Prevalence, incidence, and outcomes of hepatitis E virus coinfection in patients with chronic hepatitis C.

This study aimed to elucidate the anti-hepatitis E virus (HEV) immunoglobulin G (IgG) prevalence and incidence of seroconversion and seroreversion as well as its risk factors and to analyze the clinical outcomes of HEV and hepatitis C virus (HCV) coinfected patients compared to those of HCV-monoinfected patients. We prospectively enrolled 502 viremic HCV patients with paired plasma samples (at intervals of ≥ 12 months) from 5 tertiary hospitals. Anti-HEV IgG positivity was tested using the Wantai ELISA kit in all paired samples. Mean age was 58.2 ± 11.5 years old, 48.2% were male, 29.9% of patients had liver cirrhosis, and 9.4% of patients were diagnosed with hepatocellular carcinoma (HCC). The overall prevalence of anti-HEV IgG positivity at enrollment was 33.3%, with a higher prevalence in males and increasing prevalence according to the subject's age. During the 916.4 person-year, the HEV incidence rate was 0.98/100 person-years (9/335, 2.7%). Hepatic decompensation or liver-related mortality was not observed. There were six seroreversion cases among 172 anti-HEV-positive patients (1.22/100 person-years). In conclusion, approximately one-third of the adult Korean chronic HCV patients were anti-HEV IgG positive. The HEV incidence rate was 1 in 100 persons per year, without adverse hepatic outcomes or mortality.

Etiology and clinical characteristics of acute viral hepatitis in South Korea during 2020-2021: a prospective multicenter study.

This prospective, 12-center study investigated the etiology and clinical characteristics of acute viral hepatitis (AVH) during 2020-2021 in South Korea, and the performance of different diagnostic methods for hepatitis E virus (HEV). We enrolled 428 patients with acute hepatitis, of whom 160 (37.4%) were diagnosed with AVH according to predefined serologic criteria. The clinical data and risk factors for AVH were analyzed. For hepatitis E patients, anti-HEV IgM and IgG were tested with two commercial ELISA kits (Abia and Wantai) with HEV-RNA real-time RT-PCR. HAV, HEV, HBV, HCV, Epstein-Barr virus (EBV), cytomegalovirus, and herpes simplex virus accounted for AVH in 78.8% (n = 126), 7.5% (n = 12), 3.1% (n = 5), 1.9% (n = 3), 6.9% (n = 11), 1.2% (n = 2), and 0.6% (n = 1) of 160 patients (median age, 43 years; men, 52.5%; median ALT, 2144 IU/L), respectively. Hospitalization, hemodialysis, and intensive care unit admission were required in 137 (86.7%), 5 (3.2%), and 1 (0.6%) patient, respectively. Two patients developed acute liver failure (1.3%), albeit without mortality or liver transplantation. Ingestion of uncooked clams/oysters and wild boars' blood/bile was reported in 40.5% and 16.7% of patients with HAV and HEV, respectively. The concordance rate between the anti-HEV-IgM results of both ELISA kits was 50%. HEV RNA was detected in only 17% of patients with HEV. The diagnosis of HEV needs clinical consideration due to incomplete HEV diagnostics.

Soluble Programmed Cell Death Ligand-1 (sPD-L1) Levels in Various Cancer Types and Normal Populations.

BACKGROUND: To date, PD-L1 expression in tumor tissue, assessed by immunohistochemical stain, is clinically applicable as a predictive companion biomarker for PD-1/PD-L1 inhibitor which has been highlighted over the past several years. Before blood-based sPD-L1 enters clinical use, it is critical to establish the reference range. This study was designed to investigate soluble sPD-L1 levels in various cancer patients and normal population. METHODS: For the detection of sPD-L1, 4 cancer groups (hepatocellular carcinoma, lung cancer, bladder cancer, gastric cancer) and healthy volunteers' samples were analyzed using an ELISA kit. Using a receiver operating characteristic curve, optimal sPD-L1 cutoff levels were determined. RESULTS: The mean serum sPD-L1 level of the normal population was 59.97 pg/mL (range; 23.780 - 115.2 pg/mL). In various cancer types, serum sPD-L1 levels ranged from 38.696 pg/mL to 228.77 pg/mL, and cutoff values under AUC ranged from 60.307 pg/mL to 64.371 pg/mL. CONCLUSIONS: sPD-L1 can be used as a screening biomarker in various cancer patients referring to optimal cutoff levels suggested.

