First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer. @*Materials and Methods@#Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses. @*Results@#Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients. @*Conclusion@#BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.

Comparative Interrupted Time Series Analysis of Direct Medical Expense and Length of Stay in Elderly Patients with Femoral Neck Fractures Who Underwent Total Hip Arthroplasty and Hemiarthroplasty: A Real World Nationwide Database Study

Background@#The objective of our study was to analyze the postoperative direct medical expenses and hospital lengths of stay (LOS) of elderly patients who had undergone either hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures and to determine the indication of THA by comparing those variables between the 2 groups by time. @*Methods@#In this comparative large-sample cohort study, we analyzed data from the 2011 to 2018 Korean National Health Insurance Review and Assessment Service database. The included patients were defined as elderly individuals aged 60 years or older who underwent HA or THA for a femoral neck fracture. A 1:1 risk-set matching was performed on the propensity score, using a nearest-neighbor matching algorithm with a maximum caliper of 0.01 of the hazard components. In comparative interrupted time series analysis, time series were constructed using the time unit of one-quarter before and after 3 years from time zero. For the segmented regression analysis, we utilized a generalized linear model with a gamma distribution and logarithmic link function. @*Results@#A total of 4,246 patients who received THA were matched and included with 4,246 control patients who underwent HA. Although there was no statistically significant difference in direct medical expense and hospital LOS for the first 6 months after surgery, direct medical expenses and hospital LOS in THA were relatively reduced compared to the HA up to 24 months after surgery (p < 0.05). In the subgroup analysis, the THA group’s hospital LOS decreased significantly compared to that of the HA group during the 7 to 36 months postoperative period in the 65 ≤ age < 80 age group (p < 0.05). Direct medical expenses of the THA group significantly decreased compared to those of the HA group during the period from 7 to 24 months after surgery in the men group (p < 0.05). @*Conclusions@#When performing THA in elderly patients with femoral neck fractures, the possibility of survival for at least 2 years should be considered from the perspective of medical expense and medical utilization. Additionally, in healthy and active male femoral neck fracture patients under the age of 80 years, THA may be more recommended than HA.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study

Background@#Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. @*Methods@#We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan–Meier (KM) method. @*Results@#Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010–1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312–7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). @*Conclusion@#Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

A machine learning-based approach for predicting renal function recovery in general ward patients with acute kidney injury

Acute kidney injury (AKI) is a significant challenge in healthcare. While there are considerable researches dedicated to AKI patients, a crucial factor in their renal function recovery, is often overlooked. Thus, our study aims to address this issue through the development of a machine learning model to predict restoration of kidney function in patients with AKI. Methods: Our study encompassed data from 350,345 cases, derived from three hospitals. AKI was classified in accordance with the Kidney Disease: Improving Global Outcomes. Criteria for recovery were established as either a 33% decrease in serum creatinine levels at AKI onset, which was initially employed for the diagnosis of AKI. We employed various machine learning models, selecting 43 pertinent features for analysis. Results: Our analysis contained 7,041 and 2,929 patients’ data from internal cohort and external cohort respectively. The Categorical Boosting Model demonstrated significant predictive accuracy, as evidenced by an internal area under the receiver operating characteristic (AUROC) of 0.7860, and an external AUROC score of 0.7316, thereby confirming its robustness in predictive performance. SHapley Additive exPlanations (SHAP) values were employed to explain key factors impacting recovery of renal function in AKI patients. Conclusion: This study presented a machine learning approach for predicting renal function recovery in patients with AKI. The model performance was assessed across distinct hospital settings, which revealed its efficacy. Although the model exhibited favorable outcomes, the necessity for further enhancements and the incorporation of more diverse datasets is imperative for its application in real- world.

