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.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

The Wikstroemia genus is highly regarded in traditional Asian medicine for its diverse therapeutic applications, including the treatment of inflammatory and infectious conditions. Among its members,Wikstroemia trichotoma (Thunb.) Makino remains a promising medicinal resource which is yet to be chemicallycharacterized. To ensure the chemical consistency of W. trichotoma, we developed and validated the first HPLC method for the simultaneous quantification of three major marker compounds: chlorogenic acid (1), miconioside B (2), and matteucinol 7-O-apiofuranosyl(1→6)-glucopyranoside (3). Chromatographic separation was achieved on a C18 column using a gradient elution system of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Detection was optimized using a photodiode array (PDA) detector at 280 and 325 nm, based on the absorption maxima of the markers. The method was validated in accordance with the International Council for Harmonisation (ICH) and the Ministry of Food and Drug Safety (MFDS) guidelines. The results demonstrated high linearity (r2 > 0.999), with limits of detection and quantitation ranging from 4.28–6.42 and 12.97–19.47 μg/ mL, respectively. Intra- and inter-day precision (% RSD ≤ 1.83%) and accuracy (recoveries of 92.5–101.7%) were within acceptable limits. Quantitative analysis revealed the contents of 1, 2, and 3 in the W. trichotoma extract to be 19.9, 139.8, and 264.9 mg/g, respectively. This study provides a reliable analytical framework for the standardization, quality control, and future pharmacological evaluation of W. trichotoma.

Background: Rosacea is a chronic inflammatory disorder characterized by flushing, erythema, papules/pustules, and telangiectasia. Several clinical studies have investigated the efficacy of botulinum neurotoxin A (BoNT/A) in the treatment of rosacea, but its mechanism of action remains unclear. Objective: This study aims to examine the potential role of BoNT/A in a mouse model of rosacea-like skin lesions induced by the 37-amino acid C-terminal cathelicidin peptide (LL-37). Methods: Mice were randomly divided into 4 groups: Control, LL-37, LL-37 + BoNT/A, and LL-37 + dexamethasone. Results: BoNT/A treatment alleviated skin damage, reduced skin thickness, and decreased mast cell infiltration. Furthermore, BoNT/A improved redness score severity and redness area while enhancing skin barrier function by suppressing transepidermal water loss and increasing skin hydration. At the molecular level, BoNT/A decreased the mRNA levels of interleukin (IL)-6 and tumor necrosis factor-α, which are known as pro-inflammatory cytokines. It also downregulated the expression of pyrin domain-containing protein 3, caspase-1, and IL-1 beta in the LL-37-injected dorsal skin. Furthermore, BoNT/A prevented LL-37-mediated upregulation of neurovascular-associated factors, including CD31, transient receptor potential vanilloid 1, calcitonin-related polypeptide alpha, vascular endothelial growth factor, chymase 1, and tryptase alpha/beta 1. Conclusion These results indicate that BoNT/A effectively alleviates inflammatory and vascular responses in a rosacea mouse model, highlighting its potential as a promising preventive approach for rosacea.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

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: Opioids remain widely used for postoperative pain control after total knee arthroplasty (TKA); however, concerns about adverse effects and dependency drive interest in opioid-sparing alternatives. This study evaluated the efficacy and safety of opioid-sparing patient-controlled analgesia (PCA) after TKA. Methods: In this prospective, randomized, double-blind, non-inferiority study, 98 patients undergoing TKA under spinal anesthesia received either opioid-based PCA (continuous infusion of 1200 μg fentanyl, n = 49) or opioid-sparing PCA (continuous infusion of 150 mg ketorolac tromethamine and 100 mg nefopam hydrochloride, n = 49). Both groups received patient-controlled boluses of 300 μg fentanyl. The primary endpoint was the visual analog scale (VAS) pain score at rest on postoperative day (POD) 1, assessed using a 1.5-point non-inferiority margin. Secondary endpoints included additional analgesics, mobility, postoperative pain at rest and during ambulation, and adverse effects on PODs 1 and 2. Results: The mean VAS score at rest on POD 1 was 5.45 ± 2.48 in the opioid-based PCA group and 5.90 ± 2.31 in the opioid-sparing PCA group. The mean difference was 0.45 points (95% CI, −0.36 to 1.25), within the prespecified non-inferiority margin. Pain scores at each time point were non-inferior in the opioid-sparing group, whereas rescue analgesic requirements were significantly reduced on POD 2 (P = 0.006). Nausea and vomiting on POD 1 were more frequent with opioid-based group (34.7% vs. 12.2%, P = 0.009). Conclusions Opioid-sparing PCA with ketorolac and nefopam provides non-inferior analgesia to opioid-based PCA, while reducing opioid consumption and drug-related adverse effects after TKA.

