Chonbuk National University Hospital

Kim B.R., Ko H., Son D., Shim J.E., Kim Y.H.

Kim Y.L., Nguyen T.T., Hwang S., Kang J., Chae J., Oh S.

Abstract Objectives: The aim of this prospective, longitudinal study was to validate video-oculography (VOG) for early detection of myasthenia gravis (MG) in patients with clinical suspicion of MG but lacking confirmatory laboratory results. Methods: Thirteen individuals suspected of having MG were studied using a 3-dimensional VOG system. Oculomotor fatigability, defined as the decrement (%) between the second and the last 5 average measures, was calculated. Results: Significant reductions in oculomotor ranges were found, exceeding previous cutoff values for horizontal saccades (16.4 ± 9.8%), vertical saccades (18.7 ± 12.6%), horizontal smooth pursuit (15.7 ± 6.0%), and vertical smooth pursuit (27.2 ± 17.4%). Despite initially negative laboratory tests, many participants later tested positive on the neostigmine test (92.3%) and repetitive nerve stimulation tests (69.2%). Conclusions: VOG is a reliable diagnostic tool for MG, particularly useful for seronegative patients, allowing for earlier and more accurate diagnosis than conventional methods.

Lee S.Y., Choi H.

ABSTRACTThe HLA‐C*14:02:41 allele is distinguished from HLA‐C*14:02:01:01 by a single synonymous change at c.606G>C.

Jung S., Cho K., Jung E., Son D., Byun J., Kim S., Chae S., Yang J., Lee S., Lim S.

Background: Probiotics have been shown to enhance cognitive function in individuals with mild cognitive impairment (MCI), but their efficacy varies, depending on the strain and dosage. Objectives: Clinical investigations are crucial to confirm their safety, efficacy, and mechanism of action. This study was designed to assess the effective dosage, safety, and efficacy of MH-Pro, a test product containing Lacticaseibacillus rhamnosus CBT-LR5 (LR5) and skim milk (non-fat dry milk), in improving cognitive function and related physiological changes in older adults suspected of MCI over 12 weeks. Methods: In total, 20 participants (mean age: 68.9 years) were randomly assigned in a 1:1 ratio to either a low-dose group (1 × 1010 CFU LR5 with 1622 mg) or a high-dose group (1 × 1010 CFU LR5 with 4055 mg skim milk) in a double-blind, parallel-group clinical trial. Results: After 12 weeks, the low-dose group showed significant improvements in the MOCA-K subdomains, specifically in naming (p = 0.01) and delayed recall (p = 0.003). Additionally, levels of amyloid-β1 40/42 in the blood significantly decreased (p = 0.03) following supplementation in the low-dose group. The high-dose group exhibited significant improvement in orientation (p = 0.05). Moreover, overall cognitive enhancement was observed in the low-dose group (p = 0.003), while the high-dose group showed a trend toward improvement (p = 0.06). Fecal analysis revealed significant changes in bacterial composition, with an increase in Lacticaseibacillus after 12 weeks of MH-Pro consumption. Together, these findings provide foundational evidence suggesting that MH-Pro supplementation may serve as a potential intervention for enhancing cognitive function through gut–brain axis pathways in the elderly population. However, given the small sample size and the predominance of female participants, the impact of the outcome may be limited. Further large-scale studies are necessary to validate these preliminary results. Conclusions: This study provides foundational evidence to recognize the use of LR5 and skim milk to prepare a probiotic supplement that enhances cognitive function in the aging population.

Park W., Lee S.K., Gwack J., Lee S.Y., Cho Y.G., Kang S., Park J.

