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The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort. Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed. Eighty-one patients received perampanel, including 39 females with median age 64 [17–91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03–1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58–0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic–clonic seizure: OR = 4.14, 95% CI 0.98–17.47, p = 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment. Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

Surgical decisions and methods of surgery highly influence long term QoL for breast cancer (BC) survivors. This study is aimed towards an exploration of the dynamic changes in quality of life (QoL), anxiety/depression status, and body image (BI) among women with BC who received a mastectomy compared with those receiving breast reconstruction (BR) within an 8-year follow-up period.Women with major BC surgeries were invited to complete the World Health Organization Quality of Life-Brief (WHOQOL-BREF), the European quality of life five dimensions questionnaire (EQ-5D), and a body image scale within 8 years of surgery. Kernel smoothing methods were applied to describe dynamic changes in QoL, anxiety/depression, and BI at different time points. Linear mixed effects models were constructed to identify the interaction between time, different types of surgery, and the determinants of QoL in these patients.After 1:10 propensity score matching, a total of 741 women who had undergone a BR and mastectomy were included. The BR group exhibited a high WHOQOL QoL score one to five years after surgery with some fluctuations. The mastectomy group had comparatively stable QoL scores on WHOQOL items and were less depressed/anxious. The BR group generally showed fluctuating, higher BI scores two years after surgery, but they exhibited more anxiety/depression during follow up for 8 years. Medical comorbidities, the status of anxiety/depression, and BI were the major factors influencing all domains and items of the WHOQOL BREF among women with BC.The mastectomy group showed a decreased trend toward depression in patients with BC. The BR group showed a significant improvement in QoL in the first 5 years with massive fluctuations. These findings should be considered and discussed in patient participatory decision-making and promotion of QoL for breast cancer survivors.

Background: The association between the biomarkers of environmental exposure, oxidative stress, and health-related behaviors in community residents living in an endemic viral hepatitis area and near petrochemical industrial complexes remains unclear. From a health promotion perspective, healthcare providers must know what to do for residents concerned about their health and living environment, especially for individual-level and modifiable risk factors. Therefore, we aimed to explore the factors associated with urinary 1-hydroxypyrene (1-OHP) and malondialdehyde (MDA). Methods: A community-based, cross-sectional study was conducted between July 2018 and February 2019 in western coastal Yunlin County, Taiwan. All participants lived within a 10 km radius of a large petrochemical complex and did not work in the factory. This study was conducted with the local hospital through annual community health screening. Biological samples were collected and biomarkers determined and quantified in the central laboratory of the collaborating hospital. Results: A total of 6335 adult residents completed the study. The mean age was 47.7 (SD = 16) years. Out of the total population, 56.4% were female, 30.1% had metabolic syndrome (MetS), and 16.8% and 14.3% had hepatitis B virus antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) positivity, respectively. The median 1-OHP and MDA level was 0.11 and 0.9 μg/g creatinine with an interquartile range of 0.07–0.18, and 0.4–1.5, respectively. The MDA levels correlated with specific diseases. The multivariable ordinal logistic regression model revealed that female sex, smoking, betel nut use, HBsAg, and anti-HCV positivity were associated with higher 1-OHP levels. In men, MetS was associated with higher 1-OHP levels and regular exercise with lower 1-OHP levels. High MDA levels were associated with smoking, betel nut users, HBsAg, and anti-HCV positivity. Conclusions: The findings highlight the importance of initiating individualized health promotion programs for residents near petrochemical factories, especially for adults with substance-use and cardiometabolic risk factors. Furthermore, it is crucial to provide further treatment to patients with viral hepatitis.

