Background: Psoriasis is a chronic inflammatory skin disorder typified by well-demarcated erythematous plaques with scales. While considered an immune-driven condition, its underlying molecular triggers remain insufficiently defined. Cold-inducible RNA-binding protein (CIRP), a stress-response protein, has recently been recognized as a damage-associated molecular pattern that can stimulate immune responses. Objective: This study aimed to explore the potential association between circulating CIRP levels and the clinical as well as histological characteristics of psoriasis. Methods: Serum CIRP concentrations were analyzed in 67 individuals diagnosed with psoriasis and 20 healthy controls. Relationships between CIRP expression and various clinical and histological indices were also examined. Results: Patients with psoriasis exhibited significantly elevated serum CIRP levels compared to healthy individuals. Although correlations were observed between CIRP and certain clinical and histological indicators, CIRP levels did not significantly differ based on disease severity (Psoriasis Area and Severity Index score), joint involvement, or nail changes. Conclusion Our findings support the notion that CIRP may be involved in the immunopathogenesis of psoriasis and could be considered a prospective target for therapeutic modulation.

Background: Alitretinoin, a pan-retinoid receptor agonist approved for chronic hand eczema, exhibits immunomodulatory effects that may benefit alopecia areata (AA). However, clinical evidence for its use in AA is limited. Objective: To evaluate alitretinoin's clinical efficacy and immunological mechanism in patients with AA. Methods: We reviewed retrospectively twenty-one patients with AA who were treated with alitretinoin, either as monotherapy (n=9) or add-on therapy (n=12). Treatment response was assessed using the Severity of Alopecia Tool (SALT) scores, and in vitro studies used human outer root sheath cells stimulated with interferon-γ and polyinosinic:polycytidylic acid to investigate the drug’s effects on inflammatory pathways. Results: Both groups showed significant reductions in SALT scores (p=0.04 and p=0.02, respectively). Patients with baseline SALT scores below 50 demonstrated superior improvement.Adverse events were mild, with headache (33.3%) and cheilitis (4.8%) being the most common. In vitro, alitretinoin suppressed interleukin-6 and tumor necrosis factor-α expression, decreased phosphorylation of signal transducer and activator of transcription (STAT) 1/STAT3, and downregulated major histocompatibility complex class I expression, suggesting restoration of hair follicle immune privilege. Conclusion Alitretinoin appears to be a safe and potentially effective treatment for patients with mild to moderate AA unresponsive to conventional therapies. Its role as a monotherapy or adjunctive option in selected cases warrants further investigation through larger controlled studies.

Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

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.

Objective: To evaluate the diagnostic performance of the “probable hepatocellular carcinoma (HCC)” category in the Korean Liver Cancer Association-National Cancer Center (KLCA-NCC) v2022 guidelines. Materials and Methods: This multicenter retrospective study included patients at risk of HCC who underwent gadoxetic acid-enhanced MRI between January 2015 and June 2018; a subgroup of these patients also underwent liver CT. Eligible patients had at least one non-cystic lesion (≥10 mm) with a reference standard. Four radiologists interpreted the images independently and the results were pooled. The performance of “definite HCC” and “probable HCC” together and “probable HCC” alone were compared between v2018 and v2022. Results: A total of 2,237 patients (1,666 men; mean age, 59 ± 11 years) with 2,445 lesions were included. In v2022, 1.5% (143/9,780) of the lesions were additionally categorized as “probable HCC” by four reviewers on MRI; among these, 104 lesions were not HCCs. Focal nodular hyperplasia (FNH) or FNH-like nodules constituted 90.4% (94/104) of the false positives. When “definite HCC” and “probable HCC” were combined, v2022 showed higher sensitivity (83.7% [5,670/6,776] vs. 83.1% [5,631/6,776]) but lower specificity (77.1% [2,316/3,004] vs. 80.6% [2,420/3,004]) than v2018 (P < 0.001). For “probable HCC” alone, v2022 showed a lower positive predictive value (PPV) than v2018 (64.1% [373/582] vs. 76.1% [334/439], P < 0.001). In v2022, lesions with non-rim arterial-phase hyperenhancement (APHE) showed a lower PPV than those without APHE (42.3% [91/215] vs. 76.8% [282/367], P < 0.001). In the CT subgroup (n = 1,590), 1.6% (99/6,360) of the lesions were reassessed as “probable HCC,” and its PPV was 83.8% (83/99) in v2022 whereas no lesions were classified as “probable HCC” under v2018. Conclusion The revised “probable HCC” category in the KLCA-NCC v2022 aligns with updates in the diagnostic flow, demonstrating acceptable performance on MRI and CT. Notably, FNH or FNH-like nodules can be misclassified as “probable HCC” when MRI is used.

