1.Serum proteomics and machine learning unveil new diagnostic biomarkers for tuberculosis in adolescents and young adults.
Yu CHEN ; Hongxiang XU ; Yao TIAN ; Qian HE ; Xiaoyun ZHAO ; Guobin ZHANG ; Jianping XIE
Chinese Journal of Biotechnology 2025;41(4):1478-1489
Adolescents and young adults (AYAs) are one of the major populations susceptible to tuberculosis. However, little is known about the unique characteristics and diagnostic biomarkers of tuberculosis in this population. In this study, 81 AYAs were recruited, and the high-quality serum proteome of the AYAs with tuberculosis was profiled by quantitative proteomics. The data of serum proteomics indicated that the relative abundance of hemoglobin and apolipoprotein was significantly reduced in the patients with active tuberculosis (ATB). The pathway enrichment analysis showed that the downregulated proteins in the ATB group were mainly involved in the antioxidant and cell detoxification pathways, indicating extensive oxidative stress damage. Random forest (RF) and extreme gradient boosting (XGBoost) were employed to evaluate protein importance, which yielded a set of candidate proteins that can distinguish between ATB and non-ATB. The analysis with the support vector machine algorithm (recursive feature elimination) suggested that the combination of apolipoprotein A-I (APOA1), hemoglobin subunit beta (HBB), and hemoglobin subunit alpha-1 (HBA1) had the highest accuracy and sensitivity in diagnosing ATB. Meanwhile, the levels of hemoglobin (HGB) and albumin (ALB) can be used as blood biochemical indicators to evaluate changes in the protein levels of APOA1 and HBB. This study established the serum proteome landscape of AYAs with tuberculosis and identified new biomarkers for the diagnosis of tuberculosis in this population.
Humans
;
Proteomics/methods*
;
Biomarkers/blood*
;
Adolescent
;
Young Adult
;
Apolipoprotein A-I/blood*
;
Machine Learning
;
Tuberculosis/blood*
;
Proteome/analysis*
;
Male
;
Hemoglobins/analysis*
;
Female
;
Blood Proteins/analysis*
;
Adult
2.Evaluation of uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculous empyema.
Yu Hui JIANG ; Lei SHEN ; Qi Bin LIU ; Xi Yong DAI ; Jian SHENG ; Xiao Yu LIU
Chinese Journal of Surgery 2023;61(2):156-161
Objective: To examine the safety and efficacy of the uniportal video-assisted thoracoscopic decortication in treatment of drug-resistant tuberculosis empyema. Methods: From January 2018 to December 2020, 122 cases of tuberculous empyema treated by decortication in Department of Surgery, Wuhan Pulmonary Hospital were retrospectively analyzed, including 100 males and 22 females, aged(M(IQR)) 29.5(28.0) years (range: 13 to 70 years). According to the surgical approach and drug resistance, patients with drug-resistant tuberculosis who underwent uniportal video-assisted thoracoscopic decortication were included in group A (n=22), and those who underwent thoracotomy decortication were included in group B (n=28). Drug-sensitive patients who underwent uniportal video-assisted thoracoscopic decortication were included in group C (n=72). There was no statistical difference in the baseline data of the three groups (P>0.05). The operation, early postoperative recovery, and prognosis-related indicators were compared among three groups by Kruskal-Wallis test and χ2 test by Mann-Whitney U test and Bonferroni method between groups A and B, groups A and C. Results: The intraoperative blood loss of group A, group B, and group C was 200(475) ml, 300(200) ml, and 225(300) ml, respectively. There was no significant difference in intraoperative hemorrhage (H=2.74, P=0.254) and treatment outcome (χ2=4.76, P=0.575) among the three groups. Compared with group B, the operation time of group A (302.5(187.5) minutes vs. 200.0(60.0) minutes, U=171.0, P=0.007) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0 (2.2) months, U=146.5, P=0.032) were longer, and the postoperative drainage duration (9.5(7.8) days vs. 13.0(10.0) days, U=410.0, P=0.044), and the postoperative