Background: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0–1, 2–3, 4–5, and 6–9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell’s concordance index (C-index), and the Kaplan–Meier method. Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13). Conclusion mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Background/Aims: H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. Methods: A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. Results: According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. Conclusions DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756).

Purpose: To evaluate the anti-inflammatory and antioxidative effects of extracorporeal shockwave therapy (ESWT) on prostatitis and explore the mechanism of alleviating pain. Materials and Methods: For in vitro testing, RWPE-1 cells were randomly divided into 5 groups: (1) RWPE-1 group (normal control), (2) LPS group (lipopolysaccharide inducing inflammation), (3) 0.1ESWT group (treated by 0.1 mJ/mm2 energy level), (4) 0.2ESWT group (treated by 0.2 mJ/mm2 energy level), and (5) 0.3ESWT group (treated by 0.3 mJ/mm2 energy level). After ESWT was administered, cells and supernatant were collected for ELISA and western blot. For in vivo testing, Sprague-Dawley male rats were randomly divided into 3 groups: (1) normal group, (2) prostatitis group, and (3) ESWT group (n=12 for each). Prostatitis was induced by 17 beta-estradiol and dihydrotestosterone (DHT) administration. Four weeks after ESWT, the pain index was assessed for all groups and prostate tissues were collected for immunohistochemistry, immunofluorescence, apoptosis analysis and, western blot. Results: Our in vitro studies showed that the optimal energy flux density of ESWT was 0.2 mJ/mm2. In vivo, ESWT ameliorated discomfort in rats with prostatitis and inflammation symptoms were improved. Compared to normal rats, overexpressed NLRP3 inflammasomes triggered apoptosis in rats with prostatitis and this was improved by ESWT. TLR4-NFκB pathway was overactive after experimental prostatitis, compared to normal and ESWT groups, and prostatitis induced alterations in BAX/BAK pathway were inhibited by ESWT. Conclusions ESWT improved CP/CPPS by reducing NLRP3 inflammasome and ameliorated apoptosis via inhibiting BAX/BAK pathway in a rat model. TLR4 may play a key role in bonding NLRP3 inflammasome and BAX/BAK pathways. ESWT might be a promising approach for the treatment of CP/CPPS.

Background: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

Objectives: Monkeypox outbreaks in nonendemic countries have been reported since early May 2022. The first case of monkeypox in the Republic of Korea was confirmed in a patient who traveled to Europe in June 2022, and an attempt was made to isolate and identify the monkeypox virus (MPXV) from the patient’s specimens. Methods: Clinical specimens from the patient were inoculated in Vero E6 cells. The isolated virus was identified as MPXV by the observation of cytopathic effects on Vero E6 cells, transmission electron microscopy, conventional polymerase chain reaction (PCR), and sequencing of PCR products. Results: Cytopathic effects were observed in Vero E6 cells that were inoculated with skin lesion swab eluates. After multiple passages from the primary culture, orthopoxvirus morphology was observed using transmission electron microscopy. In addition, both MPXV-specific (F3L and ATI) and orthopoxvirus-specific genes (A39R, B2R, and HA) were confirmed by conventional PCR and Sanger sequencing. Conclusion These results indicate the successful isolation and identification of MPXV from the first patient in the Republic of Korea. The isolated virus was named MPXV-ROK-P1-2022.

Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. Methods: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. Conclusions PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Purpose: Inhalation of air containing high amounts of particular matter (PM) causes various respiratory disorders including asthma, chronic obstructive pulmonary disease, and lung cancer. The changes of expression of inflammatory factors by polydeoxyribonucleotide (PDRN) administration in the PM10-exposed trachea inflammation model were evaluated. Methods: PM10 was administered to mouse trachea to induce acute inflammatory damage, and changes in inflammatory factors were observed after administration of PDRN and 3,7-dimethyl-1-propargylxanthine (DMPX) for 3 days daily. Expression of inflammatory cytokines, adenosine A2A receptor (A2AR), protein kinase A (PKA), 3΄,5΄-cyclic adenosine monophosphate responsive element binding protein (CREB) were detected by enzyme‐linked immunosorbent assay, immunofluorescence, and western blot assay. Results: PM-exposed trachea showed increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β expression, and expression of TNF-α and IL-1β was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased nuclear factor (NF)-κB phosphorylation, and phosphorylation of nuclear factor-kappa B was inhibited by PDRN treatment in PM-exposed mice. PM-exposed trachea showed increased expression of A2AR, but PDRN treatment more enhanced A2AR expression in PM-exposed mice. PKA phosphorylation was not changed and CREP phosphorylation was decreased, however PDRN treatment increased phosphorylation of PKA and CREB in PM-exposed mice. DMPX treatment blocked all the effects of PDRN on PM-exposed mice, demonstrating that the action of PDRN occurs via A2AR. Conclusions PDRN treatment attenuated inflammation in the trachea of the PM10-exposed mice. This improving effect of PDRN can be ascribed to the activation of A2AR through the cAMP-PKA pathway.

Purpose: Acute respiratory distress syndrome (ARDS) is characterized by its acute onset of symptoms such as bilateral pulmonary infiltrates, severe hypoxemia, and pulmonary edema. Many patients with ARDS survive in the acute phase, but then die from significant lung fibrosis. Methods: The effect of combination therapy with polydeoxyribonucleotide (PDRN) and pirfenidone on ARDS was investigated using human lung epithelial A549 cells. ARDS environment was induced by treatment with lipopolysaccharide and transforming growth factor (TGF)-β. Enzyme-linked immunoassay for connective tissue growth factor (CTGF) and hydroxyproline were conducted. Western blot for collagen type I, fibroblast growth factor (FGF), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 was performed. Results: In this study, 8-μg/mL PDRN enhanced cell viability. Combination therapy with PDRN and pirfenidone and pirfenidone monotherapy suppressed expressions of CTGF and hydroxyproline and inhibited expressions of collagen type I and FGF. Combination therapy with PDRN and pirfenidone and PDRN monotherapy suppressed expression of TNF-α and IL-1β. Conclusions The combination therapy with PDRN and pirfenidone exerted stronger therapeutic effect against lipopolysaccharide and TGF-β-induced ARDS environment compared to the PDRN monotherapy or pirfenidone monotherapy. The excellent therapeutic effect of combination therapy with PDRN and pirfenidone on ARDS was shown by promoting the rapid anti-inflammatory effect and inhibiting the fibrotic processes.

BACKGROUND: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by arterial and venous thrombosis or pregnancy morbidity in patients with persistent antiphospholipid antibodies. However, nationwide population-based epidemiology studies regarding APS are still unavailable. METHODS: We analyzed claims data extracted from the Korean Health Insurance and Review Agency (HIRA) covering more than 52 million Koreans, between January 1, 2008, and December 31, 2017. Patients diagnosed with APS, as determined by the Korean Classification of Disease, 7th edition (D68.6), and a rare intractable disease program (V253), were identified in HIRA. RESULTS: A total of 3,088 newly diagnosed incident cases of 1,215 men and 1,873 women were identified during 2009–2016. The mean age was 44.6 ± 16.6 (men, 47.4 ± 16.3; women, 42.8 ± 16.6) years. The incidence was 0.75 per 105 person-year (95% confidence interval, 0.73–0.78). The prevalence in 2016 was 6.19 per 105 people. For incident cases, women showed incidence peak at ages of 30–39 years and 70–79 years, whereas for men, it was highest at ages of 70–79 years only. Of all patients, 1,766 (57%, 810 men and 956 women) had primary APS, 1,322 (43%, 405 men and 917 women) had secondary APS, and 845 (27%, 216 men and 629 women) were associated with systemic lupus erythematosus (SLE). CONCLUSION The incidence of APS differs according to age groups and gender. The incidence of primary APS was higher than that of secondary APS in both gender. Furthermore, as already reported, secondary APS is highly associated with SLE; however, we observed that rheumatoid arthritis is also highly related.

Creatinine ; Humans ; Male ; Meals ; Methods ; Nitrogen ; Osmolar Concentration ; Potassium ; Sodium ; Sodium, Dietary ; Specific Gravity ; Urea ; Urine Specimen Collection