Effect of Counting Error Prevention Training on Operating Room Nurses’ Counting Error Prevention Awareness and Perceptions of Patient Safety

Background@#This study aimed to identify changes in counting error prevention awareness and patient safety perception through counting error prevention education to operating room nurses. @*Methods@#This was a one-group, pretest-posttest, quasi-experimental study. The participants were operating room nurses. A total of 46 nurses were recruited, and data was collected between October 1 and 31, 2022. Measures used for this study assessed counting error prevention awareness and patient safety perception. The data were analyzed using paired t-tests. @*Results@#The counting error prevention awareness of the participants increased significantly from 3.68 to 3.95 points before and after education, respectively (t=-5.07, P<0.001), while patient safety perception significantly increased from 3.95 to 4.20 points before and after training, respectively (t=-2.68, P=0.010). @*Conclusions@#Counting error prevention awareness and patient safety perception of operating room nurses prevent fatal damage to patients with surgeries and lower mortality. The results of this study suggest the necessity of various education methods to reduce medical accidents among surgical patients and to raise patient safety perception for operating room nurses.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn’s disease

Background/Aims@#A poor prognostic factor for Crohn’s disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. @*Methods@#This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). @*Results@#Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong’s test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. @*Conclusions@#This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

The Association between Serum Lipid Levels and Tinnitus Prevalence and Severity in Korean Elderly:A Nationwide Population-Based Cross-Sectional Study

Purpose@#We aimed to investigate the association between serum lipid level and tinnitus risk in Korean older adults. @*Materials and Methods@#This study used data from the 2016–2018 Korea National Health and Nutrition Examination Survey. Overall, 6021 subjects aged ≥60 years were included. Hypertriglyceridemia was defined as a serum triglyceride level of ≥200 mg/dL.The high-risk threshold of the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio was defined as above 5.0.The presence of tinnitus was assessed via health interviews. Tinnitus severity was classified as “not annoying,” “irritating,” and “severely annoying and causing sleep problems.” Multivariate logistic regression analysis was performed to examine the association between serum lipid level and tinnitus risk. @*Results@#The odds ratio (OR) of tinnitus was 1.27-times higher in the group with hypertriglyceridemia than in the group without hypertriglyceridemia after adjusting for age, sex, hypertension, diabetes, dyslipidemia, anemia, current smoking, obesity, noise exposure, stress cognition, and depressive mood or anxiety [95% confidence interval (CI) 1.04–1.56, p=0.022]. The OR of tinnitus was 1.21-times higher in the group with a high TC/HDL-C ratio than in the group without a high TC/HDL-C ratio after adjusting for the same variables as above (95% CI 1.02–1.44, p=0.025). @*Conclusion@#This study revealed that hypertriglyceridemia and high TC/HDL-C ratio were significantly associated with an increased OR of tinnitus in Korean older adults.

A Case of Palisaded Neutrophilic and Granulomatous Dermatitis Associated with an Initial Presentation in Ankylosing Spondylitis

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an inflammatory dermatosis associated with systemic immune-mediated diseases such as rheumatoid arthritis, systemic sclerosis, lupus erythematosus, and ulcerative colitis. Histologically, serial development of leukocytoclastic vasculitis is shown from an early stage, which can progress to palisading granuloma in the fully developed stage and to fibrosis in the final stage. A 32-yearold man presented with ankylosing spondylitis showing multiple erythematous papules on his fingers, elbows, knees, and left auricle. Histologic examination from his skin lesion revealed a perforating palisading granuloma with leukocytoclastic vasculitis, which was consistent with PNGD. Therefore, this study reported a case of PNGD accompanied by ankylosing spondylitis as an initial presentation.

An Overview of the Initiatives and Activities of the Korean Blood Safety Project Group over a Ten Year Period: 2012∼2021 / 대한수혈학회지

Background@#The study aimed to review the initiatives and activities of the Korean Blood Safety Project Group (KBSPG) from 2012 to 2021 to present its work domestically and internationally, and to set up future directions for the KBSPG. @*Methods@#Details of the KBSPG’s projects were organized by task. This project was supported by the Korean Ministry of Health and Welfare. The final annual reports and data posted on the website of the KBSPG were used for analysis. @*Results@#The KBSPG completed 14 tasks, including training and sharing of the latest information with workers of blood centers and transfusion services in medical institutes, external proficiency surveys for donor blood screening tests, and maintenance of a national registration system. The results of these tasks have contributed to the fulfillment of work of the relevant national departments, the establishment and operation of related websites, the publication of annual reports, the implementation of workshops and training programs, the operation of regional networks for blood transfusion management, and the production and distribution of information leaflets and training videos.Additionally, the KBSPG has developed and revised guidelines and standards and published related papers. @*Conclusion@#The KBSPG’s continuous efforts improved the quality of blood centers and transfusion services in medical institutes, thus contributing to the national blood management services. To further improve blood management work and ensure blood safety, the KBSPG must expand its scope and continue to pursue its important mission. (Korean J Blood Transfus 2023;34:1-11)

