A new basic thoracoscopic surgical skill training and assessment system using automatic scoring techniques.

PURPOSE: We report a new thoracoscopic surgical skill training and assessment system with automatic scoring techniques, the Huaxi Intelligent Thoracoscopic Skill Training and Assessment (HITSTA) system. We also evaluated the discriminative ability of this system compared to our conventional scoring method at our institution. METHODS: We retrospectively collected training data of thoracic board-certified thoracic surgeons at West China Hospital, Sichuan University from January 1, 2018 to January 1, 2019. Surgeons were assessed by HITSTA system and human examiners simultaneously. Total scores were summed from 3 tasks (grasping with delivery, pattern cutting, and suture with knot). Bland-Altman analysis was used to test agreement of scores made by HITSTA system (automatic scoring) and human examiners (manual scoring). Differentiation ability was also compared between the two scoring methods. RESULTS: Thirty-nine surgeons were recruited. Scores made by HITSTA system and human examiners were not consistent. For suture with knot, automatic scoring method could detect the score differences between different training status (trained: 26.92 ± 12.04, untrained: 19.85 ± 11.12; p = 0.026) and training duration (< 10 h: 20.67 ± 15.23, ≥ 10 h: 31.92 ± 5.56; p = 0.003). For total scores, automatic scoring approach could discriminate between different training status (trained: 71.90 ± 12.63; untrained: 61.41 ± 13.87; p = 0.016) and training duration (< 10 h: 65.23 ± 15.31; ≥ 10 h 77.23 ± 6.94; p = 0.046). CONCLUSION: HITSTA system could discriminate the different levels of thoracoscopic surgical skills better than the traditional manual scoring method. Larger prospective studies are warranted to validate the differentiation ability of HITSTA system.

Metformin promotes smear conversion in tuberculosis-diabetes comorbidity and construction of prediction models.

BACKGROUND: The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a global health concern. Metformin is commonly used in DM but the potential effectiveness in comorbid patients is uncertain. This retrospective study aims to investigate the effect of metformin on TB-DM comorbidity and construct prediction models. METHODS: Patients diagnosed with TB-DM in West China Hospital were retrospectively enrolled from Nov 2013 to Sep 2019. Electronic health records of patients were extracted. Two-month smear conversion (2SC) was considered an outcome indicator of TB. Univariate and multivariate logistic regression (LR) were used to assess the role of metformin and other independent predictors. Meanwhile, prediction models were built by LR, elastic net regression, support vector machine, k-nearest neighbors, and random forest. RESULTS: A total of 927 individuals were recruited, among which 408 (44.01%) were metformin-exposed patients. A higher 2SC rate was observed in the metformin users. Other impact factors such as smoking, glucose, and creatinine levels were also identified. Multivariable models were then constructed using filtered variables. The support vector machine model yields the highest AUC (0.808, 95% CI: 0.767-0.849) and specificity (83.24%). LR model outperformed others in terms of sensitivity (69.71%). CONCLUSION: This retrospective study of a large population from southwestern China provides strong clinical evidence for the positive effects of metformin in TB-DM. Metformin is associated with a better therapeutic outcome and promising for the adjuvant therapy of TB-DM. Furthermore, a combination of support vector machine and LR models is recommended to discriminate the patients with poor treatment outcomes.

Systematic evaluation, verification and comparison of tuberculosis-related non-coding RNA diagnostic panels.

We systematically summarized tuberculosis (TB)-related non-coding RNA (ncRNA) diagnostic panels, validated and compared panel performance. We searched TB-related ncRNA panels in PubMed, OVID and Web of Science up to 28 February 2020, and available datasets in GEO, SRA and EBI ArrayExpress up to 1 March 2020. We rebuilt models and synthesized the results of each model in validation sets by bivariate mixed models. Specificity at 90% sensitivity, area under curve (AUC) and inconsistence index (I2 ) were calculated. NcRNA biofunctions were analysed. Nineteen models based on 18 ncRNA panels (miRNA, lncRNA, circRNA and snoRNA panels) and 18 datasets were included. Limited available datasets only allowed to evaluate miRNA panels further. Cui 2017 and Latorre 2015 exhibited specificity >70% at 90% sensitivity and AUC >80% in all validation sets. Cui 2017 showed higher specificity at 90% sensitivity (92%) and AUC (95%) and lower heterogeneity (I2  = 0%) in ethological-confirmation validation sets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that most ncRNAs in panels involved in immune cell activation, oxidative stress, and Wnt and MAPK signalling pathway. Cui 2017 outperformed other models in both all available and aetiological-confirmed validation sets, meeting the criteria of target product profile of WHO. This work provided a basis for clinical choice of TB-related ncRNA diagnostic panels to a certain extent.

