Serum D-Lactate, a Novel Serological Biomarker, Is Promising for the Diagnosis of Periprosthetic Joint Infection

Background: Although many markers are used for diagnosis of periprosthetic joint infection (PJI), serological screening and diagnosis for PJI are still challenging. We evaluated the performance of serum D-lactate and compared it with ESR, coagulation-related biomarkers and synovial D-lactate for the diagnosis of PJI.Methods: Consecutive patients with preoperative blood and intraoperative joint aspiration of a prosthetic hip or knee joint before revision arthroplasty were prospectively included. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society, and the diagnostic values of markers were estimated based on receiver operating characteristic (ROC) curves by maximizing sensitivity and specificity using optimal cutoff values.Results: Of 52 patients, 26 (50%) were diagnosed with PJI, and 26 (50%) were diagnosed with aseptic failure. ROC curves showed that serum D-lactate, fibrinogen (FIB) and ESR had equal areas under the curve (AUCs) of 0.80, followed by D-dimer and fibrin degradation product, which had AUCs of 0.67 and 0.69, respectively. Serum D-lactate had the highest sensitivity of 88.46% at the optimal threshold of 1.14 mmol/L, followed by FIB and ESR, with sensitivities of 80.77% and 73.08%, respectively, while there were no significant differences in specificity (73.08%, 73.08% and 76.92%, respectively). Conclusion: Serum D-lactate showed similar performance to FIB and ESR for diagnosis of PJI. The advantages of serum D-lactate are pathogen-specific, highly sensitive, minimally invasive and rapidly available making serum D-lactate useful as a point-of-care screening test for PJI.

Comparison of Diagnostic Values of Maternal Arginine Concentration for Different Pregnancy Complications: A Systematic Review and Meta-Analysis

Abnormal arginine metabolism contributes to the development of intrauterine growth restriction (IUGR), preeclampsia (PE), and gestational diabetes mellitus (GDM), which increase the health burden of mothers and induce adverse birth outcomes. However, associations between maternal arginine concentration and different pregnancy complications have not been systematically compared. The PubMed, ScienceDirect, and Web of Science databases were searched for peer-reviewed publications to evaluate the diagnostic value of plasma arginine concentration in complicated pregnancies. Standardized mean difference (SMD) of the arginine concentration was pooled by a random effects model. The results show that increased maternal arginine concentrations were observed in IUGR (SMD: 0.48; 95% CI: 0.20, 0.76; I2 = 47.0%) and GDM (SMD: 0.46; 95% CI: 0.11, 0.81; I2 = 82.3%) cases but not in PE patients (SMD: 0.21; 95% CI: −0.04, 0.47; I2 = 80.3%) compared with the normal cohorts. Subgroup analyses indicated that the non-fasting circulating arginine concentration in third trimester was increased significantly in GDM and severe IUGR pregnancies, but the change mode was dependent on ethnicity. Additionally, only severe PE persons were accompanied by higher plasma arginine concentrations. These findings suggest that maternal arginine concentration is an important reference for assessing the development of pregnancy complications.

Globulin and albumin to globulin ratio precisely diagnose periprosthetic joint infection and determine the timing of second-stage reimplantation

Background Periprosthetic joint infection (PJI) is one of the most challenging complications of total joint arthroplasty (TJI). An early and accurate diagnosis of PJI is associated with better treatment outcomes. However, whether the platelet-related markers and globulin-related markers can be used to assist the diagnosis of PJI remains elusive. Methods A total of 206 patients who underwent revision hip or knee arthroplasty in our institution were divided into two groups: 79 patients in PJI group and 127 patients in aseptic failure group. The levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), platelet-related markers including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT) and PLT to MPV ratio (PMR) and globulin-related markers such as globulin (GLB), albumin to globulin ratio (AGR) and PLT to AGR ratio were compared. The diagnostic value was measured using area under the curve (AUC) after constructing receiver operating characteristic (ROC) curves. The potential of each marker for determining the timing of second-staged reimplantation was also evaluated. Results Significantly increased levels of ESR, CRP, PLT, PCT, PMR, GLB and PLT to AGR ratio were identified in PJI group, while decreased levels of MPV and AGR were also found. The diagnostic values of all platelet-related markers and GLB were considered as fair, and good diagnostic values of AGR and PLT to AGR ratio were found, which were comparable to those of ESR and CRP. The levels of GLB and AGR can also be used to predict negative culture result and the timing of second-stage reimplantation. Conclusions Globulin and albumin to globulin ratio were found to have good diagnostic values for PJI, and they can precisely predict the culture results and persistent infection.

