Diagnostic accuracy and cellular origin of pleural fluid CXCR3 ligands for tuberculous pleural effusion.

BACKGROUND: Pleural biomarkers represent potential diagnostic tools for tuberculous pleural effusion (TPE) due to their advantages of low cost, short turnaround time, and less invasiveness. This study evaluated the diagnostic accuracy of two CXCR3 ligands, C-X-C motif chemokine ligand 9 (CXCL9) and CXCL11, for TPE. In addition, we investigated the cellular origins and biological roles of CXCL9 and CXCL11 in the development of TPE. METHODS: This double-blind study prospectively enrolled patients with undiagnosed pleural effusion from two centers (Hohhot and Changshu) in China. Pleural fluid on admission was obtained and levels of CXCL9 and CXCL11 were measured by an enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve and the decision curve analysis (DCA) were used to evaluate their diagnostic accuracy and net benefit, respectively. THP-1 cell-derived macrophages were treated with Bacillus Calmette-Guérin (BCG), and quantitative real-time PCR (qRT-PCR) and ELISA were used to determine the mRNA and protein levels of CXCL9 and CXCL11. The chemoattractant activities of CXCL9 and CXCL11 for T helper (Th) cells were analyzed by a transwell assay. RESULTS: One hundred and fifty-three (20 TPEs and 133 non-TPEs) patients were enrolled in the Hohhot Center, and 58 (13 TPEs and 45 non-TPEs) were enrolled in the Changshu Center. In both centers, we observed increased CXCL9 and CXCL11 in TPE patients. The areas under the ROC curves (AUCs) of pleural CXCL9 and CXCL11 in the Hohhot Center were 0.70 (95 % CI: 0.55-0.85) and 0.68 (95 % CI: 0.52-0.84), respectively. In the Changshu Center, the AUCs of CXCL9 and CXCL11 were 0.96 (95 % CI: 0.92-1.00) and 0.97 (95 % CI: 0.94-1.00), respectively. The AUCs of CXCL9 and CXCL11 decreased with the advancement of age. The decision curves of CXCL9 and CXCL11 showed net benefits in both centers. CXCL9 and CXCL11 were upregulated in BCG-treated macrophages. Pleural fluid from TPE and conditioned medium from BCG-treated macrophages were chemotactic for Th cells. Anti-CXCL9 or CXCL11 neutralizing antibodies could partly block the chemotactic activity. CONCLUSIONS: Pleural CXCL9 and CXCL11 are potential diagnostic markers for TPE, but their diagnostic accuracy is compromised in elderly patients. CXCL9 and CXCL11 can promote the migration of peripheral Th cells, thus representing a therapeutic target for the treatment of TPE.

Pleural fluid carbohydrate antigen 72-4 and malignant pleural effusion: a diagnostic test accuracy study.

BACKGROUND: The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE. OBJECTIVE: We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE. DESIGN: A prospective, preregistered, and double-blind diagnostic test accuracy study. METHODS: We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA). RESULTS: In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67. CONCLUSION: Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts.

BACKGROUND: Lung cancer is the most common cause of malignant pleural effusion (MPE). Serum human epididymis secretory protein 4 (HE4) is a useful diagnostic marker for lung cancer. OBJECTIVE: This study aimed to evaluate the diagnostic accuracy of pleural fluid HE4 for MPE. DESIGN: A prospective, double-blind diagnostic test accuracy study. METHODS: Patients with undiagnosed pleural effusion were enrolled in two cohorts (Hohhot and Changshu). Electrochemiluminescence immunoassay was used to detect pleural fluid HE4. The diagnostic accuracy of HE4 was evaluated by a receiver operating characteristic (ROC) curve, and the net benefit of HE4 was assessed by a decision curve analysis (DCA). RESULTS: A total of 66 MPEs and 86 benign pleural effusions (BPEs) were enrolled in the Hohhot cohort. In the Changshu cohort, 26 MPEs and 32 BPEs were enrolled. In both cohorts, MPEs had significantly higher pleural fluid HE4 than BPEs. The area under the ROC curve (AUC) of HE4 was 0.73 (95% CI: 0.64-0.81) in the Hohhot cohort and 0.79 (95% CI: 0.67-0.91) in the Changshu cohort. At a threshold of 1300 pmol/L, HE4 had sensitivities of 0.44 (95% CI: 0.33-0.56) in the Hohhot cohort and 0.54 (95% CI: 0.35-0.73) in the Changshu cohort. The corresponding specificities were 0.90 (95% CI: 0.83-0.95) in the Hohhot cohort and 0.94 (95% CI: 0.84-1.00) in the Changshu cohort. In subgroup analyses, HE4 had an AUC (95% CI) of 0.78 (0.71-0.85) in exudates and an AUC of 0.69 (0.57-0.81) in patients with negative effusion cytology. The DCA revealed that HE4 determination had a net benefit in both cohorts. CONCLUSION: Pleural fluid HE4 has moderate diagnostic accuracy for MPE and has net benefit in pleural effusion patients with unknown etiology.

