Interferon-Gamma Release Assay Combined with Renal Indicators to Reduce the False-Negativity of Latent Tuberculosis Infection in End-Stage Renal Disease with Hemodialysis Patients.

BACKGROUND: Tuberculosis (TB) is still the main cause of mortality due to a single transfectant, Mycobacterium tuberculosis (MTB). Latent tuberculosis infection (LTBI) is a condition characterized by the presence of tuberculosis (TB) that is not clinically apparent but nonetheless shows a sustained response to MTB. Presently, tuberculin skin test (TST) and interferon gamma (IFN-γ) release assays (IGRAs) are mainly used to detect LTBI via cell-mediated immunity of T-cells. For people with end-stage renal disease (ESRD), the diagnosis of patients infected with MTB is difficult because of T-cell dysfunction. To get more accurate diagnosis results of LTBI, it must compensate for the deficiency of IGRA tests. METHODS: Sixty-seven hemodialysis (HD) patients and 96 non-HD patients were enrolled in this study and the study population is continuously included. IFN-γ levels were measured by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. Kidney function indicators, blood urea nitrogen (BUN), serum creatinine (Cr), and estimated glomerular filtration rate (eGFR) were used to compensate for the declined IFN-γ levels in the IGRA test. RESULTS: In individuals who were previously undetected, the results of compensation with serum Cr increased by 10.81%, allowing for about 28% more detection, and compensation with eGFR increased by 5.41%, allowing for approximately 14% more detectable potential among them and employing both of them could enhance the prior shortcomings of IGRA tests. when both are used, the maximum compensation results show a sensitivity increase rate of 8.81%, and approximately 23% of patients who were previously undetectable may be found. CONCLUSION: Therefore, the renal function markers which are routine tests for HD patients to compensate for the deficiency of IGRA tests could increase the accuracy of LTBI diagnosis.

Nursing undergraduates' ageism and attitudes toward dementia: Serial multiple mediating effects of person-centered care and compassion - A cross-sectional survey.

Background: Although ageism has a strong relationship with attitudes toward dementia, no study has confirmed how person-centered care and compassion mediate the relationship between nursing students' ageism and attitudes toward dementia. Objectives: This study aimed to examine the mediating effects of person-centered care competency and compassion competency on ageism and attitudes toward dementia among nursing undergraduates. Participants: Participants were 295 undergraduate nursing students from four universities. Methods: A descriptive cross-sectional electronic survey was conducted, involving the selection of four Korean nursing schools for the study. Data was obtained via an online survey conducted from March to July 2022. Data were analyzed with Pearson's correlations, and multi-mediating effects using the PROCESS Macro for software, utilizing bootstrap techniques. Results: Attitudes toward dementia was correlated with ageism (r = -0.386, p < 0.001), person-centered care (r = 0.422, p < 0.001), and compassion competency (r = 0.457, p < 0.001). The total effect (ß = -0.326, p < 0.001) and direct effect (ß = -0.243, p < 0.001) of ageism on attitudes toward dementia were significant. Ageism does not have a direct effect on compassion competency (Std. estimate = -0.0213, CI: -0.0518∼0.0048). However, person-centered care and compassion competency had multiple serial mediating effects on the relationship between ageism and attitudes toward dementia (Std. estimate = -0.0357, CI: -0.0624∼-0.0145). Conclusions: Person-centered care and compassion competency may mediate the association between ageism and attitudes toward dementia. Ageism was negatively associated with person-centered care and compassion competency, which in turn positively contributed to attitudes toward dementia. Therefore, an educational program that considers the interaction between generations and the context of older people must be applied to increase person-centered care and compassion competency.

Mixed Method Evaluation of ACTS: Advancing Connection Through Storytelling-A Novel Approach to Improve Older Adult Engagement and Staff Interactions in Korean Nursing Homes.

