Search

Background. As the imbalance in organ demand and supply is getting worse,

After attaining a qualified medical capacity in organ transplantation, Korea has been struggling to increase the number of deceased organ transplants to reach self-sufficiency. As one of these efforts, Korea revised the organ transplantation law in 2010 by adding three articles the mandatory reporting based on the recommendation of the 3rd Global Consultation on Organ Transplantation of Madrid in 2010. Along with the new constitution, considerable efforts have been initiated to upgrade the deceased organ transplantation system while maintaining the virtues of fairness, justice, and transparency. The Korean Society of Transplantation played a critical role in revising the law as well as in establishing organizations such as the Korean Organ Donation Agency (KODA; 2009), the Vitallink (2009), and the Korean Organ Transplantation Registry (KOTRY; 2010). By the activities of these professional organizations, Korea could implement fundamental programs such as mandatory reporting and could develop various education programs for organ donation for students and the general population. As a result, the number of deceased donors increased from 1.08 p.m.p. (2000) to 9.23 p.m.p.(2020). Further efforts are needed to increase the number of organ donor cardholders and family consent rates by well-designed, target-specific education programs to overcome traditional negative cultural barriers toward organ donation. The community atmosphere of honoring and thanking donors and their families should be nurtured by national and regional activities of life-sharing weeks linked with organ donor memorial parks.

Background: Bedside insertion of peripherally inserted central catheters (PICCs) has higher rates of malposition than fluoroscopic-guided PICC placement. This study evaluated the success rate of bedside PICC placement, variations in tip location, and risk factors for malposition. Methods: This retrospective study included patients who underwent bedside PICC placement from January 2013 to September 2014 in a single institution. The procedure was conducted under ultrasound guidance or by a blind method. After PICC placement, tip location was determined by chest X-ray. Results: The overall venous access success rate with bedside PICC placement was 98.1% (1,302/ 1,327). There was no significant difference in the venous access success rate between ultrasound-guided placement (868/880, 98.6%) and a blind approach placement (434/447, 97.1%). Optimal tip position was achieved on the first attempt in 1,192 cases (91.6%). Repositioning was attempted in 65 patients; 60 PICCs were repositioned at the bedside, two PICCs were repositioned under fluoroscopic guidance, and three PICCs moved to the desired position without intervention. Final optimal tip position after repositioning was achieved in 1,229 (94.4%). In logistic regression analysis, five factors associated with tip malposition included female sex (Exp(B), 1.687; 95% confidence interval [CI], 1.180 to 2.412; P=0.004), older age (Exp(B), 1.026; 95% CI, 1.012 to 1.039; P

Background/Objective: The aim of this study was to evaluate the technical success rates, primary patency, and complications for TASC C and D aorto-iliac lesions treated by endovascular procedures. Additionally, the influence of the access site and the clinical outcomes were analyzed. Methods: Between 2008 and 2014, data from 39 patients with 45 chronic iliac artery stenosis and/or occlusion who were treated with endovascular treatment were retrospectively reviewed. Results: The procedure time was longer for TASC D lesions than for TASC C lesions (163 ± 82 min vs. 105 ± 34 min; p = 0.002), where there was the more common use of brachial and femoral approach simultaneously. There were two perioperative deaths associated with TASC D lesions caused by one iliac artery rupture and one postoperative hospital-acquired pneumonia. The total perioperative complication rate was higher in the TASC D lesions than in TASC C lesions [five (18.5%) vs. zero; p = 0.073]. The corresponding 2-year primary patency rates were 94.9% in TASC C lesions and 88.4% in TASC D lesions. The simultaneous brachial and femoral approach took the longest procedure time (226 ± 157 min). Conclusion: This study demonstrated that the outcomes of endovascular treatment for TASC C and D aorto-iliac lesions were acceptable, with better technical success in TASC C lesions than in TASC D lesions. Furthermore, the 2-year patency rate for both TASC C and TASC D lesions was acceptable. Additionally, brachial access was useful for complex anatomy, but the failure rate was high.

Background and objectives: Endovenous treatment is increasingly supplanting open surgery for the treatment of varicose veins. Among emerging endovenous techniques, radiofrequency ablation (RFA) with a ClosureFast catheter is popular in Korea. The objective of this study was to evaluate and compare the efficacy and patient-reported outcomes of RFA of varicose veins. Methods: This is a retrospective study of a prospectively registered database of patients who underwent RFA for varicose veins from 2012 to 2013 in St. Mary's Hospital in Seoul. Korea. Efficient ClosureFast RFA catheters (Medtronic, San Jose, CA, USA) were used. The techniques used for RFA of varicose veins were performed according to the manufacturer's recommendations. Duplex scans and venous clinical severity scores (VCSSs) were used to document treatment outcome and patient symptoms before and after the procedures. Treatment outcomes were estimated before the procedure and 3 months, 6 months, and 12 months after the procedure. Outcomes were analyzed by paired t test, chi-square test, or Fisher's exact test as well as by logistical regression. Results: A total of 117 patients were evaluated for 183 consecutive RFA procedures (183 limbs). The initial technical success was 97.3% (178/183). The estimated mean VCSS changed over time from 4.0 ± 1.67 at preprocedure to 0.6 ± 1.05, 0.5 ± 1.02, and 0.6 ± 1.14 at 3 months, 6 months, and 12 months after the procedure, respectively. The improved VCSS was maintained 1 year after the procedure (p

Adventitial cystic disease of the common femoral vein is a rare condition. We herein report the case of a 50-year-old woman who presented with painless swelling in her left lower leg that resembled deep vein thrombosis. She underwent femoral exploration and excision of the cystic wall. The presentation, investigation, treatment, and pathology of this condition are discussed with a literature review.