The effect of polycyclic aromatic hydrocarbons on changes in the brain structure of firefighters: An analysis using data from the Firefighters Research on Enhancement of Safety & Health study.

Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic matter, and firefighters are highly exposed to these toxic compounds at fire sites. Exposure to PAHs can cause cognitive decline and neurodegeneration; however, to date, few studies have examined the potential effects of PAH exposure on structural changes in the brain. We aimed to investigate the association between the four types of PAH metabolites and the corresponding changes in neuroimaging markers based on smoking status and hypertension in male firefighters. For this, we utilized the 2-year follow-up data of 301 Korean male firefighters aged over 40 years. The concentrations of four PAH metabolites in urine were measured. Subcortical volume and cortical thickness were estimated using 3 T magnetic resonance imaging of the brain. A generalized linear model was used to investigate the effects of PAHs on changes in the subcortical volume and cortical thickness. We found an association between 1-hydroxyphenathrene (1-OHPHE) and 2-hydroxyfluorene (2-OHF) and changes in several brain regions in all the study participants. Individuals who had never smoked showed significantly thinner frontal (p < 0.001), parietal (p < 0.001), temporal (p < 0.001), and cingulate lobes (p < 0.001) with 1% increase each in the urinary concentration of 1-OHPHE. Hypertension interacted with the concentration of 1-OHPHE to reduce the volume of gray matter and cause cortical thinning in the frontal, parietal, and temporal lobes. Exposure to PAHs may reduce cortical thickness and subcortical volume, which are definitive markers of neurodegeneration. Notably, hypertension can accelerate the degenerative effects of PAHs.

Colonoscopy Versus Fecal Immunochemical Test for Reducing Colorectal Cancer Risk: A Population-Based Case-Control Study.

INTRODUCTION: Use of colonoscopy or the fecal immunochemical test (FIT) for colorectal cancer (CRC) prevention is supported by previous studies. However, there is little specific evidence regarding comparative effectiveness of colonoscopy or FIT for reducing CRC risk. In this study, we compared the association of CRC risk with colonoscopy and FIT using a nationwide database. METHODS: This population-based case-control study used colonoscopy and FIT claims data from the Korean National Health Insurance System from 2002 to 2013. Data were analyzed from 61,221 patients with newly diagnosed CRC (case group) and 306,099 individuals without CRC (control group). Multivariable logistic regression models were used to evaluate the association between CRC and colonoscopy or FIT. RESULTS: Colonoscopy was associated with a reduced subsequent CRC risk (adjusted odds ratio [OR] 0.29). Stronger associations were found between colonoscopy and distal CRC, compared with proximal CRC (0.24 vs 0.47). In an analysis stratified by sex, the association was weaker in female subjects compared with male subjects (0.33 vs 0.27). Any FIT exposure was associated with CRC risk with an OR of 0.74; this association was stronger for distal cancer. As the frequency of cumulative FIT assessments increased (from 1 to ≥5), the OR of FIT exposure for CRC gradually decreased from 0.81 to 0.45. DISCUSSION: The association of colonoscopy or FIT with reduced CRC risk was stronger for distal CRC than for proximal CRC. FIT showed less CRC risk reduction than colonoscopy. However, as the frequency of cumulative FIT assessments increased, the association with CRC prevention became stronger.

Novel indel mutation in the N gene of SARS-CoV-2 clinical samples that were diagnosed positive in a commercial RT-PCR assay.

Commercially available reverse transcription-polymerase chain reaction (RT-PCR) kits are being used as an important tool to diagnose SARS-CoV-2 infection in clinical laboratories worldwide. However, some kits lack sufficient clinical evaluation due to the need for emergency use caused by the current COVID-19 pandemic. Here we found that a novel insertion/deletion mutation in the nucleocapsid (N) gene of SARS-CoV-2 samples is a cause of negative results for the N gene in a widely used assay that received emergency use authorization (EUA) from US FDA and Conformite Europeenne-in vitro diagnostics (CE-IVD) from EU. Although SARS-CoV-2 is diagnosed positive by other target probes in the assay, our findings provide an evidence of the genetic variability and rapid evolution of SARS-CoV-2 as well as a reference in designing commercial RT-PCR assays.

