Acute cellular rejection (ACR) following heart transplantation (TPL) compromises graft function and survival. The programmed cell death-1 (PD-1)/PD-1 ligand-1 (PD-L1) pathway represents an immune checkpoint that maintains peripheral immune tolerance, but its expression and significance in human cardiac allografts with ACR remain unclear. Thus, we investigated PD-1/ PD-L1 expression in endomyocardial biopsies from heart TPL recipients to clarify the role of this pathway in the ACR of human cardiac allografts and explore the potential of therapeutic modulation of PD-1/PD-L1 in this setting. Methods: Endomyocardial biopsies of 78 patients with heart TPL were subjected to immunohistochemistry for PD-L1, PD-1, CD4, and CD8. PD-L1 expression and quantities of PD-1+, CD4+, and CD8+ infiltrating lymphocytes were evaluated according to clinicopathological features, ACR presence, and clinical outcomes. Results: Allografts with high-grade ACR (International Society for Heart and Lung Transplantation grades 2R and 3R) demonstrated markedly higher PD-L1 expression than did those without ACR (62.5% vs. 16.1%, p < .001). PD-L1 expression was positively associated with CD4+ lymphocyte infiltration (p = .025), whereas CD8 and PD-1+ lymphocyte counts were higher in PD-L1-positive allografts without reaching statistical significance (p = .059 and p = .390, respectively). Serial biopsies revealed that PD-L1 expression was upregulated in patients with high-grade ACR compared with that in previous non-ACR tissues, and follow-up biopsies were performed after ACR resolution. Conclusions: The PD-1/PD-L1 pathway is involved in ACR regulation in human cardiac allografts. Increased PD-L1 expression during ACR may represent a counteractive mechanism to limit alloimmune-mediated tissue injury, supporting PD-1/PD-L1 as a potential therapeutic target in heart TPL recipients.

Objective: Although most gallbladder polyps are benign, some neoplastic polyps may be malignant or may serve as precursors to malignancy. Distinguishing neoplastic and non-neoplastic polyps using imaging examinations remains a major challenge.This meta-analysis aimed to identify the ultrasound (US) features that are significantly associated with neoplastic polyps. Materials and Methods: The MEDLINE, EMBASE, Cochrane, and KoreaMed databases were searched for articles published up to August 31, 2025. Bivariate random-effects models were used to calculate the meta-analytic pooled diagnostic odds ratios (DORs), sensitivities, and specificities, along with their 95% confidence intervals (CIs), for each US imaging feature in the diagnosis of neoplastic polyps. Results: Thirty studies evaluating 8,953 patients, including 1,216 (13.6%) patients with neoplastic polyps, were included.Among the nine evaluated US imaging features, namely, size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, heterogeneous echogenicity, gallbladder wall thickening (GBWT), absence of hyperechoic spot, and vascularity, eight were significantly associated with neoplastic polyps: size ≥10 mm (DOR: 6.23 [95% CI: 1.86– 20.90]), sessile morphology (DOR: 3.54 [1.93–5.97]), single polyp (DOR: 2.21 [1.76–2.74]), coexisting gallstones (DOR:1.86 [1.29–2.60]), hypoechogenicity (DOR: 3.55 [1.47–7.30]), GBWT (DOR: 9.38 [1.47–32.20]), absence of hyperechoic spots (DOR: 4.23 [2.46–6.83]), and vascularity (DOR: 9.72 [5.81–15.30]). Of these, size ≥10 mm demonstrated the highest pooled sensitivity (0.79 [95% CI: 0.68–0.87]), whereas hypoechogenicity showed the highest pooled specificity (0.93 [95% CI: 0.82–0.98]). Conclusion Eight US imaging features (size ≥10 mm, sessile morphology, single polyp, coexisting gallstones, hypoechogenicity, GBWT, absence of hyperechoic spots, and vascularity) were significantly associated with the presence of neoplastic polyps.These features may facilitate the management of gallbladder polyps.

