ABSTRACT
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
Dysregulated energy homeostasis leads to obesity. The brain, particularly hypothalamus and brain stem, plays a key role in the control of food intake and homeostatic regulation of energy metabolism. Food reward-related hedonic controls integrate with homeostatic controls to regulate body weight. The brain determines energy status by receiving peripheral signals, such as nutrients, gut-derived satiety signals, and adiposity-related hormones, via the circulation or through afferent fibers of the vagus nerve. Significant advances in understanding of the molecular mechanisms of appetite control and energy metabolism drove the pursuit of anti-obesity drugs in recent years. The development of incretins as drugs for type 2 diabetes provided unprecedented results in body weight loss. Recently, clinical study results with incretin-based poly-agonists reported mean weight loss greater than 10%, inspiring confidence in development of anti-obesity medications. Here, I briefly review how brain and peripheral signals integrate and interact to regulate homeostatic and hedonic eating behavior and discuss the mechanism of action of recently developed anti-obesity drugs.
ABSTRACT
Paraquat is a fatal, rapid-acting, nonselective herbicide. Despite the restriction of production and sales of the herbicide in Korea since 2012, already purchased paraquat can incur poisoning. This article describes a 25-month-old boy who accidentally ingested old paraquat on a rural road. After initial decontamination at 2 outside hospitals, he was transferred to the intensive care unit. Given the urine drug concentration of 20,000 ng/mL 2 hours after the intoxication, he received charcoal hemoperfusion and continuous venovenous hemofiltration to enhance the excretion of the herbicide. In 36 hours after intoxication, it was not detected in the urine. The boy was discharged uneventfully on day 8. This case highlights the importance of hemoperfusion in paraquat poisoning.
ABSTRACT
Sestrin2, a well-known adenosine monophosphate-activated protein kinase (AMPK) regulator, plays a protective role against metabolic stress. The β3-adrenergic receptor (β3AR) induces fat browning and inhibits muscle atrophy in an AMPK-dependent manner. However, no prior research has examined the relationship of sestrin2 with β3AR in body composition changes. In this study, CL 316,243 (CL), a β3AR agonist, was administered to wild-type and sestrin2-knockout (KO) mice for 2 weeks, and fat and muscle tissues were harvested. CL induced AMPK phosphorylation, expression of brown-fat markers, and mitochondrial biogenesis, which resulted in the reduction of lipid droplet size in inguinal white adipose tissue (iWAT). These effects were not observed in sestrin2-KO mice. In CL-treated soleus muscle, sestrin2-KO was related to decreased myogenic gene expression and increased levels of muscle atrophy-related molecules. Our results suggest that sestrin2 is associated with beneficial β3AR-mediated changes in body composition, especially in iWAT and in the soleus.
ABSTRACT
Endothelial dysfunction is strongly linked with inflammatory responses, which can impact cardiovascular disease. Recently, G protein-coupled receptor 40 (GPR40) has been investigated as a modulator of metabolic stress; however, the function of GPR40 in vascular endothelial cells has not been reported. We analyzed whether treatment of GPR40-specific agonists modulated the inflammatory responses in human umbilical vein endothelial cells (HUVECs). Treatment with LY2922470, a GPR40 agonist, significantly reduced lipopolysaccharide (LPS)-mediated nuclear factor-kappa B (NF-κB) phosphorylation and movement into the nucleus from the cytosol. However, treatment with another GPR40 agonist, TAK875, did not inhibit LPS-induced NF-κB activation. LPS treatment induced expression of adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and attachment of THP-1 cells to HUVECs, which were all decreased by LY2922470 but not TAK875. Our results showed that ligand-dependent agonism of GPR40 is a promising therapeutic target for overcoming inflammatory reactions in the endothelium.
ABSTRACT
Background@#The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. @*Methods@#The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. @*Results@#A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). @*Conclusion@#The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.
ABSTRACT
Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.
ABSTRACT
BackgroundThe age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.MethodsThe fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.ResultsIn multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.ConclusionBoth FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.