hospitalization time (12.0(7.8) days vs. 14.5(4.8) days, U=462.2, P=0.020) were shorter. There was no significant difference in complications between group A and group B (63.6%(14/22) vs. 71.4%(20/28), χ2=0.34, P=0.558). Compared with group C, the postoperative drainage duration of group A (9.5(7.8) days vs. 7.0(4.0) days, U=543.5, P=0.031), the postoperative hospitalization time (12.0(7.8) days vs. 9.0(4.0) days, U=533.0, P=0.031) and postoperative pulmonary reexpansion duration (4.5(3.0) months vs. 3.0(2.0) months, U=961.5, P=0.001) were longer. The operation time (302.5(187.5) minutes vs. 242.5(188.8) minutes, U=670.5, P=0.278), and complications (63.6%(14/22) vs. 40.3%(29/72), χ2=3.70, P=0.054) were not different between group A and group C. Conclusions: For drug-resistant tuberculous empyema, the uniportal video-assisted thoracoscopic decortication can achieve the same good therapeutic effect as drug-sensitive tuberculous empyema, and it is as safe as thoracotomy. At the same time, it has the advantage of minimally invasive and can accelerate the early postoperative recovery of patients.
Female
;
Male
;
Humans
;
Empyema, Tuberculous/surgery*
;
Retrospective Studies
;
Thoracic Surgery, Video-Assisted
;
Drainage
;
Blood Loss, Surgical
;
Tuberculosis, Multidrug-Resistant/surgery*
3.A preliminary study on the surgical timing of spinal tuberculosis.
Yang-Hui JIN ; Shi-Yuan SHI ; Qi ZHENG ; Jian SHEN ; Xiao-Zhang YING ; Bo ZHU
China Journal of Orthopaedics and Traumatology 2021;34(8):717-724
OBJECTIVE:
To observe the changes of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and nerve function in patients with spinal tuberculosis before and after surgery, explore the timing of surgical intervention, and evaluate its influence on surgical safety.
METHODS:
A retrospective analysis was conducted on 387 patients with spinal tuberculosis who received surgical treatment from March 2012 to March 2017, including 278 males and 109 females, aged 12 to 86 years old with an average of (49.9±19.1) years. There were 64 cases of cervical tuberculosis, 86 cases of thoracic tuberculosis, 76 cases of thoracolumbar tuberculosis and 161 cases of lumbar tuberculosis. There were 297 patients with single segmental involvementand 90 patients with multiple segmental involvement. Among them, 62 cases presented neurological damage, and preoperative spinal cord neurological function depended on ASIA grade, 5 cases of grade A, 8 cases of grade B, 39 cases of grade C, and 10 cases of grade D. According to the duration of preoperative antituberculosis treatment, the patients were divided into group A (256 cases, receiving conventional quadruple antituberculosis treatment for 2-4 weeks before surgery) and group B (131 cases, receiving conventional quadruple antituberculosis treatment for more than 4 weeks before surgery). The two groups were compared in terms of gender, age, preoperative complicated pulmonary tuberculosis, lesion site, lesion scope, surgical approach, drug resistance and other general clinical characteristics. ESR, CRP, visual analogue scale(VAS), Oswestry Disability Index (ODI), Frankel grade and postoperative complications were observed.
RESULTS:
All 387 patients were followed up for 12 to 36 (18.3±4.5) months. There were no significant differences in gender, age, preoperative pulmonary tuberculosis, lesion site, lesion range, surgical approach, preoperative drug resistance and other characteristics between two groups. A total of 32 patients in two groups did not heal after surgery, with an incidence rate of 8.27%. The VAS and spinal cord dysfunction index of the two groups were significantly improved after surgery (
CONCLUSION
After 2-4 weeks of anti tuberculosis treatment before operation, patients with spinal tuberculosis could be operated upon with ESR and CRP in a descending or stable period. In principle, patients with spinal tuberculosis and paraplegia should be treated as soon as possible after active preoperative management of the complication without emergency surgery.
Adolescent
;
Adult
;
Aged
;
Aged, 80 and over
;
Blood Sedimentation
;
Child
;
Female
;
Humans
;
Male
;
Middle Aged
;
Retrospective Studies
;
Spinal Fusion
;
Thoracic Vertebrae
;
Tuberculosis, Spinal/surgery*
;
Young Adult
4.Rifampicin-Induced Thrombocytopenia: A case report
Denise C. De Los Reyes ; Maria Carmen D. Ang ; Heide P. Abdurahman ; Jessie F. Orcasitas
Philippine Journal of Internal Medicine 2021;59(1):62-66
INTRODUCTION:
The worldwide prevalence of adverse drug reactions (ADR) to anti-TB medication ranges from 8% to
85%. Major adverse reactions include hepatic, renal, and hematologic disorders of which, Rifampicin-induced thrombocytopenia is one of these rare complications.
CASE:
A 58-year-old Filipino male developed respiratory and gastrointestinal bleeding with a severe drop in platelet count after several days of anti-tuberculosis (anti-TB) medications. The patient had oral mucosal petechiae, blood-streaked sputum, and epistaxis. The symptoms progressed to the formation of small adherent clots beneath the tongue, gum bleeding, melena, massive epistaxis, and hemoptysis with continued intake of the anti-TB drugs. The patient had anemia, normal WBC and differential count, and thrombocytopenia of 3 x 10^3/uL, a drop from 235 x 10^3/uL five days prior. The bleeding resolved with the discontinuation of the drugs. A slow graded oral challenge to each of the drugs was done to identify the culprit medication. There was a recurrence of bleeding and a decrease in the platelet count after administration of rifampicin. The anti-TB medications were modified not to include rifampicin. The patient was discharged with no signs of bleeding and a normal complete blood count.
CONCLUSION
TB is a prevalent disease in our country, and its medications can cause adverse drug reactions. Rifampicin-induced thrombocytopenia is a rare and life-threatening condition that physicians must be aware of and able to recognize promptly and treat properly to prevent recurrence of similar cases in the future. The patient should be forewarned not to take rifampicin and any fixed-dose combination drugs containing rifampicin.
Rifampin
;
Thrombocytopenia
;
Blood Platelets
;
Tuberculosis
5.Clinical characteristics and related factors of rheumatoid arthritis complicated with tuberculosis infection.
Guo TANG ; Li LONG ; Ya Xin HAN ; Qing PENG ; Jia Jun LIU ; Hua SHANG
Journal of Peking University(Health Sciences) 2020;52(6):1029-1033
OBJECTIVE:
To investigate the clinical characteristics and high risk factors of Rheumatoid arthritis (RA) complicated with tuberculosis infection.
METHODS:
Patients with rheumatoid arthritis diagnosed in the hospital of Sichuan Provincial People's Hospital from January 2007 to January 2017 was retrospectively collected, who were enrolled in the study group. A control group was randomly selected from the RA patients hospitalized in the same period without co-infection at a ratio of 1 :2. The general data, clinical data, laboratory test data, treatment plan, etc. of the two groups were collected in detail for single factor statistical analysis. Then multivariate Logistic regression was used to analyze the independent risk factors of RA complicated with tuberculosis infection with statistical significance in univariate analysis.