Besides lifetime risks, we estimated life expectancy (LE), expected years of life lost (EYLL), lifetime costs, and cost-per-LY (life-year) stratified by different stages of esophageal cancer (EC). From the Taiwan Cancer Registry, we collected 14,420 EC to estimate the incidence rates during 2008–2014. They were followed to 2015 to obtain the survival function, which was extrapolated to lifetime by a semiparametric method. We abstracted the monthly healthcare expenditures from the reimbursement database of National Health Insurance, which were multiplied with the corresponding survival probabilities to quantify lifetime cost and cost-per-LY after adjustments. About 93.7% of patients were male; 90.8% had squamous cell carcinoma. Most patients were diagnosed at advanced stages, with 44.6% and 28.3% at stages III and IV. The lifetime risk of EC in males increased in Taiwan with a cumulative incidence rate (CIR30–84) of 0.0146% (2008~2010) to 0.0165% (2013–2014). The EYLL for stages I-IV were 15.8, 17.5, 20.5, and 22.5, while the average of cost-per-LY for stages I-IV were US$ 6,987, $8,776, $12,153, and $22,426. EC in Taiwan appears to have shifted into younger ages groups and incidence is still increasing. Strategies for prevention, early diagnosis and treatment are warranted to improve the cost-effectiveness and control of this cancer.

Background This study estimated the long-term changes of opioid agonist treatment (OAT) in quality of life (QOL) and quantified the quality-adjusted life years (QALY) from the loss of quality-adjusted life expectancy (QALE) in heroin users. Methods A total of 1283 heroin users stratified by OAT were linked to the National Mortality Registry for 8 years (2006–2014) to obtain survival functions, which were extrapolated to lifetime by applying a rolling extrapolation algorithm to survival ratio between the sub-cohorts and age- and sex-matched referents simulated from vital statistics of Taiwan. We performed cross-sectional measurement of EQ-5D on 349 participants, including those with a valid state of OAT or non-OAT plus newly recruited consecutive patients, during 2015–2017 for utility values, while the QOL of referents were abstracted from the 2009 National Health Interview Survey. The QALE was calculated by summing the products of the mean QOL and survival rate throughout life. The QALE difference between the cohort and corresponding referents was the loss-of-QALE. Results QOL of the OAT group was significantly better than that of the non-OAT group in every domain of the EQ-5D, which was quantified to be 0.23 for utility after controlling for other variables. After extrapolation to 70 years, the estimated QALE and loss-of-QALE were 17.8 and 18.2 QALY for OAT subjects, respectively, while those of the non-OAT group were 9.2 and 27.9 QALY. Conclusions Receiving OAT could reduce QALE lost by 9.7 QALYs compared with non-OAT after accounting for QOL differences along time and different age and sex distributions.

Chronic kidney disease (CKD) is a complex disorder that affects multiple organs and increases the risk of cardiovascular complications. CKD affects approximately 12% of the population in Taiwan. Loss of kidney function leads to accumulation of potentially toxic compounds such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS), two protein-bound uremic solutes that can stimulate the progression of CKD. The aim of this study was to assess whether IS and pCS levels were correlated with CKD stage. We developed and validated a method for quantitating total and free IS and pCS in serum by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Serum samples were pretreated using protein precipitation with acetonitrile containing stable isotope-labeled IS and pCS as internal standards. After centrifugation, the supernatant was diluted and injected into a UPLC-MS/MS system. Analyte concentrations were calculated from the calibration curve and ion ratios between the analyte and the internal standard. The calibration curves were linear with a correlation coefficient of >0.999; the analytical measurement range was 0.05–5 mg/L. The limit of quantitation of this assay was 0.05 mg/L for both analytes. The reference interval was ≤0.05–1.15 mg/L for total-form IS, ≤0.05–5.33 mg/L for total-form pCS, ≤0.05 mg/L for free-form IS, and ≤0.12 mg/L for free-form pCS. A positive correlation was observed between analyte concentration and CKD stage. Our sensitive UPLC-MS/MS method for quantifying total and free-form IS and pCS in serum can be used to monitor the progression of CKD in clinical settings, identify patients at risk, and facilitate development of further therapies for this devastating disease. Keywords: Chronic kidney disease, Mass spectrometry, Uremic toxins