BACKGROUND: A culture centered on relationships and communication is necessary to improve the quality of life of older adults living in nursing homes. OBJECTIVES: To examine the effects of a storytelling program by examining the cognitive, emotional, and psychosocial changes in older adults in facilities and explore staff experience of changes in care. METHODS: This mixed method study delivered a 6-week storytelling program based on relationship-centered care for residents of nursing homes (aged >65 years). Changes in emotional expression, depression, communication skills, social support, interpersonal relationships, nurse-patient interaction, and the person-centered environment as perceived by older adults were quantitatively analyzed using pre-intervention and post-intervention surveys. Qualitative data were collected through weekly stories created by residents, followed by focus group interviews with nursing home staff, analyzed using reflexive thematic analysis to enhance understanding of the program's outcomes. RESULTS: The 42 residents reported significant changes in their emotional expression, depression, communication skills, social support, interpersonal relationships, nurse-patient interaction, and person-centered environment scores after the 6-week intervention. Analysis of the residents' stories identified 5 themes. The staff focus group interviews identified 2 themes and 7 subthemes. Intervention group residents were more likely to initiate conversations, express themselves, carefully observe themselves and others, and actively participate in social activities. CONCLUSIONS: The storytelling program was useful in reducing older adults' negative emotions by allowing them to express their thoughts and feelings and improve their relationships, creating opportunities for social interaction. These effects could help foster relationship- and communication-centered facility cultures.

A spark of change: developing an innovative gerontological nursing intervention mapping initiative for training and education (IGNITE).

BACKGROUND: With an aging global population and advancements in medical technology, there is an urgent need for innovative gerontological nursing education programs. This study aimed to develop and evaluate the Innovative Gerontological Nursing Intervention Mapping Initiative for Training and Education (IGNITE) program. This program is a digital platform-based postgraduate nursing curriculum that employs the Intervention Mapping Approach (IMA) and Transformative Learning Theory to address the evolving needs of gerontological nursing. METHODS: The IGNITE program's development process encompassed a comprehensive approach, including needs assessment, mapping of course objectives, integration of theory-based methods and strategies, course design, implementation, and rigorous evaluation. The pilot evaluation study involved pre- and post-tests focused on ageism, attitudes towards elder care, knowledge about older adults, transformative behavior change, and program satisfaction. The findings revealed significant improvements across all these dimensions, affirming the effectiveness of the program. RESULTS: The program leveraged experiential learning, critical reflection, and rational discourse to facilitate transformative educational experiences. Notably, pre- and post-test comparisons showed marked improvements in attitudes towards older adult care and dementia care knowledge. Participants expressed high satisfaction with the program, with significant reported changes in transformative behaviors. The study also illuminated the initial negative attitudes of clinical nurses towards older adults and underscored the importance of transformative learning experiences in fostering empathy and understanding. CONCLUSIONS: The IGNITE program lays a foundational framework for developing educational materials that promote transformative learning and self-reflection among healthcare professionals. This approach can lead to innovative nursing practices and personal growth. The application of the IMA and Transformative Learning Theory in gerontological nursing education shows significant promise. Future research should focus on exploring the long-term impacts of such programs and their applicability in diverse healthcare settings.

Correlation between Collagen Type I/III Ratio and Scar Formation in Patients Undergoing Immediate Reconstruction with the Round Block Technique after Breast-Conserving Surgery.

The aim of this study was to investigate the relationship between the collagen type I/III ratio and scarring in patients who underwent immediate reconstruction with the round block technique (RBT) after breast conservation surgery. Seventy-eight patients were included, and demographic and clinical characteristics were recorded. The collagen type I/III ratio was measured using immunofluorescence staining and digital imaging, and scarring was assessed using the Vancouver Scar Scale (VSS). The mean VSS scores were 1.92 ± 2.01 and 1.79 ± 1.89, as assessed by two independent plastic surgeons, with good reliability of the scores. A significant positive correlation was found between VSS and the collagen type I/III ratio (r = 0.552, p < 0.01), and a significant negative correlation was found between VSS and the collagen type III content (r = -0.326, p < 0.05). Multiple linear regression analysis showed that the collagen type I/III ratio had a significant positive effect on VSS (ß = 0.415, p = 0.028), whereas the collagen type I and collagen type III content had no significant effect on VSS. These findings suggest that the collagen type I/III ratio is associated with scar development in patients undergoing RBT after breast conservation surgery. Further research is needed to develop a patient-specific scar prediction model based on genetic factors affecting the collagen type I/III ratio.

Digital Storytelling as an Intervention for Older Adults: A Scoping Review.

