Determination of the diagnostic accuracy of nanopore sequencing using bronchoalveolar lavage fluid samples from patients with sputum-scarce pulmonary tuberculosis.

PURPOSE: The early and efficient diagnosis of patients suspected of having pulmonary tuberculosis (PTB) remains challenging. This study aimed to evaluate the accuracy of nanopore sequencing for PTB diagnosis using bronchoalveolar lavage fluid (BALF) samples and compared it with other techniques such as acid-fast bacilli smear, culture, Xpert MTB/RIF, and CapitalBio Mycobacterium reverse transcription-polymerase chain reaction (MTB RT-PCR). METHODS: We retrospectively analyzed the clinical data of 195 patients with suspected PTB who were admitted to our hospital. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of these assays were calculated and compared. RESULTS: The overall sensitivity, specificity, PPV, NPV, and AUC of nanopore sequencing were 90.70%, 84.85%, 92.13%, 82.35%, and 0.88; those of acid-fast bacilli smear were 12.40%, 98.48%, 94.12%, 36.52%, and 0.55; those of culture were 36.43%, 100%, 100%, 44.59%, and 0.68; those of Xpert MTB/RIF were 41.09%, 100%, 100%, 46.48%, and 0.71; and those of CapitalBio MTB RT-PCR were 34.88%, 98.48%, 97.83%, 43.62%, and 0.67, respectively. CONCLUSION: The nanopore sequencing assay using BALF samples showed the best diagnostic accuracy for sputum-scarce PTB. Moreover, it can improve the clinical diagnosis of PTB.

Identification of Hub Genes and Typing of Tuberculosis Infections Based on Autophagy-Related Genes.

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of morbidity and death in humans worldwide. Some autophagy genes associated with TB and some miRNAs regulating TB have been found, but the identification of autophagy-related genes in M. tuberculosis remains to be explored. Forty-seven autophagy-related genes differentially expressed in TB were identified in this study by analysis of TB-related datasets in the Gene Expression Omnibus (GEO) and autophagy-related genes in the Human Autophagy Database. The potential crucial genes affecting TB were found through the protein-protein interaction (PPI) network, and the possible pathways affected by these genes were verified. Analysis of the PPI network of miRNAs associated with M. tuberculosis infection and their target genes revealed that hsa-let-7, hsa-mir-155, hsa-mir-206, hsa-mir-26a, hsa-mir-30a, and hsa-mir-32 may regulate the expression of multiple autophagy-related genes (MAPK8, UVRAG, UKL2, and GABARAPL1) alone or in combination. Subsequently, Cytoscape was utilized to screen the differentially expressed genes related to autophagy. The hub genes (GABARAPL1 and ULK2) affecting TB were identified. Combined with Gene Set Enrichment Analysis (GSEA), the signaling pathways affected by the hub genes were verified. Finally, we divided TB patients into two subgroups based on autophagy-related genes, and the immune microenvironment of patients in different subgroups was significantly different. Our study found two autophagy-related hub genes that could affect TB and divide TB samples into two subgroups. This finding is of great significance for TB treatment and provides new ideas for exploring the pathogenesis of M. tuberculosis.

Monocyte-to-lymphocyte ratio is significantly associated with positive QuantiFERON-TB Gold-In-Tube and adult survival: an observational study.

This study aimed to find significant factors associated with tuberculosis (TB) infection and disease development. The participants were from National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI). The tuberculosis infection was defined as a positive QuantiFERON-TB Gold-In-Tube (QFT-GIT). The Least Absolute Shrinkage and Selection Operator (LASSO) model was used to screen variables associated with QFT-GIT among 23 laboratory measures. Then the logistic regression analyses were performed to assess the independent factors, followed by a comprehensive nomogram model construction. Receiver operating characteristic (ROC) and Decision Curve (DCA) analyses were used to assess the performance of comprehensive model on QFT-GIT result and death risk. Of 5256 individuals included, 521 individuals had positive QFT-GIT. LASSO analysis indicated that 11 variables were associated with QFT-GIT result, and logistic regression analyses further found sodium and monocyte-to-lymphocyte ratio (MLR) were independent factors. After adjusting for potential confounders, the correlation of sodium and MLR with QFT-GIT result was still observed. The comprehensive model based on sodium, MLR, and important clinical characteristics can predict 0.8 probability of positive QFT-GIT and achieve more clinical net benefit. ROC analysis by training and validation sets showed the favorable prediction performance. Comprehensive model also presented favorable performance in evaluating the death risk of individuals with positive QFT-GIT. We also found MLR rather than sodium was independently related to the death risk. Both MLR itself and comprehensive model were all significantly related to the positive QFT-GIT and death risk, which might participate in the initiation and progression of tuberculosis infection.

