoint was 5-day treatment failure. The secondary endpoints were 30-day rebleeding, 30-day mortality, and intraprocedural adverse events. @*Results@#Minimal EVL was associated with lower rates of hypoxia and shock during EVL than maximal EVL (hypoxia, 0.9% vs 2.9%; shock, 1.3% vs 3.4%). However, treatment failure was higher in the minimal EVL group than in the maximal EVL group (odds ratio, 1.60; 95% confidence interval, 1.06 to 2.41). Age ≥60 years, Model for End-Stage Liver Disease score ≥15, Child-Turcotte-Pugh classification C, presence of hepatocellular carcinoma, and systolic blood pressure <90 mm Hg at initial presentation were also associated with treatment failure. In contrast, 30-day rebleeding and 30-day mortality did not differ between the minimal and maximal EVL groups. @*Conclusions@#Given that minimal EVL was associated with a high risk of treatment failure, maximal EVL may be a better option for variceal bleeding. However, the minimal EVL strategy should be considered in select patients because it does not affect 30-day rebleeding and mortality.

Atorvastatin Induces FXR and CYP7A1 Activation as a Result of the Sequential Action of PPARγ/PGC-1α/HNF-4α in Hep3B Cells / 대한소화기학회지

Background/Aims@#PPARγ, farnesoid X receptor (FXR) and CYP7A1 are associated with solubility of bile. This study was performed to understand a mechanism and interactions of statin-induced PPARγ, PGC-1α and HNF-4α related to the statin-induced activation of FXR and CYP7A1, and verify whether the mevalonate pathway is involved in the mechanism. @*Methods@#MTT assays were performed using cultured human Hep3B cells to determine the effect of atorvastatin on the cell proliferation. Expression levels of indicated proteins were measured using Western blotting assays by inhibiting the protein expression or not. @*Results@#Atorvastatin increased expression of PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. PPARγ ligand of troglitazone upregulated the expression of PGC-1α, HNF-4α, FXR, and CYP7A1 in Hep3B cells. Silencing of PPARγ, PGC1α, and HNF4α using respective siRNA demonstrated that atorvastatin-induced FXR and CYP7A1 activation required sequential action of PPARγ /PGC-1α/HNF-4α. The silencing of PPARγ completely inhibited atorvastatin-induced PGC-1α expression, and the PGC1α silencing partially inhibited atorvastatin-induced PPARγ expression. The inhibition of HNF4α did not affect atorvastatin-induced PPARγ expression, but partially inhibited atorvastatin-induced PGC-1α expression. Besides, mevalonate completely reversed the effect of atorvastatin on PPARγ, PGC-1α, HNF-4α, FXR, and CYP7A1. @*Conclusions@#Atorvastatin induces FXR and CYP7A1 activation as a result of sequential action of PPARγ/PGC-1α/HNF-4α in human hepatocytes. We propose that atorvastatin enhances solubility of cholesterol in bile by simultaneously activating of FXR and CYP7A1.

Personalized Urination Activity Management Based on an Intelligent System Using a Wearable Device / 대한배뇨장애요실금학회지

Purpose@#In this study, a urinary management system was established to collect and analyze urinary time and interval data detected through patient-worn smart bands, and the results of the analysis were shown through a web-based visualization to enable monitoring and appropriate feedback for urological patients. @*Methods@#We designed a device that can recognize urination time and spacing based on patient-specific posture and consistent posture changes, and we built a urination patient management system based on this device. The order of body movements during urination was consistent in terms of time characteristics; therefore, sequential data were analyzed and urinary activity was recognized using repeated neural networks and long-term short-term memory systems. The results were implemented as a web (HTML5) service program, enabling visual support for clinical diagnostic assistance. @*Results@#Experiments were conducted to evaluate the performance of the proposed recognition techniques. The effectiveness of smart band monitoring urination was evaluated in 30 men (average age, 28.73 years; range, 26–34 years) without urination problems. The entire experiment lasted a total of 3 days. The final accuracy of the algorithm was calculated based on urological clinical guidelines. This experiment showed a high average accuracy of 95.8%, demonstrating the soundness of the proposed algorithm. @*Conclusions@#This urinary activity management system showed high accuracy and was applied in a clinical environment to characterize patients’ urinary patterns. As wearable devices are developed and generalized, algorithms capable of detecting certain sequential body motor patterns that reflect certain physiological behaviors can be a new methodology for studying human physiological behaviors. It is also thought that these systems will have a significant impact on diagnostic assistance for clinicians.

Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation

Background and Objectives@#Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. @*Methods@#Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. @*Results@#mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). @*Conclusions@#Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

Personalized Urination Activity Management Based on an Intelligent System Using a Wearable Device / 대한배뇨장애요실금학회지

Purpose@#In this study, a urinary management system was established to collect and analyze urinary time and interval data detected through patient-worn smart bands, and the results of the analysis were shown through a web-based visualization to enable monitoring and appropriate feedback for urological patients. @*Methods@#We designed a device that can recognize urination time and spacing based on patient-specific posture and consistent posture changes, and we built a urination patient management system based on this device. The order of body movements during urination was consistent in terms of time characteristics; therefore, sequential data were analyzed and urinary activity was recognized using repeated neural networks and long-term short-term memory systems. The results were implemented as a web (HTML5) service program, enabling visual support for clinical diagnostic assistance. @*Results@#Experiments were conducted to evaluate the performance of the proposed recognition techniques. The effectiveness of smart band monitoring urination was evaluated in 30 men (average age, 28.73 years; range, 26–34 years) without urination problems. The entire experiment lasted a total of 3 days. The final accuracy of the algorithm was calculated based on urological clinical guidelines. This experiment showed a high average accuracy of 95.8%, demonstrating the soundness of the proposed algorithm. @*Conclusions@#This urinary activity management system showed high accuracy and was applied in a clinical environment to characterize patients’ urinary patterns. As wearable devices are developed and generalized, algorithms capable of detecting certain sequential body motor patterns that reflect certain physiological behaviors can be a new methodology for studying human physiological behaviors. It is also thought that these systems will have a significant impact on diagnostic assistance for clinicians.

Clinical predicting factors that can distinguish superficial and deep injuries in penetrating neck injury?

Objective@#The frequency of penetrating neck injuries has gradually increased with the development of industry and the rising crime rates. There have been few studies with penetrating neck injuries reported in Korea. Thus, we analyzed clinical factors that could differentiate between superficial and deep injuries in patients with penetrating neck injuries. @*Methods@#We investigated the medical records of 90 patients with penetrating neck injuries who visited the emergency department between January 2010 and March 2020. To identify the degree of injuries, we compared age, sex, onset and arrival time, onset-to-arrival time, initial vital signs, Glasgow Coma Scale, Revised Trauma Score, cause, mechanism, location and number of injuries, anatomical zone, alcohol intake and psychiatric history were classified as early clinical factors. @*Results@#Among 90 patients, 51 had superficial injuries, and 39 had deep injuries. The early clinical factors showing statistically significant differences were the Glasgow Coma Scale, Revised Trauma Score, cause of injury and anatomical zones. As the Glasgow Coma Scale increased by 1 point, deep injuries decreased by 0.807 times compared to superficial injuries. Homicidal injuries were 3.233 times deeper than suicidal injuries. @*Conclusion@#If the Glasgow Coma Scale is low or the cause of injury is homicide, the possibility of a deep penetrating injury is high. Therefore, it is important to treat the patient carefully, considering these factors.

Percutaneous Left Atrial Appendage Occlusion Yields Favorable Neurological Outcomes in Patients with Non-Valvular Atrial Fibrillation

Background and Objectives@#Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. @*Methods@#Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. @*Results@#mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). @*Conclusions@#Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.

