Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer

Purpose@#Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. @*Methods@#CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. @*Results@#The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing no therapy-related death or general toxicity symptoms. @*Conclusion@#The results suggested that combined immune cell adaptive therapy could overcome the limited efficacy of cell immunotherapy.

Impact of Social Support during Diagnosis and Treatment on Disease Progression in Young Patients with Breast Cancer: A Prospective Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We evaluated the association between changes in social support after cancer treatment and recurrence-free survival (RFS) in such patients using a prospective cohort study. @*Materials and Methods@#Data were obtained from a prospective cohort study (NCT03131089) conducted at Samsung Medical Center (2013-2021). The primary outcome measure was RFS. Social support was measured using the social and family well-being (SFWB) domain of the Functional Assessment of Cancer Therapy-General. We calculated the changes in SFWB scores before and during treatment and the hazard ratio for RFS by comparing such changes. @*Results@#The mean±standard deviation (SD) age of the patients was 35±3.9 years, and 71.5% and 64.8% of the patients were married and had children, respectively. The mean±SD SFWB score at baseline was 20.5±5.0 out of 26. After cancer treatment, 35.9%, 10.3%, and 53.8% of the participants had increasing, unchanged, and decreasing SFWB scores, respectively. The decreasing SFWB score group had a higher risk of mortality or recurrence than the increasing group. Risk factors for the decreasing score were the presence of children during diagnosis. @*Conclusion@#In this cohort, changes in social support after treatment were associated with RFS in young patients with breast cancer. Health professionals should develop family interventions to help them receive proper social support.

Multiomics profiling of buffy coat and plasma unveils etiology-specific signatures in hepatocellular carcinoma

Background/Aims@#Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. Despite identification of several biomarkers for HCC diagnosis, challenges such as low sensitivity and intratumoral heterogeneity have impeded early detection, highlighting the need for etiology-specific blood biomarkers. @*Methods@#We generated whole-transcriptome sequencing (WTS) and targeted proteome data from buffy coat and plasma samples from HCC patients. By integrating etiological information on viral infection, we investigated the etiology-specific gene expression landscape at the blood level. Validation of differentially expressed genes (DEGs) was performed using publicly available RNA-seq datasets and qRT‒PCR with AUC analyses. @*Results@#Differential expression analyses with multiomics data revealed distinct gene expression profiles between HBV-associated HCC and nonviral HCC, indicating the presence of etiology-specific blood biomarkers. The identified DEGs were validated across multiple independent datasets, underscoring their utility as biomarkers. Additionally, single-cell RNA-seq analysis of HCC confirmed differences in DEG expression across distinct immune cell types. @*Conclusions@#Our buffy coat WTS data and plasma proteome data may serve as reliable sources for identifying etiology-specific blood biomarkers of HCC and might contribute to discovery of therapeutic targets for HCC across different etiologies.

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.

Diagnosis and Treatment of Perihilar Cholangiocarcinoma:A National Survey from the Korean Pancreatobiliary Association

Background/Aims@#Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea. @*Methods@#We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association. @*Results@#In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method. @*Conclusions@#A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.

Immune Cells Are DifferentiallyAffected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice

Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

The Impact of an Antimicrobial Stewardship Program on Days of Therapy in the Pediatric Center:An Interrupted Time-Series Analysis of a 19-Year Study

Background@#We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients. @*Methods@#A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001–2008) and the post-intervention (2009–2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patientdays, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ2 . @*Results@#The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = −16.5; 95% confidence interval [CI], −30.6 to −2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881). @*Conclusion@#The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Self-Reported Findings of the Korean Intermittent Exotropia Multicenter Study Questionnaire

Purpose@#To determine subjective symptoms and medical history of patients with intermittent exotropia in a large study population. @*Methods@#The Korean Intermittent Exotropia Multicenter Study (KIEMS) is a nationwide, observational, cross-sectional, multicenter study conducted by the Korean Association for Pediatric Ophthalmology and Strabismus including 5,385 patients with intermittent exotropia. Subjective symptoms and medical history of patients with intermittent exotropia were extracted by a comprehensive survey based on a self-administered questionnaire according to the study protocol of the KIEMS. @*Results@#The mean age of symptom onset was 5.5 years. The most common symptom reported in patients with intermittent exotropia was photophobia (52.1%), followed by diplopia at near fixation (7.3%) and distance fixation (6.2%). Preterm birth was found in 8.8%, and 4.1% had perinatal complications. A family history of strabismus was present in 14.9%, and 5.5% of patients had a family member who underwent strabismus surgery. @*Conclusions@#The KIEMS is one of the largest clinical studies on intermittent exotropia. Intermittent exotropia frequently caused photophobia and diplopia, and patients with a family history was not uncommon.

