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Aim: To identify risk factors that associated with the occurrence of venous thromboembolism (VTE) within 30 days after hysterectomy among gynecological malignant tumor patients, and to explore the value of machine learning (ML) models in VTE occurrence prediction. Methods: A total of 1087 patients between January 2019 and January 2022 with gynecological malignant tumors were included in this single‐center retrospective study and were randomly divided into the training dataset (n = 870) and the test dataset (n = 217). Univariate logistic regression analysis was used to identify risk factors that associated with the occurrence of postoperative VTE in the training dataset. Machine learning models (including decision tree (DT) model and logistic regression (LR) model) to predict the occurrence of postoperative VTE were constructed and internally validated. Results: The incidence of developing 30‐day postoperative VTE was 6.0% (65/1087). Age, previous VTE, length of stay (LOS), tumor stage, operative time, surgical approach, lymphadenectomy (LND), intraoperative blood transfusion and gynecologic Caprini (G‐Caprini) score were identified as risk factors for developing postoperative VTE in gynecological malignant tumor patients (p < 0.05). The AUCs of LR model and DT model for predicting VTE were 0.722 and 0.950, respectively. Conclusion: The ML models, especially the DT model, constructed in our study had excellent prediction value and shed light upon its further application in clinic practice. [ABSTRACT FROM AUTHOR]

In contrast to the decreasing trends in developed countries, the incidence and mortality rates of cervical squamous cell carcinoma in China have increased significantly. The screening and identification of reliable biomarkers and candidate drug targets for cervical squamous cell carcinoma are urgently needed to improve the survival rate and quality of life of patients. In this study, we demonstrated that the expression of MUC1 was greater in neoplastic tissues than in non-neoplastic tissues of the cervix, and cervical squamous cell carcinoma patients with high MUC1 expression had significantly worse overall survival than did those with low MUC1 expression, indicating its potential for early diagnosis of cervical squamous cell carcinoma. Next, we explored the regulatory mechanism of MUC1 in cervical squamous cell carcinoma. MUC1 could upregulate ITGA2 and ITGA3 expression via ERK phosphorylation, promoting the proliferation and metastasis of cervical cancer cells. Further knockdown of ITGA2 and ITGA3 significantly inhibited the tumorigenesis of cervical cancer cells. Moreover, we designed a combination drug regimen comprising MUC1-siRNA and a novel ERK inhibitor in vivo and found that the combination of these drugs achieved better results in animals with xenografts than did MUC1 alone. Overall, we discovered a novel regulatory pathway, MUC1/ERK/ITGA2/3, in cervical squamous cell carcinoma that may serve as a potential biomarker and therapeutic target in the future. Summary: MUC1 is overexpressed in cervical squamous cell carcinoma. MUC1 regulates ERK phosphorylation, and subsequently upregulates ITGA2 and ITGA3 expression to promote tumorigenesis in cervical squamous cell carcinoma. A combination drug regimen targeting MUC1 and ERK achieved better results compared than MUC1 alone. [ABSTRACT FROM AUTHOR]

Exploring the influence of pyrazinamide exposure and susceptibility on treatment response is crucial for optimizing the management of multidrug-resistant tuberculosis (MDR-TB). This study aimed to investigate the association between pyrazinamide exposure, susceptibility, and response to MDR-TB treatment, as well as find clinical thresholds for pyrazinamide. A prospective multi-center cohort study of participants with MDR-TB using pyrazinamide was conducted in three TB-designated hospitals in China. Univariate and multivariate analyses were applied to investigate the associations. Classification and Regression Tree (CART) analysis was used to identify clinical thresholds, which were further evaluated by multivariate analysis and receiver operating characteristic (ROC) curves. The study included 143 patients with MDR-TB. The exposure/susceptibility ratio of pyrazinamide was associated with two-month culture conversion (adjusted risk ratio (aRR), 1.1; 95% confidence interval (CI), 1.07–1.20), six-month culture conversion (aRR, 1.1; 95% CI, 1.06–1.16), treatment success (aRR, 1.07; 95% CI, 1.03–1.10), as well as culture conversion time (adjusted hazard ratio (aHR) 1.18; 95% CI,1.14–1.23). The threshold for optimal improvement in sputum culture results at the sixth month of treatment was determined to be a pyrazinamide AUC0–24h/MIC ratio of 7.8. In conclusion, the exposure/susceptibility ratio of pyrazinamide is associated with the treatment response of MDR-TB, which may change in different Group A drug-based regimens. [ABSTRACT FROM AUTHOR]