Prediction of Early Recanalization after Intravenous Thrombolysis in Patients with Large-Vessel Occlusion / 대한뇌졸중학회지

Background@#and Purpose We aimed to develop a model predicting early recanalization after intravenous tissue plasminogen activator (t-PA) treatment in large-vessel occlusion. @*Methods@#Using data from two different multicenter prospective cohorts, we determined the factors associated with early recanalization immediately after t-PA in stroke patients with large-vessel occlusion, and developed and validated a prediction model for early recanalization. Clot volume was semiautomatically measured on thin-section computed tomography using software, and the degree of collaterals was determined using the Tan score. Follow-up angiographic studies were performed immediately after t-PA treatment to assess early recanalization. @*Results@#Early recanalization, assessed 61.0±44.7 minutes after t-PA bolus, was achieved in 15.5% (15/97) in the derivation cohort and in 10.5% (8/76) in the validation cohort. Clot volume (odds ratio [OR], 0.979; 95% confidence interval [CI], 0.961 to 0.997; P=0.020) and good collaterals (OR, 6.129; 95% CI, 1.592 to 23.594; P=0.008) were significant factors associated with early recanalization. The area under the curve (AUC) of the model including clot volume was 0.819 (95% CI, 0.720 to 0.917) and 0.842 (95% CI, 0.746 to 0.938) in the derivation and validation cohorts, respectively. The AUC improved when good collaterals were added (derivation cohort: AUC, 0.876; 95% CI, 0.802 to 0.950; P=0.164; validation cohort: AUC, 0.949; 95% CI, 0.886 to 1.000; P=0.036). The integrated discrimination improvement also showed significantly improved prediction (0.097; 95% CI, 0.009 to 0.185; P=0.032). @*Conclusions@#The model using clot volume and collaterals predicted early recanalization after intravenous t-PA and had a high performance. This model may aid in determining the recanalization treatment strategy in stroke patients with large-vessel occlusion.

The effectiveness of interprofessional education programs for medical, nursing, and pharmacy students / 한국의학교육

Purpose@#This study is to develop an interprofessional education (IPE) program for medical, nursing, and pharmacy students and to analyze the effectiveness. @*Methods@#Subjects consisted of 116 students (41 medical, 46 nursing, and 29 pharmacy students) enrolled in their final year. Subjects were randomly assigned to either the intervention group or the control group, with 58 in each group. A pretest-posttest control group design was used. The program was operated for a single day, and consisted of small-group activities and role-play. We utilized the following tools: Perceptions towards Interprofessional Education (PIPE), Self-Efficacy for Interprofessional Experiential Learning (SEIEL), and Perception towards Interprofessional Competency (PIC). We used t-test and analysis of covariance for analysis. @*Results@#The PIPE tool revealed that the scores of the intervention group were significantly higher than those of the control group (p=0.000). The result was the same when the scores were categorized into the groups medical students (p=0.001), nursing students (p=0.000), and pharmacy students (p=0.005). The SEIEL study also indicated the intervention group scored significantly higher than the control group (p=0.000). However, pharmacy students did not reveal significant (p=0.983). The intervention group scored significantly higher than the control group in the PIC. A concluding survey of the intervention group indicated that most students were satisfied with the IPE program. @*Conclusion@#We hope this study will provide useful information for designing and improving IPE programs in other universities.

Appropriateness of the Use of Navigation System in Total Knee Arthroplasty

Background@#The aim of this study was to evaluate the difference between the planned and verified actual values in total knee arthroplasty (TKA) performed using a navigation system. @*Methods@#Sixty patients who underwent primary TKA for knee pain from March 2018 to July 2018 were included in this study.All patients underwent TKA using the latest version of a computer navigation system (Kick ver. 2.6). All TKA procedures were performed by the same surgeon. The appropriateness of the use of navigation system in each of the several steps during the operation was investigated. Implant size was assessed using a preoperative template and after registration of landmarks with the navigation system. Intraoperative measurement was conducted using a femoral sizing implant apparatus. The difference between the planned value based on the navigation system and the actual cutting value was investigated. Intraoperatively confirmed hip-knee-ankle angle was also compared to the angle measured at postoperative 3 months. @*Results@#The average time spent on the registration process was 242 seconds (range, 205–345 seconds). Intraoperative femoral component size tended to be smaller than the size recommended by the navigation system. A significant difference between the planned distal femoral cutting level (9.08 ± 0.40 mm) and the verified actual cutting level (9.87 ± 1.39 mm) was identified (p < 0.05).The difference between the planned lateral and medial tibial resection levels (10.12 ± 0.34 mm and 4.47 ± 2.17 mm, respectively) and the verified actual lateral and medial tibial resection levels (9.07 ± 1.45 mm and 3.48 ± 2.00 mm, respectively) was statistically significant. Distal femoral cutting angle in sagittal plane was significantly different but femoral and tibial cutting angles showed no significant difference between the planned and verified values. At full extension, the average coronal alignment of the implant recorded after insertion of the actual implant using the navigation system was 0.23° ± 0.51° varus and showed no significant difference from the alignment measured at postoperative 3 months (0.45° ± 0.58°). @*Conclusions@#When performing navigation-assisted TKA, surgeons should aware that frequent errors can occur on the femoral cutting level, tibial cutting level, and implant sizing despite its reported advantage in defining the mechanical limb axis.

