Dong-A University Hospital

BACKGROUND: The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied. METHODS: In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes. RESULTS: A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups. CONCLUSIONS: After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).

OBJECTIVE: The aim of the study was to evaluate the short-term outcomes of KLASS-02-RCT, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy with open distal gastrectomy (ODG). SUMMARY BACKGROUND DATA: Although several benefits of laparoscopic gastric cancer surgery have been reported, strong evidence is still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. METHODS: Enrollment criteria included histologically confirmed cT2-4a and N0-1 gastric adenocarcinoma. Thirty-day morbidity, 90-day mortality, postoperative pain, and recovery were compared between LDG and ODG groups. RESULTS: A total of 1050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1011 patients were analyzed as actual treatment group. Mean number of totally retrieved lymph nodes was similar in both groups (LDG = 46.6 vs ODG = 47.4, P = 0.451). Early morbidity rate was significantly lower after LDG (16.6%) than after ODG (24.1%; P = 0.003). Postoperative analgesics use and patients' reported pain score were significantly lower after LDG. First day of flatus was earlier after LDG (3.5 vs 3.7 d, P = 0.025) and postoperative hospital stay was shorter in LDG group (8.1 vs 9.3 d, P = 0.005). Ninety days' mortality rate was similar in both groups (LDG = 0.4% vs ODG = 0.6%, P = 0.682). CONCLUSIONS: Laparoscopic distal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer shows benefits in terms of lower complication rate, faster recovery, and less pain compared with open surgery.

OBJECTIVE: To evaluate the efficacy and safety of perampanel 2, 4, and 8 mg/day added to 1-3 concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. METHODS: During this double-blind, placebo-controlled trial, patients with persisting seizures on 1-3 AEDs were randomized to perampanel 2, 4, and 8 mg/day or placebo following a 6-week baseline phase. Perampanel was titrated weekly by 2 mg/day and maintained at the dose achieved for 13 weeks. Primary endpoints were median percent change in seizure frequency and 50% responder rate. Analysis of covariance was performed on all treated patients with any seizure data (recorded in daily diaries) in the double-blind phase. RESULTS: A total of 706 patients were randomized and received trial medication; 623 completed the trial. Median percent change in seizure frequency-the primary efficacy endpoint-was -10.7%, -13.6%, -23.3%, and -30.8% for placebo, perampanel 2, 4, and 8 mg/day, respectively. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0026) and 8 mg/day (p < 0.0001). The corresponding 50% responder rates were 17.9%, 20.6%, 28.5%, and 34.9%. The difference from placebo was statistically significant for perampanel 4 mg/day (p = 0.0132) and 8 mg/day (p = 0.0003). An apparent dose response was suggested for dizziness, which was the most frequent treatment-emergent adverse event. CONCLUSIONS: This trial demonstrated that adjunctive perampanel effectively reduced seizure frequency and possessed a favorable tolerability profile in patients ≥12 years with partial-onset seizures (with or without secondary generalization), with a minimum effective dose of 4 mg/day. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 4 and 8 mg/day doses of adjunctive perampanel are effective and tolerated in reducing partial-onset seizures.