ABSTRACT
Since the first outbreak of coronavirus disease 2019 (COVID-19), ongoing efforts have been made to discover an efficacious vaccine against COVID-19 to combat the pandemic. In most countries, both mRNA and DNA vaccines have been administered, and their side effects have also been reported. The clinical course of COVID-19 and the effects of vaccination against COVID-19 are both influenced by patients’ health status and involve a systemic physiological response. In view of the systemic function of endocrine hormones, endocrine disorders themselves and the therapeutics used to treat them can influence the outcomes of vaccination for COVID-19. However, there are very limited data to support the development of clinical guidelines for patients with specific medical backgrounds based on large clinical trials. In the current severe circumstances of the COVID-19 pandemic, position statements made by clinical specialists are essential to provide appropriate recommendations based on both medical evidence and clinical experiences. As endocrinologists, we would like to present the medical background of COVID-19 vaccination, as well as precautions to prevent the side effects of COVID-19 vaccination in patients with specific endocrine disorders, including adrenal insufficiency, diabetes mellitus, osteoporosis, autoimmune thyroid disease, hypogonadism, and pituitary disorders.
ABSTRACT
BackgroundThe age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain.MethodsThe fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex.ResultsIn multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70. Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275; 95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups.ConclusionBoth FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.
ABSTRACT
Objective@#We investigated the effects of statin-ezetimibe combination therapy compared with statin-only treatment on the hazard of incident type 2 diabetes (T2D), myocardial infarction (MI), and stroke among adults with impaired fasting glucose (IFG) in a real-world setting. @*Methods@#The Korean National Health Insurance Service datasets from 2002 to 2017 were used for this propensity-matched nationwide cohort study. Among 56,633 IFG patients without baseline cardiovascular disease (CVD) and/or T2D who initiated statin therapy with or without ezetimibe, 1,155 with statin-ezetimibe combination therapy were matched based on a propensity score at a 1:5 ratio with 5,775 patients who received statin monotherapy. The hazards of T2D, MI, and stroke were compared between these treatment groups. @*Results@#The incidence rate per 1,000 person-years was 19.62 (statin monotherapy group) and 21.02 (combined treatment group) for T2D, 1.53 (statin monotherapy group) and 1.70 (combined treatment group) for MI, and 1.99 (statin monotherapy group) and 2.06 (combined treatment group) for stroke. The hazards of T2D, MI, and stroke were not significantly different between the statin monotherapy group and the statin-ezetimibe combination therapy group. @*Conclusion@#The combination of ezetimibe in addition to statin treatment was not associated with a significantly different risk of T2D and CVDs compared with statin monotherapy in Korean adults with IFG.
ABSTRACT
Purpose@#This study aimed to investigate the clinical characteristics of human parechovirus (HPeV) infection in sepsis-like syndrome in infants aged under 3 months. @*Methods@#Medical records of infants aged under 3 months with sepsis-like symptoms who were admitted between July 1, 2018 and August 31, 2018 were reviewed. A multiplex reverse transcription-polymerase chain reaction panel test was performed on the cerebrospinal fluid (CSF). Thirty-nine enrolled infants were categorized into three groups: 11 in group 1 (HPeV detected in the CSF), 13 in group 2 (enterovirus detected in the CSF), and 15 in group 3 (no virus detected in the CSF). @*Results@#Compared with groups 2 and 3, a higher proportion of group 1 had tachycardia, tachypnea, apnea, and hypotension (P<0.05). A significantly lower white blood cell (WBC) count was noted in group 1 than in groups 2 and 3 (5,622±2,355/μL, 9,397±2,282/μL, and 12,312±7,452/μL, respectively; P=0.005). The CSF WBC count was lower in group 1 than in groups 2 and 3 (0.9±1.7/μL, 85.1±163.6/μL, and 3.7±6.9/μL, respectively; P=0.068). The proportion of patients requiring inotrope support (36.6% vs. 0% and 6.6%), mechanical ventilation (18.1% vs. 0% and 0%), and high flow nasal cannula (45.4% vs. 15.3% and 6.6%) was higher in group 1 than in groups 2 and 3. All patients recovered completely without complications. @*Conclusions@#HPeV infection shows a severe clinical course and can cause a severe sepsis-like syndrome in infants aged under 3 months. Early diagnosis and proper treatment of HPeV infection are required.
ABSTRACT
Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a common form of vasculitis in childhood. Among the recent trends in Kawasaki disease, it is notable that the prevalence rate is increasing, and the proportion of “incomplete” Kawasaki disease is also increasing. A delayed diagnosis with prolonged fever can cause complications, such as coronary artery aneurysm and decreased myocardial contractility. These complications might lead to significant morbidity and mortality. Kawasaki disease is diagnosed when the patient meets the principal criteria for clinical symptoms. Following the diagnostic criteria can prevent overdiagnosis but lead to missing of the incomplete form of the disease. Therefore, it is important to accurately understand Kawasaki disease. As the coronavirus disease 2019 (COVID-19) pandemic continues, concerns about a novel severe Kawasaki-like disease in children related to COVID-19 emerges. Indeed, there have been several reports of Kawasaki-like disease related to COVID-19 in children. Kawasaki disease is no longer rare and is often encountered at hospitals. This paper will provide useful and accurate information on Kawasaki disease.
