Common variable immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized by reduced levels of immunoglobulin (Ig)G, with or without IgA and/or IgM deficiency, and hypogammaglobulinemia. Clinical manifestations are diverse, ranging from recurrent infections to autoimmune and allergic diseases. While CVID has been rarely reported in the Korean population, particularly in adults, we report 2 adult cases of CVID comorbid with asthma and Behcet’s disease. The first case of a 53-year-old with severe allergic asthma and chronic rhinosinusitis experienced recurrent respiratory infections, stomatitis, and cystitis requiring frequent antibiotic treatment. Laboratory findings indicated a T2-high asthma phenotype, with elevated serum total IgE specific IgE to dog hair and fractional exhaled nitric oxide. Immunological evaluation revealed decreased serum IgG (including IgG1 and IgG2), along with hypogammaglobulinemia. She had been treated with regular anti-IgE antibody therapy and intravenous immunoglobulin replacement therapy (IVIGRT). The second case of a 38-year-old with Behçet’s disease and uveitis had bronchial asthma and rhinitis that were exacerbated by recurrent infections despite standard asthma therapy. Laboratory findings revealed a T2-low phenotype and a marked reduction in serum IgG (including IgG1, IgG2, and IgG4), and hypogammaglobulinemia, consistent with CVID.IVIGRT effectively reduced asthma exacerbations and infection episodes in both cases. These cases highlight the clinical heterogeneity of CVID and its potential overlap with allergic and autoimmune diseases. Immunological evaluation of underlying immunodeficiency should be considered in adult patients with asthma who present with frequent exacerbations and recurrent infections. Early diagnosis and IVIGRT can prevent complications and improve outcomes.

Purpose: Esophagojejunal anastomotic leakage (EJAL) represents a severe postoperative complication following total or proximal gastrectomy. Treatment strategies include conservative management, endoscopic interventions, and surgery; however, comparative data remain limited. This study aimed to compare clinical outcomes of different strategies to identify the optimal approach based on anastomotic defect size. Materials and Methods: This retrospective study reviewed 100 patients diagnosed with EJAL between January 2015 and October 2024. Patients were categorized into four groups:conservative management, endoscopic vacuum-assisted closure (E-VAC), other endoscopic treatments, and surgery. The primary outcomes were leakage duration and length of hospital stay after EJAL diagnosis, whereas the secondary outcome was time to C-reactive protein normalization. Subgroup analyses were performed according to defect size. Results: Among the 100 patients, 76 were male and 24 were female, with a mean age of 65.7 years. Conservative treatment was the most common modality (53%), followed by other endoscopic treatments (19%), E-VAC (14%), and surgery (14%). In patients with a defect size <1 cm, conservative treatment was associated with significantly shorter leakage duration (P=0.035) and earlier resumption of diet (P=0.029) compared with endoscopic treatment.Among those with defects ≥2 cm, E-VAC demonstrated the most favorable median outcomes across all variables; however, statistical significance was not achieved because of the small sample size. Conclusions Conservative treatment appears to be the most effective treatment strategy for EJAL with anastomotic defects <1 cm. For larger defects (≥2 cm), E-VAC may offer clinical benefit, although further studies are needed to confirm its efficacy. These findings highlight the importance of individualized treatment selection based on defect size.

Objective: Janus kinase (JAK) inhibitors are widely used to treat rheumatoid arthritis (RA); however, comparative analyses regarding their adverse events remain limited. This study aimed to compare the effects of different JAK inhibitors (tofacitinib, baricitinib, and upadacitinib) on hematological parameters in patients with RA in a real-world setting. Methods: This retrospective analysis included 552 patients with RA treated with JAK inhibitors between August 2015 and February 2024. Hematological parameters, including absolute neutrophil count (ANC) and platelet count, were assessed at baseline and after 6 months of treatment. Statistical analysis was performed to evaluate changes over time, and logistic regression analysis identified factors associated with hematologic alterations. Results: The 552 patients were divided into three groups: tofacitinib (n=264), baricitinib (n=143), and upadacitinib (n=145). No significant differences in baseline hematological parameters were observed across the groups. After 6 months, ANC decreased in all groups without significant differences among them (p=0.465). Patients receiving baricitinib had significantly higher platelet counts than those receiving tofacitinib (Pillai’s trace value of 0.063, p<0.001) or upadacitinib (Pillai’s trace value of 0.029, p<0.001).Multivariate analysis revealed that baricitinib was significantly associated with increased platelet counts (odds ratio, 2.009; 95% confidence interval, 1.212~3.331; p=0.007). Conclusion Although all three JAK inhibitors reduced ANC, baricitinib was associated with a substantial increase in platelet counts. These findings highlight the differences in adverse effect profiles among JAK inhibitors, emphasizing the importance of tailored monitoring in RA management.

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: 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.

Objective: To investigate the prevalence of pathological findings and clinical outcomes of riskreducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). Methods: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/ LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea.Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. Results: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/ LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9–71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. Conclusion Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Purpose: This study aimed to define an optimal age cutoff for early-onset gastric cancer (EOGC) and compare its characteristics with those of late-onset gastric cancer (LOGC) using nationwide survey data. Methods: Using data from a nationwide survey, this comprehensive population-based study analyzed data spanning 3 years (2009, 2014, and 2019). The joinpoint analysis and interrupted time series (ITS) methodology were employed to identify age cutoffs for EOGC based on the sex ratio and tumor histology. Clinicopathologic characteristics and surgical outcomes were compared between the EOGC and LOGC groups. Results: The age cutoff for defining EOGC was suggested to be 50 years, supported by joinpoint and ITS analyses. Early gastric cancer was predominantly present in the EOGC and LOGC groups. Patients with EOGC comprised 20.3% of the total study cohort and demonstrated a more advanced disease stage compared to patients with LOGC. However, patients with EOGC underwent more minimally invasive surgeries, experienced shorter hospital stays, and had lower postoperative morbidity and mortality rates. Conclusion This study proposes an age of ≤50 years as a criterion for defining EOGC and highlights its features compared to LOGC. Further research using this criterion should guide tailored treatment strategies and improve outcomes for young patients with gastric cancer.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.