Objectives. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus causing substantial morbidity and mortality worldwide. We performed a cross-sectional investigation of SARS-CoV-2 clusters in Suzhou to determine the transmissibility of the virus among close contacts and to assess the demographic and clinical characteristics between index and secondary cases. Methods. We review the clustered patients with SARS-CoV-2 infections in Suzhou between 22 January and 29 February 2020. The demographic and clinical characteristics were compared between index and secondary cases. We calculated the basic reproduction number ( R 0 ) among close contacts with SLI model. Results. By 22 February, 87 patients with SARS-CoV-2 infection were reported, including 50 sporadic and 37 clustered cases, who were generated from 13 clusters. On admission, 5 (20.8%) out of 24 secondary cases were asymptomatic. The male ratio of index cases was significantly higher than that of secondary cases. Additionally, the index cases were more likely to have fever and increased CRP levels than the secondary cases. The R 0 values of clusters displayed a significantly declining trend over time for all clusters. The relative risk of infection in blood-related contacts of cases versus unrelated contacts was 1.60 for SARS-CoV-2 (95% CI: 0.42-2.95). Conclusions. In conclusion, SARS-CoV-2 has great person-to-person transmission capability among close contacts. The secondary cases are more prone to have mild symptoms than index cases. There is no increased RR of secondary infection in blood relatives versus unrelated contacts. The high rate of asymptomatic SARS-CoV-2 infections highlights the urgent need to enhance active case finding strategy for early detection of infectious patients. [ABSTRACT FROM AUTHOR]

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) remains a serious global public health problem in the present. TB also affects other sites (extrapulmonary tuberculosis, EPTB), and accounts for a significant proportion of tuberculosis cases worldwide. In order to comprehensively understand epidemiology of EBTB in China, and improve early diagnosis and treatment, we conducted a large-scale multi-center observational study to assess the demographic data and the prevalence of common EPTB inpatients, and further evaluate the prevalence of EPTB concurrent with Pulmonary tuberculosis (PTB) and the associations between multiple EPTB types and gender-age group in China. All consecutive age≥15yr inpatients with a confirmed diagnosis of EPTB during the period from January 2011 to December 2017 were included in the study. The descriptive statistical analysis included median and quartile measurements for continuous variables, and frequencies and proportions with 95% confidence intervals (CIs) for categorical variables. Multinomial logistic regression analysis was used to compare the association of multiple EPTB types between age group and gender. The results showed that the proportion of 15–24 years and 25–34 years in EPTB inpatients were the most and the ratio of male: female was 1.51. Approximately 70% of EPTB inpatients were concurrent with PTB or other types of EPTB. The most common of EPTB was tuberculous pleurisy (50.15%), followed by bronchial tuberculosis (14.96%), tuberculous lymphadenitis of the neck (7.24%), tuberculous meningitis (7.23%), etc. It was found that many EPTB inpatients concurrent with PTB. The highest prevalence of EPTB concurrent with PTB was pharyngeal/laryngeal tuberculosis (91.31%), followed by bronchial tuberculosis (89.52%), tuberculosis of hilar lymph nodes (79.52%), tuberculosis of mediastinal lymph nodes (79.13%), intestinal tuberculosis (72.04%), tuberculous pleurisy (65.31%) and tuberculous meningitis (62.64%), etc. The results from EPTB concurrent with PTB suggested that females EPTB inpatients were less likely to be at higher risk of concurrent PTB (aOR = 0.819, 95%CI:0.803–0.835) after adjusted by age. As age increasing, the trend risk of concurrent PTB decreased (aOR = 0.994, 95%CI: 0.989–0.999) after adjusted by gender. Our study demonstrated that the common EPTB were tuberculous pleurisy, bronchial tuberculosis, tuberculous lymphadenitis of the neck, tuberculous meningitis, etc. A majority of patients with pharyngeal/laryngeal tuberculosis, bronchial tuberculosis, tuberculosis of hilar/mediastinal lymph nodes, intestinal tuberculosis, tuberculous pleurisy, tuberculous meningitis, etc. were concurrent with PTB. Female EPTB inpatients were less likely to be at higher risk of concurrent PTB, and as age increasing, the trend risk of concurrent PTB decreased. The clinicians should be alert to the presence of concurrent tuberculosis in EPTB, and all suspected cases of EPTB should be assessed for concomitant PTB to determine whether the case is infectious and to help for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Anti-tuberculosis therapy requires at least six-month treatment with continuous administration of combined antibiotics, including isoniazid, rifampicin, pyrazinamide, and ethambutol. The long-term exposure to antibiotics could cause consequent changes in gut microbiota, which may alter the gastrointestinal function and drug absorption in patients, thereby affect the outcome of treatment. The study aims to characterize the longitudinal changes of gut microbiota among tuberculosis (TB) patients under standardized first-line treatment and provide an understanding of the association between alterations in gut microbiota composition and unfavorable clinical outcomes.Methods: The study is a multicenter, observational prospective cohort study. Three study sites are purposively selected in the western (Sichuan Province) and eastern (Jiangsu Province and Shanghai) parts of China. Three-hundred patients with bacteriologically confirmed pulmonary TB are enrolled. All eligible patients should be investigated using structured questionnaires before treatment initiation; and be followed up during the treatment at Day-14, Month-2, Month-5, the end of treatment and the sixth month after ending therapy. Stool samples are to be collected at each visit, consisting of six stool samples from each patient. Additionally, 60 healthy volunteers from Sichuan province and Shanghai city will be recruited as healthy controls to form the baseline of patient gut microbiota in the Chinese population. The dynamic changes of gut microbiota in terms of alpha diversity, beta diversity, taxonomic composition are to be illustrated individually from the time at diagnosis until the sixth month after therapy is completed. Furthermore, the diversity and component of gut microbiota will be compared between the groups with and without unfavorable treatment outcome in terms of adverse effect and treatment failure.Discussion: Studies on the clinical manifestations, adverse reactions, and gut microbiota alterations will provide scientifically-sound evidence on the impact of gut microbiota alterations on TB treatment outcomes. The study is not only useful for guiding personalized TB treatment but also sheds light on the effects of continuous antibiotics administration on gut microbiota.Trial Registration: Chinese Clinical Trial Registry, trial ID: ChiCTR1900023369, May 24, 2019. Retrospectively registered. [ABSTRACT FROM AUTHOR]

