Background/Aims: The SAMe-TT2R2 score is used for assessing anticoagulation control (AC) quality with warfarin. However, it is hard to apply SAMe-TT2R2 score in Asian patients with atrial fibrillation (AF), because it has not been proven in those populations. This study aimed to validate the SAMe-TT2R2 score in Asian patients with AF and suggest a modified SAMe- TT2R2 score for this population. Methods: We analyzed 710 Korean patients with AF who were using warfarin. The AC quality was assessed as the mean time in therapeutic range (TTR). Each component of SAMe-TT2R2 score was evaluated for the relationship with AC. Further clinical factors that predict AC were analyzed. Identified factors were re-assorted and constructed as SA2Me-TTR scoring system. Results: Of the components of the SAMe-TT2R2 score, female, age, and rhythm control were associated with AC. Heart failure and renal insufficiency were newly identified factors associated with AC. The modified SA2Me-TTR score was reconstructed with the relevant risk factors (S, female gender, 1 point; A, age < 60 yr, 2 points; Me, medical history of heart failure, 1 point; T, treatment for rhythm control, 1 point; T, history of stroke or transient ischemic attack, 1 point; R, renal insufficiency, 1 point). The modified SA2Me-TTR score demonstrated an excellent relationship with the grading of AC. The modified SA2Me-TTR score ≤ 1 identified patients with good AC (hazard ratio 2.46, 95% CI 1.75–3.47). Conclusions The modified SA2Me-TTR score was useful for guiding oral anticoagulants selection in Asian patients with AF.

Purpose: We report two cases of sudden intraocular pressure (IOP) elevation in children after steroid treatment.Case summary: (Case 1) An 8-year-old boy visited the hospital with vomiting and headache that had begun 3 days after application of dexamethasone eyedrops. IOPs were 55 and 62 mmHg in the right and left eyes, respectively; both anterior chambers were normal. The eyedrops were stopped and timolol/dorzolamide was applied twice daily. After intravenous mannitol injection, the IOPs of both eyes decreased to 18 mmHg within 24 hours. (Case 2) A 10-year-old boy diagnosed with coronavirus disease 2019 three days prior had been prescribed methylprednisolone 4 mg twice daily; he visited the hospital with headache, eye pain, and decreased vision that began 1 day after medication. IOPs were 41 and 54 mmHg in the right and left eyes, respectively; both anterior chambers were normal. After drug discontinuation, timolol/dorzolamide, brimonidine, and latanoprost eyedrops were applied. Subsequently, after intravenous mannitol injection, the IOPs decreased within 24 hours to 7 and 16 mmHg in the right and left eyes, respectively; they remained stable. However, thinning was observed in the retinal nerve fiber and ganglion cell-inner plexiform layer. Conclusions Children can develop rapid IOP elevation after even 1 day of steroid use; residual structural damage may be present, despite prompt treatment. Clinicians must closely monitor such patients for atypical IOP elevation.

While numerous studies have evaluated humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, data on the cellular responses to these vaccines remain sparse. We evaluated T cell responses to ChAdOx1-nCoV-19 and BNT162b2 vaccinations using an interferon gamma (IFN-γ) release assay (IGRA). ChAdOx1-nCoV-19- and BNT162b2-vaccinated participants initially showed stronger T cell responses than unvaccinated controls. The T cell response decreased over time and increased substantially after the administration of a BNT162b2 booster dose. Changes in the T cell response were less significant than those in the anti-receptor-binding domain IgG antibody titer. The study results can serve as baseline data for T cell responses after SARS-CoV-2 vaccination and suggest that the IGRA can be useful in monitoring immunogenicity.

Background: Several T-cell response assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are available; however, their comparability and correlations with antibody responses remain unclear. We compared four SARS-CoV-2 T-cell response assays and two anti-SARS-CoV-2 spike antibody assays. Methods: We enrolled 89 participants who had received a booster dose of the BNT162b2 vaccine after two doses of the ChAdOx1 or BNT162b2 vaccine. Fifty-six participants without breakthrough infection (BI) (ChAdOx1/BNT162b2 group: N=27; BNT162b2 group: N=29) and 33 with BI were included. We evaluated two whole-blood interferon-gamma release assays (IGRAs) (QuantiFERON and Euroimmun), T-SPOT.COVID, an in-house enzyme-linked immunospot (ELISPOT) assay (targeting the spike and nucleocapsid peptides of wild-type and Omicron SARS-CoV-2), Abbott IgG II Quant, and Elecsys Anti-S, using Mann–Whitney U, Wilcoxon signed-rank, and Spearman’s correlation tests. Results: The correlations between the IGRAs and between the ELISPOT assays (ρ=0.60–0.70) were stronger than those between the IGRAs and ELISPOT assays (ρ=0.33–0.57). T-SPOT.COVID showed a strong correlation with Omicron ELISPOT (ρ=0.70). The anti-spike antibody assays showed moderate correlations with T-SPOT.COVID, Euroimmun IGRA, and ELISPOT (ρ=0.43–0.62). Correlations tended to be higher in the BI than in the noninfected group, indicating that infection induces a stronger immune response. Conclusions T-cell response assays show moderate to strong correlations, particularly when using the same platform. T-SPOT.COVID exhibits potential for estimating immune responses to the Omicron variant. To accurately define SARS-CoV-2 immune status, both T-cell and B-cell response measurements are necessary.