Relationship between calf muscle cross-sectional area and ankle fracture.

BACKGROUND: Whether calf muscles and peroneal muscles have a role in the occurrence of an ankle fractures remains unclear. This study aimed to quantify the calf muscle mass and peroneal muscle mass in patients with an ankle fracture and in controls, then to analyze them together with demographic factors to identify the effects of the regional muscles on the risk of developing ankle fracture. METHODS: A total of 101 ankles with computed tomography (CT) images were retrospectively reviewed. Of them, 51 ankles showed fractures (all unilateral) and 50 ankles, in controls who underwent CT for screening the other diseases, were clinically diagnosed with simple contusion. The cross-sectional areas (CSA) of the calf muscles and the peroneal muscles were measured at approximately 6 cm above the Achilles myotendinous junction in the axial plane of ankle CT. These parameters were compared between the two groups and analyzed with respect to age, sex, body mass index (BMI), laterality, and bone attenuations of the ankle. RESULTS: The demographic factors, including bone attenuation of the ankle showed no significant association with ankle fracture. The ratio of the CSA of the peroneal muscle group to the CSA of the entire calf muscle group was smaller in patients with an fracture (0.12 ± 0.03) than in controls (0.14 ± 0.02) (p = 0.027). The odds ratio for the effect of the calf muscle CSA on the risk of developing ankle fractures was 1.38 (95% confidence interval 1.12-1.69, p = 0.003), whereas that for the effect of peroneal muscle CSA on the risk of developing ankle fractures was 0.18 (95% confidence interval 0.05 to 0.66, p = 0.010). CONCLUSION: The ratio of the peroneal muscle CSA to the entire calf muscle CSA was negatively related to the occurrence of ankle fractures in this study. Further prospective studies on whether peroneal muscle-strengthening exercise are effective in preventing ankle fractures may be needed. LEVEL OF EVIDENCE: III, case-control study.

Inhibitory effect of modified silkworm pupae oil in PDGF-BB-induced proliferation and migration of vascular smooth muscle cells.

Silkworm pupae oil (SPO) has been reported to have various biological activities in improving blood circulation. However, the protective action of SPO against vascular disorders remains unknown. A new formulation of SPO was prepared through an esterification and saponification process. The composition of unsaturated fatty acids in silkworm pupae oil sodium salt (SPOS) was then analyzed by LC/MS to show α-linolenic acid (11.0%), linoleic acid (73.2%), palmitic acid (3.1%), oleic acid (12.0%), and stearic acid (0.7%). The in vitro studies were performed to find out the efficacy of SPOS on platelet-derived growth factor (PDGF-BB) induced vascular smooth muscle cell (VSMC) migration and proliferation. PDGF-BB (10 ng/mL) induced abnormal migration and proliferation of VSMCs, whereas exposure to SPOS (30 µg/mL) significantly reduced the PDGF-BB-induced cell migration and proliferation. The extracellular signal-regulated kinase1/2 (ERK1/2) and phosphorylation of ERK1/2 were determined by immunoblot analysis and the ERK1/2 phosphorylation in PDGF-BB-stimulated VSMCs was downregulated by SPOS (30 µg/mL) treatment. These results indicate that SPOS may be a helpful and useful agent as a functional food and drug against vascular disorders.

Interaction between the tumor microenvironment and resection margin in different gross types of hepatocellular carcinoma.

BACKGROUND AND AIM: There is no consensus regarding the safe resection margin in hepatocellular carcinoma (HCC). Several studies reported that different gross types require different resection margins. We investigated the changes in the tumor microenvironment (TME) in different gross types of HCC. METHODS: We selected tumor tissue and normal tissue 1 and 2 cm away from the HCC. We analyzed the expression status of TME genes and the correlation between TME genes and the effective resection margin. We further divided the patients into two groups: group 1 included expanding and vaguely nodular types, whereas group 2 included nodular with perinodular extension, multinodular confluent, and infiltrative types. RESULTS: Group 2 showed 27% and 45% 5-year disease-free survival (DFS) and overall survival (OS) rates, respectively. Group 2 was a significant prognostic factor for DFS and OS. In cases with a resection margin of less than 1 cm or more than 2 cm, there were no differences in recurrence and survival rate between the two groups. Group 1 patients who had a resection margin that ranged from 1 to 2 cm showed significantly better DFS and OS rates. ß-Catenin and matrix metalloproteinase 9 expression was significantly decreased and that of E-cadherin was significantly increased according to the resection margin in group 1. CONCLUSIONS: Patients with expanding and vaguely nodular HCC may safely undergo surgical resection with a narrow resection margin, and patients with the other gross types must undergo surgical resection with more than a 2-cm resection margin because of their TME conditions.