Comorbidities and the use of comedications among patients with chronic hepatitis C in Korea: A nationwide cross-sectional study

Background/Aims@#Chronic hepatitis C (CHC) is the second leading cause of liver-related mortality and is more prevalent in the elderly population in Korea. Decisions to initiate treatment and selection of proper antiviral agents may be challenging among elderly patients due to relevant comorbidities, comedications, and drug-drug interaction (DDI). It may be helpful to understand the current demographic status and comorbidities of CHC patients in the country. @*Methods@#Patients aged ≥ 18 years and diagnosed with CHC (KCD-7 code B18.2) were extracted from the Korean Health Insurance Review & Assessment Service database in 2018. Data on comorbidities and comedications were assessed and potential DDIs were analyzed. @*Results@#A total of 50,476 patients with CHC, with a mean age of 60.3 years and 46.7% male patients were identified. The proportion of patients with cirrhosis, hepatocellular carcinoma, and liver transplantation was 6.0%, 4.1%, and 0.3%, respectively and 37.2% of patients were more than 65 years of age. The three most common comorbidities were diseases of the digestive system (83.7%), respiratory system (58.2%), and musculoskeletal system and connective tissue (57.6%). The three most common comedications were analgesics (91.6%), gastrointestinal agents (85%), and antibacterials (80.3%). Lipid-lowering agents and anticonvulsants were prescribed in 28.5% and 14.8% of patients. Rate of potential DDI for contraindication was 2.2%, 13.1%, and 15.6% with sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir. @*Conclusions@#With the increasing age of patients with CHC, comorbidity, comedication, and potential DDI should be considered when choosing antivirals in Korea. Sofosbuvir-based regimens showed favorable DDI profiles among Korean patients.

Vaccination in patients with inflammatory bowel disease–Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting

Background/Aims@#Long-term immunosuppressive therapies used to treat inflammatory bowel disease (IBD) are associated with an increased risk of infections, many of which can be prevented by vaccination. We assessed physicians’ current approaches and clinical practices regarding vaccinations for IBD patients in different Asian countries/regions. @*Methods@#An internet-based survey was conducted among members of the Asian Organization for Crohn’s and Colitis from September 2020 to November 2020. The questionnaire consisted of 2 parts covering general opinion on the relevance of vaccinations and clinical practice of vaccination. @*Results@#Overall, 384 Asian medical doctors responded to the survey. The majority of respondents considered it very (57.6%) or sufficiently (39.6%) important to perform vaccinations as recommended by the guidelines. About half of the Asian physicians (52.6%) were usually or always performing vaccinations. The influenza vaccine was the most frequently recommended vaccine for IBD patients. Half of the respondents (51.3%) did not recommend hepatitis A vaccine, especially in China (61.6%) and Japan (93.6%). The diphtheria, tetanus, and pertussis vaccine were never (35.2%) or rarely (29.4%) recommended. @*Conclusions@#The findings of this survey indicated similarities among countries/regions in terms of the current approaches and practices regarding vaccination of IBD patients; however, there are some differences that might reflect each country’s domestic vaccination guidelines and health insurance particularly with certain vaccines in some countries/regions. Although Asian physicians largely recommend vaccination, more awareness among doctors and Asian consensus regarding differences in IBD vaccination among countries/regions may be required.

Efficacy and safety of 1 L polyethylene glycol plus ascorbic acid for bowel preparation in elderly: comparison with oral sulfate solution

Background/Aims@#Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). @*Methods@#A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. @*Results@#Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. @*Conclusions@#The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.