Intensive Care Antifungal Stewardship Programme Based on T2Candida PCR and Candida Mannan Antigen: A Prospective Study

Non-culture-based biomarkers may improve diagnosis and antifungal treatment (AFT) of invasive candidiasis (IC). We evaluated an antifungal stewardship programme (AFSP) in a prospective intensive care unit (ICU) study, which included T2Candida and Candida mannan antigen (MAg) screening of patients with sepsis and a high risk of IC. Patients with non-neutropenic sepsis and a high risk of IC from two large tertiary ICUs were prospectively included, during a one-year period. IC was classified as proven, likely, possible or unlikely. The AFSP, diagnostic values of T2Candida and MAg, and the consumption of antifungals were evaluated. An amount of 219 patients with 504 T2Candida/MAg samples were included. IC was classified as proven in 29 (13.2%), likely in 7 (3.2%) and possible in 10 (5.5%) patients. Sensitivity/specificity/PPV/NPV values, comparing proven/likely versus unlikely IC, were 47%/100%/94%/90% for BC alone, 50%/97%/75%/90% for T2Candida alone, and 39%/96%/67%/88% for MAg alone. For the combination of T2Candida/MAg taken ≤3 days after AFT initiation, sensitivity/specificity/PPV/NPV was 70%/90%/63%/93%. T2Candida/MAg contributed to early (<3 days) AFT initiation in 13%, early AFT discontinuation in 25% and abstaining from AFT in 24% of patients. No reduction in overall use of AFT during the study period compared with the previous year was observed. An AFSP based on T2Candida and MAg screening contributed to a reduction of unnecessary treatment, but not overall AFT use. The diagnostic performance of T2Candida was lower than previously reported, but increased if T2Candida was combined with MAg.

ThinPrep cytology combined with HPV detection in the diagnosis of cervical lesions in 1622 patients

The timely detection of precancerous lesions and early intervention can greatly reduce cervical cancer occurrence. The current study aimed to assess the diagnostic value and accuracy of different methods of cervical lesion screening. A total of 1622 females who visited the Outpatient Department of Xinjiang Uyghur Autonomous Region People’s Hospital between January and December 2018 were consecutively enrolled. All participants underwent separate high-risk human papilloma virus (HR-HPV) DNA detection, ThinPrep cytology testing (TCT) and colposcopic biopsy. Their medical records were retrospectively analyzed. While considering biopsy outcomes as the gold standard, the diagnostic values of TCT, HR-HPV testing, and TCT+HR-HPV testing for cervical cancer screening were compared. The sensitivity, specificity and Youden index of each method were calculated. Among the different methods, TCT+HR-HPV testing had the highest sensitivity (89.8%), followed by TCT (79.9%) and HR-HPV testing (49.2%). The combined method also had the highest Youden value, and its screening outcomes exhibited the highest consistency with those of biopsy. In addition, the combined method had the largest area under the receiver operating characteristic (ROC) curve, which was 0.673 (0.647, 0.699), compared with any other screening method. Compared with TCT or HR-HPV testing alone, TCT+HR-HPV testing serves as a better screening method for cervical cancer and precancerous lesions.

LncRNA-mRNA Expression Pattern in Invasive Pituitary Adenomas: A Microarray Analysis

Backgrounds: Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression of various cancer types; however, their roles in the development of invasive pituitary adenomas (PAs) remain to be investigated.Methods: lncRNA microarray was performed in three invasive and three noninvasive PAs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed, and coexpression networks between lncRNA and mRNA were constructed. Furthermore, three differentially expressed lncRNAs were selected for validation by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in PA samples. The diagnostic values of these three lncRNAs were further evaluated by receiver operating characteristic (ROC) analysis.Results: A total of 8872 lncRNAs were identified in invasive and paired noninvasive PAs using lncRNA microarray. Among these, the differentially expressed lncRNAs included 81 that were upregulated and 165 that were downregulated. GO enrichment and KEGG pathway analysis showed that these differentially expressed lncRNAs were associated with post-translational modifications of proteins. Furthermore, we performed target gene prediction and coexpression analysis. The interrelationships between the lncRNAs and mRNAs with significant differential expression were identified. Additionally, three differentially expressed lncRNAs were selected for validation in 41 PA samples by qRT-PCR. The expression levels of FAM182B, LOC105371531, and LOC105375785 in the invasive PAs were significantly (P < 0.05) lower than in the noninvasive PAs, and these results were consistent with the microarray data. ROC analysis suggested that FAM182B and LOC105375785 expression levels could be used to distinguish invasive PAs from noninvasive PAs.Conclusion: Our findings demonstrated the lncRNAs expression patterns in invasive PAs. Thus, FAM182B and LOC105375785 may be involved in the invasiveness of PAs and serve as new candidate biomarkers for the diagnosis of invasive PAs.