Background: This study aimed to investigate the adding value of MRI over CT for preoperative cytoreductive surgery with hyperthermic intraperitoneal chemotherapies (CRS/HIPEC). Methods: Imaging and intraoperative peritoneal cancer index (PCI) were calculated in 62 patients with peritoneal metastasis. Predictive models for the completeness of cytoreductive score using PCI data were established using decision tree algorithms. Results: In gastric cancer patients, a large discrepancy and poor agreement was appreciated between CT and surgical PCI, and a nonsignificant difference was noted between MRI and surgical PCI. In colon cancer patients, a better agreement and higher correlation with a smaller error was observed in PCI score using MRI than in that using CT. However, the addition of MRI to CT was limited for appendiceal and ovarian cancer patients. For predicting incomplete cytoreduction, CT models yielded inadequate accuracy while MRI models were more accurate with fair discrimination ability. Conclusions: CT was suitable for estimating PCI and surgery outcome in appendiceal and ovarian cancer patients, while further MRI in addition to CT was recommended for colon and gastric cancer patients. However, for classifying patients with peritoneal carcinomatosis into complete and incomplete cytoreduction, MRI was more effective than CT.

Background/Purpose We estimated loss-of-life expectancy (LE) and lifetime medical expenditures (LME) stratified by stages to evaluate the cost-effectiveness of breast cancer (BC) screening in Taiwan. Methods We interlinked four national databases- Cancer Registry, Mortality Registry, National Health Insurance Claim, and Mammography Screening. A cohort of 123,221 BC was identified during 2002–2015 and followed until December 31, 2017. We estimated LE and loss-of-LE by rolling extrapolation algorithm using age-, sex-, and calendar-year-matched referents simulated from vital statistics. LME was estimated by multiplying monthly cost with survival probability and adjusted for annual discount rate. We calculated incremental cost-effectiveness ratio (ICER) by comparing the loss-of-LE of those detected by screening versus non-screening after accounting for administration fees and radiation-related excess BC. Results The LEs of stages I, II, III, and IV were 31.4, 27.2, 20.0, and 5.2 years, respectively, while the loss-of-LEs were 1.2, 4.9, 11.7, and 25.0 years with corresponding LMEs of US$ 73,791, 79,496, 89,962, and 66,981, respectively. The difference in LE between stages I and IV was 26.2 years while that of loss-of-LE was 23.8 years, which implies that a potential lead time bias may exist if diagnosis at younger ages for earlier stages were not adjusted for. The ICER of mammography seemed cost-saving after the coverage exceeded half a million. Conclusion Mammography could detect BC early and be cost-saving after adjustment for different distributions of age and calendar year of diagnosis. Future studies exploring healthcare expenditure and impaired quality of life for false-positive cases are warranted.

The effective dose of perampanel in status epilepticus (SE), refractory SE (RSE), and super-refractory SE (SRSE) in humans is unknown, and the potential of perampanel in treating SE has not been evaluated in a large cohort.Data of intensive care patients with RSE and SRSE treated with perampanel were retrospectively reviewed and analyzed.Eighty-one patients received perampanel, including 39 females with median age 64 [17-91] years, perampanel responders (n = 27), and non-responders (n = 54). The initial perampanel dose was positively associated with treatment response in patients with RSE or SRSE (OR = 1.27, 95% CI 1.03-1.57, p = 0.025), while the maximum dose was negatively associated with treatment response (OR = 0.74, 95% CI 0.58-0.96, p = 0.022). Hypoxia caused seizures in six patients; five died in hospital and one had severe disability. A statistically non-significant tendency toward better response was found in patients with unique SE type and cause, particularly in nonconvulsive status epilepticus (NCSE) without coma (NCSE without coma vs. generalized tonic-clonic seizure: OR = 4.14, 95% CI 0.98-17.47, p = 0.053). In the high-dose (≥ 16 mg/day) groups, although distributions of modified Rankin Scale (mRS) scores were similar between perampanel responders and non-responders at discharge, a greater proportion of perampanel responders had less change in mRS scores from baseline than did perampanel non-responders (median mRS: 0 vs 4, p = 0.064). No cardiorespiratory adverse events or laboratory abnormalities were noted with perampanel treatment.Perampanel is effective and has a satisfactory safety profile in the emergency treatment of established RSE and SRSE.