Prognostication of Hepatocellular Carcinoma Using Artificial Intelligence

Hepatocellular carcinoma (HCC) is a biologically heterogeneous tumor characterized by varying degrees of aggressiveness.The current treatment strategy for HCC is predominantly determined by the overall tumor burden, and does not address the diverse prognoses of patients with HCC owing to its heterogeneity. Therefore, the prognostication of HCC using imaging data is crucial for optimizing patient management. Although some radiologic features have been demonstrated to be indicative of the biologic behavior of HCC, traditional radiologic methods for HCC prognostication are based on visually-assessed prognostic findings, and are limited by subjectivity and inter-observer variability. Consequently, artificial intelligence has emerged as a promising method for image-based prognostication of HCC. Unlike traditional radiologic image analysis, artificial intelligence based on radiomics or deep learning utilizes numerous image-derived quantitative features, potentially offering an objective, detailed, and comprehensive analysis of the tumor phenotypes. Artificial intelligence, particularly radiomics has displayed potential in a variety of applications, including the prediction of microvascular invasion, recurrence risk after locoregional treatment, and response to systemic therapy. This review highlights the potential value of artificial intelligence in the prognostication of HCC as well as its limitations and future prospects.

Current Treatment Patterns and the Role of Upfront Autologous Stem Cell Transplantation in Patients with Peripheral T-Cell Lymphoma: A Korean Nationwide, Multicenter Prospective Registry Study (CISL 1404) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer. @*Materials and Methods@#Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient’s body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumor 1.1. Secondary endpoints included time-to-progression (TTP), duration-of-response (DoR), overall survival (OS), and adverse events. @*Results@#A total of 87 patients were enrolled from 11 institutions in Korea. Hormone receptor was positive in 54 (62.1%) patients and six (6.9%) had human epidermal growth factor receptor 2–positive disease. Forty-eight patients (85.1%) had visceral metastasis and 74 (55.2%) had more than three sites of metastases. The ORR of SOX regimen was 38.5% (95% confidence interval [CI], 26.9 to 50.0) with a median TTP of 6.0 months (95% CI, 5.1 to 6.9). Median DoR and OS were 10.3 months (95% CI, 5.5 to 15.1) and 19.4 (95% CI, not estimated) months, respectively. Grade 3 or 4 neutropenia was reported in 28 patients (32.1%) and thrombocytopenia was observed in 23 patients (26.6%). @*Conclusion@#This phase II study showed that SOX regimen is a reasonable option in metastatic breast cancer previously treated with anthracyclines and taxanes.

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Optimal Use and Need for Therapeutic Drug Monitoring of Teicoplanin in Children: A Systematic Review

Background@#Teicoplanin is a glycopeptide antimicrobial that treats serious invasive infections caused by gram-positive bacteria, such as the methicillin-resistant Staphylococcus aureus. Despite some comparable advantages, there is no guideline or clinical recommendation for teicoplanin in the pediatric population, unlike vancomycin where abundant studies and the recently revised guideline on therapeutic drug level monitoring (TDM) exist. @*Methods@#The systematic review was performed in accordance with the preferred reporting items for systematic reviews. Two authors (JSC and SHY) searched PubMed, Embase, and Cochrane Library databases using relevant terms independently. @*Results@#Fourteen studies were finally included with a total of 1,380 patients. TDM was available in 2,739 samples collected in the nine studies. Dosing regimens varied widely, and eight studies used recommended dosing regimens. Timing for measuring TDM was mostly 72–96 hours or longer after the initiation of the first dose, which was expected to be a steadystate. The majority of studies had target trough levels of 10 µg/mL or above. Three studies reported that the clinical efficacy and treatment success rate of teicoplanin was 71.4%, 87.5%, and 88%. Adverse events associated with teicoplanin use were described in six studies with a focus on renal and/or hepatic impairment. Except for one study, no significant relation was noted between the incidence of adverse events and trough concentration. @*Conclusion@#Current evidence on teicoplanin trough levels in pediatric populations is insufficient due to heterogeneity. However, target trough levels with favorable clinical efficacy are achievable by recommended dosing regimen in the majority of patients.