PURPOSE It is unclear whether laparoscopic distal gastrectomy for locally advanced gastric cancer is oncologically equivalent to open distal gastrectomy. The noninferiority of laparoscopic subtotal gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer compared with open surgery in terms of 3-year relapse-free survival rate was evaluated. PATIENTS AND METHODS A phase III, open-label, randomized controlled trial was conducted for patients with histologically proven locally advanced gastric adenocarcinoma suitable for distal subtotal gastrectomy. The primary end point was the 3-year relapse-free survival rate; the upper limit of the hazard ratio (HR) for noninferiority was 1.43 between the laparoscopic and open distal gastrectomy groups. RESULTS From November 2011 to April 2015, 1,050 patients were randomly assigned to laparoscopy (n = 524) or open surgery (n = 526). After exclusions, 492 patients underwent laparoscopic surgery and 482 underwent open surgery and were included in the analysis. The laparoscopy group, compared with the open surgery group, suffered fewer early complications (15.7% v 23.4%, respectively; P = .0027) and late complications (4.7% v 9.5%, respectively; P = .0038), particularly intestinal obstruction (2.0% v 4.4%, respectively; P = .0447). The 3-year relapse-free survival rate was 80.3% (95% CI, 76.0% to 85.0%) for the laparoscopy group and 81.3% (95% CI, 77.0% to 85.0%; log-rank P = .726) for the open group. Cox regression analysis after stratification by the surgeon revealed an HR of 1.035 (95% CI, 0.762 to 1.406; log-rank P = .827; P for noninferiority = .039). When stratified by pathologic stage, the HR was 1.020 (95% CI, 0.751 to 1.385; log-rank P = .900; P for noninferiority = .030). CONCLUSION Laparoscopic distal gastrectomy with D2 lymphadenectomy was comparable to open surgery in terms of relapse-free survival for patients with locally advanced gastric cancer. Laparoscopic distal gastrectomy with D2 lymphadenectomy could be a potential standard treatment option for locally advanced gastric cancer.

BACKGROUND: Procedural results for percutaneous coronary intervention (PCI) in coronary vessels with chronic total occlusion (CTO) have improved in recent years, and PCI strategies have moved toward more complete revascularization with more liberal use of CTO-PCI. However, evidence evaluating CTO-PCI is limited to observational studies and small clinical trials. METHODS: In this open-label, multicenter, randomized, noninferiority trial, PCI-eligible patients were assigned to receive either 1 of 2 strategies: PCI or no PCI for the qualifying de novo CTO lesion with the option for PCI of obstructive non-CTO lesions at the discretion of the operator. The primary end point was a composite of death, myocardial infarction, stroke, or any revascularization. Health-related quality of life was assessed at baseline and at 1, 6, 12, 24, and 36 months. Because of slow recruitment, the trial was stopped before completion of the 1284 planned enrollments. RESULTS: Between March 2010 and September 2016, 834 patients were randomly assigned to the CTO-PCI (n=417) or no CTO-PCI (n=398) strategy. Among the patients assigned to the no CTO-PCI strategy, 78 (19.6%) crossed over to receive staged CTO-PCI within 3 days of randomization. The overall CTO-PCI success rate was 90.6%. Serious nonfatal complications associated with CTO-PCI occurred in 3 patients (1 stroke, 1 cardiac tamponade, and 1 patient with recurrent episodes of ventricular tachyarrhythmia induced by intracoronary thrombus). Approximately half of the patients in each group underwent PCI for an average of 1.3 non-CTO lesions, resulting in a comparable residual SYNTAX score (Synergy Between PCI With TAXUS and Cardiac Surgery; 3.7±5.4 versus 4.0±5.9, P=0.42) confined to non-CTO vessels. During a median follow-up of 4.0 years (interquartile range, 2.4 to 5.1 years), there was no significant difference between the CTO-PCI and the no CTO-PCI strategies in the incidence of the primary end point (22.3% versus 22.4%, hazard ratio, 1.03; 95% CI, 0.77 to 1.37; P=0.86). Both CTO-PCI and no CTO-PCI strategy were associated with significant improvements but without between-group differences in disease-specific health status that was sustained through 36 months. CONCLUSIONS: CTO-PCI was feasible with high success rates. There was no difference in the incidence of major adverse cardiovascular events with CTO-PCI versus no CTO-PCI, but the study was limited by low power for clinical end points and high crossover rates between groups. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01078051.

Abstract East Asian patients have reduced anti-ischemic benefits and increased bleeding risk during antithrombotic therapies compared with Caucasian patients. As potent P2Y12 receptor inhibitors (e.g., ticagrelor and prasugrel) and direct oral anticoagulants are commonly used in current daily practice, the unique risk–benefit trade-off in East Asians has been a topic of emerging interest. In this article, we propose updated evidence and future directions of antithrombotic treatment in East Asian patients.

