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: Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases. Methods: Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis. Results: All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases. Conclusions Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Objectives: Lonely death is defined as “a person living in a state of social isolation, disconnected from family, relatives, and others, who dies from suicide, illness, or other causes”. This study investigated the characteristics of individuals who die alone in Korea. Methods: We constructed a database of lonely death cases by linking data from the Korea Crime Scene Investigation Unit of the Korea National Police Agency with National Health Insurance Service (NHIS) records. A descriptive analysis was performed to evaluate the demographics, underlying diseases, and healthcare utilization patterns among lonely death cases. Results: Among the 3122 individuals identified as lonely death cases, 2621 (84.0%) were male and 501 (16.0%) were female. The most common age group was 50-59 years (n=930, 29.8%). The NHIS covered 2161 individuals (69.2%), whereas 961 individuals (30.8%) were enrolled in Medical Aid (MA). The highest number of lonely deaths occurred in Seoul areas, with 1468 cases (47.0%). Mood disorders were diagnosed in 1020 individuals (32.7%), and various alcohol-related diseases, including alcoholic liver disease, were also observed. Outpatient visits increased leading up to death but declined in the final 3 months, while hospitalizations decreased and emergency room visits slightly increased. Conclusions Most lonely death cases involved male in their 50s, with a disproportionately high number of MA beneficiaries compared to the general population. Many of these individuals also experienced mental health issues or alcohol-related disorders. Preventing social isolation and strengthening social safety nets are critical to reducing the occurrence of lonely deaths.

Objective: This study aimed to explore the relationship between circulating vascular endothelial growth factor (VEGF) levels and Behçet’s disease (BD), as well as to examine the association between VEGF gene polymorphisms and BD. Methods: We conducted a comprehensive search of the MEDLINE, Embase, and Web of Science databases to identify relevant research articles. A meta-analysis was performed to compare serum or plasma VEGF levels in BD patients with those in control groups. Additionally, we evaluated the potential associations between BD susceptibility and specific VEGF polymorphisms, namely –634 C/G, +936 C/T, and the 18 bp insertion/deletion (I/D) at –2549. Results: The analysis included 15 studies with a total of 1,020 BD patients and 1,031 controls. BD patients exhibited significantly higher circulating VEGF levels compared to controls (standardized mean difference [SMD]=1.726, 95% confidence interval [CI]=1.030~2.421, p<0.001). Elevated VEGF levels were noted among BD patients from European and Arab populations. Subgroup analysis further confirmed the increase in VEGF levels across different data types and sample sizes. Patients with active BD had higher VEGF levels than those with inactive BD (SMD=0.635, 95% CI=0.092~1.177, p=0.022). However, no significant association was found between BD and the VEGF –634 C allele (odds ratio=1.023, 95% CI=0.707~1.481, p=0.904). Similarly, no association was detected between BD and the VEGF +936 C/T or 18 bp I/D at –2549 polymorphisms. Conclusion Our meta-analysis showed a strong association between elevated circulating VEGF levels and BD. However, the VEGF polymorphisms examined in this study do not appear to be associated with susceptibility to BD.

The management of rheumatoid arthritis (RA) follows a treat-to-target approach, as recommended by guidelines from the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR). RA treatment recommendations include an emphasis on frequent disease activity assessments to optimize therapy, recognizing the possibility of timely therapies to slow progression and improve long-term results. The evaluation of joint inflammation, pain, physical function, and clinical indicators is required for comprehensive RA therapy. Current therapeutic goals include achieving low disease activity or remission to enhance the quality of life (QoL) for patients. ACR-endorsed RA disease activity measures, such as the Disease Activity Score in 28 Joints with erythrocyte sedimentation rate or C-reactive protein level, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Patient Activity Scale-II, and Routine Assessment of Patient Index Data 3, are recommended for their precision and sensitivity in supporting treat-to-target strategies. The ACR and EULAR have implemented Boolean-based and index-based remission criteria (SDAI and CDAI, respectively) to evaluate therapeutic effectiveness. The use of these markers regularly aligns with the ACR guidelines, improving adherence to quality indicators in clinical practice and confirming the provision of high-quality RA therapy. This review examines disease activity, function, and QoL measurements in line with the ACR and EULAR guidelines to aid doctors in treating Korean patients with RA.

Objective: This study aimed to investigate the link between circulating interleukin-18 (IL-18) levels and adult-onset Still’s disease (AOSD). Methods: A thorough search was performed on MEDLINE, Embase, and Web of Science to find relevant articles. A meta-analysis was conducted to compare serum/plasma IL-18 levels in AOSD patients to those in control subjects. Results: The meta-analysis included 13 studies with a total of 562 AOSD patients and 790 controls. The results showed a significant increase in IL-18 levels in the AOSD group compared to the control group (standard mean difference [SMD]=1.899, 95% confidence interval [CI]=1.078~2.720, p<0.001). When stratified by ethnicity, higher IL-18 levels were found in both Asian and European populations with AOSD. Subgroup analysis, regardless of variable adjustments, consistently indicated significantly higher IL-18 levels in the AOSD group. Significant elevations in IL-18 levels were observed in both small (n<50) and large groups (n>50), as well as in original and imputed data groups after data type stratification. Free IL-18 levels were significantly higher in the active group compared to the inactive group (SMD=0.900, 95% CI=0.532~1.268, p<0.001). The meta-analysis showed a positive correlation between IL-18 levels and ferritin (correlation coefficient=0.542, 95% CI=0.431~0.637, p<0.001) and C-reactive protein. Conclusion This meta-analysis demonstrated a significant increase in circulating IL-18 levels and a positive correlation between IL-18 levels and ferritin and C-reactive protein levels in patients with AOSD.

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.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.