Dysbiosis in the bile microbiota of cholangiocarcinoma (CCA) patients suggests a potential role for microbial alterations in the pathogenesis of CCA. This study aimed to investigate bile microbial communities in patients with CCA and compare them to those in individuals with benign biliary diseases as a control (CTR) group. Microbial profiling was conducted using next-generation sequencing (NGS), targeting the V3–V4 regions of the 16S rRNA gene, followed by bioinformatics analysis using the VSEARCH and EzBioCloud platforms. Alpha and beta diversity analyses were performed to assess microbial richness and structural differences. The linear discriminant analysis effect size (LEfSe) was utilized to identify potential microbial biomarkers. Results: This study identified distinct microbial profiles in the two groups at both the phylum and genus levels. In the CTR group, Pseudomonadota (65%) was the dominant phyla, while Bacillota (49%) was more abundant in the CCA group. At the genus level, Escherichia (29%), Enterobacteriaceae (12%), Enterococcus (8%), Ralstonia (8%), and Clostridium (5%) were more prevalent in the CTR group, whereas Streptococcus (34%), Ralstonia (8%), and Veillonella (5%) were dominant in the CCA group. Although an alpha diversity analysis showed no statistically significant differences in species richness or diversity between groups, a beta diversity analysis revealed significant structural differences associated with disease severity. Our comparative microbiome study using LEfSe analysis suggested a statistically significant inhibition of normal intestinal bacterial flora in patients with CCA who had not received any treatment. These findings suggest that microbial dysbiosis may play a role in the pathogenesis of CCA. Specific microbial taxa were identified as potential biomarkers for distinguishing benign from malignant diseases. These results underscore the potential role of microbial dysbiosis in CCA pathogenesis and highlight the bile microbiota’s utility as a diagnostic marker for biliary diseases.

Gweon T., Kang S., Na S., Oh D.J., Kim S.W., Seo G.S., Cho J.Y.

Background/Objectives: Clostridioides difficile infection (CDI) is an important nosocomial diarrheal disease. The benefits of the probiotic Bacillus licheniformis (B. licheniformis) in the preservation of intestinal microbiota have not been studied in patients with CDI to date. Therefore, we aimed to investigate the efficacy of B. licheniformis in preserving the intestinal microbiota in patients with CDI. Methods: A multicenter, randomized, placebo-controlled trial was carried out at six academic centers in Korea. Individuals diagnosed with mild to moderate CDI were included in this trial. CDI was treated with vancomycin 125 mg four times daily for two weeks. Along with vancomycin, B. licheniformis was administered for five days in this study, while a placebo was given to the placebo group. Microbiome analysis was performed before and five days after administering vancomycin and B. licheniformis or placebo, using 16S rRNA amplicon sequencing. Alpha and beta diversity was compared between the two groups. Results: A total of 35 participants were finally included in this study, with 16 in the study group and 19 in the placebo group. The alpha diversity was similar in both groups before CDI treatment. After five days of the administration of vancomycin and B. licheniformis or placebo, alpha diversity did not decrease in the study group (Chao1 index, p = 0.665; observed features, p = 0.692). In contrast, alpha diversity decreased in the placebo group (Chao1 index, p = 0.011; observed features, p = 0.011). Beta diversity did not differ between the two groups. Conclusions: The addition of B. licheniformis to vancomycin was effective in preserving gut microbiota in patients with CDI.

Han K., Ko M.

Background/Objectives: This clinical trial aimed to determine whether perturbation-based gait training (PBGT) on a split-belt treadmill enhances balance and muscle strength in older adults, comparing its effectiveness with walking-only training on a treadmill. Methods: This single-center, prospective, single-blind (assessor), randomized controlled trial included 24 older adults from the Rehabilitation Center of Jeonbuk National University Hospital. Participants were equally divided into the PBGT and control groups. Both groups underwent 12 training sessions, three times a week for 4 weeks, for a total of 43 min per session. The outcomes, including the Five Times Sit-to-Stand Test (FTSST), Falls Efficacy Scale International, timed up-and-go (TUG) test, functional reach test, and lower-extremity manual muscle test scores, were measured at three time points: pre-training, post-training, and four weeks after training. Results: While there were no significant differences between the two groups, the PBGT group demonstrated significant improvements in its FTSST and TUG values. Conclusions: Unpredictable perturbation training on a split-belt treadmill can be safely performed by older adults and may serve as an alternative exercise method to enhance physical performance and balance ability for fall prevention.

Lee J., Lim J., Jeon Y., Kim D., Lee D.