Identification of CALU and PALLD as Potential Biomarkers Associated With Immune Infiltration in Heart Failure

Background: Inflammatory activation and immune infiltration play important roles in the pathologic process of heart failure (HF). The current study is designed to investigate the immune infiltration and identify related biomarkers in heart failure patients due to ischemic cardiomyopathy.Methods: Expression data of HF due to ischemic cardiomyopathy (CM) samples and non-heart failure (NF) samples were downloaded from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CM and NF samples were identified. Single sample gene set enrichment analysis (ssGSEA) was performed to explore the landscape of immune infiltration. Weighted gene co-expression network analysis (WGCNA) was applied to screen the most relevant module associated with immune infiltration. The diagnostic values of candidate genes were evaluated by receiver operating curves (ROC) curves. The mRNA levels of potential biomarkers in the peripheral blood mononuclear cells (PBMCs) isolated from 10 CM patients and 10 NF patients were analyzed to further assess their diagnostic values.Results: A total of 224 DEGs were identified between CM and NF samples in GSE5406, which are mainly enriched in the protein processing and extracellular matrix related biological processes and pathways. The result of ssGSEA showed that the abundance of dendritic cells (DC), mast cells, natural killer (NK) CD56dim cells, T cells, T follicular helper cells (Tfh), gammadelta T cells (Tgd) and T helper 2 (Th2) cells were significantly higher, while the infiltration of eosinophils and central memory T cells (Tcm) were lower in CM samples compared to NF ones. Correlation analysis revealed that Calumenin (CALU) and palladin (PALLD) were negatively correlated with the abundance of DC, NK CD56dim cells, T cells, Tfh, Tgd and Th2 cells, but positively correlated with the level of Tcm. More importantly, CALU and PALLD were significantly lower in PBMCs from CM patients compared to NF ones.Conclusion: Our study revealed that CALU and PALLD are potential biomarkers associated with immune infiltration in heart failure due to ischemic cardiomyopathy.

Investigation of hub gene associated with the infection of Staphylococcus aureus via weighted gene co-expression network analysis

Introduction Staphylococcus aureus is a gram-positive bacterium that causes serious infection. With the increasing resistance of bacteria to current antibiotics, it is necessary to learn more about the molecular mechanism and cellular pathways involved in the Staphylococcus aureus infection. Methods We downloaded the GSE33341 dataset from the GEO database and applied the weighted gene co-expression network analysis (WGCNA), from which we obtained some critical modules. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were applied to illustrate the biological functions of genes in these modules. We constructed the protein-protein interaction (PPI) network by Cytoscape and selected five candidate hub genes. Five potential hub genes were validated in GSE30119 by GraphPad Prism 8.0. The diagnostic values of these genes were calculated and present in the ROC curve based on the GSE13670 dataset. Their gene functions were analyzed by Gene Set Enrichment Analysis (GSEA). Results A co-expression network was built with 5000 genes divided into 11 modules. The genes in green and turquoise modules demonstrated a high correlation. According to the KEGG and GO analyses, genes in the green module were closely related to ubiquitination and autophagy. Subsequently, we picked out the top five hub genes in the green module. And UBB was determined as the hub gene in the GSE30119 dataset. The expression level of UBB, ASB, and MKRN1 could significantly differentiate between Staphylococcus aureus infection and healthy controls based on the ROC curve. The GSEA analysis indicated that lower expression levels of UBB were associated with the P53 signal pathway. Conclusions We identified some hub genes and significant signal enrichment pathways in Staphylococcus aureus infection via bioinformatics analysis, which may facilitate the development of potential clinical therapeutic strategies.