Eosinophilic lung diseases are a diverse group of pulmonary disorders associated with peripheral or tissue eosinophilia. They are classified as eosinophilic lung diseases of unknown cause (simple pulmonary eosinophilia [SPE], acute eosinophilic pneumonia [AEP], chronic eosinophilic pneumonia [CEP], idiopathic hypereosinophilic syndrome [IHS]), eosinophilic lung diseases of known cause (allergic bronchopulmonary aspergillosis [ABPA], bronchocentric granulomatosis [BG], parasitic infections, drug reactions), and eosinophilic vasculitis (allergic angiitis, granulomatosis [Churg-Strauss syndrome]). The percentages of eosinophils in peripheral blood and bronchoalveolar lavage fluid are essential parts of the evaluation. Chest computed tomography (CT) demonstrates a more characteristic pattern and distribution of parenchymal opacities than does conventional chest radiography. At CT, SPE and IHS are characterized by single or multiple nodules with a surrounding ground-glass-opacity halo, AEP mimics radiologically hydrostatic pulmonary edema, and CEP is characterized by nonsegmental airspace consolidations with peripheral predominance. ABPA manifests with bilateral central bronchiectasis with or without mucoid impaction. The CT manifestations of BG are nonspecific and consist of a focal mass or lobar consolidation with atelectasis. The most common CT findings in Churg-Strauss syndrome include sub-pleural consolidation with lobular distribution, centrilobular nodules, bronchial wall thickening, and interlobular septal thickening. The integration of clinical, radiologic, and pathologic findings facilitates the initial and differential diagnoses of various eosinophilic lung diseases.

Despite the great socioeconomic burden of stroke, there have been few reports of stroke statistics in Korea. In this scenario, the Epidemiologic Research Council of the Korean Stroke Society launched the "Stroke Statistics in Korea" project, aimed at writing a contemporary, comprehensive, and representative report on stroke epidemiology in Korea. This report contains general statistics of stroke, prevalence of behavioral and vascular risk factors, stroke characteristics, pre-hospital system of care, hospital management, quality of stroke care, and outcomes. In this report, we analyzed the most up-to-date and nationally representative databases, rather than performing a systematic review of existing evidence. In summary, one in 40 adults are patients with stroke and 232 subjects per 100,000 experience a stroke event every year. Among the 100 patients with stroke in 2014, 76 had ischemic stroke, 15 had intracerebral hemorrhage, and nine had subarachnoid hemorrhage. Stroke mortality is gradually declining, but it remains as high as 30 deaths per 100,000 individuals, with regional disparities. As for stroke risk factors, the prevalence of smoking is decreasing in men but not in women, and the prevalence of alcohol drinking is increasing in women but not in men. Population-attributable risk factors vary with age. Smoking plays a role in young-aged individuals, hypertension and diabetes in middle-aged individuals, and atrial fibrillation in the elderly. About four out of 10 hospitalized patients with stroke are visiting an emergency room within 3 hours of symptom onset, and only half use an ambulance. Regarding acute management, the proportion of patients with ischemic stroke receiving intravenous thrombolysis and endovascular treatment was 10.7% and 3.6%, respectively. Decompressive surgery was performed in 1.4% of patients with ischemic stroke and in 28.1% of those with intracerebral hemorrhage. The cumulative incidence of bleeding and fracture at 1 year after stroke was 8.9% and 4.7%, respectively. The direct costs of stroke were about ₩1.68 trillion (KRW), of which ₩1.11 trillion were for ischemic stroke and ₩540 billion for hemorrhagic stroke. The great burden of stroke in Korea can be reduced through more concentrated efforts to control major attributable risk factors for age and sex, reorganize emergency medical service systems to give patients with stroke more opportunities for reperfusion therapy, disseminate stroke unit care, and reduce regional disparities. We hope that this report can contribute to achieving these tasks.

