Conversion or reversion of interferon gamma release assays for Mycobacterium tuberculosis infection: a systematic review and meta-analysis.

BACKGROUND: Interferon-gamma release assays (IGRA) are widely used for diagnosis of latent tuberculosis infection. However, with repeat testing, IGRA transformation (conversion or reversion) may be detected and is challenging to interpret. We reviewed the frequency of and risk factors for IGRA transformation. METHODS: We screened public databases for studies of human participants that reported the frequency of IGRA transformation. We extracted study and subject characteristics, details of IGRA testing and results. We calculated the pooled frequency of IGRA transformation (and transient transformation) and examined associated risk factors. RESULTS: The pooled frequency of IGRA conversion or reversion from 244 studies was estimated at 7.3% (95% CI 6.1-8.5%) or 22.8% (20.1-25.7%), respectively. Transient conversion or reversion were estimated at 46.0% (35.7-56.4%) or 19.6% (9.2-31.7%) of conversion or reversion events respectively. Indeterminate results seldom reverted to positive (1.2% [0.1-3.5%]). IGRA results in the borderline positive or negative range were associated with increased risk of conversion or reversion (pooled OR: conversion, 4.15 [3.00-5.30]; reversion, 4.06 [3.07-5.06]). BCG vaccination was associated with decreased risk of conversion (0.70, 0.56-0.84), cigarette smoking with decreased risk of reversion (0.44, 0.06-0.82), and female sex with decreased risk of either conversion or reversion (conversion, 0.66 [0.58-0.75]; reversion, 0.46 [0.31-0.61]). CONCLUSIONS: IGRA conversion is less common than reversion, and frequently transient. Research is needed to determine whether individuals with reversion would benefit from tuberculosis preventive treatment. Re-testing of people with indeterminate results is probably not indicated, since indeterminate results seldom revert to positive.

Diagnostic value of the cerebrospinal fluid lipoarabinomannan assay for tuberculous meningitis: a systematic review and meta-analysis.

Objective: This systematic review aims to evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) lipoarabinomannan (LAM) assays in detecting tuberculous meningitis (TBM). Methods: A systematic review search was conducted in PubMed and five other databases up to April 2023. Studies that evaluated the diagnostic accuracy of CSF LAM assays were included with either definitive or composite reference standard used as the preferred reference standard. The quality of the included studies was assessed using the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis and calculated the summary diagnostic statistics. Results: A total of six studies, including a sample size of 999, were included in the final analysis. The pooled sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of CSF LAM for diagnosing TBM were determined to be 0.44 (95% CI: 0.31-0.58), 0.89 (95% CI: 0.81-0.93), and 0.76 (95% CI: 0.73-0.80), respectively. Significant heterogeneity was observed in both sensitivity (Q = 73.82, p < 0.01; I2 = 86.45, 95%CI: 79.64-93.27) and specificity (Q = 95.34, p < 0.01; I2 = 89.51, 95% CI: 84.61-94.42). Regression analysis indicated that the study design (retrospective vs. prospective) was associated with the heterogeneity of pooled sensitivity and specificity (all p < 0.05). Conclusion: Although more prospective studies are required to validate the role of the CSF LAM assay, current evidence supports that the performance of the CSF LAM assay is unsatisfactory for the TBM diagnosis. Additionally, the optimization of the CSF LAM assay (e.g., improvements in CSF collection and preparation methods) should be considered to improve its performance.

The performance of interferon gamma release assays in patients with nontuberculous mycobacterial infection: a systematic review and meta-analysis.