Absence of significant association between UGT2B4 genetic variants and the susceptibility to anti-tuberculosis drug-induced liver injury in a Western Chinese population.

WHAT IS KNOWN AND OBJECTIVE: Combination regimens of six-month duration may increase the incidence of anti-tuberculosis drug-induced liver injury (ATLI), which is clinically characterized by mild cholestasis and hepatocanalicular lesions. UGT2B4 is a predominant UDP-glucuronosyltransferase enzyme in the human liver that plays an important role in the detoxification of bile acids, which yields water-soluble inactive compounds that can easily be excreted in the bile or urine. This study aimed to investigate the potential association between UGT2B4 variants and the susceptibility to ATLI. METHODS: Genomic DNA was extracted from whole blood sample of each patient, and all SNPs were genotyped using an improved multiplex ligation detection reaction method. Clinical symptoms and laboratory results were recorded regularly. Five genetic variants at UGT2B4(rs1131878, rs1966151, rs28361541, rs4557343 and rs79407331) were identified in a prospective study of 118 ATLI cases and 628 non-ATLI controls. All participants were treated by first-line anti-TB drugs in Western China Hospital. The potential association between SNPs, ATLI risk and clinical phenotypes were determined based on the distribution of allelic frequencies and different genetic models. RESULTS AND DISCUSSION: Statistical comparisons of cases and controls after correction for multiple testing did not yield any significant association between genetic variants at UGT2B4 and risk of ATLI via the analyses of single locus and subgroup differences. WHAT IS NEW AND CONCLUSION: This is the first study aimed to investigate the association of UGT2B4 polymorphisms with ATLI risk. Our results revealed that UGT2B4 genetic variants are unlikely to confer susceptibility to ATLI in the Western Chinese Han population.

Prognostic value of lymph node ratio in non-small-cell lung cancer: a meta-analysis.

BACKGROUND: This meta-analysis aimed to investigate the prognostic value of lymph node ratio in non-small-cell lung cancer. METHODS: We searched systematically for eligible studies in PubMed, Web of Science, Medline (via Ovid) and Cochrane library through 6 November 2018. The primary outcome was overall survival. Disease-free survival and cancer-specific survival were considered as secondary outcomes. Hazard ratio with corresponding 95% confidence interval were pooled. Quality assessment of included studies was conducted. Subgroup analyses were performed based on N descriptors, types of tumor resection, types of lymphadenectomy and study areas. Sensitivity analysis and evaluation of publication bias were also performed. RESULTS: Altogether, 20 cohorts enrolling 76 929 patients were included. Mean Newcastle-Ottawa Scale was 7.65 ± 0.59, indicating the studies' quality was high. The overall result showed non-small-cell lung cancer patients with lower lymph node ratio was associated with better overall survival (HR: 1.946; 95% CI: 1.746-2.169; P < 0.001), disease-free survival (HR: 2.058; 95% CI: 1.717-2.467; P < 0.001) and cancer-specific survival (HR: 2.149; 95% CI: 1.864-2.477; P < 0.001). Subgroup analysis prompted types of lymphadenectomy and the station of positive lymph node have an important effect on the prognosis. No significant discovery was found in sensitivity analysis. CONCLUSION: Patients with lower lymph node ratio was associated with better survival, indicating that lymph node ratio may be a promising prognostic predictor in non-small-cell lung cancer. The type of lymphadenectomy, an adequate examined number and the removed stations should be considered for more accurate prognosis assessment.