Characteristics of stroke cases, acute stroke care, and outcomes after stroke differ according to geographical and cultural background. To provide epidemiological and clinical data on stroke care in South Korea, we analyzed a prospective multicenter clinical stroke registry, the Clinical Research Center for Stroke-Fifth Division (CRCS-5). Patients were 58% male with a mean age of 67.2±12.9 years and median National Institutes of Health Stroke Scale score of 3 [1-8] points. Over the 6 years of operation, temporal trends were documented including increasing utilization of recanalization treatment with shorter onset-to-arrival delay and decremental length of stay. Acute recanalization treatment was performed in 12.7% of cases with endovascular treatment utilized in 36%, but the proportion of endovascular recanalization varied across centers. Door-to-IV alteplase delay had a median of 45 [33-68] min. The rate of symptomatic hemorrhagic transformation (HT) was 7%, and that of any HT was 27% among recanalization-treated cases. Early neurological deterioration occurred in 15% of cases and were associated with longer length of stay and poorer 3-month outcomes. The proportion of mRS scores of 0-1 was 42% on discharge, 50% at 3 months, and 55% at 1 year after the index stroke. Recurrent stroke up to 1 year occurred in 4.5% of patients; the rate was higher among older individuals and those with neurologically severe deficits. The above findings will be compared with other Asian and US registry data in this article.

Mercury occurs in various chemical forms, and it is different to health effects according to chemical forms. In consideration of the point, the evaluation of the mercury exposure to human distinguished from occupational and environmental exposure. With strict to manage occupational exposure in factory, it is declined mercury intoxication cases by metallic and inorganic mercury inhalation to occupational exposure. It is increasing to importance in environmental exposure and public health. The focus on the health impact of exposure to mercury is more on chronic, low or moderate grade exposure-albeit a topic of great controversy-, not high concentration exposure by methylmercury, which caused Minamata disease. Recently, the issue of mercury toxicity according to the mercury exposure level, health effects as well as the determination of what mercury levels affect health are in the spotlight and under active discussion. Evaluating the health effects and Biomarker of mercury exposure and establishing diagnosis and treatment standards are very difficult. It can implement that evaluating mercury exposure level for diagnosis by a provocation test uses chelating agent and conducting to appropriate therapy according to the result. but, indications for the therapy of chelating agents with mercury exposure have not yet been fully established. The therapy to symptomatic patients with mercury poisoning is chelating agents, combination therapy with chelating agents, plasma exchange, hemodialysis, plasmapheresis. But the further evaluations are necessary for the effects and side effects with each therapy.

PURPOSE: As a result of various independently proposed nomenclatures and classifications, there is confusion in the diagnosis and prediction of biological behavior of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). A comprehensive nationwide study is needed in order to understand the biological characteristics of GEP-NETs in Korea. MATERIALS AND METHODS: We collected 4,951 pathology reports from 29 hospitals in Korea between 2000 and 2009. Kaplan-Meier survival analysis was used to determine the prognostic significance of clinicopathological parameters. RESULTS: Although the GEP-NET is a relatively rare tumor in Korea, its incidence has increased during the last decade, with the most significant increase found in the rectum. The 10-year survival rate for well-differentiated endocrine tumor was 92.89%, in contrast to 85.74% in well differentiated neuroendocrine carcinoma and 34.59% in poorly differentiated neuroendocrine carcinoma. Disease related death was most common in the biliary tract (62.2%) and very rare in the rectum (5.2%). In Kaplan-Meier survival analysis, tumor location, histological classification, extent, size, mitosis, Ki-67 labeling index, synaptophysin expression, lymphovascular invasion, perineural invasion, and lymph node metastasis showed prognostic significance (p<0.05), however, chromogranin expression did not (p=0.148). The 2000 and 2010 World Health Organization (WHO) classification proposals were useful for prediction of the prognosis of GEP-NET. CONCLUSION: The incidence of GEP-NET in Korea has shown a remarkable increase during the last decade, however, the distribution of tumors in the digestive system differs from that of western reports. Assessment of pathological parameters, including immunostaining, is crucial in understanding biological behavior of the tumor as well as predicting prognosis of patients with GEP-NET.

Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive drugs to treat a wide range of diseases. However, they are also associated with a number of side effects, including new-onset hyperglycemia in patients without a history of diabetes mellitus (DM) or severely uncontrolled hyperglycemia in patients with known DM. Glucocorticoid-induced diabetes mellitus (GIDM) is a common and potentially harmful problem in clinical practice, affecting almost all medical specialties, but is often difficult to detect in clinical settings. However, scientific evidence is lacking regarding the effects of GIDM, as well as strategies for prevention and treatment. Similarly to nonsteroid-related DM, the principles of early detection and risk factor modification apply. Screening for GIDM should be considered in all patients treated with medium to high doses of glucocorticoids. Challenges in the management of GIDM stem from wide fluctuations in postprandial hyperglycemia and the lack of clearly defined treatment protocols. Together with lifestyle measures, hypoglycemic drugs with insulin-sensitizing effects are indicated. However, insulin therapy is often unavoidable, to the point that insulin can be considered the drug of choice. The treatment of GIDM should take into account the degree and pattern of hyperglycemia, as well as the type, dose, and schedule of glucocorticoid used. Moreover, it is essential to instruct the patient and/or the patient's family about how to perform the necessary adjustments. Prospective studies are needed to answer the remaining questions regarding GIDM.

BACKGROUND & AIMS: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. METHODS: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS). RESULTS: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006). CONCLUSION: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. LAY SUMMARY: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.

Uterine curettage or surgical trauma can cause uterine vascular abnormalities, including pseudoaneurysms, acquired arteriovenous malformations (AVMs), arteriovenous fistulas, and rupture of vessels. Recognition of these abnormalities as the cause of hemorrhage is important, since these abnormalities can be treated safely and effectively with transcatheter arterial embolization but may be worsened by uterine curettage, precipitating massive uterine bleeding. Ultrasonography (US) is the most commonly performed initial imaging examination for evaluation of abnormal uterine bleeding. Color and duplex Doppler US allows convincing detection and diagnosis of these vascular abnormalities and helps differentiate vascular abnormalities that require embolization from nonvascular abnormalities. In cases of pseudoaneurysms, color and duplex Doppler US shows a blood-filled cystic structure with swirling arterial flow. In cases of AVMs, color Doppler US shows an intense vascular tangle, whereas duplex Doppler US shows low-resistance, high-velocity arterial flow. Cases of an AVM combined with a pseudoaneurysm demonstrate the findings of both AVMs and pseudoaneurysms. Transcatheter arterial embolization after angiography is the therapy of choice for these vascular abnormalities, with the advantage of retained reproductive capacity. Routine use of color and duplex Doppler US during examination of abnormal uterine bleeding is recommended to identify and characterize the vascular abnormality.

BACKGROUND AND PURPOSE: In order to improve inter-rater reliability and minimize diagnosis of undetermined etiology for stroke subtype classification, using a stroke registry, we developed and implemented a magnetic resonance imaging (MRI)-based algorithm for acute ischemic stroke subtype classification (MAGIC). METHODS: We enrolled patients who experienced an acute ischemic stroke, were hospitalized in the 14 participating centers within 7 days of onset, and had relevant lesions on MR-diffusion weighted imaging (DWI). MAGIC was designed to reflect recent advances in stroke imaging and thrombolytic therapy. The inter-rater reliability was compared with and without MAGIC to classify the Trial of Org 10172 in Acute Stroke Treatment (TOAST) of each stroke patient. MAGIC was then applied to all stroke patients hospitalized since July 2011, and information about stroke subtypes, other clinical characteristics, and stroke recurrence was collected via a web-based registry database. RESULTS: The overall intra-class correlation coefficient (ICC) value was 0.43 (95% CI, 0.31-0.57) for MAGIC and 0.28 (95% CI, 0.18-0.42) for TOAST. Large artery atherosclerosis (LAA) was the most common cause of acute ischemic stroke (38.3%), followed by cardioembolism (CE, 22.8%), undetermined cause (UD, 22.2%), and small-vessel occlusion (SVO, 14.6%). One-year stroke recurrence rates were the highest for two or more UDs (11.80%), followed by LAA (7.30%), CE (5.60%), and SVO (2.50%). CONCLUSIONS: Despite several limitations, this study shows that the MAGIC system is feasible and may be helpful to classify stroke subtype in the clinic.