BACKGROUND: The actual positive rate of interferon gamma release assays (IGRAs) in patients with nontuberculous mycobacteria (NTM) infections remains unclear. This review and meta-analysis present the prevalence of positive IGRAs (T-SPOT.TB and QuantiFERON [QFT] tests) among patients infected with NTM isolates (with or without ESAT-6/CFP-10). METHODS: Several databases, including PubMed, Scopus, Embase, and Web of Science were searched (until June 18th, 2022). Studies that had the following data were included: (1) results of T-SPOT.TB, QuantiFERON (QFT) test, or both, (2) NTM species, and (3) NTM diseases, or NTM colonization. The metaprop command that incorporates a Freeman-Tukey double arcsine transformation is used for pooling proportions. RESULTS: A total of 11 articles (n = 929) were deemed eligible for inclusion. Meta-analysis identified that the overall pooled positive and indeterminate rates of IGRA results in patients with NTM infections was 16% and 5%, respectively. Subgroup analysis showed that the positive rate of IGRAs in patients infected with NTM (without ESAT-6/CFP-10) was 7% (95% CI, 1%-18%), and 44% (95%CI, 22%-68%) in patients infected with NTM (with ESAT-6/CFP-10). In addition, the indeterminate rate of QFT (7%, 95% CI: 4%-12%) was higher than that of T-SPOT.TB (0%; 95% CI, 0%-2%) among the overall population with NTM infections. CONCLUSIONS: The IGRAs have a moderate positive rate for the diagnosis of NTM (expressing ESAT-6/CFP-10) infections, and a significant indeterminate rate is observed among the overall population infected with NTM. However, these findings should be interpreted with caution because of the high heterogeneity among studies.

The role of Bacillus Calmette-Guérin administration on the risk of dementia in bladder cancer patients: a systematic review and meta-analysis.

Background: Previous cohort studies have found an association between Bacillus Calmette-Guérin (BCG) administration and incident dementia. In the systematic review and meta-analysis, we aimed to summarize the current evidence of the effect of BCG use on the risk of developing dementia. Methods: We searched six databases until 20 May 2023 for studies investigating the risk of dementia and BCG administration. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled in the meta-analysis. Meta-regression, subgroup, and sensitivity analysis were conducted as well. Results: Of the 4,043 records initially evaluated, five articles were included for final analysis, with a total of 45,407 bladder cancer (BC) patients. All five studies were evaluated and rated as with high quality, and a low possibility of publication bias was indicated. A significant association between BCG and the incidence of dementia in BC patients was found in all five studies. Although a high heterogeneity (I2 = 84.5%, p < 0.001) was observed, the pooled HR was 0.55 (0.42-0.73), indicating that BCG exposure or treatment reduced the risk of incident dementia by 45%. Moreover, the sensitivity analysis showed good robustness of the overall effect with no serious publication bias. Conclusion: BCG administration is associated with a significantly lower risk of developing dementia. However, an epidemiological cohort is needed to establish a relationship between BCG use and incident dementia in the normal population. Once the relationship is confirmed, more people may benefit from the association. Systematic review registration: identifier: CRD42023428317.

Interferon-γ release assay and mantoux response in infants with tuberculous meningitis in low and intermediate burden countries.

AIM: Until now, the performance of interferon-γ release assay (IGRA) and Mantoux tests remains unclear in infant tuberculous meningitis (TBM). Therefore, a systematic review is performed to evaluate the sensitivity of IGRA and Mantoux tests for the diagnosis of infant TBM in low and intermediate tuberculosis (TB) burden countries, while following PRISMA. METHODS: Several databases, including PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials, were searched. Articles describing the results of IGRA or Mantoux tests among infant TBM were included for analysis. Data, such as age, sex, Mantoux test or IGRA, and cerebrospinal fluid (CSF) microbiological examinations (such as acid-fast bacilli (AFB) smear, TB PCR, and TB culture), were extracted from each study. RESULTS: A total of 31 articles were enrolled for further analysis, including 48 cases. The mean age was 9.4 ± 5.8 months and boys accounted for 57.1% of infants (24/42). Mantoux test was positive in 57.4% (27/47) of tested infants and IGRA was positive in 77.8% (7/9) of infants. In addition, among the infants with confirmed TB, 18 (52.9%, 18/34) of them have positive Mantoux responses and 7 (20.0%, 7/35) have positive IGRA results. CONCLUSIONS: In low or intermediate TB burden countries, the Mantoux test has a poor performance for diagnosing TBM among infants, and IGRAs appear to have a moderate sensitivity for the diagnosis of infant TBM.

Diagnostic Yield of Nucleic Acid Amplification Tests in Oral Samples for Pulmonary Tuberculosis: A Systematic Review and Meta-analysis.