Pueraria lobata (Willd.) has been used as food since ancient times, and its roots have been used mainly as a traditional herbal medicine to treat various diseases in East Asia. Puerarin is one of the major active ingredients in the roots of P. lobata. The purpose of this study was to examine the effects of the methanol extract of P. lobata roots (PRME) and puerarin on apoptosis in cervical cancer and inflammation-relieving effects in vaginitis. First, we prepared the PRME and confirmed the puerarin content of PRME through HPLC analysis. We performed a TUNEL assay, Hoechst 33342 staining, and western blotting using HeLa cells, a human cervical cancer cell line. Both the PRME and puerarin exhibited antiproliferative effects in HeLa cells by inducing apoptosis through the activation of the extrinsic death receptor and intrinsic mitochondrial pathways, thereby demonstrating their anticancer efficacy against human cervical cancer. Next, a mouse model of vaginitis induced by Gardnerella vaginalis (GV) infection was established by inoculating C57BL/6 mice with β-estradiol-3-benzoate and GV (1 × 108 CFU). Histological analysis and PCR confirmed that the administration of PRME or puerarin to GV-infected mice alleviated reproductive tract vaginitis symptoms. Additionally, we confirmed that PRME or puerarin treatment decreased myeloperoxidase activity and reduced inflammation by regulating cytokines through the secretion of inflammatory mediators in mouse vaginal tissue. These results demonstrate that PRME and puerarin can be used as potential adjuvants or therapeutic agents with anticancer and anti-inflammatory properties to inhibit the progression of human cervical cancer and alleviate vaginitis.

Lee K., Jung J., Kwon W., Kim D., Park M., Choi I.J., Lee J., Yoon Y.H., Lee J.H., Lee S.R., Lee P.H., Lee S., Yoo K.D., Yun K.H., Lee H., et. al.

Owing to limited data on the optimal timing of rotational atherectomy (RA), we sought to evaluate the clinical impact of the early application of the RA strategy. Consecutive patients with severe coronary artery calcification were enrolled, who underwent percutaneous coronary intervention (PCI) using RA between January 2010 and October 2019 at 9 tertiary centers. Direct RA was defined as the early application of RA before the balloon was expanded to a size more than or equal to 2.0 mm. The primary endpoint was the composite outcome of technical failure or severe coronary dissection (type D, E, or F) during entire procedure. Of 581 lesions, 360 (62.0%) lesions underwent direct RA. The technical success rate was higher in the direct RA group than in the indirect RA group (97.5% vs. 93.7%, p = 0.021). The primary endpoint was more frequently observed in the indirect RA group than in the direct RA group (24.4% vs. 11.9%, p < 0.001). Multivariate logistic regression analysis revealed that the risk of the primary endpoint was higher in the indirect RA group than in the direct RA group (odds ratio 2.512, 95% CI 1.547–4.078, p < 0.001). Early application of RA may reduce the incidences of in-hospital adverse events and procedure-related complications.

Choi J.Y., Lee C., Joo H., Sim Y.S., Lee J., Lee H., Yoo K.H., Park S.J., Na J.O., Khor Y.H.

Accurate spirometry interpretation is critical in the diagnosis and management of chronic obstructive pulmonary disease (COPD). With increasing efforts for a unified approach by the Global Lung Function Initiative (GLI), this study evaluated the application of race-specific 2012-GLI and race-neutral 2022-GLI reference equations compared to Choi's reference equations, which is derived and widely used in South Korea, for spirometry interpretation in Northeast Asian patients with COPD.

Lee S.J., Shin Y., Cha S.A., Kim K.M., Kang K.P.

Rationale: It is often challenging to differentiate between IgG4-related disease (IgG4-RD) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) due to their similar clinical presentations. Recently, growing evidence has suggested a strong connection between AAV and IgG4-RD. Patient concerns: A 60-year-old woman was transferred to our hospital with fever and kidney dysfunction. Abdominal computed tomography revealed widespread infiltrative lesions in both kidneys. Diagnoses: Laboratory tests and subsequent renal biopsy confirmed both antineutrophil cytoplasmic antibody-associated vasculitis and IgG4-related disease. Interventions: We initiated plasmapheresis, oral cyclophosphamide, and high-dose glucocorticoids for treatment. Despite this, the patient’s condition worsened, requiring emergency hemodialysis. Outcomes: After 3 months of continued immunosuppressive treatment, renal function improved and hemodialysis was discontinued. Lessons: Our case showed an overlap of AAV and IgG4‐RD, which might support the hypothesis of an overlap syndrome of AAV and IgG4-RD. Clinicians should have a high index of suspicion when diagnosing fever of unknown origin, with the possibility of overlapping AAV and IgG4-RD.

Lee J.S., Kang H.G., Ahn S.H., Song T., Shin D., Bae H., Kim C.H., Heo S.H., Cha J., Lee Y.B., Kim E.G., Park M.S., Park H., Kim J., Yu S., et. al.

ImportanceNelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species.ObjectiveTo evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy.Design, Setting, and ParticipantsThis multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset.InterventionPatients were assigned in a 1:1 ratio to receive intravenous infusions of nelonemdaz twice a day for 5 days or a matching placebo.Main Outcomes and MeasuresThe primary end point was a favorable shift in the modified Rankin scale (mRS) 12 weeks after stroke onset. The secondary end points included various composites of the mRS at 5 and 12 weeks, symptomatic intracranial hemorrhage, and infarct volume. Both intention-to-treat and per-protocol analyses were conducted.ResultsA total of 496 patients were enrolled across 24 Korean stroke centers, of whom 39 dropped out (254 men [55.6%]; mean [SD] age, 72.9 [12.1] years). Baseline characteristics of study participants did not significantly differ. For the primary end point, the distribution of the mRS scores at 12 weeks did not significantly differ between the nelonemdaz and placebo groups (common odds ratio, 0.95; 95% CI, 0.69-1.31). For the secondary end points, a median of mRS at 5 weeks (3 vs 3) and mRS 0 at 12 weeks (18.1% vs 18.2%) did not differ substantially between groups. The occurrence of symptomatic intracranial hemorrhage (2.7% vs 0.9%) and infarct volume within 24 hours of the last trial drug infusion (42 vs 38 mL) did not differ significantly between groups. No serious adverse events were reported regarding the trial drug and placebo.Conclusions and RelevanceIn this randomized clinical trial, nelonemdaz did not meet the primary efficacy end point compared with placebo.Trial RegistrationClinicalTrials.gov Identifier: NCT05041010

Choi C., Kim M.G., Kim J.H.

The effect of lowering uric acid levels on renal function in patients with diabetic kidney disease remains unclear. Previous randomized controlled trials (RCTs) have reported conflicting results regarding the effects of xanthine oxidase inhibitors on renal function. This study aimed to examine the renoprotective effects of xanthine oxidase inhibitors (febuxostat and topiroxostat) in patients with diabetic kidney disease. Relevant RCTs were searched using PubMed, Embase, and Cochrane Central databases. Ultimately, five RCTs were included in the meta-analysis. The assessed renal endpoints included changes in the estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. The meta-analysis was conducted using Review Manager version 5.4. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for changes in renal endpoints between the groups after the study period. A subgroup analysis was conducted based on the type of intervention, results of the risk of bias assessment, and baseline renal function. Although the use of febuxostat or topiroxostat did not induce a significant change in eGFR compared with the placebo, it showed a tendency to delay renal function decline (SMD = 0.32, 95% CI = [− 0.00; 0.64]). There was no significant difference in albuminuria between the two groups (SMD = 0.26, 95% CI = [− 0.10; 0.62]). This study suggests the potential of febuxostat or topiroxostat to delay renal function decline in patients with diabetes and underlying renal impairment, that needs to be confirmed in further studies. INPLASY registration number 202450024.

Kim J.H., Kim S., Song D.S., Kim H.Y., Yoon E.L., Park J.W., Kim T.H., Jung Y., Suk K.T., Yim H.J., Kwon J.H., Lee S.W., Kang S.H., Kim M.Y., Jeong S.W., et. al.

Yu B.R., Choi W.K., Cho D.H., Lee N.

Rationale: Aggressive angiomyxoma (AAM) is an exceptionally rare mesenchymal tumor that predominantly manifests in the female genital organs during the reproductive age. Its rarity alone makes it a fascinating subject for study. The diagnosis of AAM necessitates differentiation from other benign or mesenchymal tumors and can be confirmed through immunohistochemistry (IHC) staining. Surgical resection is the primary treatment, and adjuvant treatment can be used as hormonal therapy with gonadotropin-releasing hormone agonists, selective estrogen receptor modulators, and aromatase inhibitors. Patient concerns: A 44-year-old premenopausal Korean woman presented with a growing perineal mass and frequent urination. Diagnoses: Histopathological findings confirmed AAM, with IHC staining showing estrogen receptor, progesterone receptor, actin and desmin positivity, and CD34 and S100 negativity. Interventions: The mass was excised transvaginally under general anesthesia. Outcomes: The patient showed no signs of recurrence 6 months postoperatively. Lessons: AAM in the vagina is a rare tumor that requires differential diagnosis using IHC staining. Previously, we reviewed reported cases and confirmed the feasibility and effectiveness of surgery as the main treatment. This might reassure us about the potential successful treatment of AAM. Adjuvant hormonal therapy with gonadotropin-releasing hormone agonists, selective estrogen receptor modulators, and aromatase inhibitors can further reduce the risk of recurrence.