Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

BACKGROUND: Retinal degenerative disease (RDD), one of the most common causes of blindness, is predominantly caused by the gradual death of retinal pigment epithelial cells (RPEs) and photoreceptors due to various causes. Cell-based therapies, such as stem cell implantation, have been developed for the treatment of RDD, but potential risks, including teratogenicity and immune reactions, have hampered their clinical application. Stem cell-derived extracellular vesicles (EVs) have recently emerged as a cell-free alternative therapeutic strategy; however, additional invasiveness and low yield of the stem cell extraction process is problematic. METHODS: To overcome these limitations, we developed therapeutic EVs for the treatment of RDD which were extracted from tonsil-derived mesenchymal stem cells obtained from human tonsil tissue discarded as medical waste following tonsillectomy (T-MSC EVs). To verify the biocompatibility and cytoprotective effect of T-MSC EVs, we measured cell viability by co-culture with human RPE without or with toxic all-trans-retinal. To elucidate the cytoprotective mechanism of T-MSC EVs, we performed transcriptome sequencing using RNA extracted from RPEs. The in vivo protective effect of T-MSC EVs was evaluated using Pde6b gene knockout rats as an animal model of retinitis pigmentosa. RESULTS: T-MSC EVs showed high biocompatibility and the human pigment epithelial cells were significantly protected in the presence of T-MSC EVs from the toxic effect of all-trans-retinal. In addition, T-MSC EVs showed a dosedependent cell death-delaying effect in real-time quantification of cell death. Transcriptome sequencing analysis revealed that the efficient ability of T-MSC EVs to regulate intracellular oxidative stress may be one of the reasons explaining their excellent cytoprotective effect. Additionally, intravitreally injected T-MSC EVs had an inhibitory effect on the destruction of the outer nuclear layer in the Pde6b gene knockout rat. CONCLUSIONS Together, the results of this study indicate the preventive and therapeutic effects of T-MSC EVs during the initiation and development of retinal degeneration, which may be a beneficial alternative for the treatment of RDD.

Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.

Background and Objectives: There is no clear standard for the difference in the thresholds of auditory brainstem response (ABR) and pure tone audiometry (PTA) when using ABR to evaluate the reliability of PTA. Therefore, we assessed the difference in the thresholds of ABR and PTA for each frequency. Consequently, we present here the actual difference values between the two tests that can be used as a reference in the clinic.Subjects and Method We retrospectively assessed the audiometry results of 129 ears. Ears in which the hearing thresholds of each frequency continuously declined were classified as the downward group. We compared the average of differences between the two tests by frequency. The differences were compared for each hearing level from 50 dB or higher. Results: For all ears, the appropriate range of difference value was ±5 dB at 2 kHz. At 1 kHz, the ABR threshold was 10 dB higher than PTA, and it was 10 dB less than PTA at 4 kHz. In the downward group, the difference value increased by 10 dB at 1 kHz and 4 kHz. In the subgroups at each hearing level, the difference value showed similar results (p<0.05). Conclusion The difference in the threshold, regardless of the severity or tendency of hearing loss, was the smallest at 2 kHz and the range was ±5 dB. ABR was 10 dB higher at 1 kHz and and 10 dB lower at 4 kHz than PTA. In the downward group, the difference at 1 kHz and 4 kHz increased by 10 dB each.

Background and Objectives: Patients with hearing loss and tinnitus experience difficulty in engaging in daily conversations. However, only few studies have examined how tinnitus affects individual speech discrimination to comprehend speech. This study aimed to analyze the correlation between tinnitus frequency and speech discrimination in patients with hearing loss and tinnitus.Subjects and Method A total of 275 ears with hearing impairment were retrospectively analyzed via audiometry and tinnitogram. The ears were divided into three groups depending on the frequency of their tinnitus. Average pure tone audiometry (PTA), hearing threshold of tinnitus frequency, speech discrimination test (SDT), degree of discrepancy between tinnitus frequency and worst PTA frequency were collected and compared among the three groups. Results: No significant difference was observed in PTA in the three patient groups. Hearing threshold of tinnitus frequency was the highest at 78.27 dB in the high-frequency group and the lowest at 45.14 dB in the low-frequency group. SDT was significantly lower (53.69%) in the low-frequency group. The correlation between tinnitus loudness and SDT was the strongest in the low-frequency group. The degree of discrepancy between tinnitus frequency and worst PTA frequency was also significantly observed in the low-frequency group. Conclusion Patients who are severely affected by tinnitus are found to have significant discrepancy between tinnitus frequency and worst PTA frequency, indicating decreased SDT.

Objective: To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. Methods: In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. Results: The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. Conclusion The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

Background and Objectives: The diagnosis of hearing impairment is based on repeated audiometry, including pure tone audiometry (PTA), speech reception threshold test (SRT), and speech discrimination test (SDT). SDT results particularly show a wide discrepancy upon repeated testing, while malingering is suspected when having more than 12% difference between 3 individual SDT results. Therefore, in this study, we compared the proportion of malingering found in repeated SDT with that found in other audiometric tests and analyzed the characteristics of malingering group in order to reevaluate the current criteria of defining malingering.Subjects and Method We retrospectively assessed the audiometry results of 113 patients (226 ears) with hearing impairment. Each ear was divided into a malingering group and a true hearing loss group. The proportion of ears corresponding to each malingering criterion was compared using a chi-square test. An independent sample t-test was performed to identify the differences between the characteristics between the two groups. Results: The number of ears that met the malingering criteria were 19 (8.41%) in PTA, 15 (6.64%) in SRT, and 75 (33.19%) in SDT. There was a significant difference in the proportion of malingering between the 3 hearing test modalities (p<0.001). There was no significant difference in auditory brainstem response, mean age and sex distribution between the malingering group and the true hearing loss group. Conclusion When conducting repeated SDT, there is a risk of misdiagnosing an actual hearing loss patient as a malingering patient under the current malingering criteria. Therefore, the current criteria on SDT requires reevaluation.