Pan-cancer analysis identifies the IRF family as a biomarker for survival prognosis and immunotherapy.

IRF family genes have been shown to be crucial in tumorigenesis and tumour immunity. However, information about the role of IRF in the systematic assessment of pan-cancer and in predicting the efficacy of tumour therapy is still unknown. In this work, we performed a systematic analysis of IRF family genes in 33 tumour samples, including expression profiles, genomics and clinical characteristics. We then applied Single-Sample Gene-Set Enrichment Analysis (ssGSEA) to calculate IRF-scores and analysed the impact of IRF-scores on tumour progression, immune infiltration and treatment efficacy. Our results showed that genomic alterations, including SNPs, CNVs and DNA methylation, can lead to dysregulation of IRFs expression in tumours and participate in regulating multiple tumorigenesis. IRF-score expression differed significantly between 12 normal and tumour samples and the impact on tumour prognosis and immune infiltration depended on tumour type. IRF expression was correlated to drug sensitivity and to the expression of immune checkpoints and immune cell infiltration, suggesting that dysregulation of IRF family expression may be a critical factor affecting tumour drug response. Our study comprehensively characterizes the genomic and clinical profile of IRFs in pan-cancer and highlights their reliability and potential value as predictive markers of oncology drug efficacy. This may provide new ideas for future personalized oncology treatment.

Clinical utility of procalcitonin and its association with pathogenic microorganisms.

In this review, we summarize the relationship of PCT with pathogens, evaluate the clinical utility of PCT in the diagnosis of clinical diseases, condition monitoring and evaluation, and guiding medical decision-making, and explore current knowledge on the mechanisms by which pathogens cause changes in PCT levels. The lipopolysaccharides of the microorganisms stimulate cytokine production in host cells, which in turn stimulates production of serum PCT. Pathogens have different virulence mechanisms that lead to variable host inflammatory responses, and differences in the specific signal transduction pathways result in variable serum PCT concentrations. The mechanisms of signal transduction have not been fully elucidated. Further studies are necessary to ascertain the PCT fluctuation range of each pathogen. PCT levels are helpful in distinguishing between certain pathogens, in deciding if antibiotics are indicated, and in monitoring response to antibiotics.

Development of Laboratory Parameters-Based Formulas in Predicting Short Outcomes for Adult Hemophagocytic Lymphohistiocytosis Patients with Different Underlying Diseases.

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a severe disease with high mortality. The purpose of this investigation was to build models to predict 30-day death in total and subgroup HLH patients based on available and cheap laboratory parameters. METHOD: The research contained 431 adults HLH patients from January 2015 to September 2021 in the hospital. Logistic regression and receiver operating characteristic (ROC) were utilized to build models. RESULTS: Results suggested that age, ferritin, lymphocyte (LY), international normalized ratio (INR), thrombin time (TT), globulin, uric acid (UA), chloride, activated partial thromboplastin time (APTT), aspartate aminotransferase (AST), triglycerides (TG), total bilirubin (TB), and indirect bilirubin (IB) were independent factors in HLH and subgroups. Then, models adapted to patients with different underlying diseases were established based on these factors. Area under curve (AUC) of these models was excellent: HLH patients: 0.838 (p < 0.001); infection-associated HLH (I-HLH) patients: 0.913 (p < 0.001); malignancy-associated HLH (M-HLH): 0.921 (p < 0.001) and 0.809 (p < 0.001) for two or more different etiologies-associated HLH (Mix-HLH patients). In addition, UA, TT, and chloride were firstly confirmed as independent factors in adult HLH. CONCLUSION: Four models depending on biomarkers that available and affordable in clinical practice were built. With these models, high-risk patients with different underlying diseases could be easily identified.

Global prevalence of occult hepatitis B: A systematic review and meta-analysis.

The study aimed to investigate the prevalence and risk factors associated with occult hepatitis B virus (HBV) infection (OBI) in the global population. We searched PubMed, Embase, CINAHL, Cochrane and Web of Science from database inception through 27 Dec, 2018. Studies reporting HBV-DNA serological data in previously undiagnosed hepatitis B patients were included. The data were further categorized according to the presence of risk factors. After an initial screening of 2,325 records, we finally included 98 articles about the prevalence of OBI from 34 countries and regions. The OBI prevalence was 0.82% (95% CI:0.69-0.96) in the general population, 16.26% (95% CI:10.97-22.34) in HIV patients, 13.99% (95% CI:8.33-20.79) in patients with other liver diseases, 4.25% (95% CI:1.64-7.87) in haemodialysis patients and 5.14% (95% CI:2.26-9.01) patients with other risk factors. In conclusion, OBI prevalence varies significantly across different populations and nations, which deserve attention from the public health authorities. Our results generate further epidemiological data to identify the population with OBI, which has important clinical implications in finding these high-risk populations to design preventive and management strategies.