Efficiency and safety of TachoSil® in the treatment of postoperative air leakage following pulmonary surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: There has been still no consensus whether to apply TachoSil® to reduce the incidence of air leakage after pulmonary surgery. We conducted this meta-analysis of randomized controlled trials (RCTs) to identify the efficiency and safety of TachoSil® applied in the prevention of postoperative air leakage following pulmonary surgery. METHODS: We performed a systematic electronic search through EMABSE, PubMed and Web of Science up to March 2018. Summary risk ratio (RR) and weight mean difference (WMD) with corresponding 95% confidence intervals (CI) were calculated to analyze the outcomes. Fixed effect or random effect model was used to pool the estimates. Two independent reviewers assessed the quality of included studies using Cochrane risk-of-bias tool for RCTs. RESULTS: We included six RCTs with a total of 921 patients. Compared with standard treatment (suturing, stapling techniques or electrocautery), TachoSil® was associated with the decreased air leak duration (WMD: -3.32 days; 95% CI: -5.34--1.31; P = 0.001), chest tube duration (WMD: -1.99 days; 95% CI: -3.14--0.84; P = 0.0007), hospital stay (WMD: -1.89 days; 95% CI: -2.42--1.35; P < 0.0001), and incidence of prolonged air leak (RR: 0.57; 95% CI: 0.35-0.92; P = 0.02). No significant difference was found between the two groups regarding the incidence of postoperative complications (RR: 0.86; 95% CI: 0.69-1.06; P = 0.16). CONCLUSIONS: TachoSil® was safe, cost-effective and superior over standard treatment for patients who underwent pulmonary surgery in decreasing incidence of postoperative air leak, air leak duration, chest tube duration and the length of hospital stay.

Large-scale analysis reveals splicing biomarkers for tuberculosis progression and prognosis.

BACKGROUND: Emerging evidence suggests that aberrant alternative splicing (AS) may play an important role in tuberculosis (TB). However, current knowledge regarding the value of AS in TB progression and prognosis remains unclear. METHOD: Public RNA-seq datasets related to TB progression and prognosis were searched and AS analyses were conducted based on SUPPA2. Percent spliced in (PSI) was used for quantifying AS events and multiple machine learning (ML) methods were employed to construct predictive models. Area under curve (AUC), sensitivity and specificity were calculated to evaluate the model performance. RESULTS: A total of 1587 samples from 7 datasets were included. Among 923 TB-progression related differential AS events (DASEs), 3 events (GET1-skipping exon (SE), TPD52-alternative first exons (AF) and TIMM10-alternative 5' splice site (A5)) were selected as candidate biomarkers; however, their predictive performance was limited. For TB prognosis, 5 events (PHF23-AF, KIF1B-SE, MACROD2-alternative 3' splice site (A3), CD55-retained intron (RI) and GALNT11-AF) were selected as candidates from the 1282 DASEs. Six ML methods were used to integrate these 5 events and XGBoost outperformed than others. AUC, sensitivity and specificity of XGBoost model were 0.875, 81.1% and 83.5% in training set, while they were 0.805, 68.4% and 73.2% in test set. CONCLUSION: GET1-SE, TPD52-AF and TIMM10-A5 showed limited role in predicting TB progression, while PHF23-AF, KIF1B-SE, MACROD2-A3, CD55-RI and GALNT11-AF could well predict TB prognosis and work as candidate biomarkers. This work preliminarily explored the value of AS in predicting TB progression and prognosis and offered potential targets for further research.

Single-Cell Sequencing Reveals Functional Alterations in Tuberculosis.

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23 990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.

Integrating Paper-Based Microfluidics and Lateral Flow Strip into Nucleic Acid Amplification Device toward Rapid, Low-Cost, and Visual Diagnosis of Multiple Mycobacteria.

Efficient diagnosis of mycobacterial infections can effectively manage and prevent the transmission of infectious diseases. Unfortunately, existing diagnostic strategies are challenged by long assay times, high costs, and highly specialized expertise to distinguish between pulmonary tuberculosis (PTB) and nontuberculous mycobacterial pulmonary diseases (NTM-PDs). Herein, in this study, an optimized 3D paper-based analytical device (µPAD) is incorporated with a closed lateral flow (LF) strip into a loop-mediated isothermal amplification (LAMP) device (3D-µPAD-LF-LAMP) for rapid, low-cost, and visual detection of pathogenic mycobacteria. The platform's microfluidic feature enhanced the nucleic acid amplification, thereby reducing the costs and time as compared to boiling, easyMAG, and QIAGEN techniques. Moreover, the LF unit is specifically designed to minimize aerosol contamination for a user-friendly and visual readout. 3D-µPAD-LF-LAMP is optimized and assessed using standard strains, demonstrating a limit of detection (LOD) down to 10 fg reaction-1 . In a cohort of 815 patients, 3D-µPAD-LF-LAMP displays significantly better sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy than conventional bacterial culture and Xpert techniques. Collectively, 3D-µPAD-LF-LAMP demonstrates enhanced accessibility, efficiency, and practicality for the diagnosis of multiple pathogenic mycobacteria, which can be applied across diverse clinical settings, thereby ultimately improving public health outcomes.