Whether the coexistence of anti-A/B antibody and donor specific anti-HLA antibody (HLA-DSA) has a synergistic impact on the development of acute antibody-mediated rejection (AAMR) in kidney transplant recipients (KTRs) is unclear. This study includes 92 KTRs who received a kidney from an ABO-incompatible (ABOi) donor or were presensitized to donor HLA (HLAs) and 292 controls (CONT). HLAs was defined as a crossmatch positivity or the presence of HLA-DSA. We compared the incidence of AAMR among ABOi (n = 58), ABOi+HLAs (n = 12), HLAs (n = 22), and CONT (n = 292) groups and evaluated the risk factors and antibody type (anti-A/B vs. HLA-DSA) responsible for AAMR. AAMR developed less frequently in ABOi and CONT than in the ABOi+HLAs or HLAs (P < 0.05 for all); however, there was no difference between the ABOi+HLAs and HLAs groups. AAMR developed more frequently with strong HLA-DSA at baseline; however, high baseline anti-A/B titer did not affect AAMR development. Strong baseline HLA-DSA was an independent predictor for AAMR, however the baseline anti-A/B titer was not. All four AAMR episodes in ABOi+HLAs were positive to HLA-DSA but not to anti-A/B. In conclusion, ABO incompatibility does not increase the risk for AAMR in HLAs KTRs.

The aim of this study is to investigate the usefulness of the GFR-estimating equations to predict renal function in kidney donors before and after transplantation. We compared the performance of 24-hour-urine-based creatinine clearance (24 hr urine-CrCl), the Cockcroft-Gault formula (eGFRCG), the Modification of Diet in Renal Disease equation (eGFRMDRD), and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) with technetium-diethylenetriaminepentaacetic acid ((99m)Tc-DTPA) clearance (mGFR) in 207 potential kidney donors and 108 uninephric donors. Before donation, eGFRCKD-EPI showed minimal bias and did not show a significant difference from mGFR (P = 0.65, respectively) while 24 hr urine-CrCl and eGFRMDRD significantly underestimated mGFR (P

Egg quality serves as an early indicator of successful hatching and larval quality, both important for continuous larval culture production. The current study aimed to demonstrate the comparative effect of a formulated extruded pellet (EP) against a raw fish-based moist pellet (MP) as broodstock diet of olive flounder (Paralichthys olivaceus) on the egg quality and level of growth-related factors during the embryonic development of fertilized eggs. The egg quality parameters such as spawned eggs volume, fertilization rate, egg diameter, oil globule diameter, oil globule volume, hatching rate, malformation rate, and survival activity index (SAI) were compared after feeding either EP or MP to broodstocks for 2 months. Besides, the study assessed the time to reach embryonic stages and the concentration of growth-related factors (growth hormone, insulin-like growth factor, and lipovitellin) at various developmental stages. The results showed that spawned eggs volume, fertilization rate, oil globule volume, and SAI were higher in the EP group compared to the MP group. In contrast, higher egg diameter, oil globule diameter, hatching rate, and lower malformation rate were observed in the MP group compared to the EP group. Nevertheless, no significant difference was observed in most parameters (p > 0.05). The proximate composition of fertilized eggs revealed significantly higher protein (including amino acids) and lipid contents in the MP group than in the EP group (p < 0.05). In contrast, the fatty acids EPA and DHA content was significantly higher in the EP group than in the MP group (p < 0.05). Comparison of the time to complete embryogenesis until hatching into larvae of fertilized eggs showed that there was a difference between diets with EP group faster than MP. The concentration of growth-related factors in various developmental stages was affected by experimental diets. The former two were higher in the EP group, while the latter was higher in the MP group. The findings of this study demonstrate the positive effects and suitability of an EP diet as a broodstock diet for olive flounder seed production. However, maintaining the consistency and quality of the diet’s constituents is likely crucial to sustaining these positive effects.

Background We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Methods Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate

ABSTRACT Aims The aim of this study was to better understand how the chemotherapy drug doxorubicin contributes to the development of β‐cell dysfunction and to explore its relationship with mitochondrial aldehyde dehydrogenase‐2 (ALDH2). Materials and Methods In order to investigate this hypothesis, doxorubicin was administered to INS‐1 cells, a rat insulinoma cell line, either with or without several target protein activators and inhibitors. ALDH2 activity was detected with a commercial kit and protein levels were determined with western blot. Mitochondrial ROS, membrane potential, and lipid ROS were determined by commercial fluorescent probes. The cell viability was measured by CCK‐assay. Results Exposure of INS‐1 cells to doxorubicin decreased active insulin signaling resulting in elevated ALDH2 degradation, compared with control cells by the induction of acid sphingomyelinase mediated ceramide induction. Further, ceramide induction potentiated doxorubicin induced mitochondrial dysfunction. Treatment with the ALDH2 agonist, ALDA1, blocked doxorubicin‐induced acid sphingomyelinase activation which significantly blocked ceramide induction and mitochondrial dysfunction mediated cell death. Treatment with the ALDH2 agonist, ALDA1, stimulated casein kinase‐2 (CK2) mediated insulin signaling activation. CK2 silencing neutralized the function of ALDH2 in the doxorubicin treated INS‐1 cells. Conclusions Mitochondrial ALDH2 activation could inhibit the progression of doxorubicin induced pancreatic β‐cell dysfunction by inhibiting the acid sphingomyelinase induction of ceramide, by regulating the activation of CK2 signaling. Our research lays the foundation of ALDH2 activation as a therapeutic target for the precise treatment of chemotherapy drug induced β‐cell dysfunction.

BackgroundCardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD).MethodWe enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR

Abstract Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin.

The continuous monitoring of the health status of patients is essential for the effective monitoring of disease progression and the management of symptoms. Recently, health monitoring using non-contact sensors has gained interest. Therefore, this study aimed to investigate the use of non-contact sensors for health monitoring in hospital settings and evaluate their potential clinical applications. A comprehensive literature search was conducted using PubMed to identify relevant studies published up to February 26, 2024. The search terms included “hospital,” “monitoring,” “sensor,” and “non-contact.” Studies that used non-contact sensors to monitor health status in hospital settings were included in this review. Of the 38 search results, five studies met the inclusion criteria. The non-contact sensors described in the studies were radar, infrared, and microwave sensors. These non-contact sensors were used to obtain vital signs, such as respiratory rate, heart rate, and body temperature, and were then compared with the results from conventional measurement methods (polysomnography, nursing records, and electrocardiography). In all the included studies, non-contact sensors demonstrated a performance similar to that of conventional health-related parameter measurement methods. Non-contact sensors are expected to be a promising solution for health monitoring in hospital settings.

According to the green growth and carbon-neutral policy in Korea, the installation of large-capacity ESSs is rapidly being increased, but a total number of 50 ESS fire cases have occurred since the end of 2023. ESSs are typically composed of series-parallel connections with numerous Li-ion batteries, and when the temperature of a deteriorated cell increases due to thermal, electrical, and mechanical stress, thermal runaway can occur due to additional heat generated by an internal chemical reaction. Here, an internal chemical reaction in a Li-ion battery results in the different characteristics on the decomposition reaction and heat release depending on the operation conditions in the ESS, such as the rising temperature rate, convective heat transfer coefficient, and C-rate of charging and discharging. Therefore, this paper presents mathematical equations and modeling of thermal runaway, composed of the heating device section, heat release section by chemical reaction, chemical reaction section at the SEI layer, chemical reaction section between the negative and positive electrodes and solvents, and chemical reaction section at the electrolyte by itself, based on MATLAB/SIMULINK (2022), which were validated by a thermal runaway test device. From the simulation and test results based on the proposed simulation modeling and test device according to the operation conditions in ESSs, it was found that the proposed modeling is an effective and reliable tool to evaluate the processing characteristics of thermal runaway because the occurrence time intervals and maximum temperatures had almost the same values in both the test device and simulation modeling. Accordingly, it was confirmed that the rising temperature rate and the convective heat transfer coefficient were more critical in the thermal runaway than the C-rate of charging and discharging.

Background To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P

Abstract Background Tuberculosis is an infectious disease influenced by social factors rather than a simple infectious disease. In this study, we investigated the relationship between tuberculosis rates and socioeconomic status. Methods This study was conducted using data of the 49,483 participants of the Korean National Health and Nutrition Examination Survey (KNHANES) VI–VIII (2013–2021). The relationships between tuberculosis rates and the quartiles of monthly household income and education level were examined using a multivariate logistic regression analysis. Results The KNHANES data revealed that the prevalence of tuberculosis as substantially related to monthly household income (odds ratio [OR], 6.0; 95% confidence interval [CI], 1.1–32.0 for lowest vs. highest incomes) and education level (OR, 3.8; 95% CI, 1.2–12.0 for 10–12 years vs. ≥13 years; OR, 4.1; 95% CI, 1.2–14.8 for ≤ 6 years vs. ≥13 years). Furthermore, current tuberculosis treatment was significantly related to monthly household income and education level. Conclusion There were substantial correlations between tuberculosis rates and socioeconomic status in South Korea.

Abstract In this study, the potential of Chlorella sorokiniana JD1-1 for biodiesel production was evaluated using domestic wastewater (DWW) as a diluent for locally-generated livestock wastewater (LWW). This strategy aimed to provide sustainable wastewater treatment, reduce environmental impacts, enhance cost-effectiveness, and promote biodiesel production. LWW was diluted with tap water and DWW at ratios of 75%, 50%, and 25% (v/v), and the effects on microalgal growth, nutrient removal efficiency, and lipid yield were evaluated. Although the maximum biomass concentration was observed in the artificial growth medium (BG-11) (1170 mg L−1), 75% dilution using tap water (610 mg L−1) and DWW (780 mg L−1) yielded results comparable to the exclusive use of DWW (820 mg L−1), suggesting a potential for substitution. Total nitrogen (TN) removal rates were consistently high under all conditions, particularly in samples with higher concentrations of LWW. Conversely, total phosphorus (TP) concentrations decreased under most conditions, although some displayed large increases. Further studies are necessary to optimize the nutrient balance while maintaining economic feasibility and maximizing biodiesel production.

