Routine Test Results Research Articles

The alcohol biomarker phosphatidylethanol (PEth) – test performance and experiences from routine analysis and external quality assessment

Phosphatidylethanol (PEth) are membrane molecules formed from phosphatidylcholine and ethanol through transphosphatidylation catalyzed by phospholipase D. Measurement of the main PEth form 16:0/18:1 is used as a specific and sensitive alcohol biomarker, since its formation requires ethanol, it accumulates in the blood upon repeated ethanol exposure, and it is only slowly eliminated during abstinence. PEth formation correlates with alcohol intake at the population level, albeit with considerable inter-individual variation as for the half-life during withdrawal. Over the past decade, the use of PEth has increased significantly and the applications have broadened. In Sweden, routine decision limits and the interpretation of test results for PEth were harmonized in 2013, using < 0.05 µmol/L (∼35 µg/L) as the recommended lower reporting limit and values > 0.30 µmol/L (∼210 µg/L) to indicate regular high alcohol intake. Routine test results show a large variation with about half being < 0.05 µmol/L and some even exceeding 10 µmol/L. In 2013, an external quality assessment (EQA) scheme for PEth 16:0/18:1 measurement in whole blood was also started (Equalis, Uppsala, Sweden), presently involving 56 laboratories from 13 countries. The agreement of PEth results between the laboratories has gradually improved to a CV < 15%. The current clinical and scientific information suggests that PEth values below the lower reporting limit (typically ∼0.03–0.05 µmol/L, or ∼20–35 µg/L) indicates sobriety or only low or occasional alcohol consumption, while regular high alcohol intake at levels corresponding to harmful drinking is required in most cases to reach PEth values > 0.30 µmol/L.

Parameters Predicting Microvascular Invasion and Poor Differentiation in Hepatocellular Carcinoma Patients with Normal Alpha-fetoprotein Level Before Liver Transplantation.

The aim of this study is to evaluate the parameters that might be associated with pathologically diagnosed microvascular invasion and poor differentiation, using complete blood count and routine clinical biochemistry test results, in hepatocellular carcinoma patients before liver transplantation. The data of patients who underwent liver transplantation for hepatocellular carcinoma at our institute, between March 2006 and November 2021, was researched retrospectively. The incidence of microvascular invasion was 28.6%, poor differentiation rate was 9.3%, hepatocellular carcinoma recurrence rate after liver transplantation was 12.1%, and median time to recurrence was 13 months, in the patients with normal alpha-fetoprotein levels. After univariate and multivariate analysis, maximum tumor diameter > 4.5 cm and the number of nodules (n > 5) were found to be independent risk factors for microvascular invasion, and number of nodules > 4 and mean platelet volume ≤8.6 fL were found to be independent risk factors for poor differentiation. Serum alpha-fetoprotein levels were still within the normal range at the recurrence time, in 53% of the patients who had recurrence after liver transplantation, but surprisingly were elevated in 47% of the patients at time of hepatocellular carcinoma recurrence. In hepatocellular carcinoma patients with normal alpha-fetoprotein levels before liver transplantation, independent risk factors of the presence of microvascular invasion were maximum tumor diameter and number of nodules, and independent risk factors of poor differentiation were mean platelet volume and number of nodules. Furthermore, serum alpha-fetoprotein levels were still normal at time of recurrence in 53% of hepatocellular carcinoma patients whose alpha-fetoprotein levels were normal before liver transplantation but were elevated in 47% of the patients at recurrence time, despite having normal levels before liver transplantation.

Improvements to the procedure for determination of the residual lifetime of railway vehicles

Existing research concerning the extention of the service life of various types of railway vehicles and assessing its remaining lifetime has been reviewed and analyzed. It has been established that the vast majority of studies relate to the assessment of the residual lifetime of various types of railway rolling stock based on the results of technical diagnostics and routine tests, as well as the assessment of corrosion wear of supporting elements and vehicles bodies. At the same time, little attention has been paid to the issue of improving existing programs and procedures of complex technical diagnostics. It was determined that the set of diagnostics operations for the extension of the service life includes routine tests of a test sample and examination of the technical condition of the metal structure of each railway vehicle for mechanical and corrosive damage.It is proposed to make changes to the existing current programs and procedures in such key sections as: terminology, objects of technical diagnostics and tests, selection of a test sample for routine tests, execution order and methods of technical diagnostics and routine tests, data processing and evaluation of results. A comprehensive approach for assessing the residual lifetime of railway vehicles is also proposed.