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

Purpose: To identify clinical factors associated with the early reduction of corneal sensitivity (CS) in patients with herpes zoster ophthalmicus (HZO). Methods: Total 30 subjects were divided into two groups according to the occurrence of an early reduction of CS (group 1, normal CS; group 2, decreased CS). The demographics, ocular manifestations of HZO, and the ocular surface parameters were compared between two groups. Then, the relative risks of variables were analyzed to expect the early decrease of CS by HZO using logistic regression analysis. Results: Among total 30 subjects, the CS decreased in 10 subjects (3.2 ± 1.4 cm, group 2) and the other 20 subjects revealed normal CS (6.0 ± 0.0 cm, group 1). The age was higher in the group 2 (67.0 ± 16.6 years) than in group 1 (48.0 ± 17.6 years, p = 0.013), but sex and the comorbidity of diabetes mellitus was not difference between groups. The presence of corneal punctate epithelial erosions was a single factor among the ocular manifestations of HZO, which discriminated group 1 (5%) and group 2 (60%, p = 0.002). The ocular surface staining scores (i.e., National Eye Institute scores and Sjögren’s International Collaborative Clinical Alliance ocular surface score) were higher in group 2 (p = 0.001 and p = 0.021, respectively) than in group 1. The existence of corneal punctate epithelial erosions revealed as a sole risk factor for the early reduction of CS (odds ratio = 33.085; p = 0.016). Conclusions It is necessary to pay attention to the possible occurrence of neurotrophic keratopathy especially in older patients with HZO showing an initial presence of corneal punctate epithelial erosions.

Healthcare workers (HCWs) may be at high risk for exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their frequent contact with patients or the direct handling of respiratory samples. We investigated the seroprevalence of SARS-CoV-2 IgG in HCWs in Seoul compared to those in coronavirus disease (COVID-19) patients and community-based individuals to evaluate the antibody response. A total of 358 samples from 348 individuals (155 HCWs, 7 COVID-19 patients, and 186 community-based individuals) were collected from April to November 2020. SARS-CoV-2 IgG was detected in 1 of 155 HCWs (1 of 46 HCWs with direct contact), 7 of 7 COVID-19 patients, and none of the 186 communitybased individuals (95% CI: 0.6%, 0.1 - 3.6%; 100%, 64.5 - 100%; 0.0%, 0.0 - 2.0%, respectively).The single HCW with a positive result showed 2.32 signal-to-cutoff (S/C) and 2.31 S/C at a 3-week interval. Therefore, it was assumed to be a false positive due to autoantibody or medication. The positive samples from 7 patients had a median of 3.79 S/C (range 1.72 - 6.54). The seroprevalence of SARS-CoV-2 IgG in HCWs was very low. The current infection control standard seems to be effective in protecting HCWs from COVID-19.

Healthcare workers (HCWs) may be at high risk for exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of their frequent contact with patients or the direct handling of respiratory samples. We investigated the seroprevalence of SARS-CoV-2 IgG in HCWs in Seoul compared to those in coronavirus disease (COVID-19) patients and community-based individuals to evaluate the antibody response. A total of 358 samples from 348 individuals (155 HCWs, 7 COVID-19 patients, and 186 community-based individuals) were collected from April to November 2020. SARS-CoV-2 IgG was detected in 1 of 155 HCWs (1 of 46 HCWs with direct contact), 7 of 7 COVID-19 patients, and none of the 186 communitybased individuals (95% CI: 0.6%, 0.1 - 3.6%; 100%, 64.5 - 100%; 0.0%, 0.0 - 2.0%, respectively).The single HCW with a positive result showed 2.32 signal-to-cutoff (S/C) and 2.31 S/C at a 3-week interval. Therefore, it was assumed to be a false positive due to autoantibody or medication. The positive samples from 7 patients had a median of 3.79 S/C (range 1.72 - 6.54). The seroprevalence of SARS-CoV-2 IgG in HCWs was very low. The current infection control standard seems to be effective in protecting HCWs from COVID-19.

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflammation. Benzydamine (BA) has been used as a cytokine-suppressive or non-steroidal anti-inflammatory drug that inhibits the production of pro-inflammatory cytokines or prostaglandins. However, its role in osteoclast differentiation and function remains unknown. Here, we explored the role of BA in regulating osteoclast differentiation and elucidated the underlying mechanism. BA inhibited osteoclast differentiation and strongly suppressed interleukin-1 (IL-1) production. BA inhibited osteoclast formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1 treatment. The reporter assay and the inhibitor study of IL-1 transcription suggested that BA inhibited nuclear factor-B and activator protein-1 by regulating IB kinase, extracellular signal regulated kinase and P38, resulting in the down-regulation of IL-1 expression. BA also promoted osteoblast differentiation. Furthermore, BA protected lipopolysaccharide- and ovariectomy-induced bone loss in mice, suggesting therapeutic potential against inflammation-induced bone diseases and postmenopausal osteoporosis.