Probiotics, prebiotics, and synbiotics are known to improve aquatic animals' growth and health conditions. In this study, we investigated the effect of Bacillus sp. KRF-7 (KRF-7), Bacillus sp. PM8313 (PM8313), β-glucooligosaccharide (BGO), and their synbiotics on the growth, digestive physiology, immunity, and gut microbiota of abalone, Haliotis discus hannai. The control diet (CON) was sprayed with 108 CFU/g KRF-7 (PRO1) or PM8313 (PRO2) as probiotics, 0.10% BGO (PRE) as prebiotic, and their combinations (SYN1: PRO1 + BGO; SYN2: PRO2+ BGO) as synbiotic treatments. These diets (triplicates) were given once daily to the abalone (initial body weight: 1.32 ± 0.05 g, initial shell length: 21. 69 ± 0.19 mm) for 12 weeks. The results showed that the PRE diet induced a significant 15% shell length and body weight increase against the CON (SLGR: 45.77% vs. 53.04%; WGR: 182.77% vs. 210.22%), the highest among dietary supplements (P < 0.05). The level of IGF and IGFBP in the cell-free hemolymph, protein expression of IGF signaling, and gene expression of myosin heavy chain in the adductor muscle increased significantly (P < 0.05) following dietary supplementation. Correspondingly, PRE-, PRO1-, and PRO2-fed abalone had the highest trypsin, lipase, and amylase secretion in the hepatopancreas (P < 0.05) and increased histomorphometry (stomach epithelial thickness and intestinal villi height) (P < 0.05). Regarding antioxidative capacity and immunity, the hepatopancreatic expression of SOD, CAT, IRAK-4, NF-Kb, TNF-α, and β-defensin were significantly upregulated in abalone fed with dietary additives compared to the CON (P < 0.05). In terms of gut microbiota profile, PRE-fed abalone had a significant reduction in microbial richness (P < 0.05). The phylum level was similarly occupied, while a diet-specific core microbiota at the genus level was apparent. The findings illustrated that BGO, KRF-7, and PM8313 can be used in abalone aquaculture as growth-promoting and immune-stimulating supplements.

A noncontact sensor field is an innovative device that can detect, measure, or monitor physical properties or conditions without direct physical contact with the subject or object under examination. These sensors use a variety of methods, including electromagnetic, optical, and acoustic technique, to collect information about the target without physical interaction. Noncontact sensors find wide-ranging applications in various fields such as manufacturing, robotics, automobiles, security, environmental monitoring, space industry, agriculture, and entertainment. In particular, they are used in the medical field, where they provide continuous monitoring of patient conditions and offer opportunities in rehabilitation medicine. This article introduces the potential of noncontact sensors in the field of rehabilitation medicine.

Background The preemptive visceral analgesic effect of regional nerve block has not been adequately investigated to date. We evaluated the preemptive visceral analgesic effect of thoracic paravertebral block (TPVB) in patients undergoing laparoscopic cholecystectomy (LC) in whom pre-incisional rectus sheath block (RSB) was used to minimize somatic surgical pain. Methods In this prospective, randomized, assessor-blind study, 70 patients scheduled for elective LC were randomly assigned to the pre-TPVB (n = 35) or the post-TPVB (n = 35) group. Both groups received pre-incisional RSB, and patients in the pre-TPVB group received TPVB before skin incision while those in the post-TPVB group received TPVB after skin closure. The primary outcome was the total rescue analgesic consumption (morphine equianalgesic dose) during the 24 h post-surgery. The secondary outcomes were the cumulative analgesic consumption and pain intensity for 24 h after surgery, and adverse events. Results Pre-TPVB significantly reduced total rescue analgesic consumption (estimated mean [95% CI]) during the 24 h after surgery than post-TPVB (16.9 [14.5, 19.3] vs. 25.3 [22.8, 27.7] mg, estimated difference: −8.3 [−11.8, −4.9], P < 0.001). The cumulative rescue analgesic consumption was significantly lower in the pre-TPVB group from 2–24 h after surgery (P < 0.001). The postoperative pain intensity was significantly lower in the pre-TPVB group as well at 0.5–6 h after surgery. There were no adverse events in both groups. Conclusions Pre-incisional TPVB conferred a significant preemptive visceral analgesic effect in patients undergoing LC, and significantly reduced the amount of postoperative opioid consumption.

Background: FAP radiopharmaceuticals show promise for cancer diagnosis; however, their limited tumor residency hinders treatment. This study compared two FAPi derivatives, DOTA.SA.FAPi and DOTAGA.(SA.FAPi)2, labeled with gallium-68 and lutetium-177, aiming to determine an optimum combination for creating theranostic pairs. Methods: The radiotracers were studied for lipophilicity, binding to human serum proteins, and binding to human cancer-associated fibroblasts (CAFs) in vitro, including saturation and internalization/externalization studies. PET/SPECT/CT and biodistribution studies were conducted in PC3 and U87MG xenografts for [68Ga]Ga-DOTA.SA.FAPi and [68Ga]Ga-DOTAGA.(SA.FAPi)2. [177Lu]Lu-DOTA.SA.FAPi and [177Lu]Lu-DOTAGA.(SA.FAPi)2, were evaluated in PC3 xenografts. Biodistribution studies of [68Ga]Ga-DOTA.SA.FAPi were performed in healthy male and female mice. Results: All radiotracers exhibited strong binding to FAP. Their internalization rate was fast while only [177Lu]Lu-DOTAGA.(SA.FAPi)2 was retained longer in CAFs. [68Ga]Ga-DOTAGA.(SA.FAPi)2 and [177Lu]Lu-DOTAGA.(SA.FAPi)2 displayed elevated lipophilicity and affinity for human serum proteins compared to [68Ga]Ga-DOTA.SA.FAPi and [177Lu]Lu-DOTA.SA.FAPi. In vivo studies revealed slower washout of [68Ga]Ga-DOTAGA.(SA.FAPi)2 within 3 h compared to [68Ga]Ga-DOTA.SA.FAPi. The tumor-to-tissue ratios of [68Ga]Ga-DOTAGA.(SA.FAPi)2 versus [68Ga]Ga-DOTA.SA.FAPi did not exhibit any significant differences. [177Lu]Lu-DOTAGA.(SA.FAPi)2 maintained a significant tumor uptake even after 96 h p.i. compared to [177Lu]Lu-DOTA.SA.FAPi. Conclusions: Dimeric compounds hold promise for therapy, while monomers are better suited for diagnostics. Finding the right combination is essential for effective disease management.

