Background: The use of immune checkpoint inhibitors (ICIs) for advanced cancer is increasing, particularly in combination withchemotherapy. However, previous studies have focused on immune-related adverse events (irAEs) in specific organs, with limited re-search on combination therapy. Objective: We aimed to detect signals of adverse drug reaction (ADR) in both ICIs plus chemotherapy and ICIs alone compared to chemotherapy. Methods: We investigated individual case safety reports (ICSRs) between 2014 and 2022using Korea Institute of Drug Safety and Risk Management Korean Adverse Event Reporting System database (KIDS KAERS DB(2304A0076)). We defined adverse events (AEs) and drugs using MedDRA and the national drug code directory provided by the Min-istry of Food and Drug Safety. To detect signals, we performed disproportionality analysis using indices of reporting odds ratio (ROR) and information component (IC). Results: We identified 206,959 ICSRs in the KIDS KAERS DB, of which 5,154 contained ICIs and 201,805 were for chemotherapy. Compared to chemotherapy, radiation pneumonitis (ROR, 2313.6; IC, 5.4), hyperthyroidism (ROR, 53.4; IC, 4.2), and eczema (ROR,18.3; IC, 3.4) were detected as signals for ICIs. For ICIs with chemotherapy, additional signals including heart failure (ROR 9.65; IC 2.45), proteinuria (ROR 28.67; IC 4.16), and urinary tract infections (ROR 3.46; IC 1.03) were detected. Conclusion The study highlights an essential signal of ADRs associated with ICIs, both alone and in combination therapy, with conditions such as hyperthyroidism, hypothyroidism, and pneumonitis. These AEs should be monitored in clinical settings.

Background: Stem cell-based therapy is one of the tools for acute kidney injury (AKI) treatment. Tonsil tissue is a promising alternative source for the high-yield isolation of mesenchymal stem cells (MSCs). This study was undertaken to investigate the effects of tonsil-derived MSCs (T-MSCs) in animal model of AKI induced by gentamicin (GM). Methods: Twenty Sprague-Dawley rats were divided into four groups: Control, GM (70 mg/kg/day, intraperitoneal injection for 10 days), GM + T-MSCs (1 × 107 cells, intravenous injection at 1 day after the last vehicle/GM), and T-MSCs. Renal function, apoptosis, and markers of endoplasmic reticulum stress were measured on day 16 after the first vehicle/GM. Oxidative stress was assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the expression of glutathione peroxidase (GPx) and catalase. Effects of T-MSCs on GM-induced apoptosis and oxidative stress in NRK cells were also evaluated using a co-culture technique of NRK cells and T-MSC. Results: In the GM + T-MSCs group, blood urea nitrogen, creatinine, and tubular damage score were lower compared to the GM group. T-MSCs injection decreased apoptotic cells and the expression of Bax, cytochrome c, and cleaved caspase and increased Bcl-2. T-MSC injection decreased urinary 8-OHdG and increased expression of GPx and catalase in the kidneys. Anti-human nuclei and PKH26 staining demonstrated the localization of T-MSCs in the tubules of renal cortex. In-vitro study revealed that T-MSCs or T-MSC-conditioned media ameliorated GM-induced nicotinamide adenine dinucleotide phosphate oxidase-1 expression, hydrogen peroxide generation, and apoptosis of NRK cells. Conclusion Our study demonstrated that T-MSCs ameliorated GM-induced AKI by directly incorporating into the damaged renal tubules and exerting antiapoptotic and antioxidative effects.

The accuracy and convenience of continuous glucose monitoring (CGM), which efficiently evaluates glycemic variability and hypoglycemia, are improving. There are two types of CGM: professional CGM and personal CGM. Personal CGM is subdivided into real-time CGM (rt-CGM) and intermittently scanned CGM (isCGM). CGM is being emphasized in both domestic and foreign diabetes management guidelines. Regardless of age or type of diabetes, CGM is useful for diabetic patients undergoing multiple insulin injection therapy or using an insulin pump. rt-CGM is recommended for all adults with type 1 diabetes (T1D), and can also be used in type 2 diabetes (T2D) treatments using multiple insulin injections. In some cases, short-term or intermittent use of CGM may be helpful for patients with T2D who use insulin therapy other than multiple insulin injections and/or oral hypoglycemic agents. CGM can help to achieve A1C targets in diabetes patients during pregnancy. CGM is a safe and cost-effective alternative to self-monitoring blood glucose in T1D and some T2D patients. CGM used in diabetes management works optimally with proper education, training, and follow up. To achieve the activation of CGM and its associated benefits, it is necessary to secure sufficient repetitive training and time for data analysis, management, and education. Various supports such as compensation, insurance coverage expansion, and reimbursement are required to increase the effectiveness of CGM while considering the scale of benefit recipients, policy priorities, and financial requirements.

BACKGROUND: The mesenchymal-epithelial transition factor (MET) receptor can be overexpressed in solid tumors, including small cell lung cancer (SCLC). However, the molecular mechanism regulating MET stability and turnover in SCLC remains undefined. One potential mechanism of MET regulation involves the C-terminus of Hsp70-interacting protein (CHIP), which targets heat shock protein 90-interacting proteins for ubiquitination and proteasomal degradation. In the present study, we investigated the functional effects of CHIP expression on MET regulation and the control of SCLC cell apoptosis and invasion. METHODS: To evaluate the expression of CHIP and c-Met, which is a protein that in humans is encoded by the MET gene (the MET proto-oncogene), we examined the expression pattern of c-Met and CHIP in SCLC cell lines by western blotting. To investigate whether CHIP overexpression reduced cell proliferation and invasive activity in SCLC cell lines, we transfected cells with CHIP and performed a cell viability assay and cellular apoptosis assays. RESULTS: We found an inverse relationship between the expression of CHIP and MET in SCLC cell lines (n=5). CHIP destabilized the endogenous MET receptor in SCLC cell lines, indicating an essential role for CHIP in the regulation of MET degradation. In addition, CHIP inhibited MET-dependent pathways, and invasion, cell growth, and apoptosis were reduced by CHIP overexpression in SCLC cell lines. CONCLUSION: CHIP is capable of regulating SCLC cell apoptosis and invasion by inhibiting MET-mediated cytoskeletal and cell survival pathways in NCI-H69 cells. CHIP suppresses MET-dependent signaling, and regulates MET-mediated SCLC motility.
Apoptosis ; Blotting, Western ; Cell Line ; Cell Proliferation ; Cell Survival ; Heat-Shock Proteins ; Humans ; Lung Neoplasms ; Small Cell Lung Carcinoma* ; Ubiquitin ; Ubiquitination

PURPOSE: To determine the window of time during which osteoporosis affects the management of spinal surgery and the mechanism of bone metabolism changes in males with osteoporosis by examining changes in bone metabolism in young castrated male rats. MATERIALS AND METHODS: A total of 30 Sprague-Dawley rats were randomly allocated into two study groups. Group 1 (control) received a sham surgery and Group 2 received bilateral orchiectomy to change bone mineral density (BMD). Serum osteocalcin, alkaline phosphatase (ALP), and collagen type 1 cross-linked C-telopeptide (CTX) were analyzed at postoperative date (POD) 8, 10, and 12 weeks. BMDs were measured using micro computed tomography scans. RESULTS: Femoral and lumbar BMDs were decreased in the orchiectomy groups. BMDs in the sham and orchiectomy groups showed statistically differences at POD 8, 10, and 12 weeks for the femur (p=0.032, 0.008, 0.008) and lumbar spine (p=0.151, 0.008, 0.008, respectively). Serum osteocalcin, ALP, and CTX decreased gradually; however, N-terminal type 1 procollagen (P1NP) showed a slight increase yet no significant change. CONCLUSION: In young castrated male rats, a significant decrease in BMD was observed after orchiectomy due to the mixture of two detrimental factors. Young castrated male rats did not reach peak BMD. Increased bone turnover causes bone resorption to exceed bone formation. This study may contribute to the creation of a valuable model for studies of male osteoporosis and the spinal surgery field.
Alkaline Phosphatase ; Animals ; Bone Density ; Bone Remodeling ; Bone Resorption ; Collagen ; Femur ; Humans ; Male* ; Metabolism* ; Orchiectomy ; Osteocalcin ; Osteogenesis ; Osteoporosis ; Procollagen ; Rats* ; Rats, Sprague-Dawley ; Spine

