scholarly journals Clinical Performance of BAL Metagenomic Next-Generation Sequence and Serum (1,3)-β-D-Glucan for Differential Diagnosis of Pneumocystis jirovecii Pneumonia and Pneumocystis jirovecii Colonisation

Author(s):  
Li Liu ◽  
Mingjuan Yuan ◽  
Yi Shi ◽  
Xin Su

BackgroundDifferentiating Pneumocystis jirovecii infection from colonisation is crucial for appropriate therapy administration. In this study, we evaluated the performance of bronchoalveolar lavage fluid (BAL) metagenomic next-generation sequencing (mNGS) and serum 1,3-β-D-glucan (BDG) tests in differentiating colonisation and infection with P. jirovecii.MethodsFrom January 2018 to March 2021, 47 patients were enrolled in this study at the Hunan Provincial People’s Hospital. The final diagnosis was used as a reference, and cases were classified into the P. jirovecii pneumonia (PJP) group or the P. jirovecii colonisation (PJC) group. Clinical data were recorded. The performances of mNGS and BDG were compared.ResultThe fungal load significantly differed between patients with PJP and PJC, with median reads of 3,215.79 ± 1,797 vs. 5.61 ± 0.88 in the PJP and PJC groups, respectively (P < 0.0001). BDG also significantly differed between the two groups, with a median titre of 233.60 ± 39.65 pg/ml in the PJP group and 68.48 ± 19.21 pg/ml in the PJC group (P = 0.0006). The area under the curve was 0.973 (95%CI: 0.868–1.007) for mNGS of the BAL and 0.879 (95%CI: 0.769–0.989) for the serum BDG. The optimal threshold value for discriminating P. jirovecii infection from colonisation appeared to be 14 reads (sensitivity, 83.3%; specificity, 95.7%; positive likelihood ratio, 19.2) and BDG = 88.6 pg/ml (sensitivity, 79.2%; specificity, 92.9%; positive likelihood ratio, 18.2). No correlation between mNGS reads and the BDG titre was found in mNGS-positive patients (r2 = 0.0076, P = 0.583). The levels of lactate dehydrogenase and C-reactive protein were significantly higher in the PJP group than in the PJC group.ConclusionBAL mNGS and serum BDG are useful adjunct tests that can assist with differentiating between colonisation and infection of P. jirovecii.

2020 ◽  
Vol 6 (4) ◽  
pp. 200
Author(s):  
Shiwei Zhou ◽  
Kathleen A. Linder ◽  
Carol A. Kauffman ◽  
Blair J. Richards ◽  
Steve Kleiboeker ◽  
...  

We evaluated the performance of the (1,3)-β-d-glucan (BDG) assay on bronchoalveolar lavage fluid (BALF) as a possible aid to the diagnosis of Pneumocystis jirovecii pneumonia. BALF samples from 18 patients with well-characterized proven, probable, and possible Pneumocystis pneumonia and 18 well-matched controls were tested. We found that the best test performance was observed with a cut-off value of 128 pg/mL; receiver operating characteristic/area under the curve (ROC/AUC) was 0.70 (95% CI 0.52–0.87). Sensitivity and specificity were 78% and 56%, respectively; positive predictive value was 64%, and negative predictive value was 71%. The low specificity that we noted limits the utility of BALF BDG as a diagnostic tool for Pneumocystis pneumonia.


2021 ◽  
Author(s):  
wenzhang long ◽  
kunting xiao ◽  
yongqiang yuan

Abstract PurposeWe conducted a meta-analysis to evaluate the diagnostic performance of various levels of serum (1-3)-Beta-D-glucan(BDG) for Pneumocystis jirovecii(PJ) infection using Fungitell assay.MethodsEMBASE, MEDLINE, and the reference lists of relevant studies were identified up to March 12,2021, with no language restrictions. Meta-analysis was performed using random-effects models for bivariate analysis. Subgroup analyses were implemented in HIV-positive Pneumocystis jirovecii pneumonia (PJP), HIV-negative PJP, and PJP versus colonized patients.ResultsNineteen individual studies that included a total of 2,310 participants met our inclusion criteria. The overall sensitivity, specificity, positive likelihood ratio(LR+) and negative likelihood ratio (LR−),and 95 % confidence interval CI of serum-BDG were 0.94(95 % CI: 0.89–0.96),0.76 (95 % CI: 0.65–0.85), 3.99 (95 % CI: 2.59–6.13),0.08 (95 % CI: 0.05–0.15), respectively. Futher stratified analysis of diagnostic values showed that various levels of serum BDG differed in sensitivity, specificity, LR+ and LR− in the diagnosis of PJP. Subgroup analyses also indicated that the cutoff value of 200 pg/mL had sufficient diagnostic accuracy in HIV-positive PJP patients versus controls. Moreover, the 80 pg/mL cutoff value had satisfactory diagnostic accuracy in PJP versus colonized patients, a overall sensitivity of 0.86 (95% CI, 0.73-0.93), a overall specificity of 0.82(95% CI,0.73-0.88), a overall LR+ 4.70(95 % CI: 3.11–7.08), and a overall LR−0.17(95 % CI: 0.09–0.34),individually.ConclusionsThis meta-analysis suggests that the optimal positive threshold for serum BDG, tested by the Fungitell assay, requires better definition and clinical validation rather than the recommended cutoff of 80pg/mL by the manufacturer in the diagnosis of PJP. These cutoff values could be further refined in additional studies that focus on populations that are as homogeneous as possible.


2021 ◽  
Vol 20 ◽  
pp. 153303382110119
Author(s):  
Wen-Ting Zhang ◽  
Guo-Xun Zhang ◽  
Shuai-Shuai Gao

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zexin Li ◽  
Kaiji Yang ◽  
Lili Zhang ◽  
Chiju Wei ◽  
Peixuan Yang ◽  
...  

Purpose. Several commercial tests have been used for the classification of indeterminate thyroid nodules in cytology. However, the geographic inconvenience and high cost confine their widespread use. This study aims to develop a classifier for conveniently clinical utility. Methods. Gene expression data of thyroid nodule tissues were collected from three public databases. Immune-related genes were used to construct the classifier with stacked denoising sparse autoencoder. Results. The classifier performed well in discriminating malignant and benign thyroid nodules, with an area under the curve of 0.785 [0.638–0.931], accuracy of 92.9% [92.7–93.0%], sensitivity of 98.6% [95.9–101.3%], specificity of 58.3% [30.4–86.2%], positive likelihood ratio of 2.367 [1.211–4.625], and negative likelihood ratio of 0.024 [0.003–0.177]. In the cancer prevalence range of 20–40% for indeterminate thyroid nodules in cytology, the range of negative predictive value of this classifier was 37–61%, and the range of positive predictive value was 98–99%. Conclusion. The classifier developed in this study has the superb discriminative ability for thyroid nodules. However, it needs validation in cytologically indeterminate thyroid nodules before clinical use.


BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e034348 ◽  
Author(s):  
Marie Barais ◽  
Emilie Fossard ◽  
Antoine Dany ◽  
Tristan Montier ◽  
Erik Stolper ◽  
...  

ObjectivesDyspnoea and chest pain are symptoms shared with multiple pathologies ranging from the benign to life-threatening diseases. A Gut Feelings Questionnaire (GFQ) has been validated to measure the general practitioner’s (GPs) sense of alarm or sense of reassurance. The aim of the study was to estimate the diagnostic test accuracy of GPs’ sense of alarm when confronted with dyspnoea and chest pain.Design and settingsProspective observational study in general practice.ParticipantsPatients aged between 18 and 80 years, consulting their GP for dyspnoea and/or chest pain, were considered for enrolment. These GPs had to complete the GFQ immediately after the consultation.Primary outcome measuresLife-threatening and non-life-threatening diseases have previously been defined according to the pathologies or symptoms in the International Classification of Primary Care (ICPC)-2 classification. The index test was the sense of alarm and the reference standard was the final diagnosis at 4 weeks.Results25 GPs filled in 235 GFQ questionnaires. The positive likelihood ratio for the sense of alarm was 2.12 (95% CI 1.49 to 2.82), the negative likelihood ratio was 0.55 (95% CI 0.37 to 0.77).ConclusionsWhere the physician experienced a sense of alarm when a patient consulted him/her for dyspnoea and/or chest pain, the post-test odds that this patient had, in fact, a life-threatening disease was about twice as high as the pretest odds.Trial registration numberNCT02932982.


2020 ◽  
pp. 028418512096390
Author(s):  
Chun-Rong Zhu ◽  
Ke-Yu Chen ◽  
Pan Li ◽  
Zhi-Yang Xia ◽  
Bin Wang

Background The sensitivity of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for detecting breast cancer was high and the specificity was relatively low. However, diffusion-weighted imaging (DWI) has a high specificity in the diagnosis of malignant lesions. Purpose To evaluate the accuracy of the multiparametric MRI (mp-MRI) in distinguishing the breast malignant lesions from the benign lesions. Material and Methods A comprehensive search of the PubMed, Embase, and Cochrane Library electronic databases was conducted up to March 2020. Data were analyzed for the following indexes: pooled sensitivity and specificity; positive likelihood ratio; negative likelihood ratio; diagnostic odds ratio; and the area under the curve. Results A total of 2356 patients with 1604 malignant and 967 benign breast lesions were included from 22 studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve for mp-MRI were 0.93, 0.85, 6.3, 0.08, 81, and 0.96, respectively. The pooled sensitivity, specificity, and area under the curve for DCE-MRI alone were 0.95, 0.71, and 0.92, respectively. The pooled sensitivity, specificity, and area under the curve for DWI alone were 0.88, 0.84, and 0.93, respectively. Conclusion The mp-MRI did not improve the sensitivity but increased the specificity for the diagnosis of breast malignant lesions.