The population of older adults is rapidly increasing worldwide. Owing to fewer interactions between generations, older adults experience ageism and various psychological issues, such as depression and loneliness. Digital storytelling (DST) has the potential to share vivid lived experiences, support the forming of social relationships, and lead to improved well-being. This scoping review examines the potential psychosocial benefits of individual DST interventions for older adults and people with dementia. We adopted the methodological framework for scoping reviews outlined in the Joanna Briggs Institute's (JBI) manual. A scoping review was performed using the following bibliographic databases: Web of Science, PubMed, Cochrane Library, CINAHL, Research Information Sharing Service, and National Assembly Library. There were 395 references retrieved, of which 19 articles were selected after applying inclusion and exclusion criteria. Our findings revealed that the most common effects of DST on older adults included the promotion of mental health, an increased amount of meaningful community connections, greater digital literacy, the mitigation of negative ageism, and enhanced intellectual ability. We suggest randomized controlled trials are conducted to confirm the efficacy of intergenerational DST intervention and the effects of DST interventions at multilevel outcomes, including the community level.

Localized gastric amyloidosis successfully treated with endoscopic submucosal dissection: A case report.

RATIONALE: Amyloidosis is a general term that refers to the extracellular deposition of amyloid. The amyloid can also be deposited in a single organ. However, cases of localized gastric amyloidosis have rarely been reported. Here, we report a case of localized gastric amyloidosis that was successfully treated with endoscopic submucosal dissection. PATIENT CONCERN: A 60-years-old man underwent esophagogastroduodenoscopy as part of a regular check-up without any comorbidities or symptoms. DIAGNOSTICS: A 12 mm-sized, round, elevated lesion with a central depression, which was covered with normal mucosa, and located on the greater curvature of the lower body of the stomach was discovered during endoscopy. Subsequently, endoscopic ultrasonography was performed, which revealed a 11.7 mm-sized, hypoechoic, heterogeneous lesion located in the muscularis mucosa and submucosa. A biopsy was performed, and amyloid deposition was confirmed. Although other investigations for checking systemic amyloidosis were performed, there were no specific findings. Therefore, the final diagnosis was localized gastric amyloidosis. INTERVENTIONS: Endoscopic submucosal dissection was performed according to the patient's request and the lesion was completely removed. OUTCOMES: The patient was followed-up for 3 years without any recurrence. CONCLUSIONS: Endoscopic submucosal dissection can be good diagnostic and treatment option for localized gastric amyloidosis.

Conditioned secretome of adipose-derived stem cells improves dextran sulfate sodium-induced colitis in mice.

BACKGROUND: Inflammatory bowel diseases (IBD) is related to uncontrolled immune response. Currently, there is no successful treatment for significant improvement in IBD. Stem cells display their therapeutic effects through their repopulating capacity or secreting factors. AIM: To investigate the effects of conditioned mouse adipose-derived stem cells (mADSCs) secretome on colitis-induced mice. METHODS: mADSCs were isolated from adipose tissue of C57BL/6 mice. Conditioned mADSCs secrectome was obtained by culturing of mADSCs with lipopolysaccharides (LPS, 1 µg/mL) for 24 h. Acute colitis was induced by 2% dextran sulfate sodium (DSS) drinking water for 7 d and then normal drinking water for 4 d. The mice were treated with normal culture medium (NM group), conditioned mADSCs secretome (CM group) or mADSCs (SC group). The length of colon and histopatholgy of colon tissues were evaluated. The mRNA expression levels of inflammatory cytokines in colon tissue and the serum interleukin (IL)-6 levels were determined. RESULTS: The isolated mADSCs maintained the mADSCs specific gene expression profiles during experiment. The conditioned mADSCs secretome released by the treatment of mADSCs with LPS contained mainly inflammatory chemokines, colony-stimulating factors and inflammatory cytokines. The loss of body weight and reduction in colon length were ameliorated in the CM group. The conditioned mADSCs secretome reduced the histological score in colon tissue. The expression of IL-1b and IL-6 mRNAs in colon tissues significantly inhibited in the CM group compared to SC group and NM group, respectively. The elevation of serum IL-6 levels was also ameliorated in the CM group. These results indicate that the conditioned mADSCs secretome suppressed the synthesis of inflammatory cytokines in damaged colon tissue and the elevation of serum IL-6 concentration in DSS-induced mice. CONCLUSION: Conditioned mADSCs secretome might play regenerative roles by the suppression of IL-6 in serum and tissue during acute colitis, and may be more effective than stem cells themselves in the regeneration of colon tissue.

Prevalence of Sarcopenia in Community-Dwelling Older Adults According to Simplified Algorithms for Sarcopenia Consensus Based on Asian Working Group for Sarcopenia.