Diagnostic value of nucleic acid amplification tests for tuberculous pleural effusion.

Diagnosing tuberculous pleural effusion (TPE) is challenging for pulmonologists and laboratory scientists. The gold standards for TPE diagnosis are pleural fluid Ziehl-Neelsen staining, Mycobacterium tuberculosis (Mtb) culture and pleural biopsy. These tools have limitations, including low sensitivity, long turnaround time and invasiveness. The nucleic acid amplification test (NAAT) is a rapid and minimally invasive tool for diagnosing TPE. This review summarizes the diagnostic accuracy of available NAATs for TPE, with a focus on the evidence from systematic reviews and meta-analyses. The NAATs summarized in this review include in-house NAATs, GeneXpert-MTB/RIF, GeneXpert-MTB/RIF Ultra, simultaneous amplification and testing-tuberculosis, FluoroType MTB and loop-mediated isothermal amplification.

Long-term stability of pleural fluid carcinoembryonic antigen and its effect on the diagnostic accuracy for malignant pleural effusion.

BACKGROUND: The in vitro stability assessment is essential for investigating the diagnostic accuracy of pleural biomarkers. This study aimed to investigate the long-term stability of pleural fluid carcinoembryonic antigen (CEA) at -80°C to -70°C. In addition, we analyzed the effects of frozen storage on the diagnostic accuracy of CEA for malignant pleural effusion (MPE). METHODS: Pleural fluid CEA of participants in two prospective cohorts were stored at -80°C to -70°C for 1-3 years. The CEA level in the stored specimen was measured with an immunoassay, and its level in the fresh specimen was extracted from medical records. The Bland-Altman method, Passing-Bablok regression, and Deming regression were used to analyze the agreement of CEA between the fresh and frozen pleural fluid. In addition, we used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CEA in the fresh and frozen specimens for MPE. RESULTS: A total of 210 participants were enrolled. The median CEA levels in frozen and fresh pleural fluid specimens were similar (frozen, 2.32 ng/mL; fresh, 2.59 ng/mL; p < 0.01). The slopes and intercepts in the Passing-Bablok regression (intercept 0.01, slope 1.04) and Deming regression (intercept 0.65; slope 1.00) were not statistically significant (p > 0.05 for all). No significant difference was observed between the area under the ROC curves of CEA in the fresh and frozen specimens (p > 0.05 for all). CONCLUSION: Pleural fluid CEA is seemingly stable when stored at -80°C to -70°C for 1-3 years. Frozen storage does not significantly affect the diagnostic accuracy of CEA for MPE.

Age affects the diagnostic accuracy of the cancer ratio for malignant pleural effusion.

BACKGROUND AND OBJECTIVE: Cancer ratio (CR), which is defined as serum lactate dehydrogenase (LDH) to pleural fluid adenosine deaminase (ADA) ratio, has been reported to be a useful diagnostic marker for malignant pleural effusion (MPE). Whether its diagnostic accuracy is affected by age remains unknown. This study aimed to investigate the effects of age on the diagnostic accuracy of CR. METHODS: The participants in this study were from a prospective cohort (SIMPLE cohort, n = 199) and a retrospective cohort (BUFF cohort, n = 158). All participants were patients with undiagnosed pleural effusion (PE). We used receiver operating characteristic (ROC) curves to evaluate the diagnostic accuracy of CR. The effect of age on the diagnostic accuracy of CR was investigated by adjusting the upper limit of age for participant enrolment. RESULTS: Eighty-eight MPE patients were verified in the SIMPLE cohort, and thirty-five MPE patients were verified in the BUFF cohort. The AUCs of CR in the SIMPLE and BUFF cohorts were 0.60 (95% CI: 0.52-0.68) and 0.63 (95% CI: 0.54-0.71), respectively. In both cohorts, the AUCs of CR decreased with the advancement of age. CONCLUSION: Age can affect the diagnostic accuracy of CR for MPE. CR has limited diagnostic value in older patients. KEY MESSAGE: Cancer ratio is a promising diagnostic marker for malignant pleural effusion. This study revealed that its diagnostic accuracy decreased in older patients. Its diagnostic accuracy is overestimated by previous studies using tuberculosis and pneumonia patients as controls.

