Pediatric pouchitis has no established treatment strategy, and management is particularly challenging in recurrent or antibiotic-refractory cases. Tumor necrosis factor alpha (TNF-α) and mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) are established and emerging therapeutic targets, respectively, in adult ulcerative colitis (UC) and pouchitis; however, their expression profiles and clinical relevance in pediatric pouchitis remain unclear. Therefore, we evaluated the pathological and clinical significance of TNF-α and MAdCAM-1 in pediatric pouchitis. We performed immunohistochemical analysis of surgically resected ileal tissues and subsequent pouch biopsy specimens obtained from 10 pediatric patients with UC. Paired pouchitis biopsies were collected during both active (high pouchitis disease activity index, PDAI) and improved (low PDAI) phases. TNF-α, MAdCAM-1, and immune cell markers (CD68, CD163, and CD8) in the mucosal stroma were quantitatively assessed using HALO image analysis. Compared with baseline ileal tissues, pouchitis specimens showed increased MAdCAM-1-positive vasculature and infiltration of CD68- and CD163-positive cells. In paired specimens, MAdCAM-1, TNF-α, and CD68 expression was significantly reduced in low-PDAI tissues. MAdCAM-1 and TNF-α expression was positively correlated with inflammatory cell infiltration. This exploratory study provided the first histological evidence that MAdCAM-1 and TNF-α could be upregulated in pediatric pouchitis and associated with disease severity, highlighting the pathological relevance of adult UC therapeutic targets in this setting.

Reducing the risk of infections associated with myelosuppression, particularly neutropenia, is crucial for ensuring chemotherapy completion and maximizing efficacy. Oral immunonutrition (OIN) containing omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has garnered attention. While OIN can reduce postoperative infections and improve prognosis, its impact on chemotherapy and chemoradiotherapy completion rates in esophageal cancer remains unclear. Therefore, retrospective and prospective (UMIN000056761) studies were conducted to evaluate the effects of OIN in patients undergoing chemotherapy or chemoradiotherapy for esophageal cancer. In the retrospective study, 32 patients were analyzed: 15 in the docetaxel, nedaplatin and 5-fluorouracil (DNF) group (OIN, 6; control, 9) and 17 in the docetaxel, cisplatin and 5-fluorouracil (DCF) with radiotherapy (DCF-RT) group (OIN, 7; control, 10). Although OIN (ProSure®) did not significantly affect the completion rates of the DNF regimen (P=0.622), it significantly improved the second-cycle completion rate of the DCF-RT regimen (P=0.030). In addition, although OIN had no significant effect on febrile neutropenia or other adverse events, except for nausea in the DNF group, first-cycle granulocyte colony-stimulating factor (G-CSF) use was significantly lower in the OIN group (P=0.001). In the prospective study, 14 patients were studied. Due to the small sample size, the primary endpoint could not be evaluated; however, OIN significantly increased the plasma-free EPA/arachidonic acid (AA) ratio on days 3 and 7 (both P=0.011), whereas the free DHA/AA ratio remained unchanged. These findings suggested that increasing the EPA/AA ratio via OIN may contribute to immune activation in cancer chemotherapy, leading to reduced G-CSF use and improved treatment completion rates. Although based on a limited number of patients, these results provide pilot evidence supporting the immunonutritional potential of OIN in esophageal cancer treatment. The prospective study (UMIN000056761) was retrospectively registered on January 21, 2025.

Background/Aim:Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients. This study aimed to analyze the clinical impact of KPNA2 expression in neuroblastoma. Materials and Methods:KPNA2 expression in 81 resected neuroblastoma sections was examined using immuno-histochemical staining. The significance and prognostic value of tumoral KPNA2 expression were analyzed using our cohort and R2 database. Results:The KPNA2 was expressed in the nucleus of neuroblastoma cells. The expression level of nuclear KPNA2 was not associated with clinicopathological factors in neuroblastoma. Among our cohort (n=81), non-radically resected neuroblastoma patients (n=37) with high KPNA2 expression had poorer prognoses than those with low KPNA2 expression. The R2 database analysis validated that the high KPNA2 expression was related to the poor prognosis in the large-scale neuroblastoma cohort. Conclusion:KPNA2 expression evaluation in neuroblastoma is a promising indicator of prognosis in non-curative resected cases. KPNA2 targeting may be a promising therapeutic strategy against advanced neuroblastoma.

PDF - 52KB, Legends for Supplementary Figures 1 and 2.

