Search

Background Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator-activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

BackgroundUteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D.MethodsWe performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks.ResultsThis study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-β and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment.ConclusionsUteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D.

Background Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM. Methods A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment. Results The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups. Conclusion Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Background: Keloids are a common fibrotic disease of the skin, with the pathological hallmark of excessive extracellular matrix synthesis due to abnormal fibroblast activity. Since keloids clinically arise in areas of high mechanical tension, the mechanotransductory pathway may be attributed to its pathogenesis. We aimed to establish a preclinical platform to elucidate the underlying mechanism of keloid development and its clinical persistence. Methods: We fabricated a mechanically stretchable polydimethylsiloxane cell culture platform; with its mimicry of the in vivo cyclic stretch of skeletal muscles, cells showed higher proliferation compared with conventional modalities. Results: In response to mechanical strain, TGF-β and type 1 collagen showed significant increases, suggesting possible TGF-β/Smad pathway activation via mechanical stimulation. Protein candidates selected by proteomic analysis were evaluated, indicating that key molecules involved in cell signaling and oxidative stress were significantly altered. Additionally, the cytoskeletal network of keloid fibroblasts showed increased expression of its components after periodic mechanical stimulation. Conclusions: Herein, we demonstrated and validated the existing body of knowledge regarding profibrotic mechanotransduction signaling pathways in keloid fibroblasts. Cyclic stretch, as a driving force, could help to decipher the tension-mediated biomechanical processes, leading to the development of optimized therapeutic targets.

ObjectivesChronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers.MethodsIn this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication.ResultsThe fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (−4.5 ± 14.1% and −1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339).ConclusionsWe observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Summary: Severe burns induce a chronic hypermetabolic state that persists well past wound closure, indicating that additional internal mechanisms must be involved. Adipose tissue is suggested to be a central regulator in perpetuating hypermetabolism, although this has not been directly tested. Here, we show that thermogenic adipose tissues are activated in parallel to increases in hypermetabolism independent of cold stress. Using an adipose tissue transplantation model, we discover that burn-derived subcutaneous white adipose tissue alone is sufficient to invoke a hypermetabolic response in a healthy recipient mouse. Concomitantly, transplantation of healthy adipose tissue alleviates metabolic dysfunction in a burn recipient. We further show that the nicotinic acetylcholine receptor signaling pathway may mediate an immune-adipose crosstalk to regulate adipose tissue remodeling post-injury. Targeting this pathway could lead to innovative therapeutic interventions to counteract hypermetabolic pathologies.

BackgroundAdherence to oral anticoagulant therapy is essential to prevent ischemic stroke in patients with atrial fibrillation (AF). ObjectiveThis study aimed to evaluate whether smartphone app–based interventions improve medication adherence in patients with AF. MethodsThis open-label, multicenter randomized controlled trial (ADHERE-App [Self-Awareness of Drug Adherence to Edoxaban Using an Automatic App Feedback System] study) enrolled patients with AF treated with edoxaban for stroke prevention. They were randomly assigned to app-conditioned feedback (intervention; n=248) and conventional treatment (control; n=250) groups. The intervention group received daily alerts via a smartphone app to take edoxaban and measure blood pressure and heart rate at specific times. The control group received only standard, guideline-recommended care. The primary end point was edoxaban adherence, measured by pill count at 3 or 6 months. Medication adherence and the proportion of adequate medication adherence, which was defined as ≥95% of continuous medication adherence, were evaluated. ResultsMedication adherence at 3 or 6 months was not significantly different between the intervention and control groups (median 98%, IQR 95%-100% vs median 98%, IQR 91%-100% at 3 months, P=.06; median 98%, IQR 94.5%-100% vs median 97.5%, IQR 92.8%-100% at 6 months, P=.15). However, the proportion of adequate medication adherence (≥95%) was significantly higher in the intervention group at both time points (76.8% vs 64.7% at 3 months, P=.01; 73.9% vs 61% at 6 months, P=.007). Among patients aged >65 years, the intervention group showed a higher medication adherence value and a higher proportion of adequate medication adherence (≥95%) at 6 months. ConclusionsThere was no difference in edoxaban adherence between the groups. However, the proportion of adequate medication adherence was higher in the intervention group, and the benefit of the smartphone app–based intervention on medication adherence was more pronounced among older patients than among younger patients. Given the low adherence to oral anticoagulants, especially among older adults, using a smartphone app may potentially improve medication adherence. Trial RegistrationInternational Clinical Trials Registry Platform KCT0004754; https://cris.nih.go.kr/cris/search/detailSearch.do?seq=28496&search_page=L International Registered Report Identifier (IRRID)RR2-10.1136/bmjopen-2021-048777