Epidemiology estimates of hepatitis D in individuals co-infected with human immunodeficiency virus and hepatitis B virus, 2002-2018: A systematic review and meta-analysis.

Hepatitis delta virus (HDV) is an obligate satellite of hepatitis B virus (HBV). HIV/HDV co-infection is associated with a high rate of hepatic decompensation events and death. We aimed to characterize the epidemiology of HDV infection in HIV/HBV co-infected individuals. We systematically searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL and Scopus for studies published from 1 Jan 2002 to 7 May 2018 measuring prevalence of HDV among the HIV population. Pooled seroprevalence was calculated with the DerSimonian-Laird random-effects model. Our search returned 4624 records, 38 of which met the inclusion and exclusion criteria. These studies included data for 63 cohorts from 18 countries and regions. The overall HDV seroprevalence of HIV-infected individuals was 1.03% (95% CI 0.43-1.85) in 2002-2018 globally. Moreover, the estimated pooled HDV seroprevalence among the general population was 1.07% (95% CI 0.65-1.59) in 2002-2018, which was not significantly different from the HDV seroprevalence of individuals living with HIV (p = 0.951). The overall HDV seroprevalence of the HBsAg positive population was 12.15% (95% CI 10.22-14.20), p = 0.434 when compared with the corresponding data of HIV/HBV co-infected individuals. This meta-analysis suggested that there was no difference between the HDV seroprevalence in HIV-infected individuals and the general population.

The effect of rheumatoid factor on three commercial immunoassays for serum cystatin C.

Cystatin C (CysC) can be used to diagnose early changes in renal insufficiency. However, there are little researches to study whether there is an interference between the level of CysC and RF. Thus, we conducted this study to investigate it. We randomly selected 30 patients with high RF (RF concentration: 552.05 ± 476.23 IU/mL) and 33 healthy subjects with RF concentration <11.1 IU/mL and CysC were measured with different reagents and instruments; Interference experiment was also be included. The results showed that the measured CysC concentration increases with increasing RF concentration in a dose-dependent manner and CysC levels are falsely increased by RF interference depends on the reagents used (CysC reagent: Whitman, Nanjing, China). Reagent manufacturers should fully consider RF interference when developing CysC reagents, and evaluate them before they are sold. When selecting CysC reagents, we should evaluate RF interference to the measurement to avoid misleading results.

Ferritin index is a strong prognostic marker in adult hemophagocytic lymphohistiocytosis.

AIMS: The relationship between ferritin levels and survival in adult hemophagocytic lymphohistiocytosis (HLH) has been evaluated in previous studies. However, Admission-to-discharge percentage ferritin reduction (named as ferritin index) level in adult patients with HLH has never been evaluated to predict 6-month survival. METHODS: The demographic, laboratory and clinical information of 102 newly diagnosed adult HLH patients were collected. Regression analysis, receiver operating curve and Kaplan-Meier curves were analysed to explore the performance of ferritin levels. RESULTS: Ferritin index and discharge ferritin level were significantly different between survivour and non-survivour group (all P < .001). Ferritin index had the highest area under the curve (AUC) for predicting the survival (AUC = 0.802, P < .001) followed by discharge ferritin (AUC = 0.746, P < .001). Kaplan-Meier analysis showed a significant difference in survival according to optimum cutoff values of ferritin index ≥ 10.19% (P < .001) or discharge ferritin ≤ 1056.1 µg/L (P < .001). Multivariate analysis confirmed that ferritin index and discharge ferritin are independent predictors of 6-month survival (ferritin index: odds ratio (HR) 6.237, 95% confidence interval (CI) 2.075-18.774, P = .001; discharge ferritin: HR 6.024, 95% CI 1.894-19.231, P = .002). In addition, the combination of a ferritin index ≥ 10.19% and discharge ferritin ≤ 1056.1 µg/L had a significantly higher 6-month survival (P < .001). CONCLUSION: Ferritin index is a better predictor of 6-month survival than admission and discharges ferritin levels in adult patients with HLH.

Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis.