Objectives: We prospectively evaluated the use of bronchoalveolar lavage fluid (BALF) specimens to assess their added incremental value to pulmonary tuberculosis (TB) diagnostic strategies used currently in a high-burden urban setting in China.Methods: A prospective study was conducted of patients with presumptive pulmonary TB registered at the Fifth Hospital of Suzhou between March 2018 and July 2018. BALF samples from patients with initial Xpert-negative sputum results were tested to diagnose TB.Results: Of 440 participants, 316 (71.8%) were initially diagnosed with TB from sputum, including 245 (55.7%) definitive TB cases based on a positive culture and/or Xpert result(s) and 71 (16.1%) positive cases based on clinical diagnosis. Of 153 patients with initial positive cultures, a significantly higher proportion were confirmed as TB-positive using Xpert (94.1%) versus smear microscopy (45.8%, P < 0.01). Xpert testing of BALF from 182 Xpert-negative cases exhibited greater detection sensitivity (97.4%) than did smear microscopy (23.4%, P < 0.01). Meanwhile, 74.1% of TB patients initially diagnosed as TB-negative via smear microscopy were identified using Xpert testing of BALF at reduced diagnostic cost/patient (from USD 266.9 to 171.5).Conclusions: BALF samples added incremental value to pulmonary TB diagnostic strategies for patients with Xpert-negative sputum. Xpert outperformed smear microscopy for tubercle bacilli detection in both sputum and BALF. [ABSTRACT FROM AUTHOR]

Publicly traded firms in China rely heavily on equity financing and are constrained in debt financing. Gaining access to the public debt market substantially alleviates the constraint. The debt ratio of the firms that have access to the public debt market is approximately 14 percent higher than the firms without access. Everything else being equal, gaining access to the public debt market significantly increases the debt ratio by 3.44 percent, and this increase is concentrated in long-term debt. We further find that non-SOEs enjoy greater benefits from access to the public debt market than SOEs, as evidenced by an increase in their total debt ratio and long-term debt ratio. For SOEs, the increase in long-term debt is offset by the decrease in short-term debt, which results in no change in total debt ratio. Our findings suggest the importance of access to the public debt market for Chinese firms, especially for non-SOEs that do not have privileged access to capital as do the SOEs. [ABSTRACT FROM PUBLISHER]