Progression of β-cell loss in diabetes mellitus is significantly influenced by persistent hyperglycemia. At the cellular level, a number of signaling cascades affect the expression of apoptotic genes, ultimately resulting in β-cell failure; these cascades have not been elucidated. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) plays a central role in the detoxification of reactive aldehydes generated from endogenous and exogenous sources and protects against mitochondrial deterioration in cells. Here we report that under diabetogenic conditions, ALDH2 is strongly inactivated in β-cells through CDK5-dependent glutathione antioxidant imbalance by glucose-6-phosphate dehydrogenase (G6PD) degradation. Intriguingly, CDK5 inhibition strengthens mitochondrial antioxidant defense through ALDH2 activation. Mitochondrial ALDH2 activation selectively preserves β-cells against high-glucose-induced dysfunction by activating AMPK and Hydrogen Sulfide (H2S) signaling. This is associated with the stabilization and enhancement of the activity of G6PD by SIRT2, a cytoplasmic NAD+-dependent deacetylase, and is thereby linked to an elevation in the GSH/GSSG ratio, which leads to the inhibition of mitochondrial dysfunction under high-glucose conditions. Furthermore, treatment with NaHS, an H2S donor, selectively preserves β-cell function by promoting ALDH2 activity, leading to the inhibition of lipid peroxidation by high-glucose concentrations. Collectively, our results provide the first direct evidence that ALDH2 activation enhances H2S-AMPK-G6PD signaling, leading to improved β-cell function and survival under high-glucose conditions via the glutathione redox balance.

ABSTRACTDespite decades of rigorous research into supercavitating flow, there is still a lack of in-depth knowledge on the properties of ventilated supercavitation with cavitators of varying angle of attack. To address this gap, this study aimed to investigate numerically the supercavity profile, internal pressure behavior, and gas leakage mechanism taking into account the effects of cavitator angle of attack. The study examined five different types of cavitator: 45°, 60°, 90°, 135° cone-shaped and disk-shaped cavitators, all with the same diameter, and evaluated them at seven attack angles (−15°, −10°, −5°, 0°, +5°, +10°, +15°). The results show that, although the maximum diameter of the supercavity remained mostly stable, changes in the cavitator’s angle of attack had a considerable effect on the length and deformation of the supercavity profile. The gas leakage mechanism typically exhibited twin-vortex and quad-vortex tubes. As the cavitator angle of attack increased, the height and distance of these tubes changed significantly, but the pressure distribution inside the cavity remained stable. The findings of this study provide useful information for minimizing supercavity deformation, which can reduce the planning effects resulting from surface–fluid interaction and ultimately enhance the stability and manoeuverability of supercavitating objects.

This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

Abstract This study analyzed the expression of growth‐related genes of olive flounder, Paralichthys olivaceus, fed a low‐fish meal (FM) diet to investigate the replacement of the FM diet in the field. The expression of growth hormone (GH)/insulin‐like growth factor (IGF) axis genes in the brain/pituitary/liver and plasma hormone concentrations were measured. A basal experimental diet was formulated using 63% FM and 12% soybean meal as the primary protein sources, and then two other diets were made by replacing 20% and 30% of the FM with soy protein concentrate, tankage meal, and poultry by‐products meal. Each diet was fed to duplicate groups of juvenile flounder (150 ± 3.0 g) twice a day. After 20 weeks, the plasma growth‐related hormone concentrations were similar between the control and FM20 groups. Moreover, GH/IGF axis gene mRNA expression in the brain/pituitary/liver was similar between the control and FM20 groups. Immunoblotting of muscle and liver showed the same pattern. This study showed the utility of replacing 20% of the FM diet and supports the possibility of field application.

Background To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. Methods This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. Results The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P

Objective This study aimed to evaluate the effect of early glycaemic variability (GV) on 28-day mortality in critically ill patients with pneumonia.Patients and methods This single-centre retrospective study included patients admitted to the intensive care unit (ICU) due to pneumonia between 2018 and 2019. A total of 282 patients (mean age, 68.6 years) with blood sugar test (BST) results measured more than three times within 48 h after hospitalization and haemoglobin A1c (HbA1c) levels recorded within 2 months were enrolled. Coefficient of variation (CV) was calculated using the BST values. The effects of GV on 28-day mortality and prolonged ICU stay (>14 days) were also assessed.Results The mean age was 60.6 years (male to female ratio, 2.5:1). The 28-day mortality rate was 31.6% (n = 89) and was not different according to the presence of diabetes (DM vs. non-DM) or HbA1c levels (≥7.5 vs. .05). However, the mortality rate was significantly higher in patients with high GV (CV ≥ 36%) than in those with low GV (CV < 36%; 37.5 vs. 25.4%, p = .028). The risk of mortality in patients with high GV was prominent in the subgroups with DM or low HbA1c levels. Among the surviving patients (n = 193), 44 remained in the ICU for more than 14 days. Compared to low GV, high GV was associated with a higher rate of prolonged ICU stay, although not statistically significant (27.8 vs. 18.5%, p = .171). After adjusting for the severity of illness and treatment strategy, CV was an independent risk factor for 28-day mortality (hazard ratio [HR], 1.01, p = .04) and prolonged ICU stay (odds ratio, 1.02; p = .04).Conclusions High GV within 48 h of ICU admission was associated with an increased 28-day mortality risk and prolonged ICU stay. Early phase GV should be carefully managed in critically ill patients with pneumonia.KEY MESSAGESThe presence of diabetes or HbA1c alone is insufficient to predict 28-day mortality and prolonged ICU stay in critically ill patients with pneumonia.High glycaemic variability (GV) within 48 h of ICU admission increases 28-day mortality and prolongs ICU stay, which is consistent after adjusting for severity of illness and treatment strategy.Patients with high GV, especially those with DM or low HbA1c levels (

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

Abstract Background The endocrine disruption of perfluorinated compounds is an emerging issue. We aimed to examine the association of serum perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) levels with incident diabetes and fasting serum glucose concentration. Methods This prospective cohort study was based on an urban-based cohort subpopulation from the Korean Genome and Epidemiology Study. Serum samples (600 µL) were received from 100 participants in the normoglycemic baseline survey (2004–2013), and concentrations of PFOA and PFOS were measured using mass spectrometry. The incidence of diabetes was tracked in the follow-up survey (2012–2016). Results The mean age was 56.4 years (men, 59%). The median serum PFOA and PFOS concentrations were 4.29 ng/mL and 9.44 ng/mL, respectively. PFOA and PFOS concentrations differed according to age, sex, and residential area. After 60 months, 23 patients had diabetes. Log-transformed PFOA (lnPFOA) and log-transformed PFOS (lnPFOS) were significantly higher in those who transitioned to diabetes than in those who did not (both p

Abstract In human colorectal cancer (CRC), TP53 is one of the most important driver genes. Immunohistochemistry (IHC) has been used most often to assess the variational status of TP53. Recently, next-generation sequencing (NGS) of the TP53 gene has increased. However, to our knowledge, a comparison between TP53 status evaluated by IHC and NGS has not been studied. Therefore, the primary aim of this study was to compare the clinical effect of TP53 status evaluated by IHC and NGS in patients with CRC. The secondary aim was to investigate the correlation between expression of p53 by IHC and variational status of TP53 by NGS. We performed immunohistochemical staining of p53 and sequencing of TP53 by NGS in 204 human samples of CRC. We then analyzed the correlation between variational status of TP53 and p53 expression, along with their prognostic impact in CRC patients. There was significant correlation between p53 expression and TP53 variation, TP53 variation and higher N stage, and positive p53 expression and higher N stage. Positive IHC expression of p53 was significantly associated with overall survival (OS) of CRC patients by univariate analysis and was revealed as an independent prognostic factor by multivariate analysis. Additionally, the nonsense/frameshift p53 expression pattern showed a significantly better prognosis than the wild type and missense p53 expression patterns. However, the variational status of TP53 was not significant in OS of CRC patients. These results suggest that IHC expression of p53 protein correlates with variation status of TP53 and expression of p53 protein rather than variation status of TP53 has more significant impact on the OS of CRC patients.

Neuroendocrine tumors (NETs) are slow-growing tumors that express high levels of somatostatin receptors (SSTRs). Recent studies have shown the superiority of radiolabeled SSTR antagonists in theranostics compared to agonists. In this prospective study, we compared the diagnostic efficacy between [68Ga]Ga-DOTANOC and [68Ga]Ga-DATA5m-LM4 in the detection of primary and metastatic lesions in patients with well differentiated gastroenteropancreatic (GEP) NETs. Histologically proven GEP-NET patients underwent [68Ga]Ga-DOTANOC & [68Ga]Ga-DATA5m-LM4 PET/CT scans, which were analyzed. The qualitative analysis involved the visual judgment of radiotracer uptake validated by the morphological findings using CT, which was considered as the reference standard. Quantitative comparisons were presented as the standardized uptake value (SUV) corrected for lean body mass: SULpeak, SULavg, and tumor-to-background ratios (TBR). In total, 490 lesions were confirmed via diagnostic CT. The lesion-based sensitivity of [68Ga]Ga-DATA5m-LM4 PET/CT was 94.28% (462/490) and 83.46% (409/490) for [68Ga]Ga-DOTANOC PET/CT (p < 0.0001). [68Ga]Ga-DATA5m-LM4 had statistical significance over [68Ga]Ga-DOTANOC in liver metastases [100% vs. 89.4%; p < 0.0001 (292 vs. 253 {283 lesions on CT})] and bone metastases [100% vs. 82.9%; p = 0.005 (45 vs. 34 {41 lesions on CT})]. Statistical significance was also noted for the TBR SULpeak of the primary and liver lesions. [68Ga]Ga-DATA5m-LM4 showed better sensitivity and a higher target-to-background ratio than [68Ga]Ga-DOTANOC PET/CT. [68Ga]Ga-DATA5m-LM4 PET/CT can be used to quantify the extent of skeletal and liver metastases for better planning of SSTR agonist- or antagonist-based therapy.