Objectives We assess the incremental cost-effectiveness ratio (ICER) of the oral cancer (OC) screening program in Taiwan. Materials and methods We interlinked the Cancer Registry, Mortality Registry, National Vital Statistics, reimbursement database of National Health Insurance, and the National Oral Cancer Screening database of Taiwan. A total of 40,092 pathologically verified OC patients were identified and followed during 2002–2014. After stratification by stages, lifetime survival curves were estimated by a rolling extrapolation algorithm to obtain life expectancy (LE), expected years of life lost (EYLL), and lifetime medical costs (LMC). Results The LE for stages I-IV were 19.5, 14.0, 11.9, and 7.7 life-years, respectively, while those of EYLL were 7.3, 12.2, 15.4, and 18.7 life-years, respectively. The LMC for stages I-IV were US$ 65,752, 60,086, 53,675, and 47,570, respectively. We assumed no life loss for stage 0 with LMC of US$ 5380 spent for the first year after diagnosis. During 2010–2013, 967 out of the 28,018 cases detected with abnormal oral pathology by screening were found to develop OC. The ICER of the screening program was US$ 28,516 per life-year saved, which could be improved to US$ 5579 per life-year saved if all cancers transformed from abnormal oral pathology were detected before stage I. Conclusion The ICER of the current OC screening program in Taiwan slightly exceeds 1 GDP (gross domestic product) per capita per life-year saved. Intensive follow-up and treatment for all patients with abnormal oral pathology would improve screening efficiency and effectiveness of prevention.

Objective This study aims to identify metabolites with altered levels of expression in patients with early and progressive stages of Alzheimer's disease (AD). Methods All participants of the study underwent genetic screening and were diagnosed using both neuropsychological assessment and amyloid imaging before metabolome analysis. According to these assessments, the patients were classified as normal (n = 15), with mild cognitive impairment (n = 10), and with AD (n = 15). Results Using a targeted metabolomic approach, we found that plasma levels of C3, C5, and C5‐DC acylcarnitines, arginine, phenylalanine, creatinine, symmetric dimethylarginine (SDMA) and phosphatidylcholine ae C38:2 were significantly altered in patients with early and progressive stages of AD. We created a predictive model based on the decision tree that included three main parameters: age, arginine and C5 plasma concentrations. The model distinguished AD patients from other participants with 60% sensitivity and 86.7% specificity. For healthy controls, the sensitivity was 85.7% and specificity was 61.5%. Multivariate ROC analysis to develop a decision tree showed that our model reached moderate diagnostic power in differentiating between older adults who are cognitively normal (AUC = 0.77) and those with AD (AUC = 0.72). Interpretation The plasma levels of arginine and valeryl carnitine, together with subject age, are promising as biomarkers for the diagnosis of AD in older adults.

AIMS AND OBJECTIVES To determine the comparative efficacy of developmental care versus standard care for reducing pain and stress in preterm infants during examinations for retinopathy of prematurity (ROP). BACKGROUND ROP examinations are routinely performed in neonatal intensive care units to detect these lesions. Pain scores recorded during and after eye examinations have revealed physiological and behavioural manifestations of pain and stress. DESIGN A randomised crossover trial was conducted. METHODS Fourteen preterm infants were evaluated. The modified developmental care bundle included environmental modifications, positioning and containment, oxygen supplementation, interaction and approach and cue-based individual care, which were applied before, during and after the ROP examination. The primary outcomes were obtained from pain and stress scores using the premature infant pain profile-revised (PIPP-R) and a behavioural evaluation. The secondary outcomes were recovery time to the baseline of the vital signs and oxygen saturation. RESULTS Statistical significances were found in the care type comparison (p = 0.013), time comparison (p