Complications Following Colonoscopy in a Nationwide Standard Cohort: A Retrospective Case-control Study.

Background/Aims: Despite the many reports of colonoscopy complications worldwide, few studies have been performed at the population level in Korea. In this study, a population-based study was performed to evaluate the incidence of post-colonoscopy perforations compared to a control group. Methods: Between January 2011 and December 2011, data for all cases (age over 45) who underwent a colonoscopy were collected from National Health Insurance Service using a random sampling method. The clinical characteristics and perforation incidence (within 30 days after the colonoscopy) of cases were identified, and cases were then compared with controls who had not undergone a colonoscopy. Results: Among 1,380,000 subjects, 31,177 cases and 62,354 controls were identified. Perforation occurred in 14 patients (0.04%) in the case group and one patient (<0.01%) in the control group (RR, 28.0; 95% CI 3.7-212.9, p<0.001). Subgroup analysis was followed according to the endoscopic procedure, gender and age. In subgroup analysis, colonoscopy-associated perforations occurred more in the therapeutic procedure (RR, 26; 95% CI 1.46-461.46), male (RR, 50; 95% CI 2.96-844.41), and age of 45-60 years (RR, 30; 95% CI 1.71-525.23). Conclusions: A colonoscopy procedure is related to an increased risk of perforation at the population level. In addition, the therapeutic procedure, male, and age of 45-60 years appeared to be associated with an increased risk of perforation.

A Comparative Study of Tensile Strength of Three Operative Fixation Techniques for Metacarpal Shaft Fractures in Adults: A Cadaver Study.

BACKGROUND: We sought to estimate the ultimate tensile strength after metacarpal shaft fracture repair in adults using three operative fixation methods: plate fixation, Kirschner wire (K-wire) fixation, and intramedullary headless compression screw fixation. We also compared the advantages and disadvantages of each operative technique. METHODS: We acquired 30 metacarpal bones from four Korean adult cadavers without trauma, operative history, or deformities. The 30 metacarpal bones were divided into ten groups consisting of three metacarpal bones each with matching sizes and lengths. They were fractured, reduced, and fixed with plate and screws, K-wires, or headless compression screws. We performed force testing, collected ultimate tensile strength data, and created a stress-strain graph. RESULTS: The ultimate tensile strength of ten groups according to the fixation method was as follows: late and screw fixation, 246.1 N (range, 175.3 to 452.4 N); K-wire fixation, 134.6 N (62.7 to 175.0 N); and intramedullary headless compression screw fixation, 181.2 N (119.2 to 211.7 N). The median tensile strength of each fixation method was significantly different. In addition, the post-hoc test showed significant difference between the plate and screw fixation and K-wire fixation, between the headless compression screw fixation and K-wire fixation, and between the headless compression screw fixation and plate and screw fixation. CONCLUSIONS: The tensile strength median values decreased in the following order showing significant differences among the fixation methods: plate and screw fixation, headless compression screw fixation, K-wire fixation. Significant differences were also observed between the plate and screw fixation and K-wire fixation, between the headless compression screw fixation and K-wire fixation, and between the headless compression screw fixation and plate and screw fixation.