The diagnostic accuracy of oral specimen nucleic acid amplification tests (NAATs) for pulmonary tuberculosis (PTB) remains controversial. We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, including studies that reported the diagnostic yield of NAATs in oral samples for PTB diagnosis. The pooled estimates, including those of sensitivity and specificity, were calculated, and a meta-regression was performed to investigate heterogeneity, which was determined using χ2 and I² tests. A total of 23 articles were included, and the pooled sensitivity, specificity, and area under the curve of NAATs in oral samples for PTB diagnosis were 50% (95% CI, 37%-63%), 97% (95% CI, 93%-99%), and 0.89 (95% CI, 86%-92%; I 2 = 99%; chi-square, 169.61; P < .001), respectively. Our data demonstrated that NAATs using oral samples have a less satisfactory sensitivity and high specificity for PTB diagnosis. However, due to significant heterogeneity, such as heterogeneity in age, the results should be interpreted with caution.

The efficacy and safety of high-dose isoniazid-containing therapy for multidrug-resistant tuberculosis: a systematic review and meta-analysis.

Objectives: Accumulating evidence are available on the efficacy of high-dose isoniazid (INH) for multidrug-resistant tuberculosis (MDR-TB) treatment. We aimed to perform a systematic review and meta-analysis to compare clinical efficacy and safety outcomes of high-dose INH- containing therapy against other regimes. Methods: We searched the following databases PubMed, Embase, Scopus, Web of Science, CINAHL, the Cochrane Library, and ClinicalTrials.gov. We considered and included any studies comparing treatment success, treatment unsuccess, or adverse events in patients with MDR-TB treated with high-dose INH (>300 mg/day or >5 mg/kg/day). Results: Of a total of 3,749 citations screened, 19 studies were included, accounting for 5,103 subjects, the risk of bias was low in all studies. The pooled treatment success, death, and adverse events of high-dose INH-containing therapy was 76.5% (95% CI: 70.9%-81.8%; I2: 92.03%), 7.1% (95% CI: 5.3%-9.1%; I2: 73.75%), and 61.1% (95% CI: 43.0%-77.8%; I2: 98.23%), respectively. The high-dose INH administration is associated with significantly higher treatment success (RR: 1.13, 95% CI: 1.04-1.22; p < 0.01) and a lower risk of death (RR: 0.45, 95% CI: 0.32-0.63; p < 0.01). However, in terms of other outcomes (such as adverse events, and culture conversion rate), no difference was observed between high-dose INH and other treatment options (all p > 0.05). In addition, no publication bias was observed. Conclusion: In MDR-TB patients, high-dose INH administration is associated with a favorable outcome and acceptable adverse-event profile. Systematic review registration: identifier CRD42023438080.

Cerebrospinal fluid findings of infant tuberculous meningitis: a scoping review.

BACKGROUND: Cerebrospinal fluid (CSF) examinations play an important role in the diagnosis of tuberculous meningitis (TBM). However, their yield in the diagnosis of infant TBM remains unclear. This scoping review aims to detail the role of CSF examination for the diagnosis of infant TBM. METHODS: A comprehensive literature search of PubMed, EBSCO, Embase, Scopus, Web of Science, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials was performed to identify articles published prior to October 14th, 2021. Articles describing the results of CSF exanimations among infant TBM were eligible for inclusion. Data extracted from each study included age, sex, CSF microbiological evidence (such as AFB smear, TB PCR, and TB culture), and routine CSF examinations (such as appearance, red blood cell count, white blood cell count, protein, and glucose). RESULTS: A total of 98 cases were included in the final analysis. The yield of microbiological methods was listed as follows: CSF AFB smear, 20.5% (9/44); CSF TB culture 47.5% (29/61); CSF TB PCR, 65.0% (26/40); the combination of them, 57.3% (47/82). According to Marais criteria, the positivities of CSF examinations were calculated as follows: WBC count (ref, 50-500/µL), 65.5% (55/84); lymphocyte predominance (ref, >0.5), 75.4% (49/65); total protein (ref, >100 mg/dL), 67.8% (59/87); glucose (ref, <2.2 mmol/L, or CSF/serum ratio < 0.5), 68.2% (58/85). CONCLUSIONS: Our data demonstrated that routine microbiological tools for infant TBM diagnosis have a sensitivity ranging from 20.5% to 65.0%, and most CSF features are non-specific and insufficient to predict a diagnosis of infant TBM. Therefore, further effort is required to develop new tools for infant TBM diagnosis.Key messages: Routine microbiological tools (such as acid-fast bacilli smear, PCR, and culture) have an unsatisfactory sensitivity for infant TBM diagnosis, and most CSF features are non-specific and insufficient to predict a diagnosis of infant TBM. Therefore, further effort is required to develop new tools for infant TBM diagnosis.

