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.

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.

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

Pheochromocytoma and paraganglioma (PPGLs) are rare catecholamine-secreting neuroendocrine tumors but can be life-threatening. Although most PPGLs are benign, approximately 10% have metastatic potential. Approximately 40% cases are reported as harboring germline mutations. Therefore, timely and accurate diagnosis of PPGLs is crucial. For more than 130 years, clinical, molecular, biochemical, radiological, and pathological investigations have been rapidly advanced in the field of PPGLs. However, performing diagnostic studies to localize lesions and detect metastatic potential can be still challenging and complicated. Furthermore, great progress on genetics has shifted the paradigm of genetic testing of PPGLs. The Korean PPGL task force team consisting of the Korean Endocrine Society, the Korean Surgical Society, the Korean Society of Nuclear Medicine, the Korean Society of Pathologists, and the Korean Society of Laboratory Medicine has developed this position statement focusing on the comprehensive and updated diagnosis for PPGLs.

Cardiac arrest (CA) is sudden loss of heart function and abrupt stop in effective blood flow to the body. The patients who initially achieve return of spontaneous circulation (RoSC) after CA have low survival rate. It has been known that multiorgan dysfunctions after RoSC are associated with high morbidity and mortality. Most previous studies have focused on the heart and brain in RoSC after CA. Therefore, the aim of this research was to perform serological, physiological, and histopathology study in the lung and to determine whether or how pulmonary dysfunction is associated with low survival rate after CA. Experimental animals were divided into sham-operated group (n=14 at each point in time), which was not subjected to CA operation, and CA-operated group (n=14 at each point in time), which was subjected to CA. The rats in each group were sacrificed at 6 hours, 12 hours, 24 hours, and 2 days, respectively, after RoSC. Then, pathological changes of the lungs were analyzed by hematoxylin and eosin staining, Western blot and immunohistochemistry for tumor necrosis factor α (TNF-α). The survival rate after CA was decreased with time past. We found that histopathological score and TNF-α immunoreactivity were significantly increased in the lung after CA. These results indicate that inflammation triggered by ischemia-reperfusion damage after CA leads to pulmonary injury/dysfunctions and contributes to low survival rate. In addition, the finding of increase in TNF-α via inflammation in the lung after CA would be able to utilize therapeutic or diagnostic measures in the future.
Animals ; Blotting, Western ; Brain ; Eosine Yellowish-(YS) ; Heart ; Heart Arrest* ; Hematoxylin ; Humans ; Immunohistochemistry ; Inflammation ; Lung* ; Models, Animal* ; Mortality ; Rats* ; Survival Rate ; Tumor Necrosis Factor-alpha*

PURPOSE: A combination of β1-adrenergic receptor (β₁-AR) blockade and β₂-AR activation might potentially be the novel therapy for treating heart failure. However, the use of β-AR agonists and/or antagonists in the clinical setting is controversial due to the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed a hemodynamic evaluation by examining the force frequency response (FFR), Frank-Starling relationship, and response to non-selective β-AR agonist (isoproterenol) in the hearts isolated from 6-month-old transgenic (TG) mice overexpressing β₁- and β₂-ARs (β₁- and β₂-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of β₁- and β₂-AR overexpression resulted in a similar maximal response to that of isoproterenol and faster temporary decline of positive inotropic response in β₂-AR TG mice. β₁-AR TG mice showed a pronounced negative limb of FFR, whereas β2-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. Contrastingly, Frank-Starling relationship was equally enhanced in both β₁- and β₂-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present study showed a difference between β₁- and β₂-AR signaling, which may be due to a difference in the desensitization of β₁- and β₂-ARs.
Animals ; Depression ; Extremities ; Heart ; Heart Failure ; Hemodynamics ; Humans ; Infant ; Isoproterenol ; Mice ; Mice, Transgenic* ; Receptors, Adrenergic*

PURPOSE: Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have a return of spontaneous circulation (ROSC) after the CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during post CA syndrome. METHODS: Asphyxial CA was induced in male Sprague-Dawley rats and the survival rate of the rats was determined during the post resuscitation phase. RESULTS: Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after the ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after the ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA. Afterwards, the histopathological changes were not significant. In addition, the levels of tumor necrosis factor-αimmunoreactivity increased gradually after CA. CONCLUSION: The survival rate of the rats 2 days post CA was very low, even though the histopathological and inflammatory changes in the heart were not pronounced in the early stages following the CA.
Animals ; Heart Arrest* ; Heart* ; Humans ; Male ; Necrosis* ; Rats* ; Rats, Sprague-Dawley ; Resuscitation ; Survival Rate ; Tumor Necrosis Factor-alpha

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.
Consensus ; High-Throughput Nucleotide Sequencing ; Humans ; Korea ; Pathology, Molecular ; Practice Guidelines as Topic ; Quality Control

OBJECTIVE: Post cardiac arrest (CA) syndrome is associated with a low survival rate in patients who initially have return of spontaneous circulation (ROSC) after CA. The aim of this study was to examine the histopathology and inflammatory response in the heart during the post CA syndrome. METHODS: We induced asphyxial CA in male Sprague-Dawley rats and determined the survival rate of these rats during the post resuscitation phase. RESULTS: Survival of the rats decreased after CA: 66.7% at 6 hours, 36.7% at 1 day, and 6.7% at 2 days after ROSC following CA. The rats were sacrificed at 6 hours, 12 hours, 1 day, and 2 days after ROSC, and their heart tissues were examined. Histopathological scores increased at 12 hours post CA and afterwards, histopathological changes were not significant. In addition, levels of tumor necrosis factor-α immunoreactivity gradually increased after CA. CONCLUSION: The survival rate of rats 2 days post CA was very low, even though histopathological and inflammatory changes in the heart were not pronounced in the early stage following CA.
Animals ; Heart Arrest* ; Heart* ; Humans ; Male ; Necrosis* ; Rats* ; Rats, Sprague-Dawley ; Resuscitation ; Survival Rate

OBJECTIVE: Combination of β₁-adrenergic receptor (AR) blockade and β₂-AR activation might be a potential novel therapy for treating heart failure. However, use of β-AR agonists and/or antagonists in the clinical setting is controversial because of the lack of information on cardiac inotropic or chronotropic regulation by AR signaling. METHODS: In this study, we performed hemodynamic evaluation by examining force frequency response (FFR), Frank-Starling relationship, and response to a non-selective β-AR agonist (isoproterenol) in hearts isolated from 6-month-old transgenic (TG) mice overexpressing β₁- and β₂-ARs (β₁- and β₂-AR TG mice, respectively). RESULTS: Cardiac physiologic consequences of β₁- and β₂-AR overexpression resulted in similar maximal response to isoproterenol and faster temporary decline of positive inotropic response in β₂-AR TG mice. β₁-AR TG mice showed a pronounced negative limb of FFR, whereas β₂-AR TG mice showed high stimulation frequencies with low contractile depression during FFR. In contrast, Frank-Starling relationship was equally enhanced in both β₁- and β₂-AR TG mice. CONCLUSION: Hemodynamic evaluation performed in the present showed a difference in β₁- and β₂-AR signaling, which may be due to the difference in the desensitization of β₁- and β₂-ARs.
Animals ; Depression ; Extremities ; Heart ; Heart Failure ; Hemodynamics ; Humans ; Infant ; Isoproterenol ; Mice ; Mice, Transgenic* ; Receptors, Adrenergic*