Machine learning algorithm to construct cuproptosis- and immune-related prognosis prediction model for colon cancer.

BACKGROUND: Over the past few years, research into the pathogenesis of colon cancer has progressed rapidly, and cuproptosis is an emerging mode of cellular apoptosis. Exploring the relationship between colon cancer and cuproptosis benefits in identifying novel biomarkers and even improving the outcome of the disease. AIM: To look at the prognostic relationship between colon cancer and the genes associated with cuproptosis and the immune system in patients. The main purpose was to assess whether reasonable induction of these biomarkers reduces mortality among patients with colon cancers. METHOD: Data obtained from The Cancer Genome Atlas and Gene Expression Omnibus and the Genotype-Tissue Expression were used in differential analysis to explore differential expression genes associated with cuproptosis and immune activation. The least absolute shrinkage and selection operator and Cox regression algorithm was applied to build a cuproptosis- and immune-related combination model, and the model was utilized for principal component analysis and survival analysis to observe the survival and prognosis of the patients. A series of statistically meaningful transcriptional analysis results demonstrated an intrinsic relationship between cuproptosis and the micro-environment of colon cancer. RESULTS: Once prognostic characteristics were obtained, the CDKN2A and DLAT genes related to cuproptosis were strongly linked to colon cancer: The first was a risk factor, whereas the second was a protective factor. The finding of the validation analysis showed that the comprehensive model associated with cuproptosis and immunity was statistically significant. Within the component expressions, the expressions of HSPA1A, CDKN2A, and UCN3 differed markedly. Transcription analysis primarily reflects the differential activation of related immune cells and pathways. Furthermore, genes linked to immune checkpoint inhibitors were expressed differently between the subgroups, which may reveal the mechanism of worse prognosis and the different sensitivities of chemotherapy. CONCLUSION: The prognosis of the high-risk group evaluated in the combined model was poorer, and cuproptosis was highly correlated with the prognosis of colon cancer. It is possible that we may be able to improve patients' prognosis by regulating the gene expression to intervene the risk score.

Diagnostic accuracy of pleural fluid to serum carcinoembryonic antigen ratio and delta value for malignant pleural effusion: findings from two cohorts.

BACKGROUND: Pleural fluid (PF) carcinoembryonic antigen (CEA) is a widely used diagnostic marker for malignant pleural effusion (MPE). Recent studies revealed that PF to serum CEA was also a promising diagnostic parameter for MPE. OBJECTIVE: We aimed to investigate whether PF to serum CEA ratio and delta CEA (PF minus serum CEA) provided added value to PF CEA in diagnosing MPE. METHODS: Patients with pleural effusion in a retrospective cohort (BUFF) and a prospective cohort (SIMPLE) were included. The clinical characteristics of the patients were extracted from their medical records. The diagnostic value of CEA ratio and delta CEA was estimated by a receiver operating characteristics (ROC) curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: A total of 148 patients in the BUFF cohort and 164 patients in the SIMPLE cohort were enrolled. The BUFF cohort had 46 MPE patients and 102 benign pleural effusion (BPE) patients, and the SIMPLE cohort had 85 MPE patients and 79 BPE patients. In both cohorts, MPE patients had significantly higher PF CEA, serum CEA, CEA ratio, and delta CEA. The area under ROC curves (AUCs) of PF CEA, CEA ratio, and delta CEA were 0.78 (95% CI: 0.67-0.88), 0.80 (95% CI: 0.72-0.89) and 0.83 (95% CI: 0.75-0.91) in the BUFF cohort, and 0.89 (95% CI: 0.83-0.94), 0.86 (95% CI: 0.80-0.92), and 0.84 (95% CI: 0.78-0.91) in the SIMPLE cohort. The differences between the AUCs of PF CEA, CEA ratio, and delta CEA did not reach statistical significance. The continuous NRI and IDI of CEA ratio and delta CEA were <0. CONCLUSION: CEA ratio and delta value cannot provide added diagnostic value to PF CEA. The simultaneous determination of serum and PF CEA should not be adopted in clinical practice.

Accuracy of the Sysmex UF-5000 analyzer for urinary tract infection screening and pathogen classification.