PURPOSE: This study sought to identify the prevalence of sarcopenia in community-dwelling Korean older adults and validate two simplified diagnostic algorithms based on the Asian Working Group for Sarcopenia (AWGS) algorithm for identifying sarcopenia. PATIENTS AND METHODS: Patients (n = 338) aged ≥65 years participated in this cross-sectional study. Muscle strength was measured by hand grip strength, physical performance by gait speed, and muscle mass by the skeletal muscle mass index (SMI). Sarcopenia was assessed using the AWGS-recommended algorithm and two simplified algorithms (A and B). Algorithms A and B were validated with respect to the AWGS-recommended algorithm using the chi-square test, and the sensitivity and specificity were obtained. RESULTS: Sarcopenia prevalence, determined using the AWGS-recommended algorithm, was 40.3% and 41.3% in men and women, respectively. The overall prevalence of sarcopenia was 41.0% by the AWGS-recommended algorithm, 37.6% by algorithm A, and 37.6% by algorithm B; 111 participants were diagnosed with sarcopenia using all three methods (p = 0.157). CONCLUSION: We established sarcopenia prevalence among rural community-dwelling adults in Korea and confirmed that the simplified algorithms were suitable for the identification of sarcopenia in rural community-dwelling older adults in Korea. Further studies are needed to assess whether these simplified algorithms are applicable to older Asian adults with functional and/or cognitive impairment and nursing home residents.

Factors Affecting Quality of Life Among the Elderly in Long-Term Care Hospitals.

BACKGROUND: There are challenges in sustaining person-centered care in aged care settings. Key related issues of concern such as quality of life among the older people in long-term care hospitals and interactions with nursing staff have been described previously. PURPOSE: This study was designed to explore the factors affecting quality of life among older people living in long-term care hospitals in South Korea. METHODS: Older adult patients (N = 202) in three long-term care hospitals completed measures of cognitive functions, depression, care dependency, and interactions between nurse and patient and a quality-of-life assessment tool. Univariate analyses were used to examine the relationships among these variables, and a multiple linear regression analysis was used to explore the extent to which these variables predicted quality of life in these patients. RESULTS: The significant factors associated with quality of life were found to be cognitive functions (r = .373, p < .001), care dependency (r = .350, p < .001), and depression (r = -.504, p < .001). The regression model with depression and care dependency as predictor variables accounted for 25.7% of the variance in quality of life. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The correlation found in this study between quality of life and depression and care dependency provides additional evidentiary support for developing and applying nursing interventions that reduce depression and care dependency in older adult populations.

Loss of HES-1 Expression Predicts a Poor Prognosis for Small Intestinal Adenocarcinoma Patients.

Objective: Hairy and enhancer of split-1 (HES-1), which is a downstream target of the Notch signaling pathway, has been linked to KRAS mutations. HES-1 has been proposed as harboring oncogenic activity in colorectal cancer but has not been investigated in adenocarcinoma of the small intestine, where the drivers of oncogenesis are not as well-understood. Materials and Methods: To investigate the clinicopathologic and prognostic implications of HES-1, HES-1 immunohistochemical expression was analyzed in digital images along with clinicopathological variables, including survival and KRAS genotype, in 185 small intestinal adenocarcinomas. Results: The loss of HES-1 expression (HES-1Loss) was observed in 38.4% (71/185) of the patients, and was associated with higher pT category (P = 0.018), pancreatic invasion (P = 0.005), high grade (P = 0.043), and non-tubular histology (P = 0.004). Specifically, in tumors with mutant KRAS (KRAS MT), HES-1Loss was related to proximal location (P = 0.024), high T and N categories (P = 0.005 and 0.047, respectively), and pancreatic invasion (P = 0.004). Patients with HES-1Loss showed worse overall survival compared to those with intact HES-1 (HES-1Intact) (P = 0.013). Patients with HES-1Loss/KRAS MT (median, 17.3 months) had significantly worse outcomes than those with HES-1Intact/KRAS WT (39.9 months), HES-1Intact/KRAS MT (47.6 month), and HES-1Loss/KRAS WT (36.2 months; P = 0.010). By multivariate analysis, HES-1Loss (hazard ratio = 1.55, 95% confidence interval (CI), 1.07-2.26; P = 0.022) remained an independent prognostic factor. Conclusion: HES-1expression can be used as a potential prognostic marker and may aid in the management of patients with small intestinal adenocarcinomas.

Genetic heterogeneity and prognostic impact of recurrent ANK2 and TP53 mutations in mantle cell lymphoma: a multi-centre cohort study.