Supplementary Figure 3 from p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases

Supplementary Figure Legends PDF file - 49K, Legend for Supplementary Figures S1-S9

PDF - 103KB, Supplementary Figure 1. Water-soluble tetrazolium (WST) assay in FBXW7 siRNA-treated cells. The proliferation rate of FBXW7 siRNA-treated cells was compared to that of control siRNA-treated and parent NSCLC cells.

Supplementary Tables S1-S2 PDF file - 41K, CRC Patient characteristics in training set (2000-2004) and validation set (2005-2008) (S1); Gene list of GSEA analysis (S2).

Supplementary Figures S1-S9 PDF file - 984K, Representative photomicrographs of tissue sections immunostained for PLS3 (S1); The clinical significance of PLS3 expression in a second independent set of 110 primary colorectal cancer samples (S2); PLS3 expression profiles in various tissues, including peripheral blood-derived cells (S3); EMT induction in CaR-1 cells by TGF-beta1 (S4); PLS3 mRNA expression in LoVo cells expressing stem cell makers (S5); Immunocytochemical staining of PLS3 in rectal cancer cell line CaR-1 and peripheral blood mononuclear cells (S6); Validation of PLS3 expression in PB after recurrence (S7); Survival curves of Dukes stage B CRC patients based on the level of CK19/CK20 mRNA expression in PB (S8); PLS3 expression profiles in several cancer cell lines (S9)

OBJECTIVES: Thoracotomy is a reliable approach for descending necrotizing mediastinitis (DNM), and the use of video-assisted thoracic surgery (VATS), a minimally invasive procedure, has been increasing. However, which approach is more effective for DNM treatment is controversial.METHODS: We analysed patients who underwent mediastinal drainage via VATS or thoracotomy, using a database with DNM from 2012 to 2016 in Japan, which was constructed by the Japanese Association for Chest Surgery and the Japan Broncho-esophagological Society. The primary outcome was 90-day mortality, and the adjusted risk difference between the VATS and thoracotomy groups using a regression model, which incorporated the propensity score, was estimated.RESULTS: VATS was performed on 83 patients and thoracotomy on 58 patients. Patients with a poor performance status commonly underwent VATS. Meanwhile, patients with infection extending to both the anterior and posterior lower mediastinum frequently underwent thoracotomy. Although the postoperative 90-day mortality was different between the VATS and thoracotomy groups (4.8% vs 8.6%), the adjusted risk difference was almost the same, -0.0077 with 95% confidence interval of -0.0959 to 0.0805 (P = 0.8649). Moreover, we could not find any clinical and statistical differences between the 2 groups in terms of postoperative 30-day and 1-year mortality. Although patients who underwent VATS had higher postoperative complication (53.0% vs 24.1%) and reoperation (37.9% vs 15.5%) rates than those who underwent thoracotomy, the complications were not serious and most could be treated with reoperation and intensive care.CONCLUSIONS: The outcome of DNM treatment does not depend on thoracotomy or VATS.

Japanese guidelines recommend surgery or chemoradiotherapy (CRT) for submucosal (T1b) esophageal cancer. Approximately 44.5% of all patients with esophageal cancer are aged ≥70 years, 1 Watanabe M Tachimori Y Oyama T et al. Comprehensive registry of esophageal cancer in Japan, 2013. Esophagus. 2021; 18: 1-24 Crossref PubMed Scopus (79) Google Scholar and hence, surgery and chemotherapy may be unsuitable owing to comorbidities associated with old age. Therefore, less-invasive and effective treatments are needed for the management of esophageal cancer, especially in elderly patients.

