Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Purpose: This study aimed to report the results of Korean Antimicrobial Resistance Monitoring System (KARMS) for uncomplicated cystitis (UC) in 2023. Materials and Methods: KARMS was established for the surveillance of antimicrobial resistance in urinary tract infections with the cooperation of Korean nationwide medical centers. Data from patients with UC have been collected in the web-based KARMS database. Demographic data, uropathogen distribution, and antimicrobial susceptibility of representative pathogens were analyzed. Results: A total of 885 patients’ data were collected in KARMS database. The mean patient age was 56.39±18.26 years. The number of postmenopausal and recurrent cystitis were 530 (61.1%) and 102 (11.5%), respectively. Escherichia coli was the most frequently identified uropathogen (654/871, 75.1%). Regarding antimicrobial susceptibility, 94.9% were susceptible to fosfomycin, 90.5% to nitrofurantoin, 58.4% to ciprofloxacin, 83.6% to cefotaxime, and 100.0% to ertapenem. ESBL positivity was 13.7% (96/702), and significantly higher in tertiary hospital (23.1%, p<0.001), postmenopausal (15.9%, p=0.044), and recurrent cystitis (24.7%, p=0.001).Fluoroquinolone resistance was significantly higher in tertiary hospital (47.4%, p=0.001), postmenopausal (44.9%, p<0.001), and recurrent cystitis (59.8%, p<0.001). In addition, postmenopausal (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.38–2.77, p<0.001) and recurrent cystitis (OR 2.37, 95% CI 1.44–3.92, p=0.001) were associated with increased fluoroquinolone resistance. Conclusions These data provide information on the distribution of uropathogen and the status of antimicrobial resistance in UC of South Korea. In addition, KARMS will be a useful reference in the future through the continuous surveillance system construction over the years.

Purpose: We aimed to evaluate the effect of long-term oral OM-89 therapy on the urinary microflora in patients with urolithiasis. Materials and Methods: Patients underwent surgical removal of urinary stones followed by no OM-89 treatment for six months or daily OM-89 administration. Urine culture and urinary polymerase chain reaction (PCR) were performed at the baseline visit (V1) and at 2 months (V2) and 6 months (V3) after the operation. Results: A total of 113 patients completed the study. The rate of urinary bacteria detection by urine culture at V3 did not differ between OM-89 treated and untreated groups (p>0.999); however, the PCR detection rate tended to be higher in OM-89 untreated group than in OM-89 treated group (p=0.052). Escherichia coli and Enterococcus spp. were the bacteria most commonly detected via both urine culture and PCR at all timepoints. Risk factors for the detection of bacteria by urine culture at V3 were positive culture at V1 (p=0.048) and female sex (p=0.048), whereas positive PCR at V3 was associated with female sex (p=0.023), positive PCR at V2 (p<0.001), and no OM-89 treatment (p=0.038). The use of OM-89 was associated with decreased rates of bacterial detection by PCR at V2 and a further decrease at V3. Conclusions Long-term immunization with OM-89 could further decrease the frequency of urinary bacterial colonization after surgical removal of urinary stones. OM-89 could be used as a complementary therapy if a retrieved stone is suspected to be related to infection.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Background/Aims: Magnifying endoscopy with narrow-band imaging (ME-NBI) enables the visualization of detailed microsurface (MS) and microvascular (MV) structures in the gastrointestinal tract. White globe appearance (WGA) is a small whitish lesion with a globular shape identified during ME-NBI for early gastric cancer (EGC). This study aimed to investigate the associations between WGA, clinicopathological characteristics, and other ME-NBI findings in patients with EGC. Methods: The presence or absence of WGA in 122 patients (126 lesions) with an endoscopic diagnosis of EGC who underwent ME-NBI before endoscopic or surgical resection was prospectively collected and retrospectively analyzed. During ME-NBI, the MS and MV patterns and the presence of WGA and white opaque substances (WOS) were investigated. EGC cases were categorized as differentiated or undifferentiated type, and mucosal, submucosal, or advanced. Results: Of 126 lesions, WGA was observed in 25 (19.8%). WGA was associated with tumor size (≤2 cm [17/63, 27.0%] vs >2 cm [8/63, 12.7%]; p=0.044), histologic type differentiated type [22/89, 24.7%] vs undifferentiated type [3/37. 8.1%]; p=0.033), and tumor location (upper third [1/11, 9.1%] vs middle third [18/58, 31.0%] and lower third [6/57, 10.5%]; p=0.017). Although WGA was observed more frequently in lesions with an oval/tubular MS pattern, a fine-network MV pattern, and the absence of WOS, the difference was not statistically significant (MS pattern, p=0.358; MV pattern, p=0.212; WOS, p=0.121, respectively). Conclusions WGA was associated with small tumor size, differentiated-type histology, and middle-third tumor location, and was more frequently observed in lesions with an oval/tubular MS and fine-network MV patterns and the absence of WOS.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

This report presents radiologic changes after clinical improvement in a patient with acute interstitial nephritis (AIN). A 45-year-old female patient was referred for decreased renal function. Eight months prior, she had undergone hysterectomy and received chemotherapy. At the start of chemotherapy, her baseline creatinine level was 0.55 mg/dL, which rose to 1.46 mg/dL. Multiple imaging modalities performed when decreased renal function was observed revealed bilateral renal enlargement with increased cortical attenuation on computed tomography (CT), cortical hyperechogenicity on ultrasonography, and diffusion restriction in the renal cortices on magnetic resonance imaging. A renal biopsy was performed, and AIN was diagnosed. Follow-up laboratory tests showed that kidney function had improved to normal levels, and CT at that time showed a reduction in the size of both kidneys. Radiologic changes can serve as clues for the diagnosis of AIN. This is the first report to confirm radiological changes after the clinical improvement of AIN, thereby providing novel information about the course of AIN.