Coffee intake one hour prior to phlebotomy produces no clinically significant changes in routine biochemical test results.

Although current guidelines recommend not drinking coffee prior to phlebotomy, our hypothesis is that drinking coffee does not affect the clinical interpretation of biochemical and haematological test results. Twenty-seven volunteers were studied in basal state (T0) and 1h after (T1) drinking coffee. Routine haematological (Sysmex-XN1000 analyser) and biochemistry parameters (Vitros 4600 analyser) were studied. Results were compared using the Wilcoxon test (P < 0.05). A clinical change was considered when mean percent difference (MD%) was higher than the reference change value (RCV). Coffee intake produced statistically, but not clinically, significant: i) increases in haemoglobin (P = 0.009), mean cell haemoglobin concentration (P = 0.044), neutrophils (P = 0.001), albumin (P = 0.001), total protein (P = 0.000), cholesterol (P = 0.025), high density lipoprotein cholesterol (P = 0.007), uric acid (P = 0.011), calcium (P = 0.001), potassium (P = 0.010), aspartate aminotransferase (P = 0.001), amylase (P = 0.026), and lactate dehydrogenase (P = 0.001), and ii) decreases in mean cell volume (P = 0.002), red cell distribution width (P = 0.001), eosinophils (P = 0.002), and lymphocytes (P = 0.001), creatinine (P = 0.001), total bilirubin (P = 0.012), phosphorus (P = 0.001), magnesium (P = 0.007), and chloride (P = 0.001). Drinking a cup of coffee 1 hour prior to phlebotomy produces no clinically significant changes in routine biochemical and haematological test results.

#3067 ALPORT SYNDROME NATURAL HISTORY FROM THE RADAR REGISTRY: ASSOCIATIONS WITH GENE, VARIANT TYPE AND SEX

Abstract Background and Aims Alport Syndrome (AS) is caused by pathogenic variants in COL4A3, COL4A4 &amp; COL4A5 genes. The clinical course of AS can be highly variable, depending on gene affected, mutation type and Male (M) or Female (F) sex. Proteinuria is associated with worse prognosis. Previous genotype-phenotype correlation studies have shown protein length altering variants are associated with a more severe phenotype in males with COL4A5 variants, however studies in females have shown contradicting results. This study aims to describe demographics and investigate renal outcomes associated with pathogenic variant type in M vs F AS patients, using longitudinal data from the National Registry of Rare Kidney Diseases (RaDaR) which recruits patients at 108 UK renal clinics. Method RaDaR is linked to Regional Genetics hubs for clinical genetic reports, renal IT systems for routine test results and the UK Renal Registry for Renal Replacement Therapy (RRT) initiation data. eGFR was calculated using CKD-EPI Cr equation (2021) or Schwartz equation for those ≤ 16 yrs. eGFR slope was calculated over the last 3 years (or 3 years prior to End Stage Kidney Disease (ESKD)/death for patients who reached those outcomes), with patients required to have a minimum of 4 values over 2 years. For genotype data, variants classified in clinically issued reports as “Pathogenic” or “Likely Pathogenic” were included and classed as: 1. Protein Length Altering and 2. Missense variants. Where both protein length altering and missense variants in the same gene were identified in an individual, the missense variant was used. Data are presented as percentages for categorical variables and mean ± SD for continuous variables. Kaplan Meier analysis and the log rank statistic were used to compare age at RRT start, stratified by gender and variant types. Lower quartile (LQ) (25%) estimates are presented where too few events have occurred to calculate a median (50%) estimate. Results Between Jan 2013–Jul 2022, 920 AS patients were recruited; 53% M vs. 47% F. Genetic test reports were available for 343/920 (37%) patients. 294/343 (86%) reported a pathogenic or likely pathogenic variant, 140 protein length altering and 154 missense. Individuals with 2x COL4A3/COL4A4 variants were youngest at RRT start, whilst females with COL4A5 variants were oldest (LQ 20.1 vs 60.9 yrs, log-rank p&amp;lt;0.0001) (Figure 1a). COL4A5 variants Males with protein length altering COL4A5 variants were younger at ESKD compared with missense variants (median age 30.2 vs 52.1 yrs, p = 0.01). Conversely 0/36 females with protein length altering COL4A5 variants had started RRT, compared with 6/37 with missense variants (p = 0.01) (Figure 1bi-ii). COL4A3 or COL4A4 variants Whilst females with heterozygous protein length altering COL4A3/4 variants were younger at RRT start vs. those with missense variants (LQ 47.1 vs 64.9 yrs, p = 0.05), age at RRT start did not differ by mutation type for males with COL4A3/4 heterozygous variants (Figure 1b iii-iv). However, males with homozygous or 2x protein length altering COL4A3/4 variants were younger at RRT start than those with missense variants (median age 20.1 vs 24.3 yrs, P = 0.05), whilst no difference was observed by variant type for females with 2x COL4A3/4 variants (Figure 1b v-vi). Proteinuria and eGFR slope were generally correlated with age at ESKD. Conclusion The observed effect of pathogenic variant type on renal outcomes varied by gene affected, number of mutations and sex. The relatively reduced severity among females harbouring a protein length altering COL4A5 variant may represent an effect of skewed X-inactivation or a missense gain-of-function mechanism. RaDaR recruits patients with a clinical diagnosis of Alport syndrome or Thin Basement Membrane Nephropathy; ascertainment of individuals with a single COL4A3 or COL4A4 variant is therefore likely to favour those with more severe kidney disease. Linkage of the RaDaR AS cohort with genetic report data is ongoing; further correlations may be observed with larger numbers.