Background The mortality rates for different cancers are no longer an efficient tool for making national policy. The purpose of this study were to quantify the lifetime risks, life expectancies (LEs) after diagnosis, expected years of life lost (EYLL), and lifetime health care expenditures for 19 major cancers in Taiwan. Methods A total of 831,314 patients with 19 pathologically proven cancers were abstracted from the Taiwan Cancer Registry from 1998 to 2012. They were linked to the National Mortality Registry (1998–2014) and National Health Insurance reimbursement database (1998–2013) for survival and health care costs. We estimated the cumulative incidence rate for ages 0–79 years and the lifetime survival function for patients with different cancer sites. The EYLL was calculated by subtracting the LE of each cancer cohort from that of the age- and sex-matched referents simulated from national life tables. The estimated lifetime cost was calculated by adding up the product of survival probability and mean cost at the corresponding duration-to-date after adjustment for the inflation to the year of 2013. Results There were 5 cancers with a lifetime risk exceeding 4%: colorectal, liver, lung, and prostate in males, and breast and colorectal in females. Cancers with EYLL of >10 years were: esophageal, intrahepatic bile ducts, liver, pancreas, oral, nasopharyngeal, leukemia, lung, and gallbladder, extrahepatic bile ducts and biliary tract in males, and intrahepatic bile ducts, pancreas, nasopharyngeal, lung, esophageal, leukemia, liver, gallbladder, extrahepatic bile ducts and biliary tract, ovary, and stomach in females. Cancers with lifetime health care expenditures exceeding US$50,000 to the National Health Insurance were as follows: leukemia, kidney, testis, renal pelvis and ureter in males, and renal pelvis and ureter, leukemia, breast, urinary bladder, kidney, ovary, and nasopharyngeal in females. All these impacts should be considered in health policy decisions. Conclusion The impacts of cancer in Taiwan are very large. Future studies must consider both quality of life and the entire impact from societal perspectives., Video abstract

Aims/Introduction Diabetic nephropathy is one of the leading causes of end-stage renal disease. Unfortunately, reliable surrogate markers for predicting the prognostic outcome of diabetic nephropathy are as yet absent. In order to find new markers in predicting the progression of diabetic nephropathy, we carried out a prospective study by investigating the correlation between serum metabolites and the annual change of estimated glomerular filtration rate (eGFR). Materials and Methods From September 2013 to September 2015, 52 diabetes patients at various stages of chronic kidney disease were enrolled. While serum levels of 175 metabolites were measured by AbsoluteIDQ™ p180 kit, only those with a significant difference in advancing chronic kidney disease stages were selected. After then, serial renal function change of these patients was followed up for 12 months, the outcome of renal function with each selected metabolite was compared according to the occurrence of a rapid decline (sustained annual decrement rate ≥5%) of eGFR. Results A total of 26 metabolites were found to be significantly associated with the severity of chronic kidney disease. Tryptophan (Trp) showed a significant association with the event of rapid decline in eGFR (P = 0.036). Serum concentration of Trp

Background Significant genetic association has been found in patients with severe carotid artery stenosis (CAS). The present study wished to investigate if metabolites may also act as biomarkers for CAS. Methods Consecutive patients with at least one carotid artery stenosis > = 60% on cerebral angiography were prospectively recruited from May 2007 to January 2016. Normal controls were recruited from outpatient clinic who had no stroke and coronary artery disease (CAD) history, and the brain magnetic resonance or computed tomographic angiography showed bilateral CAS

BACKGROUND Based on the breakthrough of genomics analysis, The Cancer Genome Atlas Research Group recently proposed an integrative genomic analysis, dividing gastric cancer (GC) into four subtypes, characterized by the chromosomal instability (CIN) status. However, the CIN status of GC is still vaguely characterized and lacking the valuable easy-to-use CIN markers to diagnosis in molecular and histological detection. AIM To explore the associations of CIN with downstream lipidomics profiles. METHODS We collected cancerous and noncancerous tissue samples from 18 patients with GC; the samples were divided into CIN and non-CIN types based on the system of The Cancer Genome Atlas Research Group and 409 sequenced oncogenes and tumor suppressor genes. We identified the lipidomics profiles of the GC samples and samples of their adjacent noncancerous tissues by using liquid chromatography–mass spectrometry. Furthermore, we selected leading metabolites based on variable importance in projection scores of > 1.0 and P < 0.05. RESULTS Twelve men and six women participated in this study; the participants had a median age of 67.5 years (range, 52–87 years) and were divided into CIN (n = 9) and non-CIN (n = 9) groups. The GC samples exhibited distinct profiles of lysophosphocholine, phosphocholine, phosphatidylethanolamine, phosphatidylinositol, phosphoserine, sphingomyelin, ceramide, and triglycerides compared with their adjacent noncancerous tissues. The glycerophospholipid levels (phosphocholine, phosphatidylethanolamine, and phosphatidylinositol) were 1.4- to 2.3-times higher in the CIN group compared with the non-CIN group (P < 0.05). Alterations in the glycerolipid and glycerophospholipid pathways indicated progression of GC toward CIN. CONCLUSION The lipidomics profiles of GC samples were distinct from those of their adjacent noncancerous tissues. CIN status of GC is primarily associated with downstream lipidomics in the glycerophospholipid pathway.