The majority of satellite galaxies around the Milky Way (MW) show disk-like distributions (the disk of satellites; DoS), which is a small-scale problem of the lambda cold dark matter cosmology. The conventional definition of the MW-like DoS is a satellite system with a minor-to-major axis ratio ( c / a ) lower than the MW’s c / a value of 0.181. Here, we question the validity of the c / a -based DoS rarity assessment and propose an alternative approach. How satellites are placed around a galaxy is dictated mainly by two factors: the distributions of the satellites’ orbital poles and their distances from the host. Based on this premise, we construct the “satellite distribution generator” code and generate 10 ^5 spatially and kinematically analogous systems (SKASs) sharing these two factors. The SKAS can disclose the intrinsic, underlying c / a probability distribution function (PDF), from which a present-day c / a value is fortuitously determined. We find that the c / a PDF of the MW DoS defined by 11 classical satellites is quite broad ( σ _c _/ _a ∼ 0.105), implying that a simple present-day c / a value, combined with its highly time-variable nature, cannot fully represent the degree of flatness. Moreover, based on the intrinsic c / a PDF, we reevaluate the rarity of the MW DoS by comparing it with Illustris TNG50-1 host–satellite systems and find that even with the new measure, the MW DoS remains rare (0.00%–3.40%). We show that the reason behind the rareness is that both orbital poles and distances of the 11 MW satellites are far more plane-friendly than those of simulated host–satellite systems, challenging the current structure and galaxy formation model.

Enhanced star formation (SF) with star-forming neighboring galaxies bolsters the hydrodynamical contributions during paired interactions. Although the relative spin orientation between interacting galaxies can influence this effect, it has not been comprehensively explored. In this study, utilizing a meticulously curated sample of nearby (0.02 < z < 0.06) spiral+spiral pairs and an isolated control sample from Sloan Digital Sky Survey Data Release 7, coupled with Galaxy Zoo 2, and an approach to estimate spin–spin alignment (SSA), we systematically compare the impact of relative orientation, $\cos \,\xi $ , on interaction-induced SF. We reveal that SSA plays a pivotal role along with the conventionally recognized parameters of projected separation and SF of neighboring galaxies. Our results show an increase in SF augmentation as configurations transition from perpendicular ( $\cos \,\xi \sim 0$ ) to well aligned ( $\cos \,\xi \gt 0.7$ ). This enhancement is especially pronounced when neighboring galaxies have higher SF, suggesting that hydrodynamical processes drive the effects of relative orientation. The heightened hydrodynamical friction, attributed to increased ram pressure and the propensity for prograde orbits in well-aligned pairs, is consistent with our findings.

A numerical detection of the τ -driven transition of galaxy spins is presented, where τ is the degree of misalignment between the initial tidal field and protogalaxy inertia tensors. Analyzing the data from the IllustrisTNG300-1 simulations, we first measure the values of τ at the protogalactic sites found by tracing the constituents of the galactic halos in the mass range of $10.5\leqslant \mathrm{log}\left[{M}_{h}/({h}^{-1}{M}_{\odot })\right]\leqslant 13$ back to the initial stage, z _i = 127. The probability density functions of τ are shown to be well modeled by the Γ-distributions, whose shape and scale parameters turn out to have universal values on a certain critical scale. Then, we investigate how the strength and tendency of the galaxy spin alignments with the principal axes of the local tidal fields depend on the initial condition, τ . It is found that on a scale lower than the critical one, the galaxy spin transition occurs at two different thresholds from the major to intermediate and from the intermediate to minor principal axes of the local tidal fields, respectively. Noting that the τ -dependent spin transition supersedes the strength of the previously found mass-dependent, morphology-dependent, and radius-dependent counterparts, we suggest that τ should be the key driver of all types of galaxy spin transitions and that the present galaxy spins are indeed excellent fossil records of their origin.

Extending geodetic and astrometric Very Long Baseline Interferometry (VLBI) observations from traditional centimeter wavebands to millimeter wavebands offers numerous scientific potentials and benefits. However, it was considered quite challenging due to various factors, including the increased effects of atmospheric opacity and turbulence at millimeter wavelengths. Here, we present the results of the first geodetic-mode VLBI experiment, simultaneously observing 82 sources at 22/43/88/132 GHz ( K / Q / W / D bands) using the Korean VLBI Network (KVN). We introduced the frequency phase transfer (FPT) method to geodetic VLBI analysis, an approach for calibrating atmospheric phase fluctuations at higher frequencies by transferring phase solutions from lower frequencies. With a 2 minute scan, FPT improved the signal-to-noise ratio of most fringes, some by over 100%, thereby enhancing the detection rate of weak sources at millimeter wavebands. Additionally, FPT reduced systematic errors in group delay and delay rate, with the weighted root mean squares (WRMS) of the postfitting residuals decreasing from 25.0 to 20.5 ps at the W band and from 39.3 to 27.6 ps at the D band. There were no notable differences observed in calibrating atmospheric phase fluctuations at the K band (WRMS = 12.4 ps) and Q band (WRMS = 11.8 ps). This experiment demonstrated that the millimeter waveband can be used for geodetic and astrometric applications with high precision.

Ultrasonography (US) is a useful diagnostic method that can be easily applied to identify the cause of metatarsalgia. The superficial location of structures in the foot, dynamic capability of US, and the ability to perform direct real-time evaluations of the pain site are also strong advantages of US as a modality for examining the foot. Moreover, knowing the possible pain sources to investigate when a patient has a specific site of pain will enhance the diagnostic quality of US, and will help radiologists to perform US efficiently and effectively. The purpose of this article is to review the common etiologies of metatarsalgia including Morton’s neuroma, plantar plate injury, synovitis, tenosynovitis, bursitis, and metatarsal fractures, and to discuss their US features.