RESULTS:
The clinical manifestations of fever (83.3%) were most common, followed by cough (69%) and body mass loss (45.2%). In the infected group, pulmonary tuberculosis accounted for 73.3%. In the infected group the chest CT showed two or more cases, accounting for 59%. There were 9 cases (33.3%) occurring in the typical tuberculosis occurrence site. Compared with the control group, the erythrocyte sedimentation rate (ESR), C-reaction protein (CRP) levels, and the daily average dose of glucocorticoid in 1 year in the infected group were higher than those in the control group. And those differences were statistically significant(P < 0.05). There were no significant differences in gender, age, disease duration, disease activity score, white blood cell (WBC), platelet (PLT), hemoglobin (Hb), immunoglobulin G (IgG), complement (C), Anti cyclic citrullinated peptide antibody (anti-CCP), CD4+T cell count, and immunosuppressant use (P > 0.05). Multivariate Logistic regression analysis showed that CRP levels(OR=1.016, 95%CI:1.002-1.031) and the daily average dose of glucocorticoid in 1 year(OR=1.229, 95%CI:1.066-1.418)were the independent risk factors of RA complica-ted with tuberculosis infection.
CONCLUSION
RA patients with tuberculosis infection are mainly phthisis. The clinical manifestations of RA combined with tuberculosis infection are lack of specificity, and the chest imaging features of pulmonary tuberculosis are diverse, which are easy to be misdiagnosed. CRP levels and the daily average dose level of glucocorticoid in 1 year were risk factors for RA and tuberculosis infection.
Arthritis, Rheumatoid/complications*
;
Autoantibodies
;
Blood Sedimentation
;
Humans
;
Peptides, Cyclic
;
Retrospective Studies
;
Rheumatoid Factor
;
Tuberculosis/epidemiology*
6.Detection of carcinoembryonic antigen levels in pleural effusion and serum and their ratio for differential diagnosis of pleural effusion resulting from tuberculosis and lung cancer.
Ruicheng LI ; Zhaowei GAO ; Ke DONG ; Huiping WANG ; Huizhong ZHANG
Journal of Southern Medical University 2019;39(2):175-180
OBJECTIVE:
To study the clinical value of detecting carcinoembryonic antigen levels in pleural effusion (PCEA) and serum (SCEA) and their ratio (P/S) in the differential diagnosis of pleural effusions resulting from tuberculosis and lung cancer.
METHODS:
This retrospectively study was conducted among 82 patients with pleural effusion caused by pulmonary tuberculous (TB; control group) and 120 patients with pleural effusion resulting from lung cancer in our hospital between April, 2016 and March, 2018. PCEA, SCEA and P/S were compared between the two groups and among the subgroups of lung cancer patients with squamous cell carcinoma (SqCa), adenocarcinoma (ACA), small cell carcinoma (SCLC). The receiveroperating characteristic curve (ROC) analysis was used to confirm the optimal critical value to evaluate the diagnostic efficiency of different combinations of PCEA, SCEA and P/S.
RESULTS:
PCEA, SCEA and P/S were significantly higher in the overall cancer patients and in all the 3 subgroups of cancer patients than in the patients with TB ( < 0.05). The areas under the ROC curve of PCEA, SCEA and P/S were 0.925, 0.866 and 0.796, respectively; PCEA had the highest diagnostic value, whose diagnostic sensitivity, specificity, accurate rate, and diagnostic threshold were 83.33%, 96.34, 88.61%, and 3.26 ng/ml, respectively; SCEA had the lowest diagnostic performance; the diagnostic performance of P/S was between that of SCEA and PCEA, but its combination with SCEA greatly improved the diagnostic performance and reduced the rates of misdiagnosis and missed diagnosis. Parallel tests showed that the 3 indexes combined had significantly higher diagnostic sensitivity than each or any two of the single indexes ( < 0.05), but the diagnostic specificity did not differ significantly. The area under the ROC curve of combined detections of the 3 indexes was 0.941 for diagnosis of lung cancer-related pleural effusion, higher than those of any other combinations of the indexes.
CONCLUSIONS
The combined detection of PCEA, SCEA and P/S has a high sensitivity for diagnosis of lung cancer-related pleural effusion and provides important information for rapid and accurate diagnosis of suspected cases.
