Purpose: Enhanced Recovery After Surgery (ERAS) protocols have demonstrated significant benefits, but their safety and effectiveness in high-risk patients remain unclear. This study evaluated clinical postoperative outcomes in elderly patients and those with comorbidities undergoing colon cancer surgery. Methods: This retrospective cohort study included 1,035 patients who underwent elective colon cancer surgery from 2017 to 2022. A standardized 25-element ERAS protocol was implemented across all groups. Patients were categorized into a control group (aged <70 years without comorbidities, n = 534) and high-risk groups including elderly patients (≥70 years, n = 312) and those with cardiac (n = 60), pulmonary (n = 81), renal (n = 24), or hepatic disease (n = 24). Results: ERAS compliance rates were significantly lower in all high-risk groups compared to controls (79.39% ± 10.9%), with renal disease patients showing the most pronounced reduction (69.69% ± 17.0%). Post-hoc analysis revealed that only renal disease patients demonstrated significantly higher complication rates (45.8% vs. 18.9%, P < 0.01). Despite lower compliance, multivariate analysis revealed ERAS compliance ≥70% as the strongest independent predictor of both length of stay (odds ratio [OR], 0.139; P < 0.001) and complications (OR, 0.298; P < 0.001), substantially outweighing patient risk factors. After adjusting for treatment factors, patient comorbidity groups showed no independent association with clinical outcomes. Conclusion ERAS protocols can be successfully implemented in high-risk patients with appropriate attention to compliance optimization. Treatment factors, particularly ERAS adherence, consistently outweigh patient risk factors in determining outcomes, and well-tailored ERAS implementation should be considered with high-risk patients for perioperative care.

Background: and PurposeInterhospital transfer is an essential practical component of regional stroke care systems. To establish an effective stroke transfer network in South Korea, an interactive transfer system was constructed, and its workflow metrics were observed. Methods: In March 2019, a direct transfer system between primary stroke hospitals (PSHs) and comprehensive regional stroke centers (CSCs) was established to standardize the clinical pathway of imaging, recanalization therapy, transfer decisions, and exclusive transfer linkage systems in the two types of centers. In an active case, the time metrics from arrival at PSH (“door”) to imaging was measured, and intravenous thrombolysis (IVT) and endovascular treatment (EVT) were used to assess the differences in clinical situations. Results: The direct transfer system was used by 27 patients. They stayed at the PSH for a median duration of 72 min (interquartile range [IQR], 38–114 min), with a median times of 15 and 58 min for imaging and subsequent processing, respectively. The door-to-needle median times of subjects treated with IVT at PSHs (n=5) and CSCs (n=2) were 21 min (IQR, 20.0–22.0 min) and 137.5 min (IQR, 125.3–149.8 min), respectively. EVT was performed on seven subjects (25.9%) at CSCs, which took a median duration of 175 min; 77 min at the PSH, 48 min for transportation, and 50 min at the CSC. Before EVT, bridging IVT at the PSH did not significantly affect the door-to-puncture time (127 min vs. 143.5 min, p=0.86). Conclusions The direct and interactive transfer system is feasible in real-world practice in South Korea and presents merits in reducing the treatment delay by sharing information during transfer.

This study aimed to estimate the medical cost of cancer in the first five years of diagnosis and in the final six months before death in people who developed cancer after human immunodeficiency virus (HIV) infection in Korea. The study utilized the Korea National Health Insurance Service-National Health Information Database (NHIS-NHID). Among 16,671 patients diagnosed with HIV infection from 2004 to 2020 in Korea, we identified 757 patients newly diagnosed with cancer after HIV diagnosis. The medical costs for 60 months after diagnosis and the last six months before death were calculated from 2006 to 2020. The mean annual medical cost due to cancer in HIV-infected people with cancer was higher for acquired immunodeficiency syndrome (AIDS)-defining cancers (48,242 USD) than for non-AIDS-defining cancers (24,338 USD), particularly non-Hodgkin’s lymphoma (53,007 USD), for the first year of cancer diagnosis. Approximately 25% of the cost for the first year was disbursed during the first month of cancer diagnosis. From the second year, the mean annual medical cost due to cancer was significantly reduced. The total medical cost was higher for non-AIDS-defining cancers, reflecting their higher incidence rates despite lower mean medical costs. The mean monthly total medical cost per HIV-infected person who died after cancer diagnosis increased closer to the time of death. The estimated burden of medical costs in patients with HIV in the present study may be an important index for defining healthcare policies in HIV patients in whom the cancer-related burden is expected to increase.

