Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

Background/Aims: Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC. Methods: In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications. Results: Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval: 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEBTACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event. Conclusions Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.

Background/Aims: Surgical resection, transplantation, and radiofrequency ablation (RFA) are generally accepted as amenable treatments for small hepatocellular carcinoma (HCC). Recently drug-eluting beads (DEB) which had several treatment advantages were introduced for transarterial chemoembolization (TACE). The aim of this study was to evaluate feasibility and safety of DEB-TACE compared with RFA for the treatment of single small HCC. Methods: In this pilot non-randomized trial, we assessed retrospective data of 40 patients who underwent DEB-TACE (n=21) or RFA (n=19) for single small (≤3 centimeter in greatest dimension) HCC. The primary outcomes were tumor response and time to recurrence. The secondary outcome was treatment-related complications. Results: Complete response rate to DEB-TACE and RFA after first follow-up assessment was 90.5% and 94.7%, respectively (P=1.000). During mean follow-up of 87.6 months (95% confidence interval: 74.4-102), 7 patients experienced local recurrence. The 6- and 12-month cumulative local recurrence rate was 5.0% and 21.8% in DEB-TACE vs. 11.1% and 17.0% in RFA group (P=0.877). A total 14 distant intrahepatic recurrences were developed and 12- and 24-month cumulative distant intrahepatic recurrence rate was 20.6% and 42.7% in DEBTACE vs. 17.2% and 36.3% in RFA group (P=0.844). Two patients experienced gangrenous cholecystitis after DEB-TACE requiring cholecystectomy as treatment-related adverse event. Conclusions Tumor response and recurrence rate after single session of DEB-TACE or RFA were similar. DEB-TACE could be applied selectively in patients with a single small HCC if the other therapeutic modality is unfeasible.

BACKGROUND: Cardiovascular disease and chronic kidney disease share several common risk factors. The Framingham risk score is hypothesized to predict chronic kidney disease development. We determined if the Framingham risk scoring system can correctly predict incident chronic kidney disease in the general population. METHODS: This study included 9,080 subjects who participated in the Korean Genome and Epidemiology Study between 2001 and 2014 and had normal renal function. The subjects were classified into low- (< 10%), intermediate- (10–20%), and high- (> 20%) risk groups based on baseline Framingham risk scores. The primary endpoint was de novo chronic kidney disease development (estimated glomerular filtration rate [eGFR], < 60 mL/min/1.73 m²). RESULTS: During a mean follow-up duration of 8.9 ± 4.3 years, 312 (5.3%), 217 (10.8%), and 205 (16.9%) subjects developed chronic kidney disease in the low, intermediate, and high risk groups, respectively (P < 0.001). Multivariable analysis after adjustment for confounding factors showed the hazard ratios for the high- and intermediate risk groups were 2.674 (95% confidence interval [CI], 2.197–3.255) and 1.734 (95% CI, 1.447–2.078), respectively. This association was consistently observed irrespective of proteinuria, age, sex, obesity, or hypertension. The predictive power of this scoring system was lower than that of renal parameters, such as eGFR and proteinuria, but increased when both were included in the prediction model. CONCLUSION: The Framingham risk score predicted incident chronic kidney disease and enhanced risk stratification in conjunction with traditional renal parameters in the general population with normal renal function.
Cardiovascular Diseases ; Cohort Studies ; Epidemiology ; Follow-Up Studies ; Genome ; Glomerular Filtration Rate ; Hypertension ; Obesity ; Prospective Studies ; Proteinuria ; Renal Insufficiency, Chronic ; Risk Factors

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.
Adult ; Bacteriuria ; Communicable Diseases ; Cystitis ; Diagnosis ; Humans ; Immunocompromised Host ; Methods ; Prostatitis ; Pyelonephritis ; Urinary Tract Infections* ; Urinary Tract*