Purpose: The purposes of this study were to develop a prediction model for pressure injury using a machine learning algorithm and to integrate it into clinical practice. Methods: This was a retrospective study of tertiary hospitals in Seoul, Korea. It analyzed patients in 12 departments where many pressure injuries occurred, including 8 general wards and 4 intensive care units from January 2018 to May 2022. In total, 182 variables were included in the model development. A pressure injury prediction model was developed using the gradient boosting algorithm, logistic regression, and decision tree methods, and it was compared to the Braden scale. Results: Among the 1,389,660 general ward cases, there were 451 cases of pressure injuries, and among 139,897 intensive care unit cases, there were 297 cases of pressure injuries. Among the tested prediction models, the gradient boosting algorithm showed the highest predictive performance. The area under the receiver operating characteristic curve of the gradient boosting algorithm's pressure injury prediction model in the general ward and intensive care unit was 0.86 (95% confidence interval, 0.83~0.89) and 0.83 (95% confidence interval, 0.79~0.87), respectively. This model was integrated into the electronic health record system to show each patient's probability for pressure injury occurrence, and the risk factors calculated every hour. Conclusion: The prediction model developed using the gradient boosting algorithm exhibited higher performance than the Braden scale. A clinical decision support system that automatically assesses pressure injury risk allows nurses to focus on patients at high risk for pressure injuries without increasing their workload. [ABSTRACT FROM AUTHOR]

Purpose: Photobiomodulation (PBM), encompassing low-energy laser treatment and light-emitting diode (LED) phototherapy, has demonstrated positive impacts on skin rejuvenation and wound healing. Organic light-emitting diodes (OLEDs) present a promising advancement as wearable light sources for PBM. However, the biological and biochemical substantiation of their skin rejuvenation and wound healing effects remains limited. This study aimed to ascertain the safety and efficacy of OLEDs as a next-generation PBM modality through comprehensive in vitro and in vivo investigations. Materials and Methods: Cell viability assays and human ex vivo skin analyses were performed after exposure to OLED and LED irradiation to examine their safety. Subsequent evaluations examined expression levels and wound healing effects in human dermal fibroblasts (HDFs) using quantitative reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, and wound healing assays post-irradiation. Additionally, an in vivo study was conducted using a ultra violet (UV)-irradiated animal skin model to explore the impact of OLED exposure on dermal collagen density and wrinkles, employing skin replica and tissue staining techniques. Results: OLED irradiation had no significant morphological effects on human skin tissue, but caused a considerably higher expression of collagen than the control and LED-treated groups. Moreover, OLED irradiation reduced the expression levels of matrix metalloproteinases (MMPs) more effectively than did LED on HDFs. OLED irradiation group in HDFs had significantly higher expression levels of growth factors compared to the control group, but similar to those in the LED irradiation group. In addition, OLED irradiation on photo-aged animal skin model resulted in increased collagen fiber density in the dermis while reducing ultra violet radiation-mediated skin wrinkles and roughness, as shown in the skin replica. Conclusion: This study established comparable effectiveness between OLED and LED irradiation in upregulating collagen and growth factor expression levels while downregulating MMP levels in vitro. In the UV-irradiated animal skin model, OLED exposure post UV radiation correlated with reduced skin wrinkles and augmented dermal collagen density. Accelerated wound recovery and demonstrated safety further underscore OLEDs' potential as a future PBM modality alongside LEDs, offering promise in the realms of skin rejuvenation and wound healing. [ABSTRACT FROM AUTHOR]