Prevalence of Culture-Confirmed Tuberculosis Among Patients with Nontuberculous Mycobacterial Disease.

Background: Currently, the prevalence of nontuberculous mycobacteria (NTM) strains isolated from mycobacterial cultures has been well characterized. However, the data on the prevalence of tuberculosis (TB) in patients with NTM disease remain unclear. Methods: Between January 2012 and August 2020, consecutive patients with positive mycobacterial cultures were included for analysis. The identification of Mycobacteria spp. was performed using the DNA array method or sequencing of 16S rDNA. NTM disease is diagnosed when the same infectious agent is identified in at least two sputum or is identified in sterile samples. Results: A total of 997 strains were isolated from 828 inpatients. Of them, 261 inpatients (31.5%) were diagnosed as NTM disease. The mean age of the 261 patients was 55.7 ±15.5 years old and 64.0% (n = 167) of them were male. The prevalence of culture-confirmed TB patients among patients with NTM disease was estimated as 8.0% (21/261). Conclusion: TB is common in NTM disease and caution should be taken when initiating the treatment of NTM disease.

The Sensitivity of Diagnostic Criteria of Marais S, et al. in Confirmed Childhood Tuberculous Meningitis.

BACKGROUND: To establish the sensitivity of the diagnostic criteria published by Marais and co-workers in 2010 for childhood tuberculous meningitis (TBM), a retrospective study on children with confirmed TBM was conducted. METHODS: Between January 2006 and December 2019, children consecutively diagnosed with TBM were recruited retrospectively at our center. TBM was defined in cases where any of the following criteria were met: the presence of acid-fast bacilli (AFB) in cerebrospinal fluid (CSF) microscopy, CSF nucleic acid amplification test (NAAT, +), or M.tuberculosis cultured from CSF. The demographic and clinical features of all enrolled patients were recorded including clinical characteristics, CSF findings, cerebral imaging features, and other evidence of TB. RESULTS: A total of 30 children with confirmed diagnosis of TBM over an 14-year period were recruited. The mean age of patients was 7.2 ± 5.1 years and 16 (53.3%) were male. The estimated mean diagnostic score was 12.7 ± 2.4. Twenty-three (76.7%; 95% CI: 59.1-88.2%) patients were classified as "probable TBM" according to the Marais criteria and 7 (23.3%; 95% CI: 11.8-40.9%) as "possible TBM." Further statistical analysis revealed significant differences in CSF scores between probable and possible TBM groups. Other variables reported at a relatively low frequency, such as symptoms and imaging features, made little contribution to TBM diagnosis according to the Marais criteria. CONCLUSION: Childhood TBM could be effectively identified by the criteria defined by Marais et al. However, further revision is required to ensure that the system is more sensitive and easier to perform in practice.

Performance of Interferon-γ Release Assays in Patients with Mycobacterium kansasii Infection.