Urinary tract infections (UTIs) are infectious diseases that commonly occur in communities. Although several international guidelines for the management of UTIs have been available, clinical characteristics, etiology and antimicrobial susceptibility patterns may differ from country to country. This work represents an update of the 2011 Korean guideline for UTIs. The current guideline was developed by the update and adaptation method. This clinical practice guideline provides recommendations for the diagnosis and management of UTIs, including asymptomatic bacteriuria, acute uncomplicated cystitis, acute uncomplicated pyelonephritis, complicated pyelonephritis related to urinary tract obstruction, and acute bacterial prostatitis. This guideline targets community-acquired UTIs occurring among adult patients. Healthcare-associated UTIs, catheter-associated UTIs, and infections in immunocompromised patients were not included in this guideline.
Adult ; Bacteriuria ; Communicable Diseases ; Cystitis ; Diagnosis ; Humans ; Immunocompromised Host ; Methods ; Prostatitis ; Pyelonephritis ; Urinary Tract Infections* ; Urinary Tract*

BACKGROUND/AIMS: Rebleeding is associated with mortality in patients with peptic ulcer bleeding (PUB), and risk stratification is important for the management of these patients. The purpose of our study was to examine the risk factors associated with rebleeding in patients with PUB. METHODS: The Korean Peptic Ulcer Bleeding registry is a large prospectively collected database of patients with PUB who were hospitalized between 2014 and 2015 at 28 medical centers in Korea. We examined the basic characteristics and clinical outcomes of patients in this registry. Univariate and multivariate analyses were performed to identify the factors associated with rebleeding. RESULTS: In total, 904 patients with PUB were registered, and 897 patients were analyzed. Rebleeding occurred in 7.1% of the patients (64), and the 30-day mortality was 1.0% (nine patients). According to the multivariate analysis, the risk factors for rebleeding were the presence of co-morbidities, use of multiple drugs, albumin levels, and hematemesis/hematochezia as initial presentations. CONCLUSIONS: The presence of co-morbidities, use of multiple drugs, albumin levels, and initial presentations with hematemesis/hematochezia can be indicators of rebleeding in patients with PUB. The wide use of proton pump inhibitors and prompt endoscopic interventions may explain the low incidence of rebleeding and low mortality rates in Korea.
Hemorrhage* ; Humans ; Incidence ; Korea ; Mortality ; Multivariate Analysis ; Peptic Ulcer Hemorrhage ; Peptic Ulcer* ; Prospective Studies ; Proton Pump Inhibitors ; Risk Factors

PURPOSE: The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. MATERIALS AND METHODS: A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. RESULTS: After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. CONCLUSION: Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.
Biopsy ; Chemoradiotherapy* ; Disease-Free Survival ; Follow-Up Studies ; Glioblastoma* ; Humans ; Korea* ; Methylation ; Radiotherapy ; Retrospective Studies* ; Survival Rate

BACKGROUND/AIMS: In Korea, there are no available multicenter data concerning the prevalence of or diagnostic approaches for non-responsive gastroesophageal reflux disease (GERD) which does not respond to practical dose of proton pump inhibitor (PPI) in Korea. The purpose of this study is to evaluate the prevalence and the symptom pattern of non-responsive GERD. METHODS: A total of 12 hospitals who were members of a Korean GERD research group joined this study. We used the composite score (CS) as a reflux symptom scale which is a standardized questionnaire based on the frequency and severity of typical symptoms of GERD. We defined "non-responsive GERD" as follows: a subject with the erosive reflux disease (ERD) whose CS was not decreased by at least 50% after standard-dose PPIs for 8 weeks or a subject with non-erosive reflux disease (NERD) whose CS was not decreased by at least 50% after half-dose PPIs for 4 weeks. RESULTS: A total of 234 subjects were analyzed. Among them, 87 and 147 were confirmed to have ERD and NERD, respectively. The prevalence of non-responsive GERD was 26.9% (63/234). The rates of non-responsive GERD were not different between the ERD and NERD groups (25.3% vs. 27.9%, respectively, p=0.664). There were no differences between the non-responsive GERD and responsive GERD groups for sex (p=0.659), age (p=0.134), or BMI (p=0.209). However, the initial CS for epigastric pain and fullness were higher in the non-responsive GERD group (p=0.044, p=0.014, respectively). CONCLUSIONS: In conclusion, this multicenter Korean study showed that the rate of non-responsive GERD was substantially high up to 26%. In addition, the patients with the non-responsive GERD frequently showed dyspeptic symptoms such as epigastric pain and fullness.
Esophagitis, Peptic ; Gastric Acid ; Gastroesophageal Reflux* ; Heartburn ; Humans ; Korea* ; Prevalence* ; Proton Pump Inhibitors ; Proton Pumps* ; Protons*

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction