Evaluation of the diagnostic performance of thyroid-stimulating immunoglobulin and thyrotropin receptor antibodies for Graves' disease.

OBJECTIVE: To evaluate thyroid-stimulating immunoglobulin (TSI) and thyrotropin receptor antibodies (TRAb) diagnostic performance for Graves' disease (GD) and determine clinical cut-off value for diagnosing GD. METHODS: Of 1369 retrospectively enrolled subjects, 1364 had a definitive diagnosis of untreated GD (GD-UT, n = 87); treated GD (GD-T, n = 206); autoimmune thyroid disease (AIT, n = 241); thyroid nodules (TN, n = 677); subacute thyroiditis (ST, n = 28); healthy subjects (HS, n = 125); other diseases with serological hyperthyroidism (n = 5) and were grouped into the following: UT-GD and control groups (AIT, TN, ST, and HS); and UT-GD and non-GD hyperthyroidism groups. Diagnostic performance of TSI and TRAb was evaluated using area under the curve (AUC) of receiver-operating characteristic (ROC) curve, and optimal clinical cut-off value was determined using maximization of Youden index. RESULTS: TRAb AUC and clinical cut-off value for diagnosing GD were 0.981 and 1.245 IU/L (sensitivity, 96.6%; specificity, 97.1%; positive predictive value [PPV], 71.8%; negative predictive value [NPV], 99.9%; positive likelihood ratio [PLR], 33.31; negative likelihood ratio [NLR, 0.035), respectively, for the GD-UT and control groups. Those for TSI were 0.992 and 0.467 IU/L (sensitivity 98.8%; specificity, 96.4%; PPV, 68.8%; NPV, 99.9%; PLR, 27.472; NLR, 0.011). Those for TRAb in GD-UT and non-GD hyperthyroidism groups were 0.923 and 1.78 IU/L (sensitivity, 92.0%; specificity, 89.1%; PPV, 93%; NPV, 87.5%; PLR, 8.44; NLR, 0.089), respectively. For TSI, these were 0.92 and 0.545 IU/L (sensitivity, 97.7%; specificity, 83.6%; PPV, 90.4%; NPV, 95.8%; PLR27.472, NLR, 0.011), respectively. CONCLUSION: TSI diagnostic performance for GD was excellent and had better sensitivity than TRAb.

Status of phlebotomy tube utilization at a major medical center. Are we using too many phlebotomy tubes?

Background and objectives: Overutilization of phlebotomy tubes at healthcare facilities leads to iatrogenic anemia, patient dissatisfaction, and increase in operational costs. In this study, we analyzed the phlebotomy tube usage data at the Zhongshan Hospital, Fudan University, to show potential inefficiencies with phlebotomy tube usage. Methods: Data of 984,078 patients with 1,408,175 orders and 4,622,349 total phlebotomy tubes were collected during years 2018-2021. Data of different patient types were compared. Furthermore, we assessed the data from subspecialty and test levels to explore the factors influencing the increase in phlebotomy tube usage. Results: We observed an overall 8% increase in both the mean number of tubes used and blood loss per order over the past 4 years. The mean blood loss per day for intensive care unit (ICU) patients was 18.7 ml (maximum 121.6 ml), which was well under the 200 ml/day threshold. However, the maximum number of tubes used reached more than 30 tubes/day. Conclusions: The 8% increase of phlebotomy tubes over 4 years should alarm laboratory managements, as tests offered are expected to increase in the future. Importantly, the whole healthcare community needs to work together to solve this problem with more creative solutions.

Comparison of the 2021 and 2009 chronic kidney disease epidemiology collaboration creatinine equation for estimated glomerular filtration rate in a Chinese population.