This study was conducted to develop job standards for clinical dietitian administering clinical nutrition therapy to diabetic patients in hospitals. Based on DACUM (Developing A Curriculum) analysis of 17 members including clinical dietitians, professors majoring in clinical nutrition and researchers, information on duties, tasks and task elements of clinical dietitians for diabetes care were derived and applied to diabetes mellitus-specific clinical nutrition care in hospitals for evaluation. The final developed job standards for clinical dietitians for diabetes care included four duties, 19 tasks and 56 task elements. The duties consisted of nutrition assessment, nutrition diagnosis, nutrition intervention, and nutrition monitoring . evaluation. For application of diabetes mellitus-specific job standards in clinical nutrition care, 108 work activities were developed and classified into 90 basic and 18 recommended types. Performance rates of standardized jobs were 80.2% at nutrition assessment, 99.6% at nutrition diagnosis, 78.5% at nutrition intervention, and 32.9% at nutrition monitoring . evaluation. These results can be applied as guidelines to implement jobs for diabetes mellitus-specific clinical nutrition services in clinical settings. In addition, they would be useful for education standards in educational institutions for education and training of clinical dietitian.
Diabetes Mellitus ; Diagnosis ; Education ; Humans ; Job Description ; Nutrition Assessment ; Nutrition Therapy* ; Nutritionists*

OBJECTIVE: To investigate a suitable animal model for studies of male osteoporosis. Osteoporosis has a particularly high incidence in postmenopausal women, resulting in a substantial amount of research with respect to this disease in women. However, research on osteoporosis in men is still lacking. METHODS: Twenty 10-week-old male Sprague Dawley rats were used in this study, including 4 rats used to establish a baseline bone mineral density (BMD). The other 16 rats were divided into two groups: a sham surgery group (n=8), which underwent a sham operation, and an orchiectomized rat group (OCX) (n=8), which underwent bilateral OCX at 10 weeks of age. Bone mineral density was measured in 4 rats from both the sham surgery group and the OCX group 8 weeks after the surgery, while BMD in the remainder of the rats was measured 10 weeks post-surgery. RESULTS: Femoral BMD at 8 weeks post-surgery was found to be significantly lower in the OCX group compared to the sham group; a finding that was also similar 10 weeks post-surgery. CONCLUSION: 8 weeks after undergoing orchiectomy performed via a scrotal, white rats are a suitable model for studies of male osteoporosis.
Animals ; Bone Density* ; Female ; Femur ; Humans ; Incidence ; Male ; Models, Animal ; Multiple Endocrine Neoplasia Type 1 ; Orchiectomy* ; Osteoporosis ; Rats* ; Rats, Sprague-Dawley

BACKGROUND: Brother of the regulator of imprinted sites (BORIS) is a putative new oncogene that is classified as a cancer germline gene; however, its role in the development of cancer is unclear. This study investigated the expression of BORIS in lung cancer and its clinical implications. METHODS: The expression of BORIS messenger ribonucleic acid (mRNA) in the sputum of 100 patients with lung cancer (50 with squamous cell carcinoma, 36 with adenocarcinoma, and 14 with small-cell carcinoma) was evaluated by reverse transcription polymerase chain reaction. RESULTS: The overall expression rate of BORIS in patients with lung cancer was 36.0%: 19 of 50 squamous cell carcinomas (38.0%), 13 of 36 adenocarcinomas (36.1%), and 4 of 14 (28.6%) small-cell carcinomas. There was no significant difference in the BORIS expression according to age, gender, or histologic type. However, the mRNA expression of BORIS was significantly related to the pathologic cancer stage (p=0.004) and lymph node metastasis (p=0.001). The expression of the melanoma antigen gene family A1-6 was not associated with the expression of BORIS. CONCLUSION: Our results suggest that the expression of BORIS might be a negative prognostic factor in lung cancers and implicate BORIS as a molecular target for immunotherapy.
Adenocarcinoma ; Carcinoma, Squamous Cell ; Humans ; Immunotherapy ; Lung Neoplasms* ; Lymph Nodes ; Melanoma ; Neoplasm Metastasis ; Oncogenes ; Polymerase Chain Reaction ; Reverse Transcription ; RNA ; RNA, Messenger ; Siblings* ; Sputum*

Saccular aneurysm of the external jugular vein presenting as a neck mass is very rare. We report the surgical treatment of an external jugular venous aneurysm in a 48-year-old female patient due to the cosmetic problem of neck engorgement, concomitant with thyroidectomy for cancer.
Aneurysm* ; Female ; Humans ; Jugular Veins* ; Middle Aged ; Neck ; Thyroidectomy ; Vascular Diseases

BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.
Administration, Oral* ; Humans ; Male ; Pharmacokinetics ; Physical Examination ; Plasma