The main mechanism of Takotsubo cardiomyopathy (TCM) is catecholamine-induced acute myocardial stunning. Pheochromocytoma, a catecholamine-secreting tumor, can cause several cardiovascular complications, including hypertensive crisis, myocardial infarction, toxic myocarditis, and TCM. A 29-year-old woman presented to our hospital with general weakness, vomiting, dyspnea, and chest pain. The patient was nullipara, 28 weeks' gestation, and had a cachexic morphology. Her cardiac enzyme levels were elevated and bedside echocardiography showed apical akinesia, suggesting TCM. The next day, she could not feel the fetal movement, and an emergency cesarean section was performed. After delivery, the patient experienced cardiac arrest and was transferred to the intensive care unit for cardiopulmonary resuscitation (CPR). Spontaneous circulation returned after 28 minutes of CPR, but cardiogenic shock continued, and extracorporeal membrane oxygenation (ECMO) was initiated. On the third day of ECMO maintenance, left ventricular ejection fraction improved and blood pressure stabilized. On the eighth day after ECMO insertion, it was removed. However, complications of the left leg vessels occurred, and several surgeries and interventions were performed. A left adrenal gland mass was found on computed tomography and was removed while repairing the leg vessels. Pheochromocytoma was diagnosed and left adrenalectomy was performed. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol‐lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash‐out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low‐density lipoprotein‐C (LDL‐C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were −23.02 (3.04) versus −7.18 (3.09) mmHg in the TRE and RE groups, respectively (p

Background/Aims Metabolic syndrome (MetS) raises the risk of cardiovascular disease and type 2 diabetes. An awareness of MetS is vital for early detection and proactive management, which can mitigate the risks associated with MetS. Therefore, our study aimed to investigate the level of awareness of MetS among the Korean population. Methods We conducted a nationwide survey between January and February 2023 among a representative sample of the Korean population using an online survey. Information regarding the awareness of MetS and its risk, the importance of lifestyle modification, and health behavior were collected. The question about the awareness of MetS was “How much do you think you know about MetS?” and there were five answers: 1) I know very well, 2) I know well, 3) I know a little, 4) I do not know, and 5) I have no idea. The high-awareness group was defined as those who answered that they knew very well or well. Results Among 1,000 participants (mean age, 45.7 ± 13.2 yr), 29% were unaware of MetS, and only 20.8% had high awareness. The high-awareness group was significantly more knowledgeable about lifestyle modifications and demonstrated better health behaviors. After adjustment for possible confounding factors, younger age, low household income, and absence of comorbidity were independently associated with a lack of awareness regarding MetS. Conclusions The high-awareness group showed greater knowledge of the importance of lifestyle modifications and better health behaviors regarding MetS. The findings highlight the need for improved public education and awareness programs regarding MetS.

High blood pressure (BP) is a significant risk factor for heart and brain diseases. Previous studies have suggested that heavy metals including lead (Pb), mercury (Hg), and cadmium (Cd) contribute to hypertension. This study examined the combined effects of heavy metals on blood pressure, considering sex differences. A health impact survey was conducted among 561 residents living near waste incineration facilities in Cheongju, Korea. Blood samples were analyzed for heavy metal concentrations and blood pressure was measured. Multiple linear regression and Bayesian kernel machine regression (BKMR) methods were used to evaluate the relationship between heavy metal exposure and BP. Men had higher blood Hg and Pb concentrations, whereas women had higher Cd levels. Multiple linear regression analysis revealed no significant association between heavy metals and systolic blood pressure. However, Cd was significantly associated with increased diastolic blood pressure for the total group and women, whereas Pb was associated with increased diastolic blood pressure in men. In the BKMR analysis, the joint effect of the three metals was significantly associated with diastolic blood pressure for individuals below the 45th percentile and above the 55th percentile in men. These findings underscore the importance of considering sex differences in environmental health studies and public health strategies.

This study aimed to determine whether amplitude modulation (A-mode) ultrasound (US) provides accurate and reliable measurements comparable to those obtained using brightness modulation (B-mode) US under diverse conditions. Thirty healthy participants (15 women and 15 men) underwent measurements of subcutaneous fat thickness (SFT), muscle thickness (MT), and muscle quality (MQ) in the trapezius and biceps brachii muscles using both US modes before and after exercises designed to stimulate the respective muscles. Among the three key indices, the results demonstrated the high validity of the A-mode, with minimal mean differences (MDs) between the two devices less than 0.91 mm and intra-class correlation coefficients (ICCs) exceeding 0.95 for all measures. In addition, the correlation coefficients between the error scores and average scores for the trapezius and biceps brachii suggested no evidence of systematic error. The trapezius MT and MQ significantly increased, and the biceps brachii MT significantly increased after the exercises (p < 0.05). Notably, both the A- and B-modes exhibited the same trend in these post-exercise changes in the muscle. This study suggests that low-cost and low-resolution A-mode US provides measurements of SFT, MT, and MQ similar to the more expensive, high-resolution B-mode imaging. A-mode US is an affordable and portable alternative for muscle assessment.