OBJECTIVES: To retrospectively compare the clinical effects of the newly released 2021 and 2009 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations for estimated glomerular filtration rate based on creatinine (eGFRcr) in a Chinese population with a broad spectrum of clinical characteristics using historical data. DESIGN AND METHODS: Patients and healthy individuals who visited the Zhongshan Hospital, Fudan University, between July 1, 2020, and July 1, 2022, were enrolled. The exclusion criteria were age < 18 years, amputees, pregnant women, patients with muscle-related diseases, and patients who had undergone ultrafiltration or dialysis. The final study population included 1,051,827 patients with a median age of 57 years; 57.24% of the enrolled individuals were men. eGFRcr was calculated using the 2009 and 2021 CKD-EPI equations and initial creatinine level. Results were evaluated statistically by sex, age, creatinine level, and CKD stage. RESULTS: The 2021 equation increased the eGFRcr in all participants compared to the 2009 equation by 4.46%. The median eGFRcr deviation of the 2021 CKD-EPI equation compared to the 2009 CKD-EPI equation was 4 ml/min/1.73 m2. 903,443 subjects (85.89%) had higher eGFRcr owing to the utilization of the 2021 CKD-EPI equation, which did not cause CKD stage change. A total of 11.57% of subjects (121,666) had improved CKD stage with the 2021 CKD-EPI equation. 1.79% (18,817) had the same CKD stage with both equations, and 0.75% (7,901) had lower eGFRcr but no change in the CKD stage with the 2021 equation. CONCLUSIONS: The 2021 CKD-EPI equation typically produces higher eGFRcr results than the 2009 version. Applying the new equation could lead to changes in the CKD stage for some patients, which doctors should consider.

Modeling of Internal Geometric Variability and Statistical Property Prediction of Braided Composites.

Due to the advantages of high specific strength, specific stiffness, and excellent fatigue resistance, carbon fiber reinforced braided composites have been widely applied in engineering. Since the molding process of braided composites is complex and immature, substantial variability of the internal geometry exists in composites, in which the yarn path with uncertainty is a main factor, so it is necessary to establish an uncertainty model to study the influence of randomness of the yarn path on mechanical properties, which is significantly related to the fatigue resistance properties of composite. An uncertain mesoscopic model with uniform distribution of yarn paths is proposed. Assuming the yarn path is spatially varying in interval range, the variability of yarn path is represented geometrically in the unit cell of composite. The three-dimensional coordinates of the yarn trajectory are calculated, the meso-uncertainty models of 2-D and 2.5-D braided composites are established. The equivalent elastic parameters and the thermal expansion coefficients are obtained by applying homogenization method and temperature field boundary conditions to the mesoscopic model. The effect of yarn path uncertainty on the statistical characteristics of elastic and thermal parameters of braided composites was studied by using Monte-Carlo simulation. A simulation method for modeling yarn path uncertainty of braided composites is provided in this paper for predicting the statistical characteristics of the equivalent elastic and thermal parameters.

Regression-Adjusted Real-Time Quality Control.

BACKGROUND: Patient-based real-time quality control (PBRTQC) has gained increasing attention in the field of clinical laboratory management in recent years. Despite the many upsides that PBRTQC brings to the laboratory management system, it has been questioned for its performance and practical applicability for some analytes. This study introduces an extended method, regression-adjusted real-time quality control (RARTQC), to improve the performance of real-time quality control protocols. METHODS: In contrast to the PBRTQC, RARTQC has an additional regression adjustment step before using a common statistical process control algorithm, such as the moving average, to decide whether an analytical error exists. We used all patient test results of 4 analytes in 2019 from Zhongshan Hospital, Fudan University, to compare the performance of the 2 frameworks. Three types of analytical error were added in the study to compare the performance of PBRTQC and RARTQC protocols: constant, random, and proportional errors. The false alarm rate and error detection charts were used to assess the protocols. RESULTS: The study showed that RARTQC outperformed PBRTQC. RARTQC, compared with the PBRTQC, improved the trimmed average number of patients affected before detection (tANPed) at total allowable error by about 50% for both constant and proportional errors. CONCLUSIONS: The regression step in the RARTQC framework removes autocorrelation in the test results, allows researchers to add additional variables, and improves data transformation. RARTQC is a powerful framework for real-time quality control research.

Insulin-like growth factor binding protein 7 as a candidate biomarker for systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease clinically characterised by skin and internal organs fibrosis with high mortality. However, the pathogenesis of SSc is still controversial and the effect of the current treatment is far from satisfactory. We aimed to find out novel candidate genes related to the pathological process in SSc. METHODS: In this study, the weighted correlation network analysis (WGCNA) was conducted to identify the key module and hub genes most related to SSc in GSE58095, a microarray dataset from the Gene Expression Omnibus (GEO) database. Also, the key module was analysed by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Then we validated hub genes in other datasets (GSE32413, GSE125362, GSE45485, GSE76885, GSE95065). The serum of 37 patients with SSc and 25 healthy control subjects (HCs) were recruited and detected by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Five interested genes (IGFBP7, LRRC32, STMN2, C1QTNF5, CPXM1) were up-regulated in SSc microarray datasets from the GEO. And the level of serum IGFBP7, which encodes a secreted protein, was upregulated in SSc patients-also in dcSSc patients and SSc with ILD patients. CONCLUSIONS: Among the five interested genes, the IGFBP7 was a novel candidate gene for SSc and may be served as potential target and early biomarker for accurate treatment, which also provides further insights into the pathogenesis of SSc at the molecular level.