The molecular features of mantle cell lymphoma (MCL), including its increased incidence, and complex therapies have not been investigated in detail, particularly in East Asian populations. In this study, we performed targeted panel sequencing (TPS) and whole-exome sequencing (WES) to investigate the genetic alterations in Korean MCL patients. We obtained a total of 53 samples from MCL patients from five Korean university hospitals between 2009 and 2016. We identified the recurrently mutated genes such as SYNE1, ATM, KMT2D, CARD11, ANK2, KMT2C, and TP53, which included some known drivers of MCL. The mutational profiles of our cohort indicated genetic heterogeneity. The significantly enriched pathways were mainly involved in gene expression, cell cycle, and programmed cell death. Multivariate analysis revealed that ANK2 mutations impacted the unfavourable overall survival (hazard ratio [HR] 3.126; P = 0.032). Furthermore, TP53 mutations were related to worse progression-free survival (HR 7.813; P = 0.043). Among the recurrently mutated genes with more than 15.0% frequency, discrepancies were found in only 5 genes from 4 patients, suggesting comparability of the TPS to WES in practical laboratory settings. We provide the unbiased genetic landscape that might contribute to MCL pathogenesis and recurrent genes conferring unfavourable outcomes.

Person-Centered Care, Job Stress, and Quality of Life Among Long-Term Care Nursing Staff.

BACKGROUND: Although it has been established that person-centered care is an essential aspect in long-term care facilities, the relationship between person-centered care and job stress among nursing staff and the effect of this relationship on their quality of life are not clear. PURPOSE: This study aims to investigate correlations among job stress, quality of life, and person-centered care of nurses as well as factors affecting the person-centered care abilities of nursing staff working at long-term care hospitals. METHODS: Nursing staff (N = 183) in three long-term care hospitals in South Korea completed a questionnaire on job stress, quality of life, and person-centered care. Data were analyzed using the SPSS 22.0 program for descriptive statistics, using an independent t test, a one-way analysis of variance, Pearson's correlation coefficient, and multiple stepwise regression analyses. RESULTS: Significant factors found to be associated with person-centered care included the quality of life (r = .411, p < .001) and job stress (r = -.305, p < .001) of the participant. The regression model with job stress and quality of life as predictor variables accounted for 29.2% of the variance in person-centered care. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Higher quality of life and lower job stress were found to increase the person-centered care abilities of nurses in long-term care facilities.

Prognostic Significance of Stromal and Intraepithelial Tumor-Infiltrating Lymphocytes in Small Intestinal Adenocarcinoma.

OBJECTIVES: Assessment of tumor-infiltrating lymphocytes (TILs) may predict the prognosis and therapeutic benefit of immunotherapy in small intestinal adenocarcinoma (SIAC) patients. METHODS: TILs were evaluated in 231 surgically resected SIACs and compared with microsatellite instability (MSI) and clinicopathologic variables. The average number of intraepithelial TILs (iTILs) and the average density of stromal TILs (sTILs) were calculated separately. RESULTS: High iTIL count (≥2 per high-power field) was associated with MSI-high, whereas high sTIL density (≥20% on ×200 magnification) was not. High iTIL count and high sTIL density were related to distal tumor location, medullary carcinoma, high Crohn-like lymphoid reaction counts, and fewer pancreatic invasions. SIAC patients with high iTIL count or high sTIL density had better survival than those with low values. On multivariate analysis, MSI, high sTIL density, proximal locations, lower N category, and absence of lymphovascular invasions and retroperitoneal seeding were the best independent prognostic predictors. CONCLUSIONS: High sTIL density can be used as a prognostic indicator and high iTIL count may provide a basis for the clinical use of targeted immunotherapy in SIAC patients.

Health personnel's experience with resident-centered care in nursing homes in Korea: A qualitative study.