The screening performance of urine flow cytometry parameters (e.g., white blood cell and bacteria) for urinary tract infection (UTI) has been widely recognized. The majority of previous studies, however, investigated the screening performance of Sysmex UF-1000i urine flow cytometer. This study aimed to investigate the screening performance of Sysmex UF-5000 analyzer, a third-generation urinary flow cytometer, for UTI and its novel parameter named Gram flag for discriminating gram-positive and negative pathogens. Urine specimens sent to the clinical microbiology laboratory of our hospital for bacterial culture between September 13, 2021, and November 15, 2021, were prospectively and consecutively collected. The Sysmex UF-5000 analyzer was used to determine urine white blood cell (WBC) and bacteria simultaneously. A chemical strip was used to assess urine nitrate. UTI was defined as positive urine bacterial culture > 104 CFU /ml. The receiver operating characteristics (ROC) curve, nomogram, decision tree, and decision curve were used to determine the screening performance of urine WBC, nitrate, and bacterial. A total of 246 UTIs and 425 non-UTIs were enrolled. The areas under the ROC curve (AUCs) for WBC and bacterial were 0.74 and 0.86, respectively. The decision curve showed that urine bacteria had a higher benefit than WBC. The nomogram indicated that urine bacterial had the largest effect on the probability of UTI. The sensitivity and specificity of the decision tree were 0.69 and 0.95, respectively. The flag of Gram-negative had a positive predictive value (PPV) of 0.93 in patients with urine bacteria > 1367 /µl. Therefore, we conclude that urine bacteria determined by the Sysmex UF-5000 had higher screening performance and greater benefit than WBC. The decision tree can be used to improve the screening performance of routine urinary parameters. The flag of Gram-negative is a reliable indicator to confirm gram-negative bacteria infection in UTI patients.

Age affects the diagnostic accuracy of serum N-terminal pro-B-type natriuretic peptide for heart failure in patients with pleural effusion.

BACKGROUND: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-recognized diagnostic marker for heart failure (HF) in patients with dyspnea or pleural effusion (PE). The effects of age on the diagnostic accuracy of NT-proBNP in dyspneic patients are widely known; however, whether its diagnostic accuracy is affected by age in patients with PE remains unknown. This study aimed to investigate the influence of age on the diagnostic accuracy of serum NT-proBNP for HF in patients with PE. METHODS: Patients with PE were recruited from the BUFF (Biomarkers for patients with Undiagnosed pleural eFFusion) cohort and the SIMPLE (a Study Investigating Markers in PLeural Effusion) cohort. Serum NT-proBNP on admission and final diagnosis were extracted from the participant's medical records. The diagnostic accuracy of serum NT-proBNP was evaluated by a operating characteristic (ROC) curve analysis. The influence of age on the diagnostic accuracy of NT-proBNP was investigated through subgroup analyses. RESULTS: One hundred and four participants were enrolled from the BUFF cohorts (HF, 32; non-HF, 72). One hundred and sixteen participants were enrolled from the SIMPLE cohort (HF, 21; non-HF, 95). The area under the ROC curve (AUCs) of NT-proBNP in the pooled cohort was 0.78 (95 %CI: 0.71 - 0.85). The AUC of NT-proBNP decreased in older patients. CONCLUSION: Serum NT-proBNP has moderate diagnostic accuracy for HF in old patients with PE. The diagnostic accuracy of serum NT-proBNP in these patients decreases with the advancement of age.

Diagnostic value of soluble biomarkers for parapneumonic pleural effusion.

Parapneumonic pleural effusion (PPE) is a common complication in patients with pneumonia. Timely and accurate diagnosis of PPE is of great value for its management. Measurement of biomarkers in circulating and pleural fluid have the advantages of easy accessibility, short turn-around time, objectiveness and low cost and thus have utility for PPE diagnosis and stratification. To date, many biomarkers have been reported to be of value for the management of PPE. Here, we review the values of pleural fluid and circulating biomarkers for the diagnosis and stratification PPE. The biomarkers discussed are C-reactive protein, procalcitonin, presepsin, soluble triggering receptor expressed on myeloid cells 1, lipopolysaccharide-binding protein, inflammatory markers, serum amyloid A, soluble urokinase plasminogen activator receptor, matrix metalloproteinases, pentraxin-3 and cell-free DNA. We found that none of the available biomarkers has adequate performance for diagnosing and stratifying PPE. Therefore, further work is needed to identify and validate novel biomarkers, and their combinations, for the management of PPE.