Background/purpose: Indoxyl sulfate (IS) is a protein-binding molecule that exhibits cardiovascular (CV) toxicity. This study determined whether the serum IS level can be used to predict the risk of major adverse CV events (MACEs) in patients with chronic kidney disease (CKD). Methods: We studied 147 patients with CKD stage 1–5 over a 3-year follow-up period. IS was measured through mass spectrometry. Patients’ demographics were collected and analyzed to predict outcomes by using multivariable Cox regression. Results: Forty-seven (32.0%) patients had MACEs. IS remained significantly associated with MACEs after multivariable regression analysis. The area under the receiver operating characteristic curve for IS levels was 0.708 (95% confidence interval: 0.618–0.798). Conclusion: IS may have a critical role in the prediction of CV disease in patients with CKD. Further large-scale investigations are warranted and suggested. Keywords: Chronic kidney disease (CKD), Indoxyl sulfate (IS), Protein-bound uremic toxins, Major adverse cardiovascular events (MACEs), Prognosis

Acute intermittent porphyria (AIP) is caused by diminished activity of porphobilinogen deaminase (PBGD). The purpose of this study was to validate and compare two assays for PBGD activity. The clinical sensitivity of the PBGD activity assays in AIP diagnosis was also evaluated.This study included 74 subjects from 18 Taiwanese families including symptomatic patients with AIP, asymptomatic carriers, and healthy family members. The specific mutations in AIP patients were identified by DNA sequencing. PBGD activity was measured in erythrocytes by quantifying formation of coproporphyrin or uroporphyrin by the enzyme using porphobilinogen (PBG) as a substrate and fluorimetry for detection.The calibration curves obtained with pure coproporphyrin or uroporphyrin were linear with correlation coefficients0.99 in the range of 0-200nM for coproporphyrin and 0-150nM for uroporphyrin. The coefficients of variation for within-run and between-day imprecision were9.8% for both assays. The three groups of subjects were used to establish the best cut-off of PBGD activity for identifying symptomatic AIP patients by using area under receiver operating characteristic curve analysis. The symptomatic AIP patients and asymptomatic carriers had significantly lower PBGD activity compared with the healthy family members (all p.001).Two different PBGD activity assays were validated. The best cut-off for coproporphyrin was derived as 46.4nmol/h/mL RBC with corresponding sensitivity of 100% and specificity of 100% and the best cut-off for uroporphyrin was derived as 43.7nkat/L RBC with corresponding sensitivity of 100% and specificity of 97.4%.

// Ya-Ching Huang 1, 2, * , Hsiao-Chen Ning 1, 2, * , Shang-Syuan Chen 1 , Chia-Ni Lin 1, 2 , I-Kwan Wang 3 , Shu-Man Weng 4 , Cheng-Hao Weng 4 , Ching-Wei Hsu 4 , Wen-Hung Huang 4 , Jang-Jih Lu 1 , Tsu-Lan Wu 1, 2 and Tzung-Hai Yen 4, 5, 6 1 Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taiwan 2 Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Linkou, Taiwan 3 Department of Nephrology, Chang Medical University Hospital and College of Medicine, China Medical University, Taichung, Taiwan 4 Department of Nephrology, Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Linkou, Taiwan 5 Kidney Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan 6 Center for Tissue Engineering, Chang Gung Memorial Hospital, Linkou, Taiwan * These authors have contributed equally to this work Correspondence to: Tzung-Hai Yen, email: m19570@adm.cgmh.org.tw Keywords: peritoneal dialysis, nickel, high sensitivity C-reactive protein, inflammation, inductively coupled plasma mass spectrometry Received: May 14, 2017 Accepted: June 30, 2017 Published: July 31, 2017 ABSTRACT This study surveyed urinary nickel concentrations in peritoneal dialysis (PD) patients, and analyzed the association of urinary nickel concentrations with clinical outcomes and inflammatory biomarkers. In total, 50 PD patients and 50 healthy controls were recruited for this study. All participants were examined for the presence of toxic trace elements (antimony, arsenic, bismuth, cadmium, copper, manganese, mercury, nickel, lead, tellurium, thallium and zinc) in their urine by using inductively coupled plasma mass spectrometry (ICP-MS). It was found that PD patients demonstrated higher urinary nickel concentrations than healthy controls (6.1±3.5 versus 2.8±1.4 μg/L, P 0.05). Thus, it is concluded that approximately half of the patients undergoing PD had elevated urinary nickel levels, and these patients also had elevated serum levels of high sensitivity C-reactive protein. Nevertheless, no other real correlations were discovered including no impact on patient outcome. Further studies are warranted.