Machine learning clinical decision support systems for surveillance: a case study on pertussis and RSV in children.

We tested the performance of a machine learning (ML) algorithm based on signs and symptoms for the diagnosis of RSV infection or pertussis in the first year of age to support clinical decisions and provide timely data for public health surveillance. We used data from a retrospective case series of children in the first year of life investigated for acute respiratory infections in the emergency room from 2015 to 2020. We collected data from PCR laboratory tests for confirming pertussis or RSV infection, clinical symptoms, and routine blood testing results, which were used for the algorithm development. We used a LightGBM model to develop 2 sets of models for predicting pertussis and RSV infection: for each type of infection, we developed one model trained with the combination of clinical symptoms and results from routine blood test (white blood cell count, lymphocyte fraction and C-reactive protein), and one with symptoms only. All analyses were performed using Python 3.7.4 with Shapley values (Shap values) visualization package for predictor visualization. The performance of the models was assessed through confusion matrices. The models were developed on a dataset of 599 children. The recall for the pertussis model combining symptoms and routine laboratory tests was 0.72, and 0.74 with clinical symptoms only. For RSV infection, recall was 0.68 with clinical symptoms and laboratory tests and 0.71 with clinical symptoms only. The F1 score for the pertussis model was 0.72 in both models, and, for RSV infection, it was 0.69 and 0.75. ML models can support the diagnosis and surveillance of infectious diseases such as pertussis or RSV infection in children based on common symptoms and laboratory tests. ML-based clinical decision support systems may be developed in the future in large networks to create accurate tools for clinical support and public health surveillance.

Detection of nidoviruses in samples collected from captive snakes in Europe between 2016 and 2021.

Nidoviruses are increasingly detected in various snake species worldwide, but much remains to be learned about their distribution and the factors influencing their epidemiology. This retrospective study evaluated the results of routine nidovirus testing, by PCR, of 5210 swab samples from pet snakes from various European countries that were submitted to a commercial veterinary laboratory in Germany between 2016 and 2021. The overall detection rate was 19.96%. However, the detection rate varied significantly depending on the snake species (p < 0.0001), with the highest rate in Indian pythons (Python molurus) (42.24%). Rates also varied depending on the season of sample collection (p < 0.0001), with the highest rate in winter (24.46%), and the country of sample origin (p < 0.0001), with the highest rate in Austria (36.69%). The detection rate also decreased significantly (p = 0.0003) over the 6-year observation period, from 26.43% to 17.64%. No information on clinical signs was available for most of the sampled snakes. The present study supplies new information on the distribution of python nidoviruses (subgenus Roypretovirus) in pet snakes in Europe and indicates a dynamic situation with possible changes in prevalence over time.

Antimicrobial Treatment of Staphylococcus aureus Biofilms.

Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.