Human Endometrium Derived Induced Pluripotent Stem Cells Are Amenable to Directed Erythroid Differentiation

BACKGROUND@#A protocol for using human endometrium derived induced pluripotent stem cells (iPSCs) to derive hematopoietic and erythroid lineages will be elaborated, through a two-phase culture system. @*METHODS@#Discarded endometrial tissues were obtained from women receiving hysterectomy in their 4th to 5th decade due to benign uterine conditions. pCE-Sox2, Oct4, Klf4, L-Myc and Lin28 episomal vectors were used to electrotransfect the endometrial stromal cells. The first 8 days involves commitment to hematopoietic stem cells through embryoid body with robust expansion on murine bone marrow stromal cells. The second phase involves feeder free conditions with hydrocortisone, stem cell factor, interleukin-3, and recombinant EPO. After 22 days of feeder free culture, the expression profiles of CD235a+ , CD34+ , CD43+ and CD 71+ were analyzed by flow cytometry and Wright-Giemsa staining for differential counting. The oxygen carrying capacity of cultured RBCs was measured using a hemoxanalyser. @*RESULTS@#As a result of inducing these cells via co-culture with murine stromal fibroblasts, all endometrium derived iPSCs were differentiated into erythroblasts with a stable yield of approximately 80% for polychromatic and orthochromatic normoblasts. The protocol for complete induction of erythroid lineage cells starting from human endometrial tissue via iPS cells has been optimized. @*CONCLUSION@#Successful directed erythroid differentiation has occurred from human endometrium-derived iPS cells. A comprehensive process of actually deriving iPS cells using discarded surgical hysterectomy specimens to the erythroid fate has significance in that the scope of using human iPSC cell lines for tissue regeneration could be expanded in the future.

Korean clinical practice guidelines on biologics for moderate to severe Crohn’s disease

Crohn’s disease (CD) is a relapsing and progressive condition characterized by diarrhea, abdominal pain, weight loss, and hematochezia that results in serious complications such as perforations, fistulas, and abscesses. Various medications, interventions, and surgical treatments have been used to treat CD. The Korean guidelines for CD management were distributed in 2012 and revised in 2017 by the Inflammatory Bowel Disease (IBD) Research Group of the Korean Association for the Study of Intestinal Diseases. Substantial progress in mucosal immunologic research has elucidated the pathophysiology of IBD, leading to development of biological agents for treatment of CD. The first developed biologic agent, tumor necrosis factor-α agents, were shown to be efficacious in CD, heralding a new era in management of CD. Subsequently, vedolizumab, a monoclonal antibody against integrin α4β7, and ustekinumab, a human monoclonal antibody that inhibits the common p40 subunit of interleukin-12 and interleukin-23, were both approved for clinical use and are efficacious and safe for both induction and maintenance of remission in moderate-to-severe CD patients. Moreover, a recent study showed the non-inferiority of CT-P13, an infliximab biosimilar, compared with infliximab in CD patients. The third Korean guidelines for CD management provide updated information regarding treatment of moderate-to-severe CD patients with biologic agents.

Reversible Gait Disturbance Due to Vitamin B12 Deficiency

Vitamin B12 deficiency causes a variety of symptoms in the hematologic, gastrointestinal tract, and neurologic deficit. We report a rare case of progressive gait disturbance, bradykinesia and dysarthria which was that vitamin B12 deficiency was diagnosed as the cause, and symptoms improved after intramuscular cobalamin treatment. Vitamin B12, homocysteine, and methylmalonic acid tests are recommended for patients with progressive gait disturbance, even in the absence of obvious anemia symptoms.

Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center

Background@#Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas. @*Methods@#This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis. @*Results@#In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively). @*Conclusions@#There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.

Relationship between Peer Relationships and Problematic Smartphone Use among Female Adolescents: The Mediating Effect of Depression

Purpose@#This study examined the mediating effects of depression on the relationship between peer relationships and problematic smartphone use in female adolescents. @*Methods@#Secondary analysis was performed on data from the Korean Children and Youth Panel Survey in 2018, a national survey conducted by Korea’s National Youth Policy Institute. Data from 1,141 female adolescents were analyzed using descriptive statistics, with independent t-test and 1-way analysis of variance, Pearson correlation coefficient, and multiple linear regression analysis. The significance of the mediating effect was verified using PROCESS macro model 4. @*Results@#The direct effects of both positive and negative peer relationships increased problematic smartphone use in female adolescents. Negative peer relationships increased problematic smartphone use via the mediating effects of depression, whereas positive peer relationships reduced problematic smartphone use via the mediating effects of depression. @*Conclusion@#Problematic smartphone use among female adolescents can be reduced by lowering the incidence of depression and developing interventions aimed at helping them resolve conflicts with friends and cope with negative emotions.