Resveratrol down-regulates a glutamate-induced tissue plasminogen activator via Erk and AMPK/mTOR pathways in rat primary cortical neurons.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene, RSV) is a polyphenolic compound present in a variety of plant species (including grapes) that produces a myriad of biological activities including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we investigate the effects of resveratrol on the basal and glutamate-stimulated expression and activity of a tissue plasminogen activator (tPA) that plays neuromodulatory or neurotoxic roles in many different neurological situations. Under basal conditions, resveratrol decreased the tPA expression and activity without affecting the tPA mRNA level in rat primary cortical neurons. RSV induced AMPK phosphorylation and inhibited mTOR phosphorylation. Inhibition of AMPK phosphorylation using compound C prevented resveratrol-induced down-regulation of tPA activity. This suggested that AMPK/mTOR-dependent translational inhibition contributes to the down-regulation of the tPA. Under glutamate-stimulated conditions of rat primary cortical neurons, tPA activity and expression were increased along with increased tPA mRNA expression but afterward treatment of RSV inhibited the glutamate-induced increase in tPA activity and expression and tPA mRNA expression. Glutamate stimulation induced activation of Akt and MAPK pathways as well as mTOR which were inhibited by RSV. Interestingly, the Erk pathway inhibitor U0126, but neither PI3K-Akt inhibitor LY294002 nor p38 inhibitor SB203580, mimicked the inhibitory action of RSV on glutamate-induced tPA up-regulation. This suggested the essential role of Erk in the transcriptional up-regulation of tPA expression, which is targeted by RSV. Glutamate stimulation induced neuronal cell death as determined by PI staining and MTT assay. However, RSV protected the cultured rat primary cortical neurons from glutamate-induced cell death as paralleled with the changes in tPA expression. These results suggested that RSV can modulate tPA activity under basal and stimulated conditions by both translational and transcriptional mechanisms. The regulation of the tPA by RSV provides additional therapeutic targets on top of the growing number of molecular substrates of RSV's action in the brain.

Clinical and histological characteristics of melanocytic nevus in external auditory canals and auricles.

Nevi, which consist of nevus cells arising from external auditory canals (EACs) and auricles, are rare and their characteristics are not thoroughly understood. The purpose of this study was to analyze the clinicopathological characteristics of melanocytic nevus (MN) in EACs and auricles. Medical records were reviewed in 35 cases with junctional, compound and intradermal nevi treated in Ajou University Hospital, Korea between 2001 and 2011. Patient demographic, location, shape, and diameter of nevi, and pathologic results were analyzed according to the location, EACs (23 cases) and auricles (12 cases). Female predominance was noted in both EAC (60.9 %, 14 cases) and auricular (75 %, 9 cases) nevi. The mean age of EAC nevi (37.1 years) was younger than that of auricular nevi (42.2 years). The chief complaint was a symptomless mass in both groups, mostly in dome-like gross appearances. The mean diameter of EAC and auricular nevi was 9.6 (3-16) mm and 12.2 (3-25) mm, respectively. Histological findings chiefly presented intradermal nevi in EACs (78.3 %) and auricles (83.3 %) which showed preference to older patients, in contrast to the compound type. All nevi including five cases with skin grafts were completely excised without any recurrence within the follow-up period (average 5.3 months). A possible dysplastic nevus was detected in only one case. All MNs in EACs or auricles reveal similar characteristics. Early and complete excision is recommended to avoid skin graft, functional problems, and the risk of malignant melanoma.

Efficacy of 3 different steroid treatments for sudden sensorineural hearing loss: a prospective, randomized trial.

OBJECTIVES: We treated patients with idiopathic sudden sensorineural hearing loss (ISSNHL) with several protocols on an outpatient department (OPD) basis. The study compared the efficacy of 3 different steroid treatments for ISSNHL. STUDY DESIGN: A prospective randomized controlled study. SETTING: Tertiary referral center. METHODS: A total of 60 patients diagnosed with ISSNHL were treated through OPD. They were randomly and equally divided into 3 groups based on therapy: oral steroid for 10 days (group I), intratympanic dexamethasone injection (ITDI) 4 times (group II), and both (group III). Pure-tone average (PTA) was measured by taking 4 frequencies (0.5, 1, 2, and 3 kHz). Hearing change was evaluated by comparing pre- and posttreatment PTAs. Recovery rate was assessed by American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Clinical Practice Guidelines. RESULTS: The hearing gain was 12.8 ± 15.4 decibels (dB) in group I, 12.1 ± 14.6 dB in group II, and 21.9 ± 26.2 dB in group III. The recovery rate was 60% in groups I and III and 55% in group II. The overall recovery rate was 58.3% (35 of 60 patients). There was no significant difference in hearing gain and recovery rates for the 3 groups. Frequency-specific hearing gain also did not differ significantly among groups. CONCLUSION: Three different treatment protocols (oral steroid, ITDI, or the combination) resulted in similar hearing recovery rates. Therefore, OPD-based systemic and/or local steroid therapy can be recommended as an initial treatment in ISSNHL.