OBJECTIVES: Changing the culture in nursing homes in South Korea comes with challenges, and the key issues of resident-centered care have been described. This study aims to describe health personnel's experience in providing resident-centered care in nursing homes. METHODS: Qualitative data were collected through individual and focus group interviews consisting of registered nurses (n = 4), certified nurse assistants (n = 2), and long-term caregivers (n = 12) working at nursing homes in South Korea. The participants (n = 18) completed the interviews from May to June 2018, and all interviews were recorded, transcribed, and analyzed by employing the content analysis method. RESULTS: Five main categories are conceptualized: (1) residents' participation in decision making, (2) the sharing of the history and story of residents, (3) the recognition of facility- or task-based attitudes, (4) the guarantee of private time and space for residents, and (5) the need for standardized guidelines. CONCLUSIONS: Results corroborate that health personnel regard resident-centered care as a desirable nursing paradigm. However, facility- or task-centered care is the most effective in hectic situations. A standardized protocol on the application of resident-centered care based on the facility-tailored specification is unavailable. Therefore, health personnel's perception and practice of resident-centered care can differ. Efficient nursing intervention programs should be developed after clarifying facility culture.

Expression of vascular endothelial growth factor as a predictor of complete response for preoperative chemoradiotherapy in rectal cancer.

Biomarkers that predict tumor response before surgical treatment are necessary to help select patients for preoperative chemoradiotherapy for rectal cancer. However, no definite predictive biomarker has been established. This study explored programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), p-signal transducer and activator of transcription 3 (p-STAT3), and death-domain associated protein as predictive biomarkers with regard to preoperative chemoradiotherapy in rectal cancer.Formalin-fixed paraffin-embedded cancer tissues from pretreatment biopsies from 31 patients who underwent preoperative chemoradiotherapy were studied. The biomarkers were evaluated by immunohistochemistry.PD-L1 positivity was found in 22.6% of 31 patients and complete response (CR) showed 33.3% and non-CR showed 18.2%. EGFR positivity was found in 71.0% of 31 patients and CR showed 88.9% and non-CR showed 73.6%. VEGF positivity was found in 83.9% of 31 patients and CR showed 88.9% and non-CR showed 81.8%. p-STAT3 positivity was found in 80.6% of 31 patients and CR showed 88.9% and non-CR showed 77.3%. On multiple logistic regression analysis, only VEGF expression was found to be a significant predictive factor for CR (P = .001). VEGF expression in pretreatment biopsies might be a predictive marker for CR after preoperative chemoradiation in rectal cancer.Although there is a restriction of small sample size, our finding suggested that this study can be foundation for a larger further study for biomarkers which can predict neoadjuvant therapy response of specimens obtained for diagnosis before surgery.

Effects of an evidence-based practice education program using multifaceted interventions: a quasi-experimental study with undergraduate nursing students.

BACKGROUND: Although Evidence-Based Practice (EBP) should be introduced early on in nursing education to develop students' independence and self-learning ability, there are few such courses for undergraduate nursing students in Korea. This study examined the effects of the EBP education program for undergraduate nursing students (EBP-EPUNS) on nursing students' knowledge, skills, attitudes, competencies, and future use of EBP. METHODS: A quasi-experimental study design with pre-test, intervention, and post-test was used. The participants were 44 nursing students (experimental: 22, control: 22). A 20-h long EBP-EPUNS consisting of 5-step EBP components was provided through 8 sessions spread across 4 weeks. RESULTS: An independent t-test and a repeated-measures ANOVA showed that the experimental group had statistically significant higher post-test scores on EBP knowledge (p < 0.001), skills (p < 0.001), attitudes (p < 0.001), competencies (p < 0.001), future use of EBP (p = 0.001), and critical thinking (p < 0.001), compared to the control group. CONCLUSION: The EBP education program was effective in improving the knowledge, skills, attitudes, competencies, and future use of EBP among nursing students. Hence, we recommend the EBP education program as a general education course for undergraduate nursing students to promote needed proficiency in EBP.

RhoGAP domain-containing fusions and PPAPDC1A fusions are recurrent and prognostic in diffuse gastric cancer.

We conducted an RNA sequencing study to identify novel gene fusions in 80 discovery dataset tumors collected from young patients with diffuse gastric cancer (DGC). Twenty-five in-frame fusions are associated with DGC, three of which (CLDN18-ARHGAP26, CTNND1-ARHGAP26, and ANXA2-MYO9A) are recurrent in 384 DGCs based on RT-PCR. All three fusions contain a RhoGAP domain in their 3' partner genes. Patients with one of these three fusions have a significantly worse prognosis than those without. Ectopic expression of CLDN18-ARHGAP26 promotes the migration and invasion capacities of DGC cells. Parallel targeted RNA sequencing analysis additionally identifies TACC2-PPAPDC1A as a recurrent and poor prognostic in-frame fusion. Overall, PPAPDC1A fusions and in-frame fusions containing a RhoGAP domain clearly define the aggressive subset (7.5%) of DGCs, and their prognostic impact is greater than, and independent of, chromosomal instability and CDH1 mutations. Our study may provide novel genomic insights guiding future strategies for managing DGCs.