• A reduced diversity of gut microbiota was observed in tuberculosis (TB) patients. • TB patients had a low abundance of short-chain fatty acid-producing genera. • Active TB patients showed a raised abundance of several conditional pathogens. • Antibiotic use before TB diagnosis could alter the gut microbiota of patients. Background: The aim of this study was to identify the differences in diversity, composition, and function of the gut microbiota between tuberculosis (TB) patients and healthy controls (HCs). Methods: A cross-sectional study was conducted in three cities of China. Stool samples from 94 treatment-naive TB patients and 62 HCs were analyzed by 16S rRNA gene sequencing. TB patients were further divided into antibiotic-free and antibiotic-exposure according to their use of non-specific antibiotics before the TB diagnosis. Results: Compared with HCs, antibiotic-free TB patients presented a different gut microbial community (P < 0.005) and decreased Shannon diversity (P < 0.005). Among TB patients, the relative abundances of short-chain fatty acid (SCFA)-producing genera such as Lachnospiraceae ND3007 group (log2(FC) = −2.74) were lower, while several conditional pathogen-related genera such as Enterococcus (log2(FC) = 12.05) and Rothia (log2(FC) = 6.322) were at higher levels. In addition, 41% of patients received antibiotics before TB diagnosis. Antibiotic exposure was correlated with an additional reduction in α diversity and depletion of SCFA-producing bacteria. Microbial functional analysis revealed that the biosynthesis capacity of amino acids and fatty acids was lower among TB patients compared to HCs. Conclusions: Significant alterations in gut microbiota composition and metabolic pathways of TB patients were observed. Antibiotic exposure could alter the gut microbiota of TB patients, which should be considered in anti-TB treatment. [ABSTRACT FROM AUTHOR]

To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. 75 patients were enrolled, with a mean age of 46.6 ± 14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P < 0.05) than the mild/moderate, and the lymphocyte was lower. The ROC test showed that the hematological parameters had a larger AUC than that of inflammatory factors. There was a significant difference in lymphocyte and fibrinogen levels between the two groups on day 1 (P < 0.05). However, NLR of the severe group was higher than the mild/moderate on days 1, 4 and 14 (P < 0.01), and so was D-dimer on days 1, 7 and 14 (P < 0.05). The common COVID-19 abnormal hematological indexes on admission included hyperfibrinogenemia, lymphopenia, the elevation of D-dimer, and leukopenia, which were significantly different between the mild/moderate and severe COVID-19 groups. Furthermore, the dynamic change of NLR and D-dimer level can distinguish severe COVID-19 cases from the mild/moderate. • Most common symptoms of Suzhou COVID-19 are fever, cough and sore throat. • COVID-19 has characteristics of abnormal hematological indexes. • NLR and D-dimer can be used as valuable biomarkers for risk stratification of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis., Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm., Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age., Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Wanli Kang et al.)

Aims: A high proportion of all patients with tuberculosis (TB) present with extrapulmonary TB (EPTB), including concurrent EPTB involving more than one extrapulmonary lesion site. However, previous reports only characterized lesions of single-site EPTB cases. This study aimed to investigate epidemiological characteristics and association rules of concurrent EPTB cases in China., Methods: An observational multi-centre study of 208,214 patients with EPTB lesions was undertaken in China from January 2011 to December 2017. Multi-variable logistic regression analysis was used to identify associations between gender and concurrent EPTB, and age and concurrent EPTB. Association rules were analysed for significance using the Apriori algorithm., Results: The most common EPTB lesion was tuberculous pleurisy (49.8%), followed by bronchial TB (14.8%) and tuberculous meningitis (7.6%). The most common type of concurrent EPTB was tuberculous pleurisy concurrent with tuberculous peritonitis (1.80%). In total, 22 association rules, including 20 strong association rules, were identified; among these, the highest confidence rates were found for tuberculous myelitis concurrent with tuberculous meningitis, and sacral TB concurrent with lumbar vertebral TB. The association rules of EPTB concurrent with other EPTB types were found to vary with gender and age. The confidence rate of tuberculous myelitis concurrent with tuberculous meningitis was higher in females (83.67%) than males, and was highest in patients aged 25-34 years (87.50%)., Conclusions: Many types of concurrent EPTB were found. Greater awareness of concurrent EPTB disease characteristics is needed to ensure timely clinical diagnosis and treatment of this disease., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Abstract: The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results.Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens.The agreement rate of 84.98% (82.85%-86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results.ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

xCT forms part of the x c - cysteine-glutamate antiporter which inhibits antimicrobial inflammatory immune functions and thus increases susceptibility to tuberculosis (TB). However, the associations between xCT gene polymorphisms and susceptibility to TB, as well as whether these modulate xCT expression or affect treatment with the xCT inhibitor sulfasalazine (SASP