Digital Breast Tomosynthesis Quality Control Manual Overview

Recently, mammography systems equipped with digital breast tomosynthesis (DBT) have become widely used in Japan. Therefore, it is urgently necessary to establish a quality control method for DBTs. So far, we have been studying acceptance tests for DBTs with reference to EUREF. In 2020, IEC 61223-3-6 was published, which provides not only acceptance tests but also constancy test methods. Therefore, we conducted data collection using DBTs sold in Japan and examined the feasibility of conducting constancy tests. Although there were some items that were difficult to implement in each device, we were able to confirm quality control items that could be implemented in many devices. In addition, we were able to confirm routine tests that enable rapid evaluation. Based on these results, we have developed a "Digital Breast Tomosynthesis Quality Control Manual". In this paper, we report an overview of the manual and the results of routine tests.

Study on the Correlation between Genital Tract Microenvironment and GBS Carrier Rate of Late-Stage Pregnant Women in Dongguan.

The carrier rate of group B Streptococcus (GBS) in the genital tract of women in the late stage of pregnancy and its correlation with the genital tract microenvironment were investigated in a group of pregnant women in Dongguan, China, to provide a basis for the clinical prevention and treatment of GBS. A retrospective analysis was done of the results of routine testing for GBS, leucorrhea and bacterial vaginosis (BV) in 6,166 women in the late stage of pregnancy (35 - 37 weeks of gestation) who underwent a prenatal examination at Dongguan Southeast Central Hospital from January 2018 to December 2020. GBS positivity was detected by RT-PCR. Normal saline floating microscopy was used to detect routine indicators of leucorrhea, including white blood cells (WBCs), Lactobacillus (Lab), vulvovaginal Candida (VVC), and trichomoniasis (TV). BV was detected based on an enzymatic reaction. The correlation between GBS infection and age and the vaginal microenvironment was determined statistically. The rate of GBS positivity was 10.53% (649/6,166) and was statistically significant for women 20 years of age (p < 0.05). Logistic regression showed that abnormal VVC, TV, BV, WBCs, and Lactobacillus were associated with GBS infection. The results of a rank sum test of the WBC group showed that the infection risk in groups with < 15 WBCs/hpf increased as the WBC count increased, but there was no statistical difference between groups with > 15 WBCs/hpf. The rank sum test results for Lactobacillus showed a significant difference between the abnormal and normal and other groups, but no significant difference between the other groups. The overall carrier rate of GBS in the genital tract of late-stage pregnant women in Dongguan was 10.53%. GBS infection is related to the genital tract microenvironment. Our results provide a basis for the prevention and treatment of clinically confirmed GBS.

Estimating the risk of incident SARS-CoV-2 infection among healthcare workers in quarantine hospitals: the Egyptian example

In response to the COVID-19 epidemic, Egypt established a unique care model based on quarantine hospitals where only externally-referred confirmed COVID-19 patients were admitted, and healthcare workers resided continuously over 1- to 2-week working shifts. Using a mathematical model accounting for the false-negative rates of RT-PCR tests, we computed the incidence rate of SARS-CoV-2 infection among HCWs, while unveiling the proportion of infections remaining undiagnosed despite routine testing. We relied on longitudinal data, including results of routine RT-PCR tests, collected within three Egyptian quarantine hospitals. We estimated an incidence rate (per 100 person-day, PD) of 1.05 (95% CrI 0.58–1.65) at Hospital 1, 1.92 (95% CrI 0.93–3.28) at Hospital 2 and 7.62 (95% CrI 3.47–13.70) at Hospital 3. We found that the risk for an HCW to be infected during a working shift lay within the range of risk levels previously documented in standard healthcare settings for Hospitals 1–2, whereas it was > threefold higher for Hospital 3. This large variation suggests that HCWs from quarantine hospitals may face a high occupational risk of infection, but that, with sufficient infection control measures, this risk can be brought down to levels similar to those observed in standard healthcare settings.

Comparison between use courier transport with pneumatic tube system on the results of routine hematology test, Prothrombin Time (PPT), Activated Partial Thromboplastin Time (APTT), and potassium