Diagnostic value of ultrasound-guided transbronchial lung biopsy in peripheral tuberculous pulmonary lesions.

BACKGROUND: To investigate the diagnostic value of bronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in tuberculous peripheral pulmonary lesions. METHODS: A total of 770 patients who completed CT imaging and ultrasound bronchoscopy were retrospectively analyzed. All patients underwent biopsy sampling as well as alveolar lavage under the guidance of ultrasound. Pathological analysis and molecular biological detection of pulmonary tuberculosis were performed in both pathological tissues and bronchoalveolar lavage fluid (BALF), and the diagnostic positive rate and diagnostic sensitivity were statistically analyzed. RESULTS: Of the 44 patients who were found to have lesions by EBUS-TBLB, 26 patients were able to achieve a definite diagnosis of PPLs, with an overall diagnostic yield of 59.1%. Of the 33 patients with all diagnosed benign lesions, 22 were diagnosed with active pulmonary tuberculosis with the diagnostic yield of 66.7%. Among above 22 cases, the overall positive rate of BALF diagnosis was as high as 95.6%, and the highest diagnostic rate of a single test was BALF XpertMTB/RIF, 59.1%. Compared with pathological tissues, the diagnostic positive rate of BALF as a diagnostic specimen was higher (p < .05). In addition, the diagnostic yield of EBUS-TBLB in pulmonary tuberculosis was not affected by patient's age, lesion extent size, EBUS probe position, presence or tracheal grade, or characteristics of lesions (all p > .05). CONCLUSION: Transbronchial radial ultrasound-guided lung biopsy of tuberculous PPLs possesses higher diagnostic rate, fewer complications and less interference, exerts potential application value in the diagnosis of tuberculous peripheral pulmonary lesions.

Neoadjuvant chemotherapy combined with immunotherapy for pulmonary large-cell neuroendocrine carcinoma: a case report.

Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC can be further divided into squamous cell carcinoma, adenocarcinoma, and large-cell neuroendocrine carcinoma (LCNEC). At present, our understanding of LCNEC is limited. LCNEC is a rare condition but is highly malignant with a poor prognosis. The mean age of onset was about 65 years old, and was highly correlated with smoking. Although many treatment methods, including surgery, radiotherapy, and chemotherapy, are available, the therapeutic effect was limited and there is still a lack of clear guidelines and recommendations for its therapy. At present, immunotherapy is rapidly developing, and its application in lung cancer is increasing. However, there is limited literature about immunotherapy in LCNEC. Here, we present a case of LCNEC at stage IIIA, which involved a 64-year-old man with a 30-year history of smoking. Enhanced chest radiography indicated a malignant tumor in the upper lobe of the left lung. We treated this patient with neoadjuvant chemo-immunotherapy with albumin paclitaxel, carboplatin, and sintilimab. We also performed postoperative chemo-immunotherapy the same as before surgery. The patient has well tolerated this treatment and remains under postoperative observation for 6 months at the time of writing.

Association between interleukin-8 -251A/T polymorphism and the risk of tuberculosis: A meta-analysis.

OBJECTIVE: The relationship between interleukin-8 (IL8) -251A/T polymorphism and tuberculosis (TB) risk remains controversial. Therefore, the present meta-analysis was performed by retrieving relevant studies from the available literature. METHODS: We comprehensively searched three databases to identify eligible literature on the relationship of IL8 -251A/T polymorphism with TB risk, calculated pooled odds ratios (OR) with 95% confidence intervals (CI), and subsequent evaluated the heterogeneity and publication bias. RESULTS: We found that IL8 -251A/T polymorphism increased TB risk (AA vs. TT: OR = 2.86, 95%CI: 1.46-5.60; AT vs. TT: OR = 1.64, 95%CI: 1.15-2.34; dominant model: OR = 1.88, 95%CI: 1.24-2.86; recessive model: OR = 1.77, 95%CI: 1.17-2.69). Subgroup analyses based on race revealed that the IL8 -251A/T polymorphism might be associated with the risk of TB in African but not Asian individuals. CONCLUSION: The IL8 -251A/T polymorphism might be related to the risk of TB. Nevertheless, large-scale studies should be performed to confirm the role of IL8 -251A/T polymorphism on TB risk.