OBJECTIVE: Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection. DESIGN: We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors. RESULTS: From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population. CONCLUSION: We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.

Comparison of two commercial quality control sera for adrenocorticotropin (ACTH) used in Elecsys® immunoassay system.

OBJECTIVES: The purpose of our study was to investigate whether the storage time and temperature of internal quality control (IQC) material influence the result of ACTH in IQC measurements. DESIGN AND METHODS: Five levels of IQC materials from two manufacturers were tested through the precision of ACTH, the three freeze/thaw cycles, and the storage time and temperature to evaluate the stability of IQC material. All commercial control materials were simultaneously tested three times a day for five consecutive days. RESULTS: Total precision of three levels of Bio-Rad IQC sera was 13.93%, 16.45%, and 15.98%, respectively, but repeatability was <2%. The concentration of ACTH decreased by 30%-50% after 3 freeze/thaw cycles. At room temperature, the concentration of ACTH from 3 levels decreased by 16.60%, 17.98%, and 17.20%, respectively, after 0.5 hours, and 70.54%, 74.36%, and 72.03%, respectively, after 4 hours. However, after 2 hours of storage at 4°C, the decline in the measured ACTH IQC was 8.04%, 11.84%, and 10.11%, respectively. Total precision of Roche IQC was 1.17% and 1.08%, respectively. After 3 freeze/thaw cycles, the concentration of ACTH decreased <5%. After 4 hours, the change of ACTH still steadied within 5% both at the room temperature and at 4°C. CONCLUSION: Roche is a better choice for ACTH of IQC material in Elecsys® immunoassay system in our study. If Bio-Rad control materials be used in Elecsys® immunoassay system for ACTH IQC testing material, it should be stored at 4°C and testing should be completed within 1 hours.

Failure of internal quality control in detecting significant reagent lot shift in serum creatinine measurement.

BACKGROUND: Internal quality control (IQC) in clinical laboratories is carried out to monitor analytical stability. Usually, the satisfactory results of the IQC ensure the acceptability of the examination results. Here, we reported that patients' creatinine results are unreliable, although the internal quality control is satisfactory. METHODS: Creatinine levels were analyzed from two quality control materials and twenty patients' specimens using two different lots of reagents. Lot-to-lot comparison was performed. The daily median values of serum creatinine levels of patients were calculated from the test results recorded in our laboratory information system. RESULTS: Although IQC was consistent, serum creatinine concentrations were higher using lot B (median: 153 µmol/L; interquartile range: 122-522 µmol/L) than using lot A (median: 133 µmol/L; interquartile range: 76-508 µmol/L) for 20 patients (P = .001). The Deming linear regression showed a best fit of y = 0.9394 × x + 45.66. R2  = .8919, and mean percentage difference between two lots was 34%. The new lot was considered unacceptable. Likewise, the median serum creatinine level from the 360 patients using lot B was 102 µmol/L, which was significantly higher than the daily medians of patients using lot A (median: 66 µmol/L; range: 61-70 µmol/L) in the previous month. CONCLUSION: The variations in creatinine concentrations proved to be due to different lots of reagents. However, IQC materials tested using both lots of reagent exhibited minimal variation. Therefore, IQC alone is insufficient for assessing laboratory analytical results. This finding prompts us to be vigilant in potential pitfall of interpreting test results based on satisfactory IQC alone.

Different free prostate-specific antigen to total prostate-specific antigen ratios using three detecting systems.

BACKGROUND: Prostate-specific antigen (PSA) is used as an indicative marker of a pathologic condition of the prostate, and the ratio of free PSA (fPSA) to total PSA (tPSA) helps to distinguish benign prostatic hyperplasia (BPH) from prostate cancer (PCa). In this study, we present some reversed ratios of fPSA to tPSA and analyze the possible mechanism. METHODS: Using the UniCel DxI800 Access Immunoassay System, eight reversed fPSA to tPSA ratios were obtained, and then these samples were retested with an Abbott Architect i2000 Immunoassay Analyser and Cobas e602. RESULTS: Four of the eight reversed ratios kept a ratio >1 using Abbott Architect i2000, and seven of them turned into a ratio <1 using Cobas e602. CONCLUSION: In consideration of the assay these three detecting systems apply, the possible reason of the reversed ratios can be heterophile antibodies. To get accurate reason, further study is required.

Preanalytical stability of adrenocorticotropic hormone depends on both time to centrifugation and temperature.