ABSTRACT
Background@#The age- and sex-related differences on the impacts of body composition on diabetes mellitus (DM) remain uncertain. @*Methods@#The fourth and fifth Korea National Health and Nutrition Examination Survey included 15,586 subjects over 30 years of age who completed dual-energy X-ray absorptiometry. We conducted a cross-sectional study to investigate whether muscle mass index (MMI), defined as appendicular skeletal muscle divided by body mass index (BMI), and fat mass index (FMI), defined as trunk fat mass divided by BMI, were differently associated with DM according to age and sex. @*Results@#In multivariate logistic regression, the risk for DM significantly increased across quartiles of FMI in men aged ≥70.Meanwhile, MMI showed a protective association with DM in men of the same age. The odds ratios (ORs) for the highest quartile versus the lowest quartile of FMI and MMI were 3.116 (95% confidence interval [CI], 1.405 to 6.914) and 0.295 (95% CI, 0.157 to 0.554), respectively. In women, the ORs of DM was significantly different across FMI quartiles in those over age 50. The highest quartile of FMI exhibited increased ORs of DM in subjects aged 50 to 69 (OR, 1.891; 95% CI, 1.229 to 2.908) and ≥70 (OR, 2.275;95% CI, 1.103 to 4.69) compared to lowest quartile. However, MMI was not significantly associated with DM in women of all age groups. @*Conclusion@#Both FMI and MMI were independent risk factors for DM in men aged 70 years or more. In women over 50 years, FMI was independently associated with DM. There was no significant association between MMI and DM in women.
ABSTRACT
With the increasing use of laundry detergent pods (LDPs) in Korea, pediatricians and emergency physicians should recognize the risk of poisoning by ingestion of the pods. This report describes a 15-month-old boy who ingested an LDP at home. At the time of hospitalization, he was alert and hemodynamically stable. However, 3 hours after the ingestion, he developed drowsiness, respiratory distress, and metabolic acidosis. Despite the initial supportive therapy, the acidosis worsened, requiring continuous renal replacement therapy. Metabolic acidosis improved within 1 hour after initiation of the continuous renal replacement therapy. He was discharged uneventfully on day 13. At 1-month follow-up, he did not show any sequelae. This case highlights the need for recognition of the risk of poisoning by LDP.
ABSTRACT
With the increasing use of laundry detergent pods (LDPs) in Korea, pediatricians and emergency physicians should recognize the risk of poisoning by ingestion of the pods. This report describes a 15-month-old boy who ingested an LDP at home. At the time of hospitalization, he was alert and hemodynamically stable. However, 3 hours after the ingestion, he developed drowsiness, respiratory distress, and metabolic acidosis. Despite the initial supportive therapy, the acidosis worsened, requiring continuous renal replacement therapy. Metabolic acidosis improved within 1 hour after initiation of the continuous renal replacement therapy. He was discharged uneventfully on day 13. At 1-month follow-up, he did not show any sequelae. This case highlights the need for recognition of the risk of poisoning by LDP.
ABSTRACT
Neurosyphilis is an infection of the brain or spinal cord that is caused by the bacterium Treponema pallidum. Syphilitic myelitis, which involves the spinal cord, is a very rare form of neurosyphilis seen in patients with syphilis. It requires differentiation from other diseases of the spinal cord, including idiopathic transverse myelitis and spinal cord infarction. Herein, we describe the presentation and diagnosis of syphilitic myelitis in a 43-year-old woman, based on a flip-flop sign and candle guttering appearance depicted in magnetic resonance imaging and laboratory tests.