Obesity is a chronic, progressive neuroendocrine disease that warrants a shift toward an “onco-bariatric” treatment paradigm. This study introduces the tri-phasic metabolic obesity (TPMO) framework, which integrates glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with metabolic bariatric surgery (MBS). Recent clinical and economic evidence—including findings from the Indiana multicenter study and the Highmark Health analysis—was reviewed to evaluate the effectiveness of the TPMO model in improving surgical and metabolic outcomes. The TPMO framework streamlines the patient journey through three synergistic phases. In the neoadjuvant phase, a 4–8-week course of GLP-1 RAs reduces liver volume and visceral fat, thereby improving surgical access, provided that treatment is discontinued 1 week before surgery to mitigate aspiration risk. During the core surgery phase, MBS provides a definitive metabolic reset and remains the most cost-effective treatment, yielding an average savings of $11,689 per patient over 2 years compared with medication alone. In the adjuvant phase, pharmacotherapy—used by 17.2% of post-bariatric patients—counteracts metabolic adaptation and supports sustained weight loss, while a high-protein intake (≥1.2 g/kg/day) is essential for preserving lean body mass. The TPMO framework represents a precision-based, synergistic standard of care designed to promote durable, cost-effective long-term metabolic health within the onco-bariatric paradigm.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Background: This study was performed to evaluate the prognostic utility of a positive T wave in lead augmented vector right (TaVR) and elevated E/e′ ratio in predicting major adverse cardiovascular events (MACE) in patients receiving maintenance hemodialysis. Methods: We retrospectively examined 296 adults on thrice-weekly hemodialysis with baseline electrocardiography and transthoracic echocardiography (October 2018–April 2024). TaVR positivity was T-wave amplitude, >0 mV and high E/e′, ≥19. Primary outcome was the first MACE—cardiovascular death, myocardial infarction, stroke, heart-failure admission, or revascularization. Multivariable Cox models adjusted for clinical covariates; incremental value was gauged with Harrell’s C-index, integrated discrimination improvement (IDI), and continuous net reclassification improvement (NRI). Sensitivity analysis was performed using a guideline-recommended E/e′ threshold of ≥15 to assess robustness. Results: Over 56.5 months (1,325 patient-years), 118 MACE occurred (8.9/100 patient-years). Incidence was higher with TaVR positivity than negativity (16.0/100 patient-years vs. 3.7/100 patient-years; log-rank p < 0.001). Adjusted hazard ratios were 3.19 (95% confidence interval [CI], 2.00–5.08) for TaVR and 2.92 (95% CI, 1.71–4.96) for high E/e′. Adding both markers to the clinical model increased the C-index from 0.65 to 0.75 (Δ 0.10) and improved IDI (0.10) and NRI (0.16) (all p < 0.01). A significant negative interaction (hazard ratio, 0.21; p = 0.01) indicated complementary but partly overlapping information. Sensitivity results were similar. Conclusion TaVR positivity is a strong independent electrocardiography predictor of cardiovascular events in hemodialysis. Combining TaVR with E/e′ adds prognostic value and supports a pragmatic two-step strategy— electrocardiography triage followed by focused echocardiography—for cardiovascular risk stratification in this high-risk population.

Accurate lesion size measurement is essential in endoscopic practice as it influences treatment strategies, surveillance decisions, and clinical outcomes, especially in colorectal polyps. Traditional measurement techniques, including visual estimation and biopsy forceps, have significant interobserver variability and procedural inefficiencies. Recent advancements in digital measurement technologies, including virtual scale endoscopy (VSE) and artificial intelligence (AI)-assisted virtual rulers, have addressed these limitations. VSE projects a virtual scale onto endoscopic images, enhancing measurement precision and reducing variability. Several studies have demonstrated its superior accuracy compared with conventional methods; however, limitations such as increased procedure time and operator training requirements persist. AI-assisted virtual rulers utilize deep learning algorithms to automate lesion size estimation, significantly improving reproducibility and diagnostic reliability. Although these technologies offer promising improvements, challenges remain, including real-time integration, standardization, and regulatory approval. Future research should focus on refining AI models, expanding validation studies, and optimizing their usability in routine practice. A hybrid approach that combines AI automation with real-time digital tools may enhance the precision and efficiency of endoscopic lesion assessment, ultimately improving patient outcomes.

Background/Aims: This study aimed to investigate the influence of metabolic dysfunction-associated steatotic liver disease (MASLD) and body mass index (BMI) on the incidence of Alzheimer disease (AD) in the general South Korean population. Methods: The National Screening Program for Transitional Ages collected data from 66-year-old dementia-free Koreans in 2010 and 2011. MASLD was diagnosed based on the fatty liver index(≥30) and the presence of metabolic components, and overweight/obese status was defined as a BMI ≥23 kg/m 2 . The primary outcome was the development of AD up to December 2021.Multivariable Cox analyses were performed to evaluate whether the presence of MASLD or overweight/obese status influenced the risk of developing AD. Results: A total of 376,902 dementia-free individuals aged 66 years were included in this cohort. The participants were categorized into four groups: overweight/obese non-MASLD (30.4%, n=114,528), overweight/obese MASLD (37.0%, n=139,551), lean non-MASLD (29.9%, n=126,692), and lean MASLD (2.7%, n=10,131). During a mean follow-up period of 10.38±1.90 years, 23,874 individuals (6.3%) were newly diagnosed with AD. Compared to the overweight/ obese non-MASLD group, the adjusted hazard ratios (95% confidence interval) for AD in the lean MASLD, lean non-MASLD, and overweight/obese MASLD groups were 1.34 (1.24 to 1.45), 1.08 (1.04 to 1.13), and 1.13 (1.09 to 1.17), respectively. Conclusions A normal/underweight BMI and the presence of MASLD synergistically increased the risk of AD. The lean MASLD group had a higher risk of developing AD than the overweight/ obese MASLD group, suggesting that the clinical relevance of MASLD for incident AD differs based on the BMI.

Induced pluripotent stem cells (iPSCs) are a promising cell source for regenerative medicine. Clinical applications require a large number of functional red blood cells (RBCs), making it essential to ensure the proliferation of actively dividing, nucleated erythroblasts derived from iPSCs. Small molecules can enhance the efficiency and frequency of iPSC-derived cell differentiation. Sirtuin 1, a key enzyme in multiple biological processes, has been implicated in enhancing iPSC-derived cell differentiation. However, the specific effects of Sirtuin 1 on erythroblast proliferation from iPSCs remain unclear. Here, we developed a protocol to examine the effects of Sirtuin 1 on erythroblasts after endothelial-to-hematopoietic transition (EHT). We found that Sirtuin 1 activation increased the frequency of CD71＋CD235a＋erythroblasts at the early stage after EHT, suggesting a role for Sirtuin 1 in the proliferation of these specified erythroblasts. These findings reveal that Sirtuin 1 activation benefits erythroblast proliferation and could be considered for translational application in large-scale RBC culture.

Purpose: Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world. Materials and Methods: We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis. Results: NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs. Conclusion Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.