Assessment of patient-based real-time quality control algorithm performance on different types of analytical error.

BACKGROUND: Patient-based real-time quality control (PBRTQC) has gained attention because of its potential to detect analytical errors in situations wherein internal quality control is less effective. Multiple PBRTQC algorithms have been proposed. However, there is a lack of comprehensive comparison of the performance of PBRTQC algorithms on different types of analytical errors. Thus, a comparative study was conducted. METHODS: The performance of six different PBRTQC algorithms was evaluated on three types of analytical errors using 906,552 test results for outpatient serum sodium, chloride, alanine aminotransferase, and creatinine at the Department of Laboratory Medicine at Zhongshan Hospital, Fudan University in 2019. The performance results were compared and assessed. RESULTS: The moving average, moving median, exponentially weighted moving average, and moving quartiles performed similarly for effectively detecting constant errors (CE) and proportional errors (PE) but not random errors (RE). The moving sum of positive patients and moving standard deviation could detect RE for serum sodium and chlorides but performed poorly on detecting the CE and PE. CONCLUSIONS: This study demonstrated the importance of assessing the potential source of error of a particular analyte and the corresponding type of analytical error before choosing a quality control algorithm for implementation.

Identification and Validation of Key Genes Associated With Systemic Sclerosis-Related Pulmonary Hypertension.

Systemic sclerosis-associated with pulmonary arterial hypertension (SSc-PAH) is still a major cause of SSc related deaths. Early diagnosis and prompt treatment are crucial to reduce the mortality of patients with SSc-PAH. To screen the candidate biomarkers and potential therapeutic targets for SSc-PAH, we analyzed the data set (GSE33463 and GSE19617) for confirming key genes in peripheral blood mononuclear cells from SSc-PAH patients. A total of 105 SSc patients from gene expression omnibus (GEO) were included as discovery cohort (n = 69) and duplication cohort (n = 36) for screening hub genes by weighted gene co-expression network analysis (WGCNA). Furthermore, an independent validation cohort (n = 40), including healthy controls, SSc and SSc-PAH patients, was used for further validation by quantitative real-time polymerase chain reaction. The results showed that four key genes, including IFIT2, IFIT3, RSAD2, and PARP14, may serve as potential biomarkers in SSc-PAH. Also, they could be independent risk factors for SSc-PAH. In conclusion, the four key genes can be expected to become the potential therapeutic targets and early biomarkers for accurate therapy and diagnosis of SSc-PAH in the future, which also provides promising insights into the pathogenesis of SSc-PAH at the molecular level.

Role of magnesium in the risk of intradialytic hypotension among maintenance hemodialysis patients.

INTRODUCTION: Intradialytic hypotension (IDH) is a common complication in end-stage renal disease patients on hemodialysis (HD). It has been documented that several factors contribute to IDH. However, the relationship between serum electrolytes and the occurrence of IDH remains unclear. Our study aims to investigate the role of serum magnesium (Mg) for the risk of IDH in maintenance HD patients. METHODS: The retrospective study included adults starting HD before January 2009 in the blood purification center, Zhongshan Hospital, Fudan University, and treated thrice weekly with standard bicarbonate dialysate by low-flux HD. Patients' characteristics including age and sex, laboratory test results were collected. IDH was defined according to kidney disease outcomes quality initiative (K/DOQI) guidelines as a decrease in systolic blood pressure (SBP) by ≥20 mmHg or a decrease in mean arterial pressure (MAP) by ≥10 mmHg associated with clinical symptoms during HD. Multivariate logistic regression was employed to explore independent risk factors for IDH. FINDINGS: Among 423 patients recruited, 175 patients (41.4%) suffered from IDH. Compared with those with non-IDH, patients with IDH presented higher predialysis serum Mg levels. Univariate correlation analysis showed that predialysis serum Mg level was negatively correlated with SBP at 3 hours, 4 hours after dialysis (3 hours SBP r = -0.134 P = 0.006, 4 hours SBP r = -0.142 P = 0.003) and was positively correlated with the differences of blood pressure (BP) (SBP and MAP) (△SBP r = 0.195 P < 0.001, △MAP r = 0.155, P = 0.001). After adjustment for predialysis blood urea nitrogen, platelet distribution width, cardiac troponin T, fasting blood glucose, ß2-microglobulin, and predialysis MAP, multivariate logistic regression analysis demonstrated that predialysis serum Mg level was one of the independent risk factors for IDH (odds ratio [95% confidence interval-CI]: 7.154 (1.568-32.637); P = 0.011). In addition, Mg levels of 1.15 mmol/L or higher were associated with a high incidence of IDH. DISCUSSION: Our findings suggested that higher predialysis serum Mg level was one of the independent risk factors for IDH among maintenance hemodialysis (MHD patients).