Purpose: Due to its rarity, treatment guidelines for appendiceal cancer have traditionally followed those established for colorectal cancer, despite showing distinct histologic and clinical features. This study aimed to compare the clinicopathologic characteristics and long-term oncologic outcomes of appendiceal cancer with those of right-sided colon cancers. Methods: We retrospectively reviewed the records of patients with stage I–III appendiceal, cecal, or ascending colon cancer who underwent curative resection between 2010 and 2020 at our center. A 1:3:3 exact matching for age, sex, TNM stage, and adjuvant chemotherapy was performed. Survival outcomes were analyzed using the Kaplan-Meier and Cox regression methods. Results: Overall, 245 patients with appendiceal cancer (n = 35), ascending colon cancer (n = 105), and cecal cancer (n = 105) were analyzed. Appendiceal cancer exhibited a higher proportion of T4 tumors and fewer harvested lymph nodes compared with ascending or cecal cancers. The mean follow-up duration was 9.5 years. The 5- and 10-year overall survival rates were lower in appendiceal cancer (66.2% and 52.9%) than in ascending (91.2% and 78.4%) or cecal cancer (88.5% and 78.3%). Similarly, the 10-year disease-free survival rate was lower in appendiceal cancer (59.2%) compared with ascending (83.1%) and cecal cancers (78.4%). Cox regression analysis identified age (≥65 years), perforation, nodal metastasis, and lymphovascular invasion as independent predictors of poor prognosis. Conclusion Appendiceal cancer exhibited significantly worse long-term survival compared to cecal or ascending colon cancer. Tumor perforation, nodal metastasis, and lymphovascular invasion were adverse prognostic factors for overall and disease-free survival.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

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: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: To develop the 2025 update to the Korean colorectal cancer (CRC) screening guidelines by systematically evaluating recent evidence, integrating domestic data, and addressing changes since the 2015 guideline revision, thereby providing an evidence-based standard for clinicians and policymakers. Methods: A multidisciplinary committee developed the guidelines using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The process included formulation of three key questions addressing screening efficacy, diagnostic accuracy, and optimal screening age and interval. A systematic review of international guidelines and primary literature was conducted, yielding 327 eligible studies. In addition, a utility-based analysis using a Markov model was performed to determine optimal screening ages and intervals. Results: The evidence synthesis identified high-certainty evidence supporting the use of the fecal immunochemical test (FIT) for reducing CRC mortality and moderate-certainty evidence for colonoscopy. Evidence for computed tomographic colonography (CTC) and stool DNA testing was rated as very low certainty. Based on the evidence review and cost-utility analysis, the committee conditionally recommends CRC screening for asymptomatic, average-risk adults aged 45–74 years using either colonoscopy every 10 years or FIT every 1–2 years. CTC and stool DNA testing were not recommended owing to insufficient evidence. Conclusion The 2025 Korean Guidelines for Colorectal Cancer Screening present updated, evidence-based recommendations tailored to the domestic healthcare context. By conditionally endorsing both colonoscopy and FIT for individuals aged 45–74 years, these guidelines aim to improve population-level screening effectiveness and reduce the burden of CRC in South Korea.