Transitional cell carcinoma (TCC) is the most common malignant tumor of the canine urinary tract. In this case study, a dog with metastatic urethral TCC was treated with sorafenib. The tumor expression levels of receptor tyrosine kinase genes, including VEGFR-1, VEGFR-2, PDGFR-α, PDGFR-β, ALK, EGFR, ErbB2, and B-RAF, were analyzed. VEGFR was overexpressed in tumor tissues compared to the normal tissues. Considering the high frequency of B-RAF mutation in canine urological tumors, the B-RAF gene was examined, and the B-RAF V595E mutation was detected in the tumor tissue. Therefore, the antitumor effect of sorafenib, a multi-tyrosine kinase inhibitor, on unresectable metastatic urethral TCC characterized by B-RAF V595E was evaluated and circulating cell-free tumor DNA (ctDNA) was assessed for monitoring the treatment response. After the initiation of oral sorafenib therapy (4 mg/kg/day escalated to 10 mg/kg/day), the dysuria was alleviated gradually, and the patient remained stable for 3 months. During that treatment period, the patient showed various levels of changes associated with B-RAF V595E mutation in ctDNA as evident from longitudinal plasma samples after initiation of sorafenib therapy. The findings of this study suggest that ctDNA may serve as a useful non-invasive tool for monitoring the treatment response to anticancer drugs.

In linear theory, the galaxy angular momentum vectors that originate from initial tidal interactions with surrounding matter distribution intrinsically develop perpendicular alignments with the directions of maximum matter compression, regardless of galaxy mass. In simulations, however, galaxy spins exhibit parallel alignments in the mass range lower than a certain threshold, which depends on redshift, web type, and background cosmology. We show that the observed three-dimensional spins of the spiral galaxies located on the void surfaces from the Sloan Digital Sky Survey indeed transit from perpendicular to parallel alignments with the directions toward the nearest void centers at the threshold zone, $9.51\leqslant \mathrm{log}[{M}_{\mathrm{th},\star }/(\,{h}^{-1}\,{M}_{\odot })]\leqslant 10.03$ . This study presents the first direct observational evidence for the occurrence of mass-dependent spin transition of real galaxies with respect to non-filamentary structures of the cosmic web, opening a way to constrain the initial conditions of the early universe by measuring the spin transition threshold.

Background: FAM83H has been implicated in cancer progression, and PD1 is an important target for anti-cancer immune checkpoint therapy. Recent studies suggest an association between FAM83H expression and immune infiltration. However, studies on the roles of FAM83H and its relationship with PD1 in breast carcinomas have been limited. Methods: Immunohistochemical expression of FAM83H and PD1 and their prognostic significance were evaluated in 198 breast carcinomas. Results: The expression of FAM83H in cancer cells was significantly associated with the presence of PD1-positive lymphoid cells within breast carcinoma tissue. Individual and co-expression patterns of nuclear FAM83H and PD1 were significantly associated with shorter survival of breast carcinomas in univariate analysis. In multivariate analysis, the expression of nuclear FAM83H (overall survival, p < 0.001; relapse-free survival, p = 0.003), PD1 (overall survival, p < 0.001; relapse-free survival, p = 0.003), and co-expression patterns of nuclear FAM83H and PD1 (overall survival, p < 0.001; relapse-free survival, p < 0.001) were the independent indicators of overall survival and relapse-free survival of breast carcinoma patients. Conclusions: This study suggests a close association between FAM83H expression and the infiltration of PD1-positive lymphoid cells in breast carcinomas and their expression as the prognostic indicators for breast carcinoma patients, and further studies are needed to clarify this relationship.

Abstract Background FAM83H was originally reported to be essential for dental enamel formation. However, FAM83H has recently been implicated in tumorigenesis and tumor progression. Analysis of a publicly available gene expression database revealed a significant correlation between FAM83H and Nectin1 mRNA expression and bladder urothelial carcinoma (BUC). Therefore, we investigated the association between FAM83H and Nectin1 expression levels and the survival and recurrence of BUC in BUC patients using a tissue microarray. Methods We performed immunohistochemical staining of FAM83H and Nectin1 in 165 human BUC tissue sections, and analyzed the prognostic significance of FAM83H and Nectin1 expression. Results Both FAM83H and Nectin1 were mainly expressed in the cytoplasm, and their expression was significantly associated. FAM83H expression was significantly correlated with higher histologic grade, higher T stage, higher TNM stage, and recurrence. Nectin1 expression was significantly associated with higher histologic grade and recurrence. Univariate analysis showed FAM83H expression and Nectin1 expression were significantly associated with worse overall survival (OS) and shorter relapse-free survival (RFS) of BUC patients. In multivariate analysis, levels of FAM83H and Nectin1 were independent indicators of shorter survival of BUC patients. Conclusions Our results suggest that FAM83H and Nectin1 are important in the progression of BUC, and that expression patterns of these two proteins can be used as prognostic indicators of survival in BUC patients.

N00N states are a key resource in quantum metrology, but the use of their multi-mode extension for multiparameter estimation has been elusive so far. Here, the authors use multi-mode N00N states - with N=2 photons in 4 modes - for multiple-phase estimation saturating the quantum Cramer-Rao bound.

Background Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9±14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, −1.1%±1.2%; P