Lead, which is widely used in industry, is a common element found in low concentrations in the Earth's crust. Implementations to reduce environmental lead concentrations have resulted in a considerable reduction of lead levels in the environment (air) and a sustained reduction in the blood lead levels of the average citizen. However, people are still being exposed to lead through a variety of routes in everyday commodities. Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. Having a carcinogenic risk as well, the IARC classifies inorganic lead compounds as probably carcinogenic to humans (Group 2A). Occupational lead poisonings have decreased due to the efforts to reduce the lead concentrations in the working environment. In contrast, health hazards associated with long-term environmental exposure to low concentrations of lead have been reported steadily. In particular, chronic exposure to low concentrations of lead has been reported to induce cognitive behavioral disturbances in children. It is almost impossible to remove lead completely from the human body, and it is not easy to treat health hazards due to lead exposure. Therefore, reduction and prevention of lead exposure are very important. We reviewed the toxicity and health hazards, monitoring and evaluation, and management of lead exposure.

<h3>Objective</h3> Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations. <h3>Methods</h3> We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations. <h3>Results</h3> We identified 113 genetic regions including 46 novel loci at genome-wide significance (p&lt;5×10⁻⁸). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r_g=−0.242) and non-albumin protein (r_g=0.238). <h3>Conclusion</h3> This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.

Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

Traditional biomarkers, including C-reactive protein, leukocytes, erythrocyte sedimentation rate, and clinical signs and symptoms, are not sufficiently sensitive or specific enough to guide treatment decisions in infectious febrile diseases. Procalcitonin (PCT) is synthesized by a large number of tissues and organs in response to invasion by pathogenic bacteria, fungi, and some parasites. A growing body of evidence supports the use of PCT as a marker to improve the diagnosis of bacterial infections and to guide antibiotic therapy. Clinically, PCT levels may help guide the need for empirical antibiotic therapy, source control for infections, and duration of antibiotic therapy. The aim of this review is to summarize the current evidence for PCT in different infections and clinical settings, and to discuss the reliability of this marker in order to provide physicians with an overview of the potential for PCT to guide antibiotic therapy.

This study evaluated the relationship of insulin resistance (IR) and glycemic control status to the presence and severity of coronary artery disease (CAD) according to diabetes. The relationship of IR parameters including homeostatic model assessment of IR (HOMA-IR), triglyceride-glucose (TyG) index, and triglyceride-to-high density lipoprotein cholesterol ratio (TG/HDL), and hemoglobin A1C (HbA1C) level to CAD and obstructive CAD was evaluated in 5,764 asymptomatic subjects who underwent coronary computed tomographic angiography. Non-diabetics (n = 4768) and diabetics (n = 996) were stratified into four groups based on the quartiles of HOMA-IR and the TyG index and were grouped based on the TG/HDL cut-offs of 3.5, respectively. CAD and obstructive CAD were defined as the presence of any plaques and plaques with ≥50% stenosis, respectively. The prevalence of CAD (59.0% vs. 39.0%) and obstructive CAD (15.0% vs. 6.6%) was higher in diabetic than in non-diabetic patients (p < 0.001, respectively). In non-diabetic patients, the adjusted odds ratio for both CAD and obstructive CAD significantly increased, but only with higher TyG index quartiles. Unlike non-diabetics, the adjusted odds ratio for obstructive CAD significantly increased in diabetic patients with a TG/HDL level ≥ 3.5. The HbA1C, rather than IR parameters, was independently associated with both CAD and obstructive CAD in diabetics. In conclusion, among IR parameters, TyG index was independently associated with the presence of CAD and obstructive CAD in non-diabetic patients. In contrast, the glycemic control status, rather than IR, was importantly related to both CAD and obstructive CAD in established diabetic patients.