Molecular and clinical characteristics of carbapenem-resistant Enterobacteriaceae isolates collected at a tertiary hospital in northern China.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) represent a severe public health problem. METHODS: In a tertiary hospital in northern China, 169 non-duplicated clinical CRE strains were analyzed by species identification, in vitro antibiotics sensitivity test, carbapenemase gene detection and genetic sequence typing. RESULTS: The CRE strains showed high resistance to most clinical antimicrobials. Enterobacter cloacae and Escherichia coli isolates mainly carried blaNDM, and Klebsiella pneumoniae isolates mainly carried blakpc. ST11 was the most common type in Klebsiella pneumoniae, and ST70 was the new emerging sequence type (ST) in Enterobacter cloacae. CONCLUSIONS: The CRE strains isolated in northern China showed multidrug-resistant phenotypes, and the new emergence of ST70 Enterobacter cloacae should be closely supervised.

Pleural fluid biochemical analysis: the past, present and future.

Identifying the cause of pleural effusion is challenging for pulmonologists. Imaging, biopsy, microbiology and biochemical analyses are routinely used for diagnosing pleural effusion. Among these diagnostic tools, biochemical analyses are promising because they have the advantages of low cost, minimal invasiveness, observer independence and short turn-around time. Here, we reviewed the past, present and future of pleural fluid biochemical analysis. We reviewed the history of Light's criteria and its modifications and the current status of biomarkers for heart failure, malignant pleural effusion, tuberculosis pleural effusion and parapneumonic pleural effusion. In addition, we anticipate the future of pleural fluid biochemical analysis, including the utility of machine learning, molecular diagnosis and high-throughput technologies. Clinical Chemistry and Laboratory Medicine (CCLM) should address the topic of pleural fluid biochemical analysis in the future to promote specific knowledge in the laboratory professional community.

Pleural fluid soluble Fas ligand and tuberculous pleural effusion: a prospective diagnostic test accuracy study.

Background: The diagnosis of tuberculous pleural effusion (TPE) is challenging for pulmonologists. Adenosine deaminase (ADA), interferon-gamma (IFN-γ), and interleukin-27 (IL-27) have some limitations for diagnosing TPE. Soluble Fas ligand (sFasL) had a high diagnostic value for TPE. However, it remains unknown: (I) whether sFasL has an additional diagnostic value to the traditional markers (e.g., ADA); (II) whether sFasL provides a net benefit in patients with undiagnosed pleural effusion; (III) factors affecting the diagnostic accuracy of sFasL for TPE. This study aimed to evaluate the additional diagnostic value and benefit of pleural fluid sFasL for TPE. Methods: We prospectively enrolled 211 patients with undiagnosed pleural effusion. The concentration of sFasL in pleural fluid was measured by an enzyme-linked immunosorbent assay (ELISA). The diagnostic accuracy and net benefit of sFasL and ADA for TPE were analyzed by a receiver operating characteristic (ROC) curve, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discriminant improvement (IDI). Results: The area under the ROC curves (AUCs) of sFasL and ADA were 0.74 (95% CI: 0.65-0.83) and 0.80 (95% CI: 0.71-0.90), respectively. The decision curve of sFasL revealed net benefit. The continuous NRI and IDI of sFasL were 0.36 (0.00-0.72, P=0.05) and 0.02 (-0.01-0.06, P=0.18), respectively. Conclusions: Pleural fluid sFasL has moderate diagnostic accuracy for TPE.

Diagnostic accuracy of pleural fluid lactate dehydrogenase to adenosine deaminase ratio for tuberculous pleural effusion: an analysis of two cohorts.

BACKGROUND: This study aimed to evaluate the diagnostic accuracy of pleural fluid (PF) lactate dehydrogenase (LDH) to adenosine deaminase (ADA) (LDH/ADA) ratio for tuberculous pleural effusion (TPE). Especially to explore whether the LDH/ADA ratio provides added diagnostic value to ADA. METHODS: The diagnostic accuracy of PF LDH/ADA ratio and ADA for TPE was evaluated in two cohorts, named the BUFF (Biomarkers for patients with Undiagnosed pleural eFFusion) cohort (62 with TPE and 194 with non-TPE) and the SIMPLE (a Study Investigating Markers in PLeural Effusion) cohort (33 with TPE and 177 with non-TPE). Receiver operating characteristic (ROC) curve and decision curve were used to measure the diagnostic accuracy of the PF LDH/ADA ratio. The added diagnostic value of the LDH/ADA ratio to ADA was evaluated with net reclassification improvement (NRI) and integrated discrimination improvement (IDI). RESULTS: The area under the ROC curves (AUCs) of PF ADA and LDH/ADA ratio in the BUFF cohort were 0.76 and 0.74, respectively. In the SIMPLE cohort, the AUCs of PF ADA and LDH/ADA ratio were 0.80 and 0.85, respectively. The decision curves of PF LDH/ADA and ADA were close in both the BUFF and SIMPLE cohorts. The NRI and IDI analyses did not reveal any added diagnostic value of LDH/ADA to ADA. CONCLUSIONS: PF LDH/ADA ratio has moderate diagnostic accuracy for TPE. It does not provide added diagnostic value beyond ADA. The current evidence does not support LDH/ADA ratio for diagnosing TPE.