Background: The emergence of omicron variants exhibiting antigenic changes has led to an increase in breakthrough infection among individuals with a wild-type SARS-CoV-2 vaccine booster. The correlation between post-booster spike-specific antibodies and omicron infection risk remains unclear. Methods: This prospective cohort study included SARS-CoV-2-naive healthcare workers with three-dose BNT162b2. Post-booster spike-specific IgG and interferon-gamma levels were measured. Breakthrough infection was documented during a 10-month omicron-predominant period. Household and healthcare contacts were followed to identify subsequent infections. The IgG titers were additionally measured at the end of follow-up, and the titers at exposure were estimated from the two-point titers. Results: Of 333 participants, 89 developed infection, of whom 37 (41.6 %) were household contacts. Kaplan-Meier curves indicated that higher IgG titers were significantly correlated with lower cumulative infection incidence (p = 0.029), whereas the interferon-gamma levels were not (p = 0.926). Multivariate Cox analysis showed that increasing IgG titers were associated with a reduced hazard ratio (HR) of 0.26 (95% CI, 0.12-0.55). Household exposure posed a greater infection risk than healthcare exposure (HRs, 11.24 [6.88-18.40] vs. 2.82 [1.37-5.44]). The difference in geometric mean IgG titers of infected and uninfected participants was significant among household contacts (20,244 AU/mL vs. 13,842 AU/mL, p = 0.031). Estimation of IgG titers at exposure showed a significantly higher infection incidence in those exposed with titers of <3,000 AU/mL than in those with higher titers (79.2 % vs. 32.3 %, p < 0.001). Conclusions: Spike-specific antibodies induced by a wild-type SARS-CoV-2 vaccine booster are suggested to be effective in protecting against omicron infection. Household exposure would be a significant source of infection for hospital healthcare workers.

Supplementary Figure Legends 1-7 from <i>p53</i>-Altered <i>FBXW7</i> Expression Determines Poor Prognosis in Gastric Cancer Cases

BACKGROUND:A cost-effective and eco-friendly method is needed for the assessment of humoral immunity against SARS-CoV-2 in large populations.OBJECTIVE:We investigated the performance of an ELISA that uses silkworm-produced proteins to quantify the strain-specific anti-Spike IgG (anti-S IgG) titer.METHODS:The OD values for the anti-His-tag antibody, a standard material of ELISA quantification, were measured. Correlations between the ELISA for each strain and the Abbott SARS-CoV-2 IgG II Quant assay for the wild type were evaluated with serum samples from nine participants with various infection and vaccination statuses.RESULTS:Linear dose-responses were confirmed by high coefficients of determination: 0.994, 0.994, and 0.996 for the wild-type, Delta, and Omicron (BA.1) strain assays, respectively. The coefficient of determination for the wild-type and Delta strain assays was high at 0.959 and 0.892, respectively, while the Omicron strain assay had a relatively low value of 0.563. Booster vaccinees showed similar or higher titers against all strains compared to infected persons without vaccination. The Omicron-infected persons without vaccination had lower antibody titers against wild type than did the vaccinated persons.CONCLUSIONS:This study provides data indicating that the ELISA with silkworm-produced proteins makes it possible to discriminate and quantify the strain-specific anti-S IgG antibody induced by vaccination or infection.

Supplementary Figure Legends 1-7 from p53-Altered FBXW7 Expression Determines Poor Prognosis in Gastric Cancer Cases

PDF - 98KB, Supplementary Figure 2. FBXW7 expression in cell lines treated with MS-275.

PDF - 88KB, Supplementary Table 1. Relationships between FBXW7 expression and clinicopathological factors in 103 patients with NSCLC. Supplementary Table 2. Univariate and multivariate analysis of clinicopathological factors affecting the overall survival rate of patients with NSCLC following surgery.

Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.

Background: A SARS-CoV-2 mRNA vaccine booster elicits sufficient antibody responses that protect against COVID-19, whereas adverse reactions such as fever have been commonly reported. Associations between adverse reactions and antibody responses have not been fully characterized, nor has the influence of antipyretic use. Methods: This is a prospective observational cohort study in Japan, following our prior investigation of BNT162b2 two-dose primary series. Spike-specific IgG titers were measured for SARS-CoV-2-naive hospital healthcare workers who received a BNT162b2 booster. The severity of solicited adverse reactions, including the highest body temperature, and self-medicated antipyretics were reported daily for seven days following vaccination through a web-based self-reporting diary. Results: The data of 281 healthcare workers were available. Multivariate analysis extracted fever after the booster dose (beta=0.305, p<0.001) as being significantly correlated with the specific IgG titers. The analysis of 164 participants with data from the primary series showed that fever after the second dose was associated with the emergence of fever after the booster dose (relative risk: 3.97 [95% confidence interval: 2.48-6.35]); however, the IgG titers after the booster dose were not affected by fever after the second dose. There were no significant differences in the IgG titers by the use, type, or dosage of antipyretic medication. Conclusions: These results suggest an independent correlation between mRNA vaccine-induced specific IgG levels and post-booster vaccination fever, without any significant influence of fever after the primary series. Antipyretic medications for adverse reactions would not interfere with the elevation of specific IgG titers.