Background Amino acids are associated with wound healing in traumatic wounds and burns, although their effects on healing in patients with diabetic foot ulcers (DFUs) are limited. This study aimed to evaluate and identify specific amino acids associated with healing outcomes of patients with DFUs. Methods Sixty-two out of 85 patients who completed the in-hospital treatment for limb-threatening DFUs were enrolled. All ulcers had epithelialization without clinical evidence of infection at discharge. The patients and their families were instructed on foot-care techniques and committed to regular follow-up for 1 year. Baseline characteristics, PEDIS wound classification, laboratory data and serum amino acid levels were used to analyze their predictive power. Results Fifty-seven patients completed the study in which 38 had healed and 19 had unhealed ulcers. The unhealed group had higher incidence of coronary artery disease and larger wound size. Most patients received endovascular therapy (81.6% healed group; 78.9% unhealed group) before enrollment. Following adjustments for clinical factors, the serum levels of arginine (326.4 μmol/L vs. 245.0 μmol/L, P = 0.045), isoleucine (166.7 μmol/L vs. 130.1 μmol/L, P = 0.019), leucine (325.8 μmol/L vs. 248.9 μmol/L, P = 0.039), and threonine (186.7 μmol/L vs. 152.0 μmol/L, P = 0.019) were significantly higher in the healed group. Conclusions The amino acids associated with wound healing in DFUs differ from those reported for traditional traumatic wounds. These findings affirm the necessity for future large-scaled studies for the application of these amino acids in DFU healing, either as prognostic predictors or supplemented regimens.

Methods for circumventing positive drug tests continue to evolve and are often spread through internet websites reporting on the proposed effectiveness of various adulteration methods. Recent claims of the use of zinc added directly to urine or ingested prior to urine collection have prompted investigation into the vulnerability of ELISA-based testing, providing interesting but inconclusive results. We investigated the potential interference of zinc used as a direct adulterant and after zinc self-administration for enzyme multiplied immunoassay technique (EMIT)-based drug abuse testing in urine. Negative urine samples and samples collected before and after zinc self-administration were fortified with d-methamphetamine, benzoylecgonine, morphine and 11-nor-9-carboxy-tetrahydrocannabinol prior to analysis by the EMIT. Our data indicate that zinc added directly to urine in concentrations 5,000 times higher than a typical random urine total zinc concentration is capable of producing false-negative results; however, self-administration of oral zinc was unable to generate random urine total zinc concentrations in the required range. Further, no evidence of a secondary interfering substance was observed as a result of oral zinc self-administration. Our results indicate that the total zinc concentrations required to directly interfere with EMIT-based testing are easily distinguishable from routine random urine total zinc concentrations, and that alleged oral ingestion of zinc does not produce total zinc concentrations capable of direct interference.

