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.

Background: There is a dearth of research on the factors linked with adverse events (AEs) associated with nirmatrelvir/ritonavir (NMVr) and molnupiravir (MOL), particularly in the elderly. Therefore, this study aimed to investigate self-reported AEs and identify factors associated with the occurrence of AEs following NMVr or MOL treatment among survey participants aged 60 years or older in South Korea. Methods: This nationwide survey was conducted through in-person interviews using structured questionnaires, from July 24 to August 31, 2023. Eligible participants included individuals aged 60 years or older who had been diagnosed with coronavirus disease 2019 (COVID-19) and received NMVr or MOL. The study outcomes included self-reported demographic, lifestyle, and health characteristics associated with the occurrence of AEs.Multivariate logistic regression analysis was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of each characteristic in participants with and without AEs. Results: Of the 520 participants, 123 (23.7%) experienced at least one AE with oral COVID-19 treatment: 21.0% (96/458) for NMVr and 43.5% (27/62) for MOL. None of the participants reported any serious AEs. Increased odds of AE occurrence were observed in participants treated with MOL compared to those treated with NMVr (aOR, 3.05; 95% CI, 1.67–5.57), a history of two or more compared to one COVID-19 diagnosis (1.93; 1.03–3.62), and selfreported health status as “Unhealthy” compared to “Healthy” (2.65; 1.31–5.36). Conclusion No AEs required further evaluation to change treatment strategies in elderly patients on NMVr or MOL. Several factors, including the use of MOL, history of COVID-19, and reported health status, were associated with an increased incidence of AEs. Both treatments may still be useful choices for patients with non-severe COVID-19 aged 60 years or older. However, close monitoring of unidentified potential harm and further investigation of the factors associated with the occurrence of AEs are needed.

Background: It remains unclear whether a combination of glycemic variability and glycated hemoglobin (HbA1c) status leads to a higher incidence of cardiovascular disease (CVD).Therefore, to investigate CVD risk according to the glucose control status during early diabetes, we examined visit-to-visit HbA1c variability among patients with type 2 diabetes (T2DM). Methods: In this 9-year retrospective study, we measured HbA1c levels at each visit and tracked the change in HbA1c levels for 3 years after the first presentation (observation window) in newly diagnosed T2DM patients. We later assessed the occurrence of CVD in the last 3 years (target outcome window) of the study period after allowing a 3-year buffering window. The HbA1c variability score (HVS; divided into quartiles, HVS_Q1–4) was used to determine visit-to-visit HbA1c variability. Results: Among 4,817 enrolled T2DM patients, the mean HbA1c level was < 7% for the first 3 years. The group with the lowest HVS had the lowest rate of CVD (9.4%; 104/1,109 patients).The highest incidence of CVD of 26.7% (8/30 patients) was found in HVS [≥ 9.0%]_Q3, which was significantly higher than that in HVS [6.0–6.9%]_Q1 (P = 0.006), HVS [6.0–6.9%]_Q2 (P = 0.013), HVS [6.0–6.9%]_Q3 (P = 0.018), and HVS [7.0–7.9%]_Q3 (P = 0.040). Conclusion To our knowledge, this is the first long-term study to analyze the importance of both HbA1c change and visit-to-visit HbA1c variability during outpatient visits within the first 3 years. Lowering glucose levels during early diabetes may be more critical than reducing visit-to-visit HbA1c variability.

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.

Background: We evaluated patients visiting a tertiary university hospital due to a diagnosis of diabetes with a goal of achieving blood glucose control and evaluated blood glucose persistence over 7 years according to the change in blood glucose evident at 3 months after the first visit. Methods: Patients treated from 2009 to 2013 were categorized into four groups according to the change in HbA1c levels during the first 3 months of follow-up (Best_group, ≥ 1.6% decrease; Better_group, 0.5–1.5% decrease; Neutral_group, maintained at −0.4% to +0.4%; Worse_group, ≥ 0.5% increase). Each patient’s blood glucose control status was then monitored for 7 years. The incidence of stroke and acute coronary syndrome during this period was confirmed. Results: Overall, 9,776 patients were included. HbA1c values were lower in the Best_group than in the other groups at all time points (all P < 0.001). The rate of reaching targets of < 6.5% or < 7.0% HbA1c decreased over time; the rate at which the estimated glomerular filtration rate decreased to < 30 or < 60 mL/min/1.73m 2 increased over time (all trends, P < 0.01). Conclusion Blood glucose control status in the first 3 months after initiating hospital care enabled estimation of the patient’s glycemic control status for the next 7 years. In cases with poor initial blood glucose control, a new or more active method of blood glucose control should be sought.

Background: Sarcopenia is a skeletal muscle disorder that involves the loss of muscle mass and function. Handgrip strength (HGS) is the most commonly used tool to assess muscle strength to diagnose sarcopenia. HGS is also associated with various diseases and health outcomes. Thus, we aimed this study to examine the HGS status in Korean adults and relevant factors of HGS. Methods: Data was obtained from the 7th Korea National Health and Nutrition Examination Survey (KNHANES), a population-based nationwide survey. The estimated mean value of HGS was calculated in each age group. The mean HGS in men and women aged over 40 was compared according to the household income level, lifestyle factors, and comorbidities. Results: A total of 16,708 participants were included in this study. The mean HGS showed a maximum value in the 30s for both men and women, and then tended to decrease with increasing age. When analyzed for people aged 40 or older, the mean HGS was significantly higher in the current or past smoker, drinker, and aerobic exercise groups in both men and women. The mean HGS was lower in the group with comorbidities such as hypertension, dyslipidemia, type 2 diabetes, and bone diseases. Conclusion Our study found that the mean HGS was significantly different between those with and without underlying chronic diseases. In groups with relevant comorbidities, close monitoring for the development of sarcopenia and taking preventive measures such as exercise and nutritional support may be recommended.

The importance of adopting healthy exercise routines has been repeatedly emphasized to individuals with diabetes mellitus (DM). However, knowledge about the risk of exercise-induced hypoglycemia is limited. Regular exercise reduces and delays the onset of DM-related complications particularly in individuals who already have DM. However, an excessive exercise can lead to hypoglycemia. Excessive exercise in the evening can cause hypoglycemia while sleeping. Furthermore, if individuals with DM want to have a greater amount of exercise, the exercise duration rather than intensity must be increased. In weight resistance exercises, it is beneficial to first increase the number of repetitions, followed by the number of sets and gradually the weight of resistance. When performing intermittent high-intensity training within a short time period, hypoglycemia may develop for an extended period after exercise. In addition to adjusting exercise regimens, the medication doses must be modified accordingly. Delaying exercise, adjusting the number of snacks consumed prior to exercise, reducing insulin dose before exercise, and injecting insulin into the abdomen rather than the limbs prevent exercise-induced hypoglycemia prior to a spontaneous exercise. Ultimately, with personal knowledge on how to prevent hypoglycemia, the effects of exercise can be maximized in individuals with DM, and a healthy lifestyle can prevent future complications.

Background: Sarcopenia is a skeletal muscle disorder that involves the loss of muscle mass and function. Handgrip strength (HGS) is the most commonly used tool to assess muscle strength to diagnose sarcopenia. HGS is also associated with various diseases and health outcomes. Thus, we aimed this study to examine the HGS status in Korean adults and relevant factors of HGS. Methods: Data was obtained from the 7th Korea National Health and Nutrition Examination Survey (KNHANES), a population-based nationwide survey. The estimated mean value of HGS was calculated in each age group. The mean HGS in men and women aged over 40 was compared according to the household income level, lifestyle factors, and comorbidities. Results: A total of 16,708 participants were included in this study. The mean HGS showed a maximum value in the 30s for both men and women, and then tended to decrease with increasing age. When analyzed for people aged 40 or older, the mean HGS was significantly higher in the current or past smoker, drinker, and aerobic exercise groups in both men and women. The mean HGS was lower in the group with comorbidities such as hypertension, dyslipidemia, type 2 diabetes, and bone diseases. Conclusion Our study found that the mean HGS was significantly different between those with and without underlying chronic diseases. In groups with relevant comorbidities, close monitoring for the development of sarcopenia and taking preventive measures such as exercise and nutritional support may be recommended.

The importance of adopting healthy exercise routines has been repeatedly emphasized to individuals with diabetes mellitus (DM). However, knowledge about the risk of exercise-induced hypoglycemia is limited. Regular exercise reduces and delays the onset of DM-related complications particularly in individuals who already have DM. However, an excessive exercise can lead to hypoglycemia. Excessive exercise in the evening can cause hypoglycemia while sleeping. Furthermore, if individuals with DM want to have a greater amount of exercise, the exercise duration rather than intensity must be increased. In weight resistance exercises, it is beneficial to first increase the number of repetitions, followed by the number of sets and gradually the weight of resistance. When performing intermittent high-intensity training within a short time period, hypoglycemia may develop for an extended period after exercise. In addition to adjusting exercise regimens, the medication doses must be modified accordingly. Delaying exercise, adjusting the number of snacks consumed prior to exercise, reducing insulin dose before exercise, and injecting insulin into the abdomen rather than the limbs prevent exercise-induced hypoglycemia prior to a spontaneous exercise. Ultimately, with personal knowledge on how to prevent hypoglycemia, the effects of exercise can be maximized in individuals with DM, and a healthy lifestyle can prevent future complications.