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.

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). @*Materials and Methods@#Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. @*Results@#Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). @*Conclusion@#Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Fibrotic Burden in the Liver Differs Across Metabolic Dysfunction-Associated Fatty Liver Disease Subtypes

Background/Aims@#Metabolic dysfunction-associated fatty liver disease (MAFLD) is categorized into three subtypes: overweight/obese (OW), leanormal weight with metabolic abnormalities, and diabetes mellitus (DM). We investigated whether fibrotic burden in liver differs across subtypes of MAFLD patients. @*Methods@#This cross-sectional multicenter study was done in cohorts of subjects who underwent a comprehensive medical health checkup between January 2014 and December 2020. A total of 42,651 patients with ultrasound-diagnosed fatty liver were included. Patients were classified as no MAFLD, OW-MAFLD, lean-MAFLD, and DM-MAFLD. Advanced liver fibrosis was defined based on the nonalcoholic fatty liver disease fibrosis score (NFS) or fibrosis-4 (FIB-4) index. @*Results@#The mean age of the patients was 50.0 years, and 74.1% were male. The proportion of patients with NFS-defined advanced liver fibrosis was the highest in DM-MAFLD (6.6%), followed by OW-MAFLD (2.0%), lean-MAFLD (1.3%), and no MAFLD (0.2%). The proportion of patients with FIB-4-defined advanced liver fibrosis was the highest in DM-MAFLD (8.6%), followed by lean-MAFLD (3.9%), OW-MAFLD (3.0%), and no MAFLD (2.0%). With the no MAFLD group as reference, the adjusted odds ratios (95% confidence intervals) for NFS-defined advanced liver fibrosis were 4.46 (2.09 to 9.51), 2.81 (1.12 to 6.39), and 9.52 (4.46 to 20.36) in OW-MAFLD, leanMAFLD, and DM-MAFLD, respectively, and the adjusted odds ratios for FIB-4-defined advanced liver fibrosis were 1.03 (0.78 to 1.36), 1.14 (0.82 to 1.57), and 1.97 (1.48 to 2.62) in OW-MAFLD, lean-MAFLD, and DM-MAFLD. @*Conclusions@#Fibrotic burden in the liver differs across MAFLD subtypes. Optimized surveillance strategies and therapeutic options might be needed for different MAFLD subtypes.

Development and Verification of Time-Series Deep Learning for Drug-Induced Liver Injury Detection in Patients Taking Angiotensin II Receptor Blockers: A Multicenter Distributed Research Network Approach / 대한의료정보학회지

Objectives@#The objective of this study was to develop and validate a multicenter-based, multi-model, time-series deep learning model for predicting drug-induced liver injury (DILI) in patients taking angiotensin receptor blockers (ARBs). The study leveraged a national-level multicenter approach, utilizing electronic health records (EHRs) from six hospitals in Korea. @*Methods@#A retrospective cohort analysis was conducted using EHRs from six hospitals in Korea, comprising a total of 10,852 patients whose data were converted to the Common Data Model. The study assessed the incidence rate of DILI among patients taking ARBs and compared it to a control group. Temporal patterns of important variables were analyzed using an interpretable timeseries model. @*Results@#The overall incidence rate of DILI among patients taking ARBs was found to be 1.09%. The incidence rates varied for each specific ARB drug and institution, with valsartan having the highest rate (1.24%) and olmesartan having the lowest rate (0.83%). The DILI prediction models showed varying performance, measured by the average area under the receiver operating characteristic curve, with telmisartan (0.93), losartan (0.92), and irbesartan (0.90) exhibiting higher classification performance. The aggregated attention scores from the models highlighted the importance of variables such as hematocrit, albumin, prothrombin time, and lymphocytes in predicting DILI. @*Conclusions@#Implementing a multicenter-based timeseries classification model provided evidence that could be valuable to clinicians regarding temporal patterns associated with DILI in ARB users. This information supports informed decisions regarding appropriate drug use and treatment strategies.