Background: In vitro and animal studies have demonstrated that bone morphogenetic protein-7 (BMP-7), renowned for its osteogenic properties, also exerts beneficial effects on muscle metabolism by enhancing myogenesis and reversing muscle atrophy. Despite being proposed as a common regulatory factor for both muscle and bone, the impact of BMP-7 on human muscle health has not been thoroughly investigated. Methods: This cross-sectional study involved 182 community-dwelling older adults who underwent a comprehensive geriatric assessment in South Korea. Sarcopenia was diagnosed using Asian-specific cutoffs, and serum BMP-7 levels were quantified via enzyme immunoassay. Results: The mean age of the participants was 72.2±7.3 years, with 62.6% being female. After adjustments for confounders, serum BMP-7 levels were not significantly different between individuals with and without sarcopenia, nor were there differences based on skeletal muscle mass, strength, or physical performance levels (p=0.423 to 0.681). Likewise, no correlations were detected between circulating BMP-7 levels and any sarcopenia assessment metrics such as skeletal muscle index, grip strength, gait speed, or chair stand completion times (p=0.127 to 0.577). No significant associations were observed between increases in serum BMP-7 concentrations and the risk of sarcopenia or poor muscle phenotypes (p=0.431 to 0.712). Stratifying participants into quartiles based on serum BMP-7 levels also indicated no differences in sarcopenia-related parameters (p=0.663 to 0.996). Conclusion Despite experimental evidence supporting BMP-7’s role in muscle metabolism, this study found no significant association between serum BMP-7 levels and clinical indicators of muscle health in older adults. These findings challenge the utility of serum BMP-7 as a biomarker for sarcopenia in this demographic.

Purpose: While colonoscopy is the standard surveillance tool for stage I colorectal cancer according to National Comprehensive Cancer Network guidelines, its effectiveness in detecting recurrence is debated. This study evaluates recurrence risk factors and patterns in stage I colorectal cancer to inform comprehensive surveillance strategies. Materials and Methods: A retrospective analysis of 2,248 stage I colorectal cancer patients who underwent radical surgery at Samsung Medical Center (2007-2018) was conducted. Exclusions were based on familial history, prior recurrences, preoperative treatments, and inadequate data. Surveillance included colonoscopy, laboratory tests, and computed tomography (CT) scans. Results: Stage I colorectal cancer patients showed favorable 5-year disease-free survival (98.3% colon, 94.6% rectum). Among a total of 1,467 colon cancer patients, 26 (1.76%) experienced recurrence. Of the 781 rectal cancer patients, 47 (6.02%) experienced recurrence. Elevated preoperative carcinoembryonic antigen levels and perineural invasion were significant recurrence risk factors in colon cancer, while tumor budding was significant in rectal cancer. Distant metastasis was the main recurrence pattern in colon cancer (92.3%), while rectal cancer showed predominantly local recurrence (50%). Colonoscopy alone detected recurrences in a small fraction of cases (3.7% in colon, 14.9% in rectum). Conclusion Although recurrence in stage I colorectal cancer is rare, relying solely on colonoscopy for surveillance may miss distant metastases or locoregional recurrence outside the colorectum. For high-risk patients, we recommend considering regular CT scans alongside colonoscopy. This targeted approach may enable earlier recurrence detection and improve outcomes in this subset while avoiding unnecessary scans for the low-risk majority.