Subject(s)
Adult , Female , Humans , Brain , Diagnosis , Infarction , Magnetic Resonance Imaging , Myelitis , Myelitis, Transverse , Neurosyphilis , Spinal Cord , Syphilis , Treponema pallidumABSTRACT
Guillain-Barré syndrome (GBS) and acute disseminated encephalomyelitis (ADEM) are demyelinating neurologic disorders with different target organs. Although they share similar pathogenetic mechanism, reports of simultaneous occurrence of the 2 disorders are rare. A 2 year 6 month old girl visited our hospital for fever, cough, and general weakness. Although the muscle power of extremities showed mild weakness and voiding difficulty, initial deep tendon reflex of both knees and ankles was normal. A nerve conduction study to evaluate the weakness revealed the absence of F waves. Cerebrospinal fluid analysis demonstrated pleocytosis with lymphocyte predominance and elevated protein levels. Magnetic resonance imaging showed abnormal T2 hyperintensity in pons, medulla and spinal cord. Serum anti-GD1b antibody was positive. Based on clinical findings, laboratory findings, nerve conduction study, and neuroimaging, the diagnosis of GBS and ADEM was made. This is the first case of GBS accompanied by ADEM in Korea.
Subject(s)
Female , Humans , Ankle , Cerebrospinal Fluid , Cough , Demyelinating Diseases , Diagnosis , Encephalomyelitis , Encephalomyelitis, Acute Disseminated , Extremities , Fever , Guillain-Barre Syndrome , Knee , Korea , Leukocytosis , Lymphocytes , Magnetic Resonance Imaging , Nervous System Diseases , Neural Conduction , Neuroimaging , Peripheral Nervous System , Pons , Reflex, Stretch , Spinal CordABSTRACT
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy characterized by predominant right ventricular fibro-fatty replacement, right ventricular dysfunction and ventricular arrhythmias. It is a rare but important cause of sudden cardiac death in children and young adults. A meta-analysis on risk stratification of major ventricular tachyarrhythmic events indicating the need for implantable cardioverter defibrillator therapy in ARVC was performed.METHODS: The pubmed database was searched from its inception to May 2015. Of the 433 citations identified, 12 were included in this meta-analysis. Data regarding major ventricular tachyarrhythmic events were retrieved in 817 subjects from the studies. For the variables, a combined odds ratio (OR) was calculated using a fixed-effects meta-analysis.RESULTS: Extensive right ventricular dysfunction (OR, 2.44), ventricular late potential (OR, 1.66), inducible ventricular tachyarrhythmia during electrophysiology study (OR, 3.67), non-sustained ventricular tachycardia (OR, 3.78), and history of fatal event/sustained VT (OR, 5.66) identified as significant risk factors (p < 0.0001).CONCLUSION: This meta-analysis shows that extensive right ventricular dysfunction, ventricular late potential, inducible ventricular tachyarrhythmia during electrophysiological study, non-sustained ventricular tachycardia, and history of sustained ventricular tachycardia/fibrillation are consistently reported risk factors of major ventricular tachyarrhythmic events indicating implantable cardioverter defibrillator therapy in patients with ARVC.
Subject(s)
Child , Humans , Young Adult , Arrhythmias, Cardiac , Arrhythmogenic Right Ventricular Dysplasia , Cardiomyopathies , Death, Sudden , Death, Sudden, Cardiac , Defibrillators , Electrophysiology , Odds Ratio , Risk Factors , Tachycardia , Tachycardia, Ventricular , Ventricular Dysfunction, RightABSTRACT
BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy characterized by predominant right ventricular fibro-fatty replacement, right ventricular dysfunction and ventricular arrhythmias. It is a rare but important cause of sudden cardiac death in children and young adults. A meta-analysis on risk stratification of major ventricular tachyarrhythmic events indicating the need for implantable cardioverter defibrillator therapy in ARVC was performed. METHODS: The pubmed database was searched from its inception to May 2015. Of the 433 citations identified, 12 were included in this meta-analysis. Data regarding major ventricular tachyarrhythmic events were retrieved in 817 subjects from the studies. For the variables, a combined odds ratio (OR) was calculated using a fixed-effects meta-analysis. RESULTS: Extensive right ventricular dysfunction (OR, 2.44), ventricular late potential (OR, 1.66), inducible ventricular tachyarrhythmia during electrophysiology study (OR, 3.67), non-sustained ventricular tachycardia (OR, 3.78), and history of fatal event/sustained VT (OR, 5.66) identified as significant risk factors (p < 0.0001). CONCLUSION: This meta-analysis shows that extensive right ventricular dysfunction, ventricular late potential, inducible ventricular tachyarrhythmia during electrophysiological study, non-sustained ventricular tachycardia, and history of sustained ventricular tachycardia/fibrillation are consistently reported risk factors of major ventricular tachyarrhythmic events indicating implantable cardioverter defibrillator therapy in patients with ARVC.