Simultaneous determination of multi-class veterinary drugs in fishery products with liquid chromatography–tandem mass spectrometry

The objective of this study was to optimize the analytical method for multi-class veterinary drug residues of 64 compounds in fishery products. Several compounds from veterinary drugs are banned or unauthorized in fishery products according to the Korean Food Code. Samples were extracted using acetonitrile/water (4:1, v/v) and the clean-up step was carried out by adding octadecylsilane and acetonitrile-saturated hexane. The target compounds were confirmed and quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The proposed method was validated according to the CODEX guidelines (CAC/GL-71), and most target compounds were found to be in acceptable quantities under the requirements of the validation guidelines. The recovery of analytes was typically in the 60–120% range, and precision, expressed as the coefficient of variation was less than 31% at all levels of concentration. The limit of quantification ranged from 0.03 to 3 μg kg−1 in the fishery products. Moreover, the application of the proposed method to 96 real samples demonstrated that no drug residues exceeded the Korean maximum residue limits (MRLs). This evaluation method provides reliable identification and quantification of multi-class veterinary drugs in fishery products and can be an efficient means to inspect drugs currently banned or not approved for aquaculture in Korea.This study was funded by Grant No. 20161MFDS623 from the Ministry of Food and Drug Safety of South Korea in 2020

Brain computed tomography angiography in postcardiac arrest patients and neurologic outcome

Objective This study aimed to analyze intracranial vessels using brain computed tomography angiography (CTA) and scoring systems to diagnose brain death and predict poor neurologic outcomes of postcardiac arrest patients. Methods Initial brain CTA images of postcardiac arrest patients were analyzed using scoring systems to determine a lack of opacification and diagnose brain death. The primary outcome was poor neurologic outcome, which was defined as cerebral performance category score 3 to 5. The frequency, sensitivity, specificity, positive predictive value, negative predictive value, and area under receiver operating characteristic curve for the lack of opacification of each vessel and for each scoring system used to predict poor neurologic outcomes were determined. Results Patients with poor neurologic outcomes lacked opacification of the intracranial vessels, most commonly in the vein of Galen, both internal cerebral veins, and the mid cerebral artery (M4). The 7-score results (P=0.04) and 10-score results were significantly different (P=0.04) between outcome groups, with an area under receiver operating characteristic of 0.61 (range, 0.48 to 0.72). The lack of opacification of each intracranial vessel and all scoring systems exhibited high specificity (100%) and positive predictive values (100%) for predicting poor neurologic outcomes. Conclusion Lack of opacification of vessels on brain CTA exhibited high specificity for predicting poor neurologic outcomes of patients after cardiac arrest

Methionine deprivation suppresses triple-negative breast cancer metastasis in vitro and in vivo

Nutrient deprivation strategies have been proposed as an adjuvant therapy for cancer cells due to their increased metabolic demand. We examined the specific inhibitory effects of amino acid deprivation on the metastatic phenotypes of the human triple-negative breast cancer (TNBC) cell lines MDA-MB-231 and Hs 578T, as well as the orthotopic 4T1 mouse TNBC tumor model. Among the 10 essential amino acids tested, methionine deprivation elicited the strongest inhibitory effects on the migration and invasion of these cancer cells. Methionine deprivation reduced the phosphorylation of focal adhesion kinase, as well as the activity and mRNA expression of matrix metalloproteinases MMP-2 and MMP-9, two major markers of metastasis, while increasing the mRNA expression of tissue inhibitor of metalloproteinase 1 in MDA-MB-231 cells. Furthermore, methionine restriction downregulated the metastasis-related factor urokinase plasminogen activatior and upregulated plasminogen activator inhibitor 1 mRNA expression. Animals on the methionine-deprived diet showed lower lung metastasis rates compared to mice on the control diet. Taken together, these results suggest that methionine restriction could provide a potential nutritional strategy for more effective cancer therapy

Frequency of Fabry disease in chronic kidney disease patients including patients on renal replacement therapy in Korea

Background Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase (α- Gal A), affecting multiple organs including kidney. In this study, we aimed to determine the prevalence of FD in patients with chronic kidney disease (CKD) including those on renal replacement therapy in Korea. Methods This is a national, multicenter, observational study performed between August 24, 2017 and February 28, 2020. Patients with the presence of proteinuria or treated on dialysis were screened by measuring the α-Gal A enzyme activity using either dried blood spot or whole blood, and plasma globotriaosylsphingosine (lyso-GL3) concentration. A GLA gene analysis was performed in patients with low α-Gal A enzyme activity or increased plasma lyso-GL3 concentration. Results Of 897 screened patients, 405 (45.2%) were male and 279 (31.1%) were on dialysis. The α-Gal A enzyme activity was measured in 891 patients (99.3%), and plasma lyso-GL3 concentration was measured in all patients. Ten patients were eligible for a GLA gene analysis: eight with low α-Gal A enzyme activity and two with increased plasma lyso-GL3 concentration. The GLA mutations were analyzed in nine patients and one patient was found with a pathogenic mutation. Therefore, one patient was identified with FD, giving a prevalence of 0.1% (1 of 897) in this CKD population. Conclusion Although the prevalence of FD in the CKD population was low (0.1%), screening tests are crucial to detect potential diseases in patients with relatives who can benefit from early treatment

Preoperative Lymph Node Staging by FDG PET/CT With Contrast Enhancement for Thyroid Cancer: A Multicenter Study and Comparison With Neck CT

Objectives The purpose of this study was to compare lymph node (LN) staging using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) with contrast-enhancement (CE) PET/CT and contrast-enhanced neck CT (neck CT) in patients with thyroid cancer with level-by-level comparison with various factors. Methods This was a retrospective multicenter study. A total of 85 patients were enrolled. Patients who underwent a preoperative evaluation by CE PET/CT and neck CT for thyroid cancer were enrolled. The gold standard for LN was the combination of surgical pathology and clinical follow-up. We compared CE PET/CT with neck CT using a level-by-level method. Factors, including age, sex, camera, arm position, tumor size, extra-thyroidal extension, tumor location, number of primary tumors, primary tumor maximum standardized uptake value, and the interval from scan to operation were also analyzed. Results Overall accuracy was 81.2% for CE PET/CT and 68.2% for neck CT. CE PET/CT was more sensitive than neck CT (65.8% vs. 44.7%). Also, CE PET/CT showed higher negative predictive value (77.2% vs. 66.1%). CE PET/CT showed good agreement with the gold standard (weighted kappa [κ], 0.7) for differentiating N0, N1a, and N1b, whereas neck CT showed moderate agreement (weighted κ, 0.5). CE PET/CT showed better agreement for the number of levels involved with the gold standard (weighted κ, 0.7) than that of neck CT with the gold standard (weighted κ, 0.5). The accuracies for differentiating N0, N1a, and N1b were 81.2% for CE PET/CT and 68.2% for neck CT. Level-by-level analysis showed that CE PET/CT was more sensitive and has higher negative predictive value for detecting ipsilateral level IV and level VI LNs than neck CT. Other analyzed factors were not related to accuracies of both modalities. Conclusion CE PET/CT was more sensitive and reliable than neck CT for preoperative LN staging in patients with thyroid cancer

A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice

Background Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. Methods A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. Results Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. Conclusion Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker