Purpose: This study aims to determine whether the translucency-based clinical grade of pterygium shows independent relationships with anterior and posterior corneal curvature and anterior wavefront aberrations, with adjustment for horizontal invasion length (HIL) measured by anterior segment (AS) swept-source optical coherence tomography (SS-OCT). Methods: This study involved 53 eyes from 51 patients diagnosed with primary nasal pterygium. The clinical grade of the pterygium was evaluated using T grade based on the fibrovascular translucency. AS SS-OCT (Anterion, Heidelberg Engineering) provided HIL (in millimeters), thickness (in micrometers), anterior/posterior keratometry at the 3.0-mm ring, and anterior corneal wavefront metrics within a 6.0-mm zone. The device was also used to evaluate the magnitudes for the individual first-to fourth-order aberrations of the anterior corneal fields. Also, the fourth- to seventh-order root mean square (RMS), RMS lower-order aberration (LoA), and RMS higher-order aberration (HoA) values were collected. For statistical analysis, Spearman rank correlation test and Pearson correlation test were performed, along with partial correlation test adjusted for HIL. Results: The mean age of subjects was 59.3 ± 11.4 years, and 51.0% were female. T grade correlated positively with HIL. HIL showed strong associations with anterior simulated keratometry (Sim K) average, anterior Sim K steep, anterior Sim K flat, and anterior corneal astigmatism—but not with posterior corneal parameters. HIL also showed significant correlations with multiple anterior corneal wavefront parameters. After adjustment for HIL, T grade remained independently correlated with anterior Sim K flat, RMS LoA, and defocus; no significant relationships were observed with other Zernike terms or posterior metrics. Additionally, T grade was positively correlated with pterygium thickness. Conclusions T grade adds independent, complementary information (associations with flat keratometry, LoA RMS, and defocus) even after controlling for HIL. Incorporating T grade into preoperative assessment may improve estimation of optical burden and surgical prognosis.

Purpose: Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response. Materials and Methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay. Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen. Conclusion Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Idiopathic pulmonary fibrosis (IPF) is characterized by maladaptive epithelial–mesenchymal crosstalk and progressive extracellular matrix accumulation, whereas currently available antifibrotic agents merely decelerate functional decline.This study investigated whether exosomes derived from human mesenchymal stem cells derived from embryonic stem cells (ESC-MSCs) restore epithelial stress responses and attenuate fibrotic remodeling. Human IPF lung transcriptomes were integrated with a bleomycin-induced murine model analyzed by RNA sequencing and protein signaling, together with cigarette smoke extract-induced injury in A549 epithelial cells. ESC-MSCs-derived exosomes exhibited typical morphology and size distribution, enrichment of tetraspanins, and absence of endoplasmic reticulum contamination, consistent with high-purity preparations. Across human IPF and bleomycin-injured lungs, transcriptomic profiling revealed prominent enrichment of extracellular matrix and cytoskeletal gene programs, whereas mitogen-activated protein kinase (MAPK) and Smad families displayed only modest alterations at the mRNA level. In vivo administration of exosomes during the fibrotic remodeling phase, via either intravenous or intratracheal delivery, resulted in improved body weight, reduced lung weight-to-body weight ratios, and decreased collagen deposition and Ashcroft scores. These structural and functional improvements were accompanied by suppression of profibrotic and mesenchymal markers and selective attenuation of activator protein-1 (AP-1) activity. In epithelial injury models, ESC-MSCs-derived exosomes enhanced cell viability, restored redox homeostasis, and constrained stress-induced mesenchymal gene expression and MAPK phosphorylation in both co-treatment and post-treatment settings. Collectively, these data support an epithelial-centered mechanism in which ESC-MSCs-derived exosomes re-establish oxidative balance and selectively restrict AP-1-driven stress signaling, thereby secondarily limiting extracellular matrix accumulation and fibrotic remodeling.