Background Accurate patient identification and specimen labeling at the time of collection are crucial steps in the prevention of medical errors, thereby improving patient safety. Methods All patient specimen identification errors that occurred in the outpatient department (OPD), emergency department (ED), and inpatient department (IPD) of a 3,800-bed academic medical center in Taiwan were documented and analyzed retrospectively from 2005 to 2014. To reduce such errors, the following series of strategies were implemented: a restrictive specimen acceptance policy for the ED and IPD in 2006; a computer-assisted barcode positive patient identification system for the ED and IPD in 2007 and 2010, and automated sample labeling combined with electronic identification systems introduced to the OPD in 2009. Results Of the 2000345 specimens collected in 2005, 1023 (0.0511%) were identified as having patient identification errors, compared with 58 errors (0.0015%) among 3761238 specimens collected in 2014, after serial interventions; this represents a 97% relative reduction. The total number (rate) of institutional identification errors contributed from the ED, IPD, and OPD over a 10-year period were 423 (0.1058%), 556 (0.0587%), and 44 (0.0067%) errors before the interventions, and 3 (0.0007%), 52 (0.0045%) and 3 (0.0001%) after interventions, representing relative 99%, 92% and 98% reductions, respectively. Conclusions Accurate patient identification is a challenge of patient safety in different health settings. The data collected in our study indicate that a restrictive specimen acceptance policy, computer-generated positive identification systems, and interdisciplinary cooperation can significantly reduce patient identification errors.

Urine drug testing is an important tool that is commonly used to assess patient compliance with prescription regimens. Point-of-collection immunoassay devices allow for timely availability of laboratory test results to guide therapy during the same office visit. Two waived immunoassay-based urine drug screen cups were evaluated in this study. The NexScreen cup and the DrugCheck Waive RT cup claim to detect 10-12 drug classes of commonly used and/or abused drugs. This study included a sensitivity and precision challenge with 4-6 replicates at concentrations 0-150% of the manufacture's claimed cutoff, using drug-free urine spiked with purified reference standards. The stability of test results was evaluated by reading the results at intervals between five and 1,440 min. Specificity was evaluated by parallel comparison of pooled patients' specimens, representing 56 patients and 41 known drug compounds. When comparing results to validated liquid chromatography-mass spectrometry results, false positives were observed in the NexScreen cups for benzodiazepine, methamphetamine, methadone, opiates and tricyclic antidepressant tests, but there were no false negatives. The DrugCheck Waive RT cups showed false negative results for barbiturates and opiates, but no false positives. Overall, the NexScreen cup demonstrated better sensitivity than claimed, whereas the sensitivity of the DrugCheck Waive RT cup did not meet claims.

e16120Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality in the United States. Due to the high prevalence of hepatitis B/C infection, HCC ranks second in can...

Background Highly pathogenic influenza viruses cause high levels of morbidity, including excessive infiltration of leukocytes into the lungs, high viral loads and a cytokine storm. However, the details of how these pathological features unfold in severe influenza infections remain unclear. Accumulation of Gr1 + CD11b + myeloid cells has been observed in highly pathogenic influenza infections but it is not clear how and why they accumulate in the severely inflamed lung. In this study, we selected this cell population as a target to investigate the extreme inflammatory response during severe influenza infection. Results We established H1N1 IAV-infected mouse models using three viruses of varying pathogenicity and noted the accumulation of a defined Gr1 + CD11b + myeloid population correlating with the pathogenicity. Herein, we reported that CCR2+ inflammatory monocytes are the major cell compartments in this population. Of note, impaired clearance of the high pathogenicity virus prolonged IFN expression, leading to CCR2+ inflammatory monocytes amplifying their own recruitment via an interferon-α/β receptor 1 (IFNAR1)-triggered chemokine loop. Blockage of IFNAR1-triggered signaling or inhibition of viral replication by Oseltamivir significantly suppresses the expression of CCR2 ligands and reduced the influx of CCR2+ inflammatory monocytes. Furthermore, trafficking of CCR2+ inflammatory monocytes from the bone marrow to the lung was evidenced by a CCR2-dependent chemotaxis. Importantly, leukocyte infiltration, cytokine storm and expression of iNOS were significantly reduced in CCR2−/− mice lacking infiltrating CCR2+ inflammatory monocytes, enhancing the survival of the infected mice. Conclusions Our results indicated that uncontrolled viral replication leads to excessive production of inflammatory innate immune responses by accumulating CCR2+ inflammatory monocytes, which contribute to the fatal outcomes of high pathogenicity virus infections.