Screening of Endophytic Fungal Isolates Against Raffaelea quercus-mongolicae Causing Oak Wilt Disease in Korea

Oak wilt disease caused by Raffaelea quercus-mongolicae has emerged obviously in Korea. We selected antifungal isolates against R. quercus-mongolicae among 368 endophytic fungal isolates from different parts of oak and pine trees. The experiment was conducted in the primary and secondary screenings by dual culture test. The antifungal activity of the selected isolates was assessed in culture filtrate test based on the inhibition rates in mycelial growth, sporulation, and spore germination of oak wilt fungus. Five isolates, E089, E199, E282, E409 and E415, showed strong antifungal activity in culture filtrate test, and their antifungal activity decreased on the culture media supplemented with heated culture filtrate. Higher mycelial growth inhibitions on the unheated media were recorded in E409 (Colletotrichum acutatum), E089 (Daldinia childiae), E415 (Alternaria alternata) and E199 (Daldinia childiae) with the inhibition rates of 79.0%, 70.1%, 68.9% and 64.5%, respectively. These isolates also had the higher sporulation inhibitions on unheated media with the rates of 96.8%, 84.2%, 82.8% and 80.5%, respectively. The spore germination of the oak wilt fungus was completely inhibited by E282 (Nectria balsamea) on both unheated and heated media. These results showed that a higher number of potent antifungal isolates against oak wilt fungus was isolated from the petiole compared to the other parts. This study could contribute to the development of biological control approaches for the management of oak wilt disease caused by R. quercus-mongolicae.

Screening of Endophytic Fungal Isolates Against Raffaelea quercus-mongolicae Causing Oak Wilt Disease in Korea

Oak wilt disease caused by Raffaelea quercus-mongolicae has emerged obviously in Korea. We selected antifungal isolates against R. quercus-mongolicae among 368 endophytic fungal isolates from different parts of oak and pine trees. The experiment was conducted in the primary and secondary screenings by dual culture test. The antifungal activity of the selected isolates was assessed in culture filtrate test based on the inhibition rates in mycelial growth, sporulation, and spore germination of oak wilt fungus. Five isolates, E089, E199, E282, E409 and E415, showed strong antifungal activity in culture filtrate test, and their antifungal activity decreased on the culture media supplemented with heated culture filtrate. Higher mycelial growth inhibitions on the unheated media were recorded in E409 (Colletotrichum acutatum), E089 (Daldinia childiae), E415 (Alternaria alternata) and E199 (Daldinia childiae) with the inhibition rates of 79.0%, 70.1%, 68.9% and 64.5%, respectively. These isolates also had the higher sporulation inhibitions on unheated media with the rates of 96.8%, 84.2%, 82.8% and 80.5%, respectively. The spore germination of the oak wilt fungus was completely inhibited by E282 (Nectria balsamea) on both unheated and heated media. These results showed that a higher number of potent antifungal isolates against oak wilt fungus was isolated from the petiole compared to the other parts. This study could contribute to the development of biological control approaches for the management of oak wilt disease caused by R. quercus-mongolicae.

Association between Expression of 8-OHdG and Cigarette Smoking in Non-small Cell Lung Cancer

BACKGROUND: Exposure to cigarette smoking (CS) is a major risk factor for the development of lung cancer. CS is known to cause oxidative DNA damage and mutation of tumor-related genes, and these factors are involved in carcinogenesis. 8-Hydroxydeoxyguanosine (8-OHdG) is considered to be a reliable biomarker for oxidative DNA damage. Increased levels of 8-OHdG are associated with a number of pathological conditions, including cancer. There are no reports on the expression of 8-OHdG by immunohistochemistry in non-small cell lung cancer (NSCLC). METHODS: We investigated the expression of 8-OHdG and p53 in 203 NSCLC tissues using immunohistochemistry and correlated it with clinicopathological features including smoking. RESULTS: The expression of 8-OHdG was observed in 83.3% of NSCLC. It was significantly correlated with a low T category, negative lymph node status, never-smoker, and longer overall survival (p < .05) by univariate analysis. But multivariate analysis revealed that 8-OHdG was not an independent prognostic factor for overall survival in NSCLC patients. The aberrant expression of p53 significantly correlated with smoking, male, squamous cell carcinoma, and Ki-67 positivity (p < .05). CONCLUSIONS: The expression of 8-OHdG was associated with good prognostic factors. It was positively correlated with never-smokers in NSCLC, suggesting that oxidative damage of DNA cannot be explained by smoking alone and may depend on complex control mechanisms.

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer

BACKGROUND: Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear. METHODS: We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed. RESULTS: Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort. CONCLUSIONS: Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Analysis of Present Status for Surgery of Benign Prostatic Hyperplasia in Korea Using Nationwide Healthcare System Data / 대한배뇨장애요실금학회지

PURPOSE: There are no established statistical data available for the comparison of different surgical methods adopted for the resection of benign prostatic hyperplasia (BPH). This study investigates the present status related to BPH surgery in Korea for the past 8 years. METHODS: National-level data from the National Health Insurance Service and National Statistical Office were analyzed in this study. From 2010 to 2017, the trends of surgeries for BPH were reviewed according to the procedure code including transurethral resection of the prostate (TURP), holmium laser enucleation of the prostate (HoLEP), or high-power potassium titanyl phosphate (KTP), and this trend also analyzed by age, geographic distribution, and hospital type. RESULTS: Over the past 8 years, there was not much change in the total number of BPH-related surgeries (range, 10,393– 11,072). Although there was not much alteration in the number of conventional TURP (from 6,801 in 2010 to 6,645 in 2017), the number of HoLEP has dramatically increased (from 278 in 2010 to 3,805 in 2017). The number of HoLEP surgeries after 2011 exceeded the number of surgeries using KTP, and the gap is anticipated to rise. The number of surgeries by age group was most common in the 70s and the total number of surgeries is decreasing in all age groups; for HoLEP, the trend is steadily increasing over the age of 60 years. Most of the BPH surgeries were performed in metropolitan areas, such as Seoul, Gyeonggi-do, and Busan, and in larger hospitals compared to smaller hospital settings. CONCLUSIONS: Through the data of the National Health Insurance Service, we could apprehend the present status of BPH-related surgery in Korea. Then, we could know about the trend according to several factors and we think these results will be valuable as academic references as well.

PI3Kδ contributes to ER stress-associated asthma through ER-redox disturbances: the involvement of the RIDD–RIG-I–NF-κB axis

Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model. In OVA/LPS-induced asthmatic mice, the activity of PI3K, downstream phosphorylation of AKT and activation of nuclear factor-κB (NF-κB) were all significantly elevated; these effects were reversed by IC87114. IC87114 treatment also reduced the OVA/LPS-induced ER stress response by enhancing the intra-ER oxidative folding status through suppression of protein disulfide isomerase activity, ER-associated reactive oxygen species (ROS) accumulation and NOX4 activity. Furthermore, inositol-requiring enzyme-1α (IRE1α)-dependent degradation (RIDD) of IRE1α was reduced by IC87114, resulting in a decreased release of proinflammatory cytokines from bronchial epithelial cells. These results suggest that PI3Kδ may induce severe airway inflammation and hyperresponsiveness by activating NF-κB signaling through ER-associated ROS and RIDD–RIG-I activation. The PI3Kδ inhibitor IC87114 is a potential therapeutic agent against neutrophil-dominant asthma.