Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: Colorectal carcinomas (CRCs) with caudal-type homeobox 2 (CDX2) loss are recognized to pursue an aggressive behavior but tend to be accompanied by a high density of tumor-infiltrating lymphocytes (TILs). However, little is known about whether there is an interplay between CDX2 loss and TIL density in the survival of patients with CRC. Methods: Stage III CRC tissues were assessed for CDX2 loss using immunohistochemistry and analyzed for their densities of CD8 TILs in both intraepithelial (iTILs) and stromal areas using a machine learning-based analytic method. Results: CDX2 loss was significantly associated with a higher density of CD8 TILs in both intraepithelial and stromal areas. Both CDX2 loss and a high CD8 iTIL density were found to be prognostic parameters and showed hazard ratios of 2.314 (1.050–5.100) and 0.378 (0.175–0.817), respectively, for cancer-specific survival. A subset of CRCs with retained CDX2 expression and a high density of CD8 iTILs showed the best clinical outcome (hazard ratio of 0.138 [0.023–0.826]), whereas a subset with CDX2 loss and a high density of CD8 iTILs exhibited the worst clinical outcome (15.781 [3.939–63.230]). Conclusions Altogether, a high density of CD8 iTILs did not make a difference in the survival of patients with CRC with CDX2 loss. The combination of CDX2 expression and intraepithelial CD8 TIL density was an independent prognostic marker in adjuvant chemotherapy-treated patients with stage III CRC.

Background: and Purpose Previous research on patients with acute ischemic stroke (AIS) has shown a 0.5% incidence of major gastrointestinal bleeding (GIB) requiring blood transfusion during hospitalization. The existing literature has insufficiently explored the long-term incidence in this population despite the decremental impact of GIB on stroke outcomes. Methods: We analyzed the data from a cohort of patients with AIS admitted to 14 hospitals as part of a nationwide multicenter prospective stroke registry between 2011 and 2013. These patients were followed up for up to 6 years. The occurrence of major GIB events, defined as GIB necessitating at least two units of blood transfusion, was tracked using the National Health Insurance Service claims data. Results: Among 10,818 patients with AIS (male, 59%; mean age, 68±13 years), 947 (8.8%) experienced 1,224 episodes of major GIB over a median follow-up duration of 3.1 years. Remarkably, 20% of 947 patients experienced multiple episodes of major GIB. The incidence peaked in the first month after AIS, reaching 19.2 per 100 person-years, and gradually decreased to approximately one-sixth of this rate by the 2nd year with subsequent stabilization. Multivariable analysis identified the following predictors of major GIB: anemia, estimated glomerular filtration rate <60 mL/min/1.73 m2 , and a 3-month modified Rankin Scale score of ≥4. Conclusion Patients with AIS are susceptible to major GIB, particularly in the first month after the onset of AIS, with the risk decreasing thereafter. Implementing preventive strategies may be important, especially for patients with anemia and impaired renal function at stroke onset and those with a disabling stroke.

Objective: To assess the feasibility of ultrafast brain magnetic resonance imaging (MRI) in pediatric patients. Materials and Methods: We retrospectively reviewed 194 pediatric patients aged 0 to 19 years (median 10.2 years) who underwent both ultrafast and conventional brain MRI between May 2019 and August 2020. Ultrafast MRI sequences included T1 and T2-weighted images (T1WI and T2WI), fluid-attenuated inversion recovery (FLAIR), T2*-weighted image (T2*WI), and diffusion-weighted image (DWI). Qualitative image quality and lesion evaluations were conducted on 5-point Likert scales by two blinded radiologists, with quantitative assessment of lesion count and size on T1WI, T2WI, and FLAIR sequences for each protocol. Wilcoxon signed-rank tests and intraclass correlation coefficient (ICC) analyses were used for comparison. Results: The total scan times for equivalent image contrasts were 1 minute 44 seconds for ultrafast MRI and 15 minutes 30 seconds for conventional MRI. Overall, image quality was lower in ultrafast MRI than in conventional MRI, with mean quality scores ranging from 2.0 to 4.8 for ultrafast MRI and 4.8 to 5.0 for conventional MRI across sequences (P < 0.001 for T1WI, T2WI, FLAIR, and T2*WI for both readers; P = 0.018 [reader 1] and 0.031 [reader 2] for DWI). Lesion detection rates on ultrafast MRI relative to conventional MRI were as follows: T1WI, 97.1%; T2WI, 99.6%; FLAIR, 92.9%; T2*WI, 74.1%; and DWI, 100%. The ICC (95% confidence interval) for lesion size measurements between ultrafast and conventional MRI was as follows: T1WI, 0.998 (0.996–0.999); T2WI, 0.998 (0.997–0.999); and FLAIR, 0.99 (0.985–0.994). Conclusion Ultrafast MRI significantly reduces scan time and provides acceptable results, albeit with slightly lower image quality than conventional MRI, for evaluating intracranial abnormalities in pediatric patients.

Objective: To test the performance of an artificial intelligence-based computer-aided diagnosis (AI-CAD) designed for fullfield digital mammography (FFDM) when applied to synthetic mammography (SM). Materials and Methods: We analyzed 501 women (mean age, 57 ± 11 years) who underwent preoperative mammography and breast cancer surgery. This cohort consisted of 1002 breasts, comprising 517 with cancer and 485 without. All patients underwent digital breast tomosynthesis (DBT) and FFDM during the preoperative workup. The SM is routinely reconstructed using DBT. Commercial AI-CAD (Lunit Insight MMG, version 1.1.7.2) was retrospectively applied to SM and FFDM to calculate the abnormality scores for each breast. The median abnormality scores were compared for the 517 breasts with cancer using the Wilcoxon signed-rank test. Calibration curves of abnormality scores were evaluated. The discrimination performance was analyzed using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity using a 10% preset threshold. Sensitivity and specificity were further analyzed according to the mammographic and pathological characteristics.The results of SM and FFDM were compared. Results: AI-CAD demonstrated a significantly lower median abnormality score (71% vs. 96%, P < 0.001) and poorer calibration performance for SM than for FFDM. SM exhibited lower sensitivity (76.2% vs. 82.8%, P < 0.001), higher specificity (95.5% vs.91.8%, P < 0.001), and comparable AUC (0.86 vs. 0.87, P = 0.127) than FFDM. SM showed lower sensitivity than FFDM in asymptomatic breasts, dense breasts, ductal carcinoma in situ, T1, N0, and hormone receptor-positive/human epidermal growth factor receptor 2-negative cancers but showed higher specificity in non-cancerous dense breasts. Conclusion AI-CAD showed lower abnormality scores and reduced calibration performance for SM than for FFDM.Furthermore, the 10% preset threshold resulted in different discrimination performances for the SM. Given these limitations, off-label application of the current AI-CAD to SM should be avoided.