Pneumatic tube system (PTS) is a transport medium that is widely used in hospitals. The samples transported via PTS would get vibrations due to changing air velocity and pressure. This unstable pressure could cause pre-analytic errors in laboratory measurements. It happened because it damages erythrocytes and lymphocytes and causes haemolysis. It has been demonstrated that these changes can alter the quality of samples and induce haemolysis by leading primarily to increase in lactate dehydrogenase (LDH) concentrations, and potassium concentration. Haemolysis is dined as the release of intracellular components of erythrocytes and other blood cells into the extracellular space of blood. It can also affect the results of in vitro platelet function test. Incorrect test results can affect the diagnosis and the treatment for patients Every hospital that uses PTS are advised to validate and investigate that PTS has the possibility of haemolysis and impacts laboratory results of blood specimens. The purpose of the study was to validate and know comparison between use courier transport with using PTS on the results of routine haematology tests, PPT, APTT, and potassium. This research was experimental research by using posttest without control. The research used statistical test which was paired t-test. The research was conducted at the Integrated Clinical Laboratory Installation of the Gadjah Mada University Academic Hospital in August – October 2020 with 30 preoperative patients. Data were analysed with Prism GraphPad 8 software. There was no significant difference between WBC, RBC, Hb, HCT, MCV, MCH, MCHC, PPT, and APTT. Moreover, there was a significant difference between the results of PLT and potassium in the samples transported via PTS and delivered by courier transport.

A lipid metabolite lipidomics assay for prediction and severity evaluation of rotator cuff injury.

ObjectiveRotator cuff injury can be caused by local inflammation and fibrosis of musculotendinous cuff. Hypercholesterolemia can lead to physiological changes of rotator cuff that resemble rotator cuff injury. However, the relationship between lipid metabolism and rotator cuff injury and its potential pathological mechanism remain unclear. Herein, we aimed to investigate the correlation between the plasma lipidome, rotator cuff injury, and successive fatty infiltration pathology, and hoped to identify biomarkers for predicting higher risk or higher severity rotator cuff injury by assessing metabolic perturbations and dyslipidemia using lipidomics.MethodsWe quantitatively analyzed 60 lipids species of seven lipids classes and subclasses from 66 subjects using lipidomics. Subjects were divided into four groups: (1) normal rotator cuff with normal clinical routine serum lipid test results (NN group = 13); (2) normal rotator cuff with abnormal clinical routine serum lipid test results (NA group = 10); (3) rotator cuff tear with normal routine serum lipid test results (RN group = 30); (4) rotator cuff tear with abnormal routine serum lipid test results (RA group = 13). Independent-sample t-tests and Kruskal-Wallis tests were used to compare lipid metabolite levels in serum between different groups in patients with rotator cuff tears. The orthogonal partial least squares-discriminant analysis (OPLS-DA) model was used to verify the ability of five lysophosphatidylcholines (LPCs) to distinguish rotator cuff injuries. In the rotator cuff tear group, magnetic resonance imaging (MRI) was used to classify fatty infiltration according to Goutallier's classification. Kruskal-Wallis tests were used to analyze molecular differences between high-grade (grade 3–4) and low-grade (grade 0–2) fatty infiltration groups. Receiver operator characteristic (ROC) curves were drawn for each diagnostic method via different metabolites. The area under the curve (AUC), cutoff, specificity, sensitivity, and accuracy of each diagnostic criterion were calculated.ResultsOur results showed that some rotator cuff injury patients yielded unique lipidomic profiles. Based on Kruskal-Wallis tests, our results showed significant differences in three lipid molecules, 17:1 Lyso PI, 18:0–22:6 PE, and 18:3 (Cis) PC, among all four groups independent of clinical blood lipid levels. Also, independent of clinical blood lipid levels, two lipid molecules, 22:0 Lyso PC and 24:0 Lyso PC, were significantly different between the two groups based on Independent sample t-tests. Kruskal-Wallis test results showed that in the rotator cuff tear group, two metabolites (24:0 SM and 16:0 ceramide) differed between high-grade and low-grade fatty infiltration. The AUC values for 22:0 Lyso PC, 24:0 Lyso PC, 18:0–22:6 PE, 24:0 SM, and 16:0 ceramide were 0.6036, 0.6757, 0.6712, 0.8333, and 0.8981, respectively.ConclusionThe results provide insight into how the metabolic mechanisms associated with dyslipidemia impact rotator cuff diseases. Five lipid molecules, 17:1 Lyso PI, 18:0–22:6 PE, 18:3 (Cis) PC, 22:0 Lyso PC, and 24:0 Lyso PC, were closely related to rotator cuff tear based on two statistical analysis methods, independent of clinical routine serum lipid test results, which indicates that lipidomics assays are more sensitive than conventional lipid tests, and more suitable for studying rotator cuff lipid metabolism. In addition, two lipid metabolites, 24:0 SM and 16:0 ceramide, are potentially useful for predicting fatty infiltration severity. Further research with a larger number of samples is needed to verify whether these two metabolites can serve as potential markers of severe fatty infiltration. The findings illuminate how metabolic mechanisms associated with dyslipidemia affect rotator cuff disease.