Cancer risk in patients with Peutz-Jeghers syndrome in Korea: a retrospective multi-center study

Background/Aims@#There have been little research on the cancer risks of patients with Peutz-Jeghers syndrome (PJS) in Korea. We aimed to investigate the clinical features of PJS patients and their cancer incidence rate. @*Methods@#Patients with PJS from nine medical centers were enrolled. In those patients diagnosed with cancer, data obtained included the date of cancer diagnosis, the tumor location, and the cancer stage. The cumulative risks of gastrointestinal cancers and extra-gastrointestinal cancers were calculated using the Kaplan-Meier method. @*Results@#A total of 96 PJS patients were included. The median age at diagnosis of PJS was 23.4 years. Cancer developed in 21 of the 96 patients (21.9%). The age of PJS diagnosis was widely distributed (0.9 to 72.4 years). The most common cancers were gastrointestinal cancer (n = 12) followed by breast cancer (n = 6). The cumulative lifetime cancer risk was calculated to be 62.1% at age 60. The cumulative lifetime gastrointestinal cancer risk was 47.1% at age 70. The cumulative lifetime extra- gastrointestinal cancer risk was 40.3% at age 60. @*Conclusions@#PJS onset may occur at any age and the risks of gastrointestinal and extra-gastrointestinal cancer are high. Thorough surveillance of PJS patients for malignancies is vital.

How Does Medical Policy on the Use of Prophylactic Antibiotics Affect Medical Costs, Length of Hospital Stay, and Antibiotic Use in Orthopedics?

Purpose@#The purpose of this study was to compare patients who had undergone spine surgery (SS) and hip arthroplasty surgery (HAS) and to analyze how medical policies drawn from “The Evaluation of the Appropriate Use of Prophylactic Antibiotics” have affected length of hospital stay (LOS), direct medical costs (DMC), and the duration of antibiotics use in Korea. @*Materials and Methods@#This retrospective nationwide study identified subjects from the Korean National Health Insurance Review and Assessment Service database from January, 2011 to December, 2018. Evaluation of HAS (control group) was implemented in 2007, and that for SS (case group) was conducted for the first time in 2014 (intervention time). In our comparative interrupted time series analysis, we compared DMC, LOS, and use of antibiotics between both groups. @*Results@#177468 patients who underwent SS and 89372 patients who underwent HAS were included in the study. In 2016, DMC increased for HAS, compared to SS, by 1.03 times (p=0.041). However, cost changes during other observational periods for SS were not higher than those for HAS (p>0.05). SS incurred a reduced LOS of 3% in the first 2 years (p<0.05). Thereafter, LOS changes in SS were not smaller than those in HAS. A decrease in the usage of total antibiotics and broad spectrum antibiotics was observed for 5 years. @*Conclusion@#This medical policy was effective in terms of reducing usage and duration of antibiotics use, especially in the first 2 years after the implementation of the policy.

CD5 Expression Dynamically ChangesDuring the Differentiation of Human CD8+ T Cells Predicting Clinical Response to Immunotherapy

Defining the molecular dynamics associated with T cell differentiation enhances our understanding of T cell biology and opens up new possibilities for clinical implications. In this study, we investigated the dynamics of CD5 expression in CD8+ T cell differentiation and explored its potential clinical uses. Using PBMCs from 29 healthy donors, we observed a stepwise decrease in CD5 expression as CD8+ T cells progressed through the differentiation stages. Interestingly, we found that CD5 expression was initially upregulated in response to T cell receptor stimulation, but diminished as the cells underwent proliferation, potentially explaining the differentiation-associated CD5 downregulation. Based on the proliferationdependent downregulation of CD5, we hypothesized that relative CD5 expression could serve as a marker to distinguish the heterogeneous CD8+ T cell population based on their proliferation history. In support of this, we demonstrated that effector memory CD8+ T cells with higher CD5 expression exhibited phenotypic and functional characteristics resembling less differentiated cells compared to those with lower CD5 expression. Furthermore, in the retrospective analysis of PBMCs from 30 non-small cell lung cancer patients, we found that patients with higher CD5 expression in effector memory T cells displayed CD8+ T cells with a phenotype closer to the less differentiated cells, leading to favorable clinical outcomes in response to immune checkpoint inhibitor (ICI) therapy. These findings highlight the dynamics of CD5 expression as an indicator of CD8+ T cell differentiation status, and have implications for the development of predictive biomarker for ICI therapy.