Increased serum calpain activity is associated with HMGB1 levels in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) or scleroderma is an intractable autoimmune disorder that affects multiple organs. The objectives were to investigate clinical correlations of serum calpain activity and high mobility group box 1 (HMGB1) levels with immunological and clinical traits. METHODS: A total of 31 patients with SSc, 20 age- and gender-matched healthy control subjects (HC), and 10 patients with other connective tissue diseases (CTD) were recruited in the study. We measured serum calpain activity and HMGB1 levels and analyzed the datasets (GSE40839, GSE48149, GSE76808, GSE81292, GSE33463, and GSE58095) from Gene Expression Omnibus (GEO) database to explore the potential mechanism by which calpain exerts its function through bioinformatics methods. RESULTS: Serum calpain activity was significantly increased in patients with SSc compared with those in HC and in patients with CTD and was correlated with serum HMGB1 levels, modified Rodnan skin score, erythrocyte sedimentation rate, mean platelet volume, and plateletcrit. Notably, serum calpain activity and HMGB1 levels in SSc patients with interstitial lung disease (ILD) were significantly higher than those in SSc patients without ILD. Serum calpain activity and HMGB1 levels could be the independent risk factors for SSc-ILD and novel biomarkers in patients with SSc. CONCLUSION: This is the first study that reports increased serum calpain activity and the correlation between calpain and HMGB1 in patients with SSc or SSc-ILD. The serum calpain activity and HMGB1 levels may serve as measures of ILD in patients with SSc. Also, calpain and HMGB1 could be potential therapeutic targets for patients with SSc or SSc-ILD in the future.

Circulating metabolite profiles to predict response to cardiac resynchronization therapy.

BACKGROUND: Heart failure is associated with ventricular dyssynchrony and energetic inefficiency, which can be alleviated by cardiac resynchronization therapy (CRT) with approximately one-third of non-response rate. Thus far, there is no specific biomarker to predict the response to CRT in patients with heart failure. In this study, we assessed the role of the blood metabolomic profile in predicting the response to CRT. METHODS: A total of 105 dilated cardiomyopathy patients with severe heart failure who received CRT were included in our two-stage study. Baseline blood samples were collected prior to CRT implantation. The response to CRT was defined according to echocardiographic criteria. Metabolomic profiling of serum samples was carried out using ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry. RESULTS: Seventeen metabolites showed significant differences in their levels between responders and non-responders, and these metabolites were primarily involved in six pathways, including linoleic acid metabolism, Valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, citrate cycle, tryptophan metabolism, and sphingolipid metabolism. A combination of isoleucine, tryptophan, and linoleic acid was identified as an ideal metabolite panel to distinguish responders from non-responders in the discovery set (n = 51 with an AUC of 0.981), and it was confirmed in the validation set (n = 54 with an AUC of 0.929). CONCLUSIONS: Mass spectrometry based serum metabolomics approach provided larger coverage of metabolome which can help distinguish CRT responders from non-responders. A combination of isoleucine, tryptophan, and linoleic acid may associate with significant prognostic values for CRT.

Strategies for enrichment of circulating tumor cells.

Circulating tumor cells (CTCs) are cells derived from the primary sites of tumor patients into peripheral blood and serve as seeds that initiate tumor metastasis to distant sites. As a primary form of "liquid biopsy", CTC enumeration has exhibited great potential as a mean to obtain diagnostic and prognostic biomarker information in various cancers. The comprehensive clinical utility of CTC tests, however, is still restricted due to the scarcity and heterogeneity of CTCs, which necessitates reliable techniques for their efficient enrichment and characterization. Numerous methods have been developed to improve yield and purity of CTC enrichment as well as detection sensitivity. In this review, we comprehensively summarize techniques for CTC enrichment and detection.