Comparative Analysis of the Effect of Peripheral Blood and Venous Blood Samples on Blood Routine Test Results

Comparative Analysis of the Effect of Peripheral Blood and Venous Blood Samples on Blood Routine Test Results

MSep: investigating physiological and immune-metabolic biomarkers in septic and healthy pregnant women to predict feto-maternal immune health – a prospective observational cohort study protocol

IntroductionMaternal sepsis remains a leading cause of death in pregnancy. Physiological adaptations to pregnancy obscure early signs of sepsis and can result in delays in recognition and treatment. Identifying biomarkers...

Genotypic and hematological characteristics of 83 β-thalassemia mutation carriers and patients from Henan Province

To investigate the genotypic and hematological characteristics of β-thalassemia patients and carriers from Henan Province of China. Clinical data of the patients and carriers were collected. Results of routine blood test, hemoglobin electrophoresis and genetic testing were retrospectively analyzed. Of the 83 β-thalassemia patients and carriers, there were 46 females and 37 males, and their mean age was 27.37 ± 14.71, ranging from 5 months to 83 years. A total of 13 types of β-thalassemia alleles (86 alleles in total) were detected, with the most common three including ISV-II-654(C>T) (33.72%), CD41-42(-TTCT) (26.74%) and CD17(A>T) (18.60%). Five rare alleles, including CD8-9(+G), IVS-II-1(G>A), CD42(T>G), and start codons ATG>AGG and ATG>ACG were identified. Among these, HBB: c.128T>G(CD42T>G) was previously unreported in China. Fifteen β-thalassemia genotypes were detected, which included 12 simple heterozygote genotypes (80 cases, 96.40%), 2 double heterozygote genotypes (2 cases, 2.40%) and 1 homozygote genotype (1 case, 1.20%). The main manifestations were mild microcytic hypochromic anemia and raised HbA2. Compared with those with a β+/βN genotype, carriers with a β0/βN genotype have lower mean corpuscular volume (MCV) and mean corpusular hemoglobin (MCH) but higher HbA2 (P<0.05). β-thalassemia is not rare in Henan Province and its characteristics are different from those in high incidence areas, which deserves close attention. The newly discovered HBB: c.128T>G (CD42T>G) has enriched the spectrum of β-thalassemia mutations in China. Above results will also facilitate genetic counseling and prenatal diagnosis of β-thalassemia in Henan Province.

Audiological and Other Factors Predicting the Presence of Misophonia Symptoms Among a Clinical Population Seeking Help for Tinnitus and/or Hyperacusis.

This paper evaluates the proportion and the audiological and other characteristics of patients with symptoms of misophonia among a population seeking help for tinnitus and/or hyperacusis at an audiology clinic (n = 257). To assess such symptoms, patients were asked “over the last 2 weeks, how often have you been bothered by any of the following problems? Feeling angry or anxious when hearing certain sounds related to eating noises, lip-smacking, sniffling, breathing, clicking sounds, tapping?”. The results of routine audiological tests and self-report questionnaires were gathered retrospectively from the records of the patients. Measures included: pure tone audiometry, uncomfortable loudness levels (ULLs), and responses to the tinnitus impact questionnaire (TIQ), the hyperacusis impact questionnaire (HIQ), and the screening for anxiety and depression in tinnitus (SAD-T) questionnaire. The mean age of the patients was 53 years (SD = 16) (age range 17 to 97 years). Fifty four percent were female. Twenty-three percent of patients were classified as having misophonia. The presence and frequency of reporting misophonia symptoms were not related to audiometric thresholds, except that a steeply sloping audiogram reduced the likelihood of frequent misophonia symptoms. Those with more frequent misophonia symptoms had lower values of ULLmin (the across-frequency average of ULLs for the ear with lower average ULLs) than those with less frequent or no reported symptoms. The reported frequency of experiencing misophonia symptoms increased with increasing impact of tinnitus (TIQ score ≥9), increasing impact of hyperacusis (HIQ score >11), and symptoms of anxiety and depression (SAD-T score ≥4). It is concluded that, when assessing individuals with tinnitus and hyperacusis, it is important to screen for misophonia, particularly when ULLmin is abnormally low or the TIQ, HIQ or SAD-T score is high. This will help clinicians to distinguish patients with misophonia, guiding the choice of therapeutic strategies.