Objective: To evaluate the performance of interferon-γ release assays (IGRAs) in patients with Mycobacterium kansasii infection. Methods: Consecutive patients between May 2012 and June 2021 who had positive for mycobacterial cultures and who underwent IGRAs (T-SPOT.TB or QuantiFERON-TB Gold [QFT-G]) were included in the analysis. The IGRA positivity rates among patients with M. kansasii isolates were then calculated. If M. kansasii was identified in at least two sputum samples or in sterile samples, M. kansasii disease was then diagnosed. Otherwise, colonisation was considered. Results: During the study period, 54 patients with M. kansasii infection underwent T-SPOT.TB (n=48) or QFT-G (n=6) assays. The mean age was 44.1±13.4 years, 85.2% (46/54) were male. Eight patients were diagnosed with M. kansasii disease and another 46 patients were considered to have colonisation. Twenty-four patients (T-SPOT.TB, n=23; QFT-G, n=1) were positive for IGRAs, for an overall rate of 44.4% (24/54; T-SPOT.TB, 47.9% [23/48]; QFT-G, 16.7% [1/6]) for IGRAs, 25.0% (2/8) for M. kansasii disease, and 47.8% (22/46) for colonisation. Conclusion: Positive IGRA rates were relatively low in patients with M. kansasii infection. More efforts are required to improve the performance of IGRAs in diagnosing M. kansasii infection.

Risk Factor for Retreatment Episode on Admission Among TB Patients With Schizophrenia.

Background: The clinical characteristics of patients with tuberculosis (TB) and schizophrenia remain largely unknown. Furthermore, TB retreatment is associated with a poor outcome. Hence, we aimed to address the risk factors of TB retreatment in schizophrenia patients in this retrospective cohort. Methods: Between March 2005 and August 2020, patients diagnosed with schizophrenia and TB were included in the study. Patient characteristics, such as demographics, medical history, underlying diseases, symptoms, outcome, and lab examinations, were collected from medical records using a structured questionnaire. TB retreatment was defined as treatment failures and relapses. Subsequently, multivariate logistic regression was performed using variables selected based on prior findings as well as factors found to be associated with a retreatment episode in univariate analyses (p < 0.1). Results: A total of 113 TB patients with schizophrenia were included. Of them, 94 (83.2%) patients were classified as initial treatment group, and 19 (16.8%) were classified as retreatment group. The mean age was 53.0 ± 23.2 years, and males accounted for 61.9% of all cases. Multivariate analysis revealed that continuous antipsychotics treatment (OR = 0.226, 95% CI: 0.074, 0.693; p = 0.009) and extra-pulmonary TB (OR = 0.249, 95% CI: 0.080, 0.783; p = 0.017) were associated with the retreatment in TB patients with schizophrenia. Conclusion: Retreatment is a significant concern for TB patients with schizophrenia. To improve the current dilemma, continuous antipsychotics treatment is required, and increasing awareness of schizophrenia would reduce the disease burden.

Factors Associated With the Presence of Tuberculous Empyema in Children With Pleural Tuberculosis.

Background: Until now, the factor of tuberculous empyema (TE) in children with pleural tuberculosis (TB) remains unclear. Therefore, a retrospective study was conducted to assess the factors associated with the presence of TE in children. Methods: Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) with suspected pleural TB were selected for further analysis. Empyema was defined as grossly purulent pleural fluid. The demographic, clinical, laboratory, and radiographic features were collected from the electrical medical records retrospectively. Univariate and multivariate logistic regressions were used to explore the factors associated with the presence of TE in children with pleural TB. Results: A total of 154 children with pleural TB (definite, 123 cases; possible, 31 cases) were included in our study and then were classified as TE (n = 27) and Non-TE (n = 127) groups. Multivariate analysis revealed that surgical treatment (age- and sex-adjusted OR = 92.0, 95% CI: 11.7, 721.3), cavity (age- and sex-adjusted OR = 39.2, 95% CI: 3.2, 476.3), pleural LDH (>941 U/L, age- and sex-adjusted OR = 14.8, 95% CI: 2.4, 90.4), and temperature (>37.2°C, age- and sex-adjusted OR = 0.08, 95% CI: 0.01, 0.53) were associated with the presence of TE in children with pleural TB. Conclusion: Early detection of the presence of TE in children remains a challenge and several characteristics, such as surgical treatment, lung cavitation, high pleural LDH level, and low temperature, were identified as factors of the presence of TE in children with pleural TB. These findings may improve the management of childhood TE.

Bronchial brushing Xpert improves the diagnostic efficiency of sputum Xpert in patients with pulmonary tuberculosis.

BACKGROUND: The role of bronchial brushing Xpert MTB/RIF (hereafter referred to as Xpert) in patients with pulmonary tuberculosis (PTB) remains unclear. Therefore, a retrospective study was conducted aiming to evaluate the diagnostic efficiency of bronchial brushing Xpert in patients with PTB. METHODS: Between July 2018 and August 2019, suspected PTB patients who were admitted to our hospital and had bronchial brushing and matched sputum collection for acid-fast bacilli (AFB) smear, mycobacterial culture, and Xpert were included for further analysis. Subsequently, PTB was defined based on mycobacterial culture, and if an alternative diagnosis was established, 'non-tuberculosis (TB)' was considered. Comparison of bronchial brushing and matched sputum examination was performed between groups. Then, the differences in the sensitivities between bronchial brushing and sputum Xpert were examined using the chi-square test. RESULTS: A total of 111 patients were included and divided into TB and non-TB groups (52 versus 59 patients). The sensitivities of Xpert against culture were calculated as follows: sputum, 44.2% (23/52); bronchial brushing, 59.6% (31/52); sputum and bronchial brushing, 69.2% (36/52). The specificities of all Xpert assays were the same (100.0%, 59/59). A significant difference was found in the comparison of the sensitivities of Xpert using sputum, bronchial brushing and both, and the sensitivity of Xpert on both sputum and bronchial brushing was higher than that on sputum alone (p < 0.05). Moreover, it appears that bronchial brushing Xpert was more sensitive than sputum Xpert in the detection of PTB. CONCLUSION: Bronchial brushing Xpert improves the diagnostic efficiency of sputum Xpert in the detection of PTB.

Normal cerebrospinal fluid protein and associated clinical characteristics in children with tuberculous meningitis.

BACKGROUND: Although abnormal cerebrospinal fluid (CSF) protein can be used to predict the outcome of tuberculous meningitis (TBM) and diagnose TBM, normal CSF protein remains a concern in patients with TBM. This retrospective study aimed to assess the clinical characteristics associated with normal CSF protein, to resolve the dilemma of CSF protein in the management of childhood TBM. METHODS: Between January 2006 and December 2019, consecutive child patients (≤15 years old, a diagnosis of TBM, and tested for CSF protein) were included for analysis. CSF protein was tested on a chemistry analyzer using the pyrogallol red-molybdate method. Abnormal CSF protein was defined as >450 mg/L. Patient characteristics were collected from the electronic medical records. Then, characteristics associated with normal CSF protein were estimated in the study, using univariate and multivariate logistic regression analysis. RESULTS: A total of 125 children who met the criteria were enrolled during the study period. Twenty-nine patients had a normal CSF protein and 96 had an abnormal CSF protein. Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2=2.486, df = 8, p = .962) revealed that vomiting (age- and sex-adjusted OR = 0.253, 95% CI: 0.091, 0.701; p = .008) and serum glucose (>5.08 mmol/L; age- and sex-adjusted OR = 0.119, 95% CI: 0.032, 0.443; p = .002) were associated with the normal CSF protein in childhood TBM. CONCLUSION: In suspected childhood TBM, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required.KEY MESSAGESIn suspected childhood tuberculous meningitis, patients without vomiting or having low serum glucose are easy to present with normal CSF protein. Hence, when interpreting the level of CSF protein in children with such characteristics, a careful clinical assessment is required.

Factors associated with negative pleural adenosine deaminase results in the diagnosis of childhood pleural tuberculosis.