Roles of alternative splicing in infectious diseases: from hosts, pathogens to their interactions.

ABSTRACT: Alternative splicing (AS) is an evolutionarily conserved mechanism that removes introns and ligates exons to generate mature messenger RNAs (mRNAs), extremely improving the richness of transcriptome and proteome. Both mammal hosts and pathogens require AS to maintain their life activities, and inherent physiological heterogeneity between mammals and pathogens makes them adopt different ways to perform AS. Mammals and fungi conduct a two-step transesterification reaction by spliceosomes to splice each individual mRNA (named cis -splicing). Parasites also use spliceosomes to splice, but this splicing can occur among different mRNAs (named trans -splicing). Bacteria and viruses directly hijack the host's splicing machinery to accomplish this process. Infection-related changes are reflected in the spliceosome behaviors and the characteristics of various splicing regulators (abundance, modification, distribution, movement speed, and conformation), which further radiate to alterations in the global splicing profiles. Genes with splicing changes are enriched in immune-, growth-, or metabolism-related pathways, highlighting approaches through which hosts crosstalk with pathogens. Based on these infection-specific regulators or AS events, several targeted agents have been developed to fight against pathogens. Here, we summarized recent findings in the field of infection-related splicing, including splicing mechanisms of pathogens and hosts, splicing regulation and aberrant AS events, as well as emerging targeted drugs. We aimed to systemically decode host-pathogen interactions from a perspective of splicing. We further discussed the current strategies of drug development, detection methods, analysis algorithms, and database construction, facilitating the annotation of infection-related splicing and the integration of AS with disease phenotype.

Prognostic value of cross-lineage expression of the myeloid-associated antigens CD13 and CD33 in adult B-lymphoblastic leukemia: A large real-world study of 1005 patients.

BACKGROUND: Cross-lineage expression of the myeloid-associated antigens CD13/CD33 is common in adult B-lymphoblastic leukemia (B-ALL) patients, yet its prognostic value is still controversial. METHODS: We conducted a retrospective study of 1005 de novo adult B-ALL patients from January 2009 to December 2019 in our hospital. Logistic and Cox regression were used to analyze the prognostic value of CD13/CD33 expression in B-ALL. A Cox regression model was established to predict overall survival (OS) for B-ALL patients. RESULTS: Of the 1005 B-ALL patients, 53.7% (n = 540) aberrantly expressed CD13/CD33 (CD13/CD33+ ). Patients in the CD13/CD33+ group showed a higher incidence of BCR::ABL1 rearrangement and minimal/measurable residual disease (MRD) positivity but similar complete remission rate, relapse-free survival, mortality, and OS with CD13/CD33- . CD13/CD33+ patients had a higher risk of MRD positivity than CD13/CD33- patients. Notably, CD13/CD33+ patients who underwent tyrosine kinase inhibitor (TKI) therapy had a better long-term prognosis than those without TKI experience. Sex, group based on CD13/CD33 expression and TKI experience and white blood cell count were variables independently associated with OS. The Cox regression model integrating these three variables showed a moderate performance for OS prediction (C-index: 0.724). CONCLUSIONS: In real-world practice, CD13/CD33 expression can predict the risk of MRD in patients without TKI experience, but has no adverse effect on the prognosis of adult B-ALL patients. Incorporating CD13/CD33 into the standard antibody panels of B-ALL diagnosis and MRD measurements can help predict relapse risk and decisions on therapy options.

From tuberculosis bedside to bench: UBE2B splicing as a potential biomarker and its regulatory mechanism.

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.

Risk factors for prolonged air leak after pulmonary surgery: A systematic review and meta-analysis.

This study aimed to comprehensively identify risk factors for the occurrence of prolonged air leak (PAL) in patients undergoing pulmonary surgery. Studies were retrieved from 3 databases, including PubMed, Web of Science, and EmBase up to 13 May 2020. We performed meta-analysis using Bayesian random effect models through divergence restricting conditional tessellation (DIRECT) algorithm. The effect size was expressed as odds ratio (OR) or mean difference (MD), each with 95% credible interval (CrI). The evidence quality was evaluated. Subgroup analyses and sensitivity analyses were conducted. Thirty-nine studies with 89006 patients were finally included. Pooled PAL incidence was 15%. Of 30 risk factors, 22 were significantly associated with increased PAL incidence. Five risk factors were ultimately selected with high evidence quality: smoking history (OR 1.84, 95%CrI 1.45 to 2.31, P<0.001), preoperative steroid use (OR 1.51, 95%CrI 0.87 to 2.65, P = 0.031), lower ratio of forced expiratory volume in 1 s and forced vital capacity (OR 1.99, 95%CrI 1.22 to 3.33, P = 0.005), non-fissureless technique (OR 2.14, 95%CrI 1.31 to 3.66, P = 0.003), and pathological TNM stage III/IV (OR 1.50, 95%CrI 1.07 to 2.12, P = 0.003). Regarding the negative impact of PAL on the personal cost and postoperative recovery, the verification of previous proposed factors and investigation of recently discovered ones both implied directions for risk stratification and the establishment of an applicable prediction model.

Deciphering a TB-related DNA methylation biomarker and constructing a TB diagnostic classifier.

We systemically identified tuberculosis (TB)-related DNA methylation biomarkers and further constructed classifiers for TB diagnosis. TB-related DNA methylation datasets were searched through October 3, 2020. Limma and DMRcate were employed to identify differentially methylated probes (DMPs) and regions (DMRs). Machine learning methods were used to construct classifiers. The performance of the classifiers was evaluated in discovery datasets and a prospective independent cohort. Eighty-nine DMPs and 24 DMRs were identified based on 67 TB patients and 45 healthy controls from 4 datasets. Nine and three DMRs were selected by elastic net regression and logistic regression, respectively. Among the selected DMRs, two regions (chr3: 195635643-195636243 and chr6: 29691631-29692475) were differentially methylated in the independent cohort (p = 4.19 × 10-5 and 0.024, respectively). Among the ten classifiers, the 3-DMR logistic regression classifier exhibited the strongest performance. The sensitivity, specificity, and area under the curve were, respectively, 79.1%, 84.4%, and 0.888 in the discovery datasets and 64.5%, 90.3%, and 0.838 in the independent cohort. The differential diagnostic ability of this classifier was also assessed. Collectively, these data showed that DNA methylation might be a promising TB diagnostic biomarker. The 3-DMR logistic regression classifier is a potential clinical tool for TB diagnosis, and further validation is needed.

Exploring the eligibility of all reported lipoarabinomannan-testing assays in different clinical situations: a systematic review and meta-analysis of 97 articles.

OBJECTIVES: How to choose proper lipoarabinomannan-testing assays for diagnosing tuberculosis (TB) in different populations baffles clinicians. This work assessed all reported lipoarabinomannan assays' performance and aimed to identify the eligibility of each assay and offer guidance for clinicians. METHODS: We searched PubMed, Embase, and Web of Science until August 23, 2020. The risk of bias was evaluated by QADAS-2. Heterogeneity was evaluated by the Cochran Q test and I2. Sensitivity and specificity were pooled by a bivariate mixed model (register number: CRD42021270506). RESULTS: A total of 97 articles, covering 144 trials, 16 assays, 45,679 participants, and eight sample types, were divided into five groups. Electrochemiluminescence (ECL) had a sensitivity of 65%, specificity of 92%, and an area under curve (AUC) of 0.85 in diagnosing pulmonary TB in adults. ECL showed a promising diagnostic ability (sensitivity: 78%; specificity: 88%; AUC: 0.88) in patients with HIV, especially for urine detection (sensitivity: 90%; specificity: 89%; AUC: 0.95). The enzyme-linked immune assay showed a preference for diagnosing TB in Asians and Africans, especially in Africans who were smear-positive (sensitivity: 80%; specificity: 88%; AUC: 0.91). CONCLUSION: ECL was recommended for diagnosing pulmonary TB in adults, especially for TB/HIV co-infection. Taking urine as a sample further enhanced ECL's diagnostic performance. Enzyme-linked immune assay was recommended as an additional TB-related detection for smear-positive Africans.

Genetic architecture of tuberculosis susceptibility: A comprehensive research synopsis, meta-analyses, and epidemiological evidence.

To date, many studies have been conducted to investigate associations between variants and tuberculosis risk; however, the results have been inconclusive. Here, we systematically provide a summary of the understanding of the genetic architecture of tuberculosis susceptibility. We searched PubMed, Embase and Web of Science to identify genetic association studies of tuberculosis published through October 31, 2021. We conducted meta-analyses for the genetic association with tuberculosis risk. We graded levels of cumulative epidemiological evidence of significant associations with risk of tuberculosis and false-positive report probability tests. We performed functional annotations for these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project and other databases. We identified 703 eligible articles comprising 298,074 cases and 879,593 controls through screening a total of 24,398 citations. Meta-analyses were conducted for 614 genetic variants in 469 genes or loci. We found 39 variants that were nominally significantly associated with tuberculosis risk. Cumulative epidemiological evidence for a significant association was graded strong for 9 variants in or near 9 genes. Among them, 5 variants were associated with tuberculosis risk in at least three main ethnicity (African, Asian and White) which together explained approximately 9.59% of the familial relative risk of tuberculosis. Data from ENCODE and other databases suggested that 8 of these 9 genetic variants with strong evidence might fall within putative functional regions. Our study summarizes the current literature on the genetic architecture of tuberculosis susceptibility and provides useful data for designing future studies to investigate the genetic association with tuberculosis risk.

Suction Versus Nonsuction Drainage After Uniportal Video-Assisted Thoracoscopic Surgery: A Propensity Score-Matched Study.

BACKGROUND: Uniportal video-assisted thoracoscopic surgery (UniVATS) was utilized with a rapid growth. The evidence is sparse, however, on whether to add external suction to water-seal drainage for chest drainage after UniVATS. This retrospective propensity score-matched study aimed to identify the necessity of adding external suction to chest drainage after UniVATS. METHODS: Patients with lung cancer who underwent UniVATS were included from our prospectively maintained database. Patients were divided into two cohorts based on the addition of external suction to postoperative water-seal drainage or not. Propensity score-matched analysis was performed to identify the impact of suction on chest tube duration, incidence of persistent air leak, hospital stay, and hospitalization cost. Multivariable model with interaction terms was constructed to identify impact of covariables on effect of suction. RESULTS: The two cohorts matched well on baseline characteristics (nonsuction: 173; suction: 96). Compared with nonsuction group, suction group showed longer median chest tube duration (3 vs. 2 days, p = 0.003), higher incidences of persistent air leak (9.4% vs. 1.2%, p = 0.003), persistent drainage (16.8% vs. 5.8%, p = 0.007), and reduced drainage volume within first 3 postoperative days (386.90 vs. 504.78 ml, p = 0.011). Resection extent was identified to mediate the relationship between suction and chest tube drainage. CONCLUSIONS: These findings discouraged adding external suction to water-seal drainage after UniVATS regarding longer chest tube duration and more persistent air leak. Patients undergoing lobectomy would benefit more from water-seal drainage without external suction compared with those doing sublobectomy.

Novel Long Non-coding RNA and LASSO Prediction Model to Better Identify Pulmonary Tuberculosis: A Case-Control Study in China.

INTRODUCTION: The insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model. METHODS: A total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression. RESULTS: The factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/. CONCLUSION: Combining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.

The prognosis predictive value of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in patients with acute myeloid leukemia detected by GeneScan.

INTRODUCTION: This study aimed to explore the significance and cut-off values of FMS-like tyrosine kinase 3-internal tandem duplications mutant allelic ratio (FLT3-ITD MR) in prognostic evaluation of acute myeloid leukemia (AML) patients. METHODS: This study enrolled 249 Chinese AML patients. The exons 14 and 15 of FLT3 gene were amplified by genomic polymerase chain reaction. GeneScan and single nucleotide sequencing were also performed. Participants were grouped into high- and low-ratio FLT3-ITD MR (FLT3-ITD MRhigh and FLT3-ITD MRlow) applying the median of FLT3-ITD MR as the cut-off ratio, and patients without FLT3-ITD were grouped as FLT3-wild type (wt). Duration of complete remission (CR), relapsed remission and overall survival (OS) were examined. RESULTS: FLT3-ITD was detected in 58 patients. The medians of FLT3-ITD MR were 0.31 and 0.29 for all AML and non-M3 patients, respectively. For all patients, FLT3-ITD MRhigh group had the lowest CR rate among these 3 groups (p < 0.001). The FLT3-wt group, FLT3-ITD MRlow and FLT3-ITD MRhigh group had the median OS of 36.00 months (range: 2.00-92.00 months), 12.00 months (range: 1.00-78.00 months) and 14.00 months (range: 0.00-79.00 months), respectively. Subjects in FLT3-ITD MRhigh group had 2.675 times (95% CI: 1.726-4.146; p < 0.001) and 1.879 times (95% CI: 1.061-3.328; p = 0.031) higher death risk than those in FLT3-wt group and FLT3-ITD MRlow group, respectively. For non-M3 patients, the median OS was 35.00 months (range: 2.00-92.00 months), 9.5 months (range: 1.00-74.00 months) and 10.00 months (range: 1.00-38.00 months) in the FLT3-wt group, FLT3-ITD MRlow group and FLT3-ITD MRhigh group, respectively. Non-M3 patients in FLT3-ITD MRhigh group had 3.301 times (95% CI: 1.423-7.661; p = 0.005) higher death risk than those in FLT3-wt group. CONCLUSION: The present study found that FLT3-ITD MR is closely related to CR and OS in AML patients. Furthermore, FLT3-ITD MR may serve as an independent prognostic factor for OS in non-M3 AML patients. Classifying risk grades based on FLT3-ITD MR is crucial for individualized treatment and prognostic evaluation.

Which sample type is better for Xpert MTB/RIF to diagnose adult and pediatric pulmonary tuberculosis?

OBJECTIVE: This review aimed to identify proper respiratory-related sample types for adult and pediatric pulmonary tuberculosis (PTB), respectively, by comparing performance of Xpert MTB/RIF when using bronchoalveolar lavage (BAL), induced sputum (IS), expectorated sputum (ES), nasopharyngeal aspirates (NPAs), and gastric aspiration (GA) as sample. METHODS: Articles were searched in Web of Science, PubMed, and Ovid from inception up to 29 June 2020. Pooled sensitivity and specificity were calculated, each with a 95% confidence interval (CI). Quality assessment and heterogeneity evaluation across included studies were performed. RESULTS: A total of 50 articles were included. The respective sensitivity and specificity were 87% (95% CI: 0.84-0.89), 91% (95% CI: 0.90-0.92) and 95% (95% CI: 0.93-0.97) in the adult BAL group; 90% (95% CI: 0.88-0.91), 98% (95% CI: 0.97-0.98) and 97% (95% CI: 0.95-0.99) in the adult ES group; 86% (95% CI: 0.84-0.89) and 97% (95% CI: 0.96-0.98) in the adult IS group. Xpert MTB/RIF showed the sensitivity and specificity of 14% (95% CI: 0.10-0.19) and 99% (95% CI: 0.97-1.00) in the pediatric ES group; 80% (95% CI: 0.72-0.87) and 94% (95% CI: 0.92-0.95) in the pediatric GA group; 67% (95% CI: 0.62-0.72) and 99% (95% CI: 0.98-0.99) in the pediatric IS group; and 54% (95% CI: 0.43-0.64) and 99% (95% CI: 0.97-0.99) in the pediatric NPA group. The heterogeneity across included studies was deemed acceptable. CONCLUSION: Considering diagnostic accuracy, cost and sampling process, ES was a better choice than other sample types for diagnosing adult PTB, especially HIV-associated PTB. GA might be more suitable than other sample types for diagnosing pediatric PTB. The actual choice of sample types should also consider the needs of specific situations.