Rationale and Design of the ISOLATION Study: A Multicenter Prospective Cohort Study Identifying Predictors for Successful Atrial Fibrillation Ablation in an Integrated Clinical Care and Research Pathway.

IntroductionContinuous progress in atrial fibrillation (AF) ablation techniques has led to an increasing number of procedures with improved outcome. However, about 30–50% of patients still experience recurrences within 1 year after their ablation. Comprehensive translational research approaches integrated in clinical care pathways may improve our understanding of the complex pathophysiology of AF and improve patient selection for AF ablation.ObjectivesWithin the “IntenSive mOlecular and eLectropathological chAracterization of patienTs undergoIng atrial fibrillatiOn ablatioN” (ISOLATION) study, we aim to identify predictors of successful AF ablation in the following domains: (1) clinical factors, (2) AF patterns, (3) anatomical characteristics, (4) electrophysiological characteristics, (5) circulating biomarkers, and (6) genetic background. Herein, the design of the ISOLATION study and the integration of all study procedures into a standardized pathway for patients undergoing AF ablation are described.MethodsISOLATION (NCT04342312) is a two-center prospective cohort study including 650 patients undergoing AF ablation. Clinical characteristics and routine clinical test results will be collected, as well as results from the following additional diagnostics: determination of body composition, pre-procedural rhythm monitoring, extended surface electrocardiogram, biomarker testing, genetic analysis, and questionnaires. A multimodality model including a combination of established predictors and novel techniques will be developed to predict ablation success.DiscussionIn this study, several domains will be examined to identify predictors of successful AF ablation. The results may be used to improve patient selection for invasive AF management and to tailor treatment decisions to individual patients.

An Investigation on Local Shearing Mechanisms of Irregular Dentate Rock Joints Using the PFC

Joint surfaces are widely distributed in natural rock mass, and their shear mechanical properties play an important role in determining the safety and stability of rock mass. Previous studies rarely discussed the contribution degree of different joint protrusions to resisting shear stress. In this study, seven irregular dentate joint profiles were proposed to represent the geometric morphology of natural joints. Joint samples were subjected to direct shear tests under constant normal stress using the particle flow code (PFC). First, the reliability of the research scheme was verified by routine test results. Secondly, based on the microcrack tracking module and the force chain analysis, the local failure modes of the joint sample after and during the shearing process are discussed in detail. The relationship between the shear stress and the number of microcracks was studied. Finally, based on the measuring circle function, the variation law of the mean stress at different joint protrusions during the shearing process was tracked. The maximum stress of each protrusion before the shear stress peak was introduced to quantitatively describe the contribution of local protrusions to shear stress. There was an important link between the size of the protrusion and the stress it can withstand. During the shearing process, the local shearing mechanism of the joint surface is controlled by the distribution of joint protrusions. The research results of this paper can provide a good idea for the follow-up joint surface research.

Development, validation and standardization of urinary 5-hydroxyindoleacetic acid determination by LC-MS/MS for implementation in quality-controlled environments

Carcinoid tumors referred to neuroendocrine neoplasms that often are indolent and may not became clinical apparent until there has been metastatic spread. Urinary 5-hydroxyindoleacetic acid (5-HIAA) was recommended as a first-line screening biomarker for the diagnosis and follow-up of carcinoid tumors. The measurement of this analyte is conventionally performed by spectrophotometer or high performance liquid chromatography, and has switched to liquid chromatography-tandem mass spectrometry (LC-MS/MS) recently. In this study, a fast, simple and reliable LC-MS/MS method has been developed and validated for 24 h urinary 5-HIAA determination and the quality assurance referring to post-implementation monitoring has been explored. 50 μL of urine was mixed with 200 μL of a 50% methanol/water solution containing the internal standard 5-HIAA-d5. The mixture was centrifuged and the supernatant was used for direct analysis by LC-MS/MS. The retention time of 5-HIAA is 2.37 min and a total run time is 4 min. This method was validated for excellent linearity from 0.675 to 43.3 μM with CVs ≤ 6.64% and good recovery in the range of 87.1%-107%. No obvious matrix effect was observed. Intra- and inter-day imprecision were below 3.95% and 4.66% respectively. The reference interval of 24-hour urinary 5-HIAA in Chinese adults was established. The quality assurance could ensure reliable and comparable results in routine clinical testing. Thus, this fast, simple and reliable LC-MS/MS method could be proposed as a tool for clinical testing of urinary 5-HIAA in quality-controlled environments.