Epidemiological characteristics and molecular evolution mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae.

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), a type of Klebsiella pneumoniae (KP) that exhibits hypervirulence and carbapenem resistance phenotypes, can cause severe infections, both hospital- and community-acquired infections. CR-hvKP has brought great challenges to global public health and is associated with significant morbidity and mortality. There are many mechanisms responsible for the evolution of the hypervirulence and carbapenem resistance phenotypes, such as the horizontal transfer of the plasmid carrying the carbapenem resistance gene to hypervirulent Klebsiella pneumoniae (hvKP) or carbapenemase-producing Klebsiella pneumoniae (CRKP) acquiring a hypervirulence plasmid carrying a virulence-encoding gene. Notably, KP can evolve into CR-hvKP by acquiring a hybrid plasmid carrying both the carbapenem resistance and hypervirulence genes. In this review, we summarize the evolutionary mechanisms of resistance and plasmid-borne virulence as well as the prevalence of CR-hvKP.

Falsely elevated D-dimer partially caused by heterophilic antibodies: A case report.

Plasma D-dimer is a screening marker for thrombosis and hemostasis disorders. Falsely elevated D-dimer may result in misdiagnosis and potentially invasive investigations. Therefore, identifying falsely elevated D-dimer is of great value in laboratory practice. D-dimer is determined by immunoassay and vulnerable to heterophilic antibody interference. Here, we reported a case of falsely elevated D-dimer partially caused by heterophilic antibodies. Dilution test, polyethylene glycol precipitation, heterophilic blocking reagent and method comparison were used to identify the heterophilic antibody interference. All these methods, except for the heterophilic blocking reagent, revealed the existence of heterophilic antibody interference. Polyethylene glycol precipitation failed to reduce the D-dimer to its reference interval. Therefore, we conclude that the falsely elevated D-dimer is partially caused by heterophilic antibody interference.

Pleural homocysteine for malignant pleural effusion: A prospective and double-blind diagnostic test accuracy study.

OBJECTIVE: To assess the accuracy of pleural fluid homocysteine for discriminating malignant pleural effusion (MPE) and benign pleural effusion (BPE). METHODS: A total of 194 patients from two cohorts (Hohhot and Changshu) with undiagnosed pleural effusion were prospectively enrolled. Their pleural homocysteine was measured, and its diagnostic accuracy and net benefit for MPE were analyzed by receiver operating characteristic (ROC) curve analysis and decision curve analysis, respectively. RESULTS: In the Hohhot cohort (n = 136) and the Changshu cohort (n = 58), MPE patients had significantly higher homocysteine levels than BPE patients. The areas under the ROC curves of homocysteine for the diagnosis of MPE were 0.61 (p = 0.027) and 0.59 (p = 0.247), respectively. The decision curves of homocysteine were close to the reference line in both the Hohhot cohort and the Changshu cohort. CONCLUSION: The diagnostic accuracy of pleural fluid homocysteine for MPE was low.

Diagnostic utility of pleural cell-free nucleic acids in undiagnosed pleural effusions.

Pleural effusion (PE) is a common sign caused by various disorders. Microbiology, histology and cytology are reference standards for these disorders. However, these diagnostic tools have limitations, including invasiveness, high cost, long turnaround time, and observer-dependent. Soluble biomarkers in pleural fluid (PF) are promising diagnostic tools because they are mininvasive, economical, and objective. Recent studies have revealed that some cell-free nucleic acids (e.g., DNA, mRNA, microRNA, and lncRNA) in PF are potential diagnostic markers for many disorders. Here, we review the performance of PF cell-free nucleic acids for differentiating and stratification of PE.