OBJECTIVE: The purpose of our study was to analyze the effects of temperature, time delay, and time to centrifugation on the stability of human plasma adrenocorticotropin (ACTH) measurements. METHODS: Twenty-one EDTA whole blood sample pools were centrifuged at 1100 ×g for 10 minutes at 4°C either immediately or after storage for 2, 4, 8, and 24 hours at 4°C or room temperature. Plasma ACTH was then measured either immediately or after 2, 4, 8, and 24 hours storage at 4°C or room temperature. RESULTS: The change in ACTH concentrations was affected significantly (from 8.1±5.0% to 12.4±2.9% at 4 hours, P<.005) by time to centrifugation at room temperature. However, it remained stable (<5% change) up to 8 hours at 4°C in samples both centrifuged immediately and uncentrifuged. CONCLUSIONS: To get accurate values of plasma ACTH concentrations, if the samples cannot be transferred to the laboratory for analysis at room temperature within 2 hours, they should be immediately stored at 4°C, and analyzed within 8 hours.

Hemolysis Affects C-Peptide Immunoassay.

BACKGROUND: C-peptide is used widely as a marker of insulin secretion, and it participates in the inflammatory response and contributes to the development of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). Previous studies have reported that C-peptide measurement was unaffected by hemolysis. However, we found that hemolysis negatively affected C-peptide assay in routine laboratory practice. We further established and validated an individualized hemolysis correction equation to correct and report accurate serum C-peptide results for hemolyzed samples. METHODS: We studied the effects of hemolysis on C-peptide assay by adding lysed self red blood cells (self-RBCs) to serum. An individualized correction equation was derived. Further, we evaluated the performance of this individualized correction equation by artificially hemolyzed samples. RESULTS: C-peptide concentration decreased with increasing degree and exposure time of hemolysis. The individualized hemolysis correction equation derived: C-Pcorr = C-Pmeas /(0.969-1.5Hbserum/plasma -5.394 ×10-5 Time), which can correct bias in C-peptide measurement caused by hemolysis. CONCLUSIONS: Hemolysis negatively affects C-peptide measurement. We can correct and report accurate serum C-peptide results for a wide range of degrees of sample hemolysis by individualized hemolysis correction equation for C-peptide assay. This correction would improve diagnostic accuracy and reduce inappropriate therapeutic decisions.

MIR106B and MIR93 prevent removal of bacteria from epithelial cells by disrupting ATG16L1-mediated autophagy.

BACKGROUND & AIMS: Variants in genes that regulate autophagy have been associated with Crohn's disease (CD). Defects in autophagy-mediated removal of pathogenic microbes could contribute to the pathogenesis of CD. We investigated the role of the microRNAs (miRs) MIR106B and MIR93 in induction of autophagy and bacterial clearance in human cell lines and the correlation between MIR106B and autophagy-related gene 16L1 (ATG16L1) expression in tissues from patients with CD. METHODS: We studied the ability of MIR106B and MIR93 to regulate ATG transcripts in human cancer cell lines (HCT116, SW480, HeLa, and U2OS) using luciferase report assays and bioinformatics analyses; MIR106B and MIR93 mimics and antagonists were transfected into cells to modify levels of miRs. Cells were infected with LF82, a CD-associated adherent-invasive strain of Escherichia coli, and monitored by confocal microscopy and for colony-forming units. Colon tissues from 41 healthy subjects (controls), 22 patients with active CD, 16 patients with inactive CD, and 7 patients with chronic inflammation were assessed for levels of MIR106B and ATG16L1 by in situ hybridization and immunohistochemistry. RESULTS: Silencing Dicer1, an essential processor of miRs, increased levels of ATG protein and formation of autophagosomes in cells, indicating that miRs regulate autophagy. Luciferase reporter assays indicated that MIR106B and MIR93 targeted ATG16L1 messenger RNA. MIR106B and MIR93 reduced levels of ATG16L1 and autophagy; these increased after expression of ectopic ATG16L1. In contrast, MIR106B and MIR93 antagonists increased formation of autophagosomes. Levels of MIR106B were increased in intestinal epithelia from patients with active CD, whereas levels of ATG16L1 were reduced compared with controls. Levels of c-Myc were also increased in intestinal epithelia of patients with active CD compared with controls. These alterations could impair removal of CD-associated bacteria by autophagy. CONCLUSIONS: In human cell lines, MIR106B and MIR93 reduce levels of ATG16L1 and autophagy and prevent autophagy-dependent eradication of intracellular bacteria. This process also appears to be altered in colon tissues from patients with active CD.