BACKGROUND: Until now, the influential factors associated with pleural adenosine deaminase (ADA) activity among children remain unclear. This retrospective study was therefore conducted aiming to investigate the factors associated with negative pleural ADA results in the diagnosis of childhood pleural tuberculosis (TB). METHODS: Between January 2006 and December 2019, children patients with definite or possible pleural TB were recruited for potential analysis. Then, patients were stratified into two categories: negative pleural ADA results group (experimental group, ≤40 U/L) and positive pleural ADA results group (control group, > 40 U/L). Univariate and multivariate logistic regression analyses were performed to estimate risk factors for negative pleural ADA results. RESULTS: A total of 84 patients with pleural TB were recruited and subsequently classified as experimental (n = 17) and control groups (n = 67). Multivariate analysis (Hosmer-Lemeshow goodness-of-fit test: χ2 = 1.881, df = 6, P = 0.930) revealed that variables, such as chest pain (age-adjusted OR = 0.0510, 95% CI: 0.004, 0.583), pleural total protein (≤45.3 g/L, age-adjusted OR = 27.7, 95% CI: 2.5, 307.7), pleural lactate dehydrogenase (LDH, ≤505 U/L, age-adjusted OR = 59.9, 95% CI: 4.2, 857.2) and blood urea nitrogen (≤3.2 mmol/L, age-adjusted OR = 32.0, 95% CI: 2.4, 426.9), were associated with negative pleural ADA results when diagnosing childhood pleural TB. CONCLUSION: Our findings demonstrated that chest pain, pleural total protein, pleural LDH, and blood urea nitrogen were associated with a negative pleural ADA result for the diagnosis of pleural TB among children. When interpreting pleural ADA levels in children with these characteristics, a careful clinical assessment is required for the pleural TB diagnosis.

Risk factors for poor outcome in childhood tuberculous meningitis.

Tuberculous meningitis (TBM) remains a serious disease for children and its risk factors of poor outcome remain unclear. Therefore, a retrospective study was conducted aiming to investigate the risk factors associated with poor outcome of childhood TBM. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of TBM were included for the analysis. The demographic, clinical, laboratory, and radiographic data were collected from the electronic medical records retrospectively. Poor outcome was defined as death or transfer to a higher-level hospital. Patients were then divided into good and poor outcome groups. Subsequently, risk factors for poor outcome were estimated using univariate and multivariate logistic regression analysis. A total of 149 children with TBM was enrolled, twenty-two patients suffered poor outcome, including 16 transfers to a higher-level hospital and 6 deaths, and the remaining 127 patients were classified as good outcome group. Further multivariate analysis revealed that coma (age- and sex-adjusted OR = 6.425, 95% CI: 1.743, 23.676; P < 0.01) and cerebrospinal fluid (CSF) protein (> 1188.3 mg/L; age- and sex-adjusted OR = 4.680, 95% CI: 1.469, 14.902; P < 0.01) were associated with the poor outcome of childhood TBM. Childhood TBM remains to have a high mortality rate in China. High CSF protein and coma were identified as risk factors for poor outcome of childhood TBM. Hence, more attention is required to be paid to suspected patients with such characteristics, thus facilitating access to optimum treatment.

Risk factors associated with surgical intervention in childhood pleural tuberculosis.

Surgical intervention use is common in the management of childhood pleural tuberculosis (TB), however, its associated risk factors remain unclear. Between January 2006 and December 2019, consecutive children patients (≤ 15 years old) who had a diagnosis of pleural TB were included for the analysis. Surgical intervention was defined as debridement (such as breaking loculations), decortication, and thoracic surgery (such as lobectomy or segmental resection). Patients undergoing surgery were included as surgical group, without surgery were classified as non-surgical group, surgical risk factors were then estimated. Univariate and multivariate logistic regression analysis were performed to evaluate the risk factors for surgical interventions. A total of 154 children diagnosed as pleural TB (definite, 123 cases; possible, 31 cases) were included in our study. Of them, 29 patients (18.8%) were classified as surgical group and 125 patients (81.2%) were classified as non-surgical group. Surgical treatments were analyzed in 29 (18.8%) patients, including debridement (n = 4), decortication (n = 21), and thoracic surgery (n = 4). Further multivariate analysis revealed that empyema (age- and sex-adjusted OR = 27.3, 95% CI 8.6, 87.1; P < 0.001) and frequency of hospitalization (age- and sex-adjusted OR = 1.53, 95% CI 1.11, 2.11; P < 0.01) were associated with the use of surgical interventions in children with pleural TB. In China, surgical interventions are still required in a significant proportion of children with pleural TB, and the surgical risk is found to be associated with the frequency of hospitalization and empyema. These findings may be helpful to improve the management of children with pleural TB and minimize the risk of poor outcomes.