BACKGROUND/OBJECTIVES: Estrogen regulates certain biological functions, including bone health, maintenance of skin components, and cardiovascular and brain protection. Estrogen deficiency manifests as hot flashes, wrinkles, skin dryness, reduced bone mineral density (BMD), sleep disorders, and cardiovascular diseases. This study aimed to investigate the effects of aerobic exercise combined with ferulic acid (FA) in ovariectomized rats.MATERIALS/METHODS: Female Sprague–Dawley rats were classified into control (N), ovariectomy (OV), ovariectomy and exercise (OV+EX), and ovariectomy and exercise with ferulic acid (OV+EX+F) groups. Following ovariectomy at 22 weeks of age, the rats were tower climbing exercise at gradually increase the load (3 days/week for 12 weeks) with or without FA (5 g/kg diet) administration. RESULTS: Estrogen deficiency in female rats (OV group) resulted in increased body weight, increased blood triglyceride (TG) levels, and decreased BMD following ovariectomy.Interestingly, compared with the rats in the OV group, the rats in the OV+EX+F group exhibited reduced body weight and blood TG levels and maintained BMD following ovariectomy, similar to those in the N group. Histological analysis of the skin of estrogen-deficient rats (OV group) revealed significantly decreased skin thickness with fewer dermal cells and distorted subcutaneous fat layers, similar to the aging phenotype. Interestingly, the rats in the OV+EX+F group exhibited rescued skin phenotypes compared with those in the OV and OV+EX groups. The skin of rats from all groups was analyzed for the expression of DNA damage and repair proteins. The OV+EX+F and OV+EX groups exhibited enhanced protein levels of pCHK1 (S345), an initiator of DNA repair signaling, and p53, indicating increased cellular DNA damage because of ovariectomy and ultimately an underlying DNA repair process. CONCLUSION Exercise with FA had beneficial effects on lipid profiles, BMD, and skin remodeling during menopause.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Background and Objectives: Evidence remains limited on the real-world prescription of very low-dose oral anticoagulation among frail patients with atrial fibrillation (AF). We described the practice patterns, effectiveness, and safety of very low-dose edoxaban (15 mg once daily). Methods: Patients with AF prescribed edoxaban 15 mg once daily in 2 tertiary hospitals between 2016 and September 2022 were included. Baseline clinical characteristics and clinical outcomes of interest were thromboembolic and bleeding events. Results: A total of 674 patients were included (mean age 78.3±9.1, 49.7% aged ≥80 years, 49.3% women, median follow-up 1.0±1.2 years). Mean CHA 2 DS 2 -VASc score was 3.9±1.6, and the modified HAS-BLED score was 2.0±1.1. Between 2016 and 2022, the number of very lowdose edoxaban prescriptions increased. The main reasons for the prescription of very lowdose were low body weight (55.5% below 60 kg), anaemia (62.8%), chronic kidney disease (40.2%), active cancer (15.3%), concomitant anti-platelet use (26.7%), and prior major bleeding (19.7%). During a median follow-up duration of 8 (interquartile range 3–16) months, overall thromboembolic and bleeding events occurred in 16 (2.3%) and 88 (13.1%) patients, respectively. Compared to the expected event rates on the established risk scoring systems, patients receiving very low-dose edoxaban demonstrated a 61% reduction in ischemic stroke, a 68% reduction of ischemic stroke/transient ischemic attack/systemic embolism, whereas a 49% increase in major bleeding. Conclusions The prescription of very low-dose edoxaban was increased over time, attributable to various clinical factors. The use of very low-dose edoxaban reduced the expected risk of thromboembolic events.

Cytomegalovirus (CMV) is a significant concern for patients with allogeneic hematopoietic cell transplantation (alloHCT). CMV management differs between institutions due to the lack of local guidelines. Here, we describe a case of refractory/resistant CMV infection treated using our institution's CMV management protocol. A 59-year-old woman who underwent allo-HCT was treated for CMV reactivation. Despite 3 months of valganciclovir administration, serum CMV level surged. CMV gene mutation test revealed a ganciclovir-resistant A594V mutation in the UL97 gene.Treatment was switched to foscarnet until the drug became unavailable nationwide. During the foscarnet shortage, cidofovir was used, leading to a decline in CMV levels when foscarnet was reintroduced and used for 2 months.Following allo-HCT, CMV prophylaxis with letermovir is crucial to prevent reactivation in seropositive recipients.CMV titers should be monitored frequently after allo-HCT. The cutoff value for preemptive therapy varies across institutions, with ganciclovir/valganciclovir usually administered as first-line therapy. Maribavir is an option in cases of ganciclovir/valganciclovir resistance or intolerance. CMV gene mutations should be examined in patients with suspected resistance after 2 weeks of appropriate treatment. This case was discussed at the Clinical Grand Round of the Annual Conference of the Korean Society of Infectious Diseases on November 2, 2023.