Carcinoembryonic Antigen
;
analysis
;
blood
;
Case-Control Studies
;
Diagnosis, Differential
;
Humans
;
Lung Neoplasms
;
blood
;
complications
;
Pleural Effusion
;
blood
;
diagnosis
;
immunology
;
Pleural Effusion, Malignant
;
blood
;
chemistry
;
diagnosis
;
ROC Curve
;
Retrospective Studies
;
Sensitivity and Specificity
;
Tuberculosis, Pulmonary
;
complications
7.Plasma levels of interferon-inducible protein 10 in patients with active pulmonary tuberculosis with different affected areas.
Haiping DONG ; Zhihui LIU ; Xiaocheng LIANG ; Yiluan JIAN ; Dexian LI ; Suihua LAO ; Feng LIANG ; Yanshan PAN ; Xiaojia KUANG
Journal of Southern Medical University 2019;39(5):609-613
OBJECTIVE:
To explore the value of interferon-inducible protein 10 (IP-10) in the auxiliary diagnosis of tuberculosis and the judgment of the severity of disease.
METHODS:
From February, 2013 to February, 2017, a total of 193 patients with TB admitted in our hospital and 84 healthy control subjects were recruited consecutively. The peripheral blood plasma levels of interferon-γ (IFN-γ) and IP-10 were detected using liquid phase chip (Luminex) technique. According to the number of lung fields affected by TB, the patients were divided into group A (with lesions in 1-2 lung fields), group B (3-4 lung fields) and group C (5-6 lung fields), The expressions of IFN-γ and IP-10 in 3 groups were compared.
RESULTS:
The plasma levels of IP-10 were significantly higher in TB patients than in the control subjects ( < 0.05), but IFN-γ levels were comparable between the two groups ( > 0.05). Among the TB patients, plasma IP-10 levels was the highest in group C ( < 0.05), and IFN-γ levels did not differ significantly among the 3 groups ( > 0.05).
CONCLUSIONS
Plasma IP-10 has a certain reference value in the auxiliary diagnosis of active tuberculosis and the judgment of the severity of the disease.
Antigens, Bacterial
;
Biomarkers
;
blood
;
Chemokine CXCL10
;
blood
;
Humans
;
Tuberculosis, Pulmonary
;
blood
;
diagnosis
8.Long Term Safety and Efficacy of Etanercept in Juvenile Idiopathic Arthritis in a Single Center
Myung Hoon BANG ; Kwang Nam KIM
Journal of Rheumatic Diseases 2019;26(3):200-205
OBJECTIVE: Our aim was to investigate the long term safety and efficacy of etanercept in children with juvenile idiopathic arthritis (JIA). METHODS: The study subjects were the 90 JIA patients treated with etanercept in the Department of Pediatrics, Hallym University Medical Center between January 2004 and December 2017. We retrospectively reviewed their medical records for age at diagnosis, duration of etanercept treatment, number of active joints, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and adverse events during treatment. RESULTS: Among the 90 patients, 38 (42.0%) were male and 52 (58.0%) were female; 15 (16.7%) had systemic onset, 41 (45.6%) had extended oligoarticular, 14 (15.6%) had rheumatoid factor-positive polyarticular, 18 (20.0%) had rheumatoid factor-negative polyarticular, and 2 (2.1%) had enthesitis-related arthritis. The median age at the start of etanercept treatment was 9 years (range, 3~18 years), and the median duration of etanercept treatment was 6 years (range, 0.5~13 years). The median number of active joints decreased from 9 to 0 after 6 months of etanercept treatment. The median CRP and ESR were within normal range after 3 months of treatment. Six patients experienced recurrence, 9 switched to other medications and 3 discontinued etanercept. Of the 14 reported adverse events, 1 was serious, and there were no tuberculosis infections or malignancies. CONCLUSION: Long-term treatment with etanercept is efficacious and safe for children with JIA. However, those with the systemic onset subtype appear to have low drug survival rate compared to those with other types of JIA.
Academic Medical Centers
;
Arthritis
;
Arthritis, Juvenile
;
Blood Sedimentation
;
C-Reactive Protein
;
Child
;
Diagnosis
;
Etanercept
;
Female
;
Humans
;
Joints
;
Male
;
Medical Records
;
Pediatrics
;
Recurrence
;
Reference Values
;
Retrospective Studies
;
Survival Rate
;
Tuberculosis
9.Screening of Serum Biomarkers for Distinguishing between Latent and Active Tuberculosis Using Proteome Microarray.
Shu Hui CAO ; Yan Qing CHEN ; Yong SUN ; Yang LIU ; Su Hua ZHENG ; Zhi Guo ZHANG ; Chuan You LI
Biomedical and Environmental Sciences 2018;31(7):515-526
OBJECTIVETo identify potential serum biomarkers for distinguishing between latent tuberculosis infection (LTBI) and active tuberculosis (TB).
METHODSA proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays (ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve (ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability.
RESULTSMicroarray results showed that levels of 152 Mycobacterium tuberculosis (Mtb)-antigen- specific IgG were significantly higher in active TB patients than in LTBI patients (P < 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031c, Rv1408, and Rv2421c had higher areas under the curve (AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability.
CONCLUSIONSeveral antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.
Adolescent ; Adult ; Aged ; Antibodies, Bacterial ; Antibody Specificity ; Antigens, Bacterial ; Biomarkers ; blood ; Female ; Humans ; Latent Tuberculosis ; blood ; diagnosis ; Logistic Models ; Male ; Middle Aged ; Mycobacterium tuberculosis ; Protein Array Analysis ; methods ; Proteome ; genetics ; Proteomics ; methods ; ROC Curve ; Young Adult
10.Factors Associated with Persistent Sputum Positivity at the End of the Second Month of Tuberculosis Treatment in Lithuania.
Saulius DIKTANAS ; Edita VASILIAUSKIENE ; Katazyna POLUBENKO ; Edvardas DANILA ; Indre CELEDINAITE ; Evelina BOREIKAITE ; Kipras MISIUNAS
Tuberculosis and Respiratory Diseases 2018;81(3):233-240
BACKGROUND: Non-conversion of sputum smear and culture prolongs the infectivity of the patient and has been associated with unfavorable outcomes. We aimed to evaluate factors associated with persistent sputum positivity at the end of two months of treatment of new case pulmonary tuberculosis (TB). METHODS: Data of 87 human immunodeficiency virus-negative patients with culture-positive drug-susceptible pulmonary TB admitted to local university hospital between September 2015 and September 2016 were reviewed. Factors associated with sputum smear and/or culture positivity at the end of the second month of treatment were analyzed. RESULTS: Twenty-two patients (25.3%) remained smear and/or culture-positive. Male sex, lower body mass index (BMI), unemployment, alcohol abuse, higher number of lobes involved and cavities on chest X-rays, shorter time to detection (TTD) on liquid cultures, higher respiratory sample smear grading and colony count in solid cultures, higher C-reactive protein, erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and anemia were all significantly associated with persistent sputum positivity. However, in the logistic regression analysis only male sex, lower BMI, alcohol abuse, higher radiological involvement, cavitation, higher smear grading, higher colony count in solid cultures and shorter TTD were determined as independent factors associated with persistent sputum positivity at the end of 2 months of treatment. CONCLUSION: In conclusion, higher sputum smear and culture grading at diagnosis, shorter TTD, higher number of lobes involved, cavitation, male sex, alcohol abuse, and lower BMI were independently associated with persistent sputum positivity. These factors should be sought when distinguishing which patients will remain infectious longer and possibly have worse outcomes.
Alcoholism
;
Anemia
;
Blood Sedimentation
;
Body Mass Index
;
C-Reactive Protein
;
Diagnosis
;
Humans
;
Leukocytosis
;
Lithuania*
;
Logistic Models
;
Male
;
Risk Factors
;
Sputum*
;
Thorax
;
Thrombocytosis
;
Treatment Outcome
;
Tuberculosis*
;
Tuberculosis, Pulmonary
;
Unemployment


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