Background/Aims: The benefits of adjuvant therapy after curative resection (CR) have been demonstrated for bile duct cancer with lymph node (LN) metastasis. However, the putative benefits of adjuvant treatment for bile duct cancer without LN metastasis remain controversial.We aimed to identify recurrence risk factors for distal bile duct cancer (DBC) without LN metastasis following CR and high-risk groups that may benefit from adjuvant treatment. Methods: We retrospectively analyzed recurrence-related factors of patients who underwent surgical resection for DBC at Yonsei University Severance Hospital from January 2010 to June 2019. Results: Of 380 DBC cases receiving CR, 248 (62.8%) were pathologically confirmed as free from LN metastasis. The recurrence rates of all cases and LN metastasis-free cases were similar at 52.4% and 46.8%, respectively. Further, distant metastasis and local recurrence were about equally frequent. Involvement of adjacent organs, the presence of an R1 resection margin (cancer cells present microscopically), lymphovascular invasion (LVI), and perineural invasion (PNI) were identified as risk factors for recurrence (R1 margin OR: 1.642, 95% CI: 1.045–2.578, p = 0.031; LVI OR: 2.049, 95% CI: 1.347–3.115, p = 0.001; PNI OR: 1.901, 95% CI: 1.170–3.088, p = 0.009). Overall survival was also significantly reduced in patients with R1 resection margins (p = 0.018), LVI (p < 0.001), or PNI (p = 0.002). Conclusions The overall risk of LN-negative DBC recurrence remains high after CR. Aggressive systemic adjuvant treatment and active surveillance are required for patients with R1 resection margins, LVI, or PNI.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Purpose: To analyze anterior, posterior, and total corneal refractive profiles and thickness using anterior segment (AS) sweptsource optical coherence tomography (SS-OCT) in Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) patients. Methods: This retrospective study compared 23 eyes from 14 patients with SJS/TEN with 23 eyes from 14 age- and sexmatched controls. AS SS-OCT measured corneal refractive profiles and pachymetry. Parameters included anterior, posterior, and total corneal power values, posterior to anterior curvature ratio, maximal corneal power, and thickness profiles. The SJS/TEN group was subdivided based on corneal opacity presence (subgroup A) or absence (subgroup B). Results: The SJS/TEN group showed significantly higher corneal astigmatism and maximal corneal power values for both anterior and posterior curvatures. Steep total corneal power and total corneal astigmatism were higher in the SJS/TEN group. The thinnest corneal thickness was lower, and its distance from the corneal vertex was greater in the SJS/TEN group. Subgroup analysis revealed that these differences were primarily attributed to the presence of corneal opacity. Additionally, automated keratometry of the anterior corneal surface showed significantly higher values, including steep, flat, and average keratometry and corneal astigmatism, in the SJS/TEN group. Conclusions AS SS-OCT shows significant alterations in both anterior and posterior corneal curvatures in patients with SJS/TEN. These findings emphasize the importance of considering posterior corneal curvature changes in pre-cataract surgery assessments and contact lens prescriptions for patients with SJS/TEN.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Purpose: To analyze anterior, posterior, and total corneal refractive profiles and thickness using anterior segment (AS) sweptsource optical coherence tomography (SS-OCT) in Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) patients. Methods: This retrospective study compared 23 eyes from 14 patients with SJS/TEN with 23 eyes from 14 age- and sexmatched controls. AS SS-OCT measured corneal refractive profiles and pachymetry. Parameters included anterior, posterior, and total corneal power values, posterior to anterior curvature ratio, maximal corneal power, and thickness profiles. The SJS/TEN group was subdivided based on corneal opacity presence (subgroup A) or absence (subgroup B). Results: The SJS/TEN group showed significantly higher corneal astigmatism and maximal corneal power values for both anterior and posterior curvatures. Steep total corneal power and total corneal astigmatism were higher in the SJS/TEN group. The thinnest corneal thickness was lower, and its distance from the corneal vertex was greater in the SJS/TEN group. Subgroup analysis revealed that these differences were primarily attributed to the presence of corneal opacity. Additionally, automated keratometry of the anterior corneal surface showed significantly higher values, including steep, flat, and average keratometry and corneal astigmatism, in the SJS/TEN group. Conclusions AS SS-OCT shows significant alterations in both anterior and posterior corneal curvatures in patients with SJS/TEN. These findings emphasize the importance of considering posterior corneal curvature changes in pre-cataract surgery assessments and contact lens prescriptions for patients with SJS/TEN.