This study aimed to establish an organoid culture model using small intestine tissues from male and female C57BL/6 mice and to compare it with rat organoid cultures derived from frozen tissues. Crypts were isolated from the small intestines of eight-week-old male and female mice and cultured in 3D extracellular matrix with Wnt, R-spondin, and Noggin. In addition, small intestine tissues from sixteen-week-old F344 rats were preserved in a storage solution immediately post-sacrifice and stored at –80°C before being transferred to a nitrogen tank. Upon thawing, crypts from frozen rat tissues failed to develop into organoids due to structural damage, suggesting the need for fresh tissues or optimized preservation methods. In contrast, mouse-derived organoids showed viability for 7 days, with distinct morphological changes and clear differentiation by Day 7. Quantitative real-time PCR analysis revealed that Lgr5, a stem cell marker, showed significantly higher expression in organoids than in tissues, confirming the successful establishment of the organoid culture. Among epithelial markers, the antimicrobial enzyme Lyz1 was more highly expressed in organoids, while Muc2, a key goblet cell marker, was more highly expressed in male tissues. The enterocyte marker Alp exhibited higher expression in male organoids compared to females, with no sex differences in tissues. These findings highlight sex-specific differences in gene expression related to small intestine differentiation and demonstrate the challenges in organoid culture from frozen rat tissues. The results suggest the importance of immediate tissue processing or improved preservation methods for successful organoid cultures.

Background: and Purpose Anti-agrin antibodies (agrin Abs) have recently been identified in patients with myasthenia gravis (MG), sometimes in conjunction with antibodies (Abs) to the acetylcholine receptor (AChR), muscle-specific tyrosine kinase (MuSK), or low-density lipoprotein receptor-related protein 4. This study aimed to develop an in-house cell-based assay (CBA) for detecting agrin Abs, and to test its application to serum samples collected from individuals diagnosed with MG. Methods: Agrin complementary DNA as cloned into a pCMV6-AC-GFP vector, which was subsequently transfected into human embryonic kidney 293T (HEK293T) cells. Transfected HEK293T cells were incubated with patient serum and antihuman immunoglobulin G Ab conjugated with a red fluorescent dye. Agrin Ab levels were measured using the CBA in 389 serum samples: 340 from patients with MG, 36 from patients with other neuromuscular diseases, and 13 from healthy controls. The presence of agrin Ab was determined based on the fluorescence intensity and colocalization using fluorescence microscopy. Results: The expression levels of agrin mRNA and protein in transfected HEK293T cells were confirmed using the reverse-transcription polymerase chain reaction and Western blotting, respectively. Agrin expression in cells was further confirmed by immunocytochemistry.Two (0.6%) of the 340 patients with MG tested positive for agrin Ab: 1 of 191 AChR-positive patients and 1 of 54 MuSK-positive patients. Conclusions We have developed and validated a novel CBA for detecting agrin Abs. This CBA was successfully applied to detect agrin Abs in serum samples obtained from individuals with MG.

Background: and Purpose We aimed to determine the proportion of Korean patients with early Alzheimer’s disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment. Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study. Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22. Conclusions Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.

Background: The number of organ transplants in South Korea has increased, with a notable rise in living donor transplants. Ensuring their long-term health and well-being is critical to address potential complications and maintain the success of the transplant programs. Methods: A diverse advisory panel, including transplant experts and coordinators, was established to evaluate the follow-up care for living donors. The panel reviewed the results of a brief survey of donors regarding their donation experience, follow-up programs, guidelines, and policies from South Korea and other countries, aiming to identify best practices and recommend improvements. Results: The study found that follow-up care for living donors in South Korea is inconsistent and lacks standardization. Significant variability exists in follow-up practices across different institutions, and comprehensive data on donor health pre- and post-donation are scarce. The need for continuous, systematic follow-up, encompassing both medical and psychological support, is emphasized to ensure donor well-being. Conclusion Improving follow-up care for living donors is essential. Establishing a national registry and increasing donor advocacy teams are meaningful steps to enhance donor care, ensure long-term health, and maintain ethical standards in organ donation.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background: Cardiovascular diseases are the leading cause of mortality after liver transplantation (LT). Although the impact of secondary tricuspid regurgitation (TR) with severe pulmonary hypertension (PH) is well investigated, the impact of primary TR with tricuspid valve incompetence (TVI) on LT outcomes remains unclear. We aimed to investigate the prevalence and impact of primary TR with TVI on LT outcomes in a large-volume LT center. Methods: We retrospectively examined 5 512 consecutive LT recipients who underwent routine pretransplant echocardiography between 2008 and 2020. Patients were categorized based on the presence of anatomical TVI, specifically defined by incomplete coaptation, coaptation failure, prolapse, and flail leaflets of tricuspid valve (TV). Propensity score (PS)-based inverse probability weighting (IPW) was used to balance clinical and cardiovascular risk variables. The outcomes were one-year cumulative all-cause mortality and 30-day major adverse cardiovascular events (MACE). Results: Anatomical TVI was identified in 14 patients (0.3%). Although rare, these patients exhibited significantly lower post-LT one-year survival rates (64.3% vs. 91.5%, P < 0.001) and higher 30-day MACE rates (42.9% vs. 16.9%, P = 0.026) than patients without TVI. They also had worse survival irrespective of echocardiographic evidence of PH (P < 0.001) and exhibited higher one-year mortality (IPW-adjusted hazard ratio: 4.09, P = 0.002) and increased 30-day MACE rates (IPW-adjusted odds ratio: 1.24, P = 0.048). Conclusions Primary TR with anatomical TVI was associated with significantly reduced one-year survival and increased post-LT MACE rates. These patients should be prioritized similarly to those with secondary TR with severe PH, with appropriate pretransplant evaluations and treatments to improve survival outcomes.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity. Methods: Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells. Results: FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells. Conclusion This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.

Purpose: Although some medications trigger the worsening of myasthenia gravis (MG), their clinical influence on patients with MG has not been significantly evaluated. We aimed to investigate whether the risk of clinical worsening of MG increases after administering cautionary drugs in patients with MG. Materials and Methods: This retrospective case-control study was based on the medical records of patients diagnosed with MG between 2007 and 2020. We analyzed the risk of MG worsening in patients exposed to cautionary drugs during the risk period, defined as 6 months from the first exposure to cautionary drugs. The risk of MG worsening in the exposed patients was compared to that in the non-exposed patients, who were individually matched in a 1:1 ratio with exposed cases for sex, age, thymoma, and autoantibodies. Results: Of the 2002 patients diagnosed with MG, 552 (27.6%) were exposed to cautionary drugs. Neuromuscular blocking agents (320 patients) and beta blockers (66123 person-days) were the most frequently prescribed medications. After exact matching, 220 exposed and 220 non-exposed patients were enrolled. The incidence rate of clinical worsening during the risk period was significantly higher in the exposed patients than in the non-exposed patients (odds ratio=4.09; 95% confidence interval, 1.88–8.90;p<0.001). Clinical worsening was observed in 31 (14.1%) of the exposed patients and in 8 (3.6%) of the non-exposed patients. Conclusion The administration of cautionary drugs increased the risk of clinical worsening in patients with MG. Clinicians should be aware of this risk when cautionary drugs need to be administered.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.