Purpose: Surgical management of obstructive left colon cancer (OLCC) is still a matter of debate. The classic Hartmann procedure (HP) has a disadvantage that requires a second major operation. Subtotal colectomy/total abdominal colectomy (STC/TC) with ileosigmoid or ileorectal anastomosis is proposed as an alternative procedure to avoid stoma and anastomotic leakage. However, doubts about morbidity and functional outcome and lack of long-term outcomes have made surgeons hesitate to perform this procedure. Therefore, this trial was designed to provide data for morbidity, functional outcomes, and long-term outcomes of STC/TC. Methods: This study retrospectively analyzed consecutive cases of OLCC that were treated by STC/TC between January 2000 and November 2020 at a single tertiary referral center. Perioperative outcomes and long-term outcomes of STC/TC were analyzed. Results: Twenty-five descending colon cancer (45.5%) and 30 sigmoid colon cancer cases (54.5%) were enrolled in this study. Postoperative complications occurred in 12 patients. The majority complication was postoperative ileus (10 of 12). Anastomotic leakage and perioperative mortality were not observed. At 6 to 12 weeks after the surgery, the median frequency of defecation was twice per day (interquartile range, 1–3 times per day). Eight patients (14.5%) required medication during this period, but only 3 of 8 patients required medication after 1 year. The 3-year disease-free survival was 72.7% and 3-year overall survival was 86.7%. Conclusion The risk of anastomotic leakage is low after STC/TC. Functional and long-term outcomes are also acceptable. Therefore, STC/TC for OLCC is a safe, 1-stage procedure that does not require diverting stoma.

Background: While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort. Methods: Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD. Results: Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs. Conclusion The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Immunologists have activated T cells in vitro using various stimulation methods, including phorbol myristate acetate (PMA)/ionomycin and αCD3/αCD28 agonistic antibodies. PMA stimulates protein kinase C, activating nuclear factor-κB, and ionomycin increases intracellular calcium levels, resulting in activation of nuclear factor of activated T cell. In contrast, αCD3/αCD28 agonistic antibodies activate T cells through ZAP-70, which phosphorylates linker for activation of T cell and SH2-domain-containing leukocyte protein of 76 kD. However, despite the use of these two different in vitro T cell activation methods for decades, the differential effects of chemical-based and antibody-based activation of primary human T cells have not yet been comprehensively described. Using single-cell RNA sequencing (scRNA-seq) technologies to analyze gene expression unbiasedly at the single-cell level, we compared the transcriptomic profiles of the non-physiological and physiological activation methods on human peripheral blood mononuclear cell–derived T cells from four independent donors. Remarkable transcriptomic differences in the expression of cytokines and their respective receptors were identified. We also identified activated CD4 T cell subsets (CD55+) enriched specifically by PMA/ionomycin activation. We believe this activated human T cell transcriptome atlas derived from two different activation methods will enhance our understanding, highlight the optimal use of these two in vitro T cell activation assays, and be applied as a reference standard when analyzing activated specific disease-originated T cells through scRNA-seq.