Otoconial Degeneration After Transient Ischemia Induced by Four-Vessel Occlusion in Rats

Background@#and Purpose Ischemia of the inner ear may damage the otoconia. However, no study has explored any changes in the configuration of otoconia after transient ischemia of the labyrinth. @*Methods@#Nineteen 7-week-old Sprague-Dawley rats were randomly assigned to either the sham (n=5) or the experimental group (n=14). The rats in the experimental group were subjected to global ischemia for 20 minutes using a four-vessel occlusion model, and were sacrificed seven days after the procedure. The rats in the sham group were sacrificed without any procedure. The otolithic organs (utricle and saccule) were dissected out for scanning electron microscope. @*Results@#The otolithic organs in the sham group showed their normal gross configuration with a dense clumping of otoconia with a normal hexagonal morphology and a smooth surface. The otolithic organs in the experimental group also maintained a grossly normal configuration, but each otoconia showed irregular surfaces with numerous cracks or furrows, especially in the periphery of the otoconial bed. @*Conclusions@#The current study showed that otoconial degeneration may occur even after transient ischemia of the labyrinth. This finding supports an association between cerebral ischemia and benign paroxysmal positional vertigo.

An Analysis of Factors Affecting Medical Operating Income at Regional Public Hospital / 보건행정학회지

Background@#Despite the various activities of the regional public hospitals, discussions are being made as to whether or not to continue due to the issue of financial deficit. Therefore, the main factors affecting the fiscal deficit were analyzed with 10-year data. @*Methods@#This study is a panel analysis that analyzed the characteristics of 34 regional public hospitals and influencing factors on medical benefits for 10 years from 2010 to 2019. First, we analyze the determinants of medically vulnerable areas set by the government, analyze the trend of medical profit per 100 beds and medical profit rate from 2010 to 2019, and identify the factors that affect them. @*Results@#Differences in medical profit per 100 beds and medical profit-to-medical profit rate were caused by market share representing regional characteristics, and both indicators improved as the number of outpatients increased. The important influencing variables are the number of doctors and nurses, and both indicators improve when there are specialists, but medical benefits decrease as the number of doctors increases when judged by the number of people per 100 beds. In addition, the number of nurses per 100 beds does not contribute to medical profit and has a negative effect on the medical profit ratio. @*Conclusion@#As only regional characteristics were taken into account for medically vulnerable areas, operational characteristics need to be considered. The greatest impact on the finances of local medical centers is the proper staffing of doctors and nurses, and their efficient arrangement is the most important factor in financial stability.

An Analysis of Factors Affecting Financial and Operating Efficiency at Regional Public Hospital / 보건행정학회지

Background@#Financial efficiency in monetary units and operational efficiency in non-monetary units are separately classified and evaluated. This is done to prevent the duplication of monetary units and non-monetary units in inputs and outputs. In addition, analyses are conducted to determine the factors that affect each aspect of efficiency. To prevent duplication of monetary and non-monetary units in inputs and outputs, financial efficiency, consisting of monetary units, and operational efficiency, comprising non-monetary units, are separately classified and evaluated. Furthermore, an analysis is conducted to identify the factors that affect each aspect of efficiency. @*Methods@#This study conducted a panel analysis of 34 regional public hospitals and influencing factors on efficiency for 5 years from 2015 to 2019. Financial efficiency and operational efficiency were calculated through data envelopment analysis. Moreover, multiple regression analysis was conducted to identify the factors that influence both financial efficiency and operational efficiency. @*Results@#The factors that affect financial efficiency include the number of medical institutions within the treatment area and the ratio of patients receiving medical care. Additionally, operational efficiency is influenced by the type of medical institution, the number of medical institutions within the treatment area, and the number of nursing positions per 100 beds. @*Conclusion@#In order for regional public hospitals to faithfully fulfill their functions and roles as regional base public hospitals, several measures are necessary. Firstly, continuous monitoring and reasonable support are required to ensure efficient operation and performance. Secondly, a financial support plan tailored to the characteristics of local medical centers is needed. Additionally, local medical centers should strive to enhance their own efficiency.