2020 ◽  
Vol 7 ◽  
Author(s):  
Ying Luo ◽  
Ying Xue ◽  
Liyan Mao ◽  
Qun Lin ◽  
Guoxing Tang ◽  
...  

Background: Tuberculous peritonitis (TP) is a common form of abdominal tuberculosis (TB). Diagnosing TP remains challenging in clinical practice. The aim of the present meta-analysis was to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and peritoneal fluid (PF) T-SPOT for diagnosing TP.Methods: PubMed, EmBase, Cochrane, Scopus, Google scholar, China national knowledge internet, and Wan-Fang databases were searched for relevant articles from August 1, 2005 to July 5, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. Diagnostic parameters including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic curve was used to determine the area under the curve (AUC).Results: Twelve studies were eligible and included in the meta-analysis. The analysis showed that the pooled sensitivity and specificity of PB T-SPOT in diagnosing TP were 0.91 (95% CI, 0.88–0.94) and 0.78 (95% CI, 0.73–0.81), respectively, while the pooled PLR, NLR, and DOR were 4.05 (95% CI, 2.73–6.01), 0.13 (95% CI, 0.07–0.23), and 37.8 (95% CI, 15.04–94.98), respectively. On the other hand, the summary estimates of sensitivity, specificity, PLR, NLR, and DOR of PF T-SPOT for TP diagnosis were 0.90 (95% CI, 0.85–0.94), 0.78 (95% CI, 0.72–0.83), 6.35 (95% CI, 2.67–15.07), 0.14 (95% CI, 0.09–0.21), and 58.22 (95% CI, 28.76–117.83), respectively. Furthermore, the AUC of PB T-SPOT and PF T-SPOT for TP diagnosis were 0.91 and 0.94, respectively.Conclusions: Our results indicate that both PB T-SPOT and PF T-SPOT can be served as sensitive approaches for the diagnosis of TP. However, the unsatisfactory specificities of these two methods limit their application as rule-in tests for TP diagnosis. Furthermore, the standardization of the operating procedure of PF T-SPOT is further needed.


2021 ◽  
Author(s):  
Jiangfeng Wu ◽  
Yue Sun ◽  
Yunlai Wang ◽  
Lijing Ge ◽  
Yun Jin ◽  
...  

Aims: In the present study, a meta-analysis was performed to evaluate the diagnostic value of endobronchial ultrasound (EBUS) elastography for differentiating benign and malignant hilar and mediastinal lymph nodes (LNs). Material and methods: A comprehensive literature search was carried out through PubMed, Embase, and Cochrane Library. Two authors screened the papers and extracted the data independently and any discrepancies were resolved by discussion. The methodolog-ical quality of each included study was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and area under the curve were calculated to evaluate the value of EBUS elastography for hilar and mediastinal LNs. Results: Seventeen studies with the number of 2307 LNs were included. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio for the diagnosis of hilar and mediastinal LNs by EBUS elastography were 0.90 (95% confidence interval [CI], 0.84-0.94), 0.78 (95% CI, 0.74-0.81), 4.1 (95% CI, 3.4-4.9), 0.12 (95% CI, 0.07-0.21) and 33 (95% CI, 17-64), respectively. Furthermore, area under the curve was calculated to be 0.86 (95% CI, 0.82-0.88). Conclusion: EBUS elastography is a valuable technology in the differentiation of benign and malignant hilar and mediastinal LNs and could provide supplementary diagnostic information during endobronchial ultrasound-guided transbronchial needle aspiration. The combination of EBUS elastography and B-mode EBUS could improve the diagnostic accuracy for hilar and mediastinal LNs.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xingyang Zhu ◽  
Haitao Zhang ◽  
Xiaobo Sun ◽  
Yijin Li ◽  
Jiahao Li ◽  
...  

Abstract Background Fibrinogen (FIB) has recently been used as a biomarker to diagnose periprosthetic joint infection (PJI), but its reliability is still questionable. The aim of this study was to investigate the accuracy of FIB in the diagnosis of PJI after joint replacement. Methods We searched for literatures published in PubMed, EMBASE, and the Cochrane Library from the time of database inception to September 2020 and screened the studies according to the inclusion criteria. Then, we calculated the diagnostic parameters of FIB, including the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), area under the curve (AUC), and diagnostic odds ratio (DOR). In addition, we implemented subgroup analyses to identify the sources of heterogeneity. Results Seven studies including 1341 patients were selected in our meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR of FIB for PJI diagnosis were 0.78 (95% confidence interval [CI], 0.73–0.82), 0.83 (95% CI, 0.81–0.86), 4.60 (95% CI, 3.30–6.42), 0.24 (95% CI, 0.18–0.34), and 20.13 (95% CI, 14.80–27.36), respectively, while the AUC was 0.896. Conclusion The present study indicated that FIB was a reliable detection method and might be introduced into the diagnostic criteria for PJI. However, more robust studies are still needed to confirm the current findings, because most of the included studies were retrospective and had small sample sizes.


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