BACKGROUND/OBJECTIVES: Weight loss via a mobile application (App) or a paper-based diary (Paper) may confer favorable metabolic and anthropometric changes. SUBJECTS/METHODS: A randomized parallel trial was conducted among 57 adults whose body mass indices (BMIs) were 25 kg/m 2 or greater. Participants randomly assigned to either the App group (n = 30) or the Paper group (n = 27) were advised to record their foods and supplements through App or Paper during the 12-week intervention period. Relative changes of anthropometries and biomarker levels were compared between the 2 intervention groups.Untargeted metabolic profiling was identified to discriminate metabolic profiles. RESULTS: Out of the 57 participants, 54 participants completed the trial. Changes in body weight and BMI were not significantly different between the 2 groups (P = 0.11). However, body fat and low-density lipoprotein (LDL)-cholesterol levels increased in the App group but decreased in the Paper group, and the difference was statistically significant (P = 0.03 for body fat and 0.02 for LDL-cholesterol). In the metabolomics analysis, decreases in methylglyoxal and (S)-malate in pyruvate metabolism and phosphatidylcholine (lecithin) in linoleic acid metabolism from pre- to post-intervention were observed in the Paper group. CONCLUSIONS In the 12-week randomized parallel trial of weight loss through a App or a Paper, we found no significant difference in change in BMI or weight between the App and Paper groups, but improvement in body fatness and LDL-cholesterol levels only in the Paper group under the circumstances with minimal contact by dietitians or health care providers.Trial Registration: Clinical Research Information Service Identifier: KCT0004226

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

Background/Aims: Platelet-derived growth factor receptor alpha-positive (PDGFRα + ) cells function in the purinergic regulation of gastrointestinal motility, and purines are reportedly inhibitory neurotransmitters in the enteric nervous system. We explore the distribution and function of PDGFRα + cells related to purinergic inhibitory neurotransmission in human right and left colons. Methods: Human colonic segments were prepared with mucosa and submucosa intact, and the circular muscle tension and longitudinal muscle tension were recorded. Purinergic neurotransmitters were administered after recording the regular contractions.Immunohistochemistry was performed on the circular muscle layers. Intracellular recording was performed on the colonic muscular layer. SK3, P2RY1, and PDGFR-α mRNA expression was tested by quantitative real-time polymerase chain reaction (qPCR). Results: Adenosine triphosphate (ATP) treatment significantly decreased the frequency and area under the curve (AUC) of the segmental contraction in right and left colons. Beta-nicotinamide adenine dinucleotide (β-NAD) decreased the frequency in the right colon and the amplitude, frequency and AUC in the left colon. Apamin significantly increased frequency and AUC in the left colon, and after apamin pretreatment, ATP and β-NAD did not change segmental contractility. Through intracellular recordings, a resting membrane potential decrease occurred after ATP administration; however, the degree of decrease between the right and left colon was not different. PDGFRα +Conclusion Purines reduce right and left colon contractility similarly, and purinergic inhibitory neurotransmission can be regulated by PDGFRα+ cells in the human colon.

Background: We aimed to investigate the comparative risk of fracture among patients with atrial fibrillation (AF) treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). Methods: Using the Korean National Health Insurance Service database, patients with AF who received a prescrip‑ tion for apixaban, dabigatran, rivaroxaban, or warfarin between 2013 and 2016 were included. Risk of major fractures (osteoporotic hip, vertebral, or pelvic fractures) were compared using inverse probability of treatment weighting. Results: There were 70,481 patients identified (41.3% women; mean [SD] age 70.5 [11.3] years); 16,992 apixaban, 22,514 dabigatran, 27,998 rivaroxaban, and 29,390 warfarin users. During a median follow-up of 390 days, 2412 major fractures occurred with weighted incidences per 100 patient-years of 2.56 for apixaban, 2.39 for dabigatran, 2.78 for rivaroxaban, and 3.43 for warfarin. NOAC use was associated with a lower risk for fracture than warfarin use: HR 0.70 (95% confidence interval [CI] 0.57–0.86) for apixaban, HR 0.69 (95% CI 0.60–0.78) for dabigatran, and HR 0.79 (95% CI 0.70–0.90) for rivaroxaban. In head-to-head comparisons between NOACs, there was no significant difference between apixaban and dabigatran. Rivaroxaban was associated with a higher risk for fracture than dabigatran (HR 1.15, 95% CI 1.02–1.31). Conclusion In patients with AF, NOAC use may result in a lower risk for osteoporotic fracture compared with warfa‑ rin use. Fracture risk does not seem to be altered by the choice of NOAC type, except for rivaroxaban. These associa‑ tions may help inform benefit–risk assessments when choosing between the different anticoagulant types.