Sporadic Early-Onset Diffuse Gastric Cancers Have High Frequency of Somatic CDH1 Alterations, but Low Frequency of Somatic RHOA Mutations Compared With Late-Onset Cancers.

BACKGROUND & AIMS: Early-onset gastric cancer, which develops in patients younger than most gastric cancers, is usually detected at advanced stages, has diffuse histologic features, and occurs more frequently in women. We investigated somatic genomic alterations associated with the unique characteristics of sporadic diffuse gastric cancers (DGCs) from younger patients. METHODS: We conducted whole exome and RNA sequence analyses of 80 resected DGC samples from patients 45 years old or younger in Korea. Patients with pathogenic germline mutations in CDH1, TP53, and ATM were excluded from the onset of this analysis, given our focus on somatic alterations. We used MutSig2CV to evaluate the significance of mutated genes. We recruited 29 additional early-onset Korean DGC samples and performed SNP6.0 array and targeted sequencing analyses of these 109 early-onset DGC samples (54.1% female, median age, 38 years). We compared the SNP6.0 array and targeted sequencing data of the 109 early-onset DGC samples with those from diffuse-type stomach tumor samples collected from 115 patients in Korea who were 46 years or older (late onset) at the time of diagnosis (controls; 29.6% female, median age, 67 years). We compared patient survival times among tumors from different subgroups and with different somatic mutations. We performed gene silencing of RHOA or CDH1 in DGC cells with small interfering RNAs for cell-based assays. RESULTS: We identified somatic mutations in the following genes in a significant number of early-onset DGCs: the cadherin 1 gene (CDH1), TP53, ARID1A, KRAS, PIK3CA, ERBB3, TGFBR1, FBXW7, RHOA, and MAP2K1. None of 109 early-onset DGC cases had pathogenic germline CDH1 mutations. A higher proportion of early-onset DGCs had mutations in CDH1 (42.2%) or TGFBR1 (7.3%) compared with control DGCs (17.4% and 0.9%, respectively) (P < .001 and P = .014 for CDH1 and TGFBR1, respectively). In contrast, a smaller proportion of early-onset DGCs contained mutations in RHOA (9.2%) than control DGCs (19.1%) (P = .033). Late-onset DGCs in The Cancer Genome Atlas also contained less frequent mutations in CDH1 and TGFBR1 and more frequent RHOA mutations, compared with early-onset DGCs. Early-onset DGCs from women contained significantly more mutations in CDH1 or TGFBR1 than early-onset DGCs from men. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times in patients with early-onset DGCs (hazard ratio, 3.4; 95% confidence interval, 1.5-7.7). RHOA activity was reduced by an R5W substitution-the RHOA mutation most frequently detected in early-onset DGCs. Silencing of CDH1, but not RHOA, increased migratory activity of DGC cells. CONCLUSIONS: In an integrative genomic analysis, we found higher proportions of early-onset DGCs to contain somatic mutations in CDH1 or TGFBR1 compared with late-onset DGCs. However, a smaller proportion of early-onset DGCs contained somatic mutations in RHOA than late-onset DGCs. CDH1 alterations, but not RHOA mutations, were associated with shorter survival times of patients, which might account for the aggressive clinical course of early-onset gastric cancer. Female predominance in early-onset gastric cancer may be related to relatively high rates of somatic CDH1 and TGFBR1 mutations in this population.

Unusual giant cell-rich variant of extraskeletal osteosarcoma in the mesentery of small intestine.

Extraskeletal osteosarcoma (EOS) is an aggressive malignant soft tissue tumor, producing neoplastic osteoid without attachment to the bone or periosteum. EOS predominantly occurs in the extremities and rarely involves the abdominal cavity. Only six cases of mesenteric EOS have been reported in the English literature. We describe an unusual case of a 70-year-old female patient, who was diagnosed to have a giant cell-rich variant of mesenteric EOS arising from small bowel mesentery. This patient presented with a mesenteric mass measuring 15.1×10.3×7.5 cm. Surgical resection of the tumor with small bowel was performed. The instrumental investigations didn't reveal metastatic lesions. The patient refused further therapeutic regimen. EOS, regardless of its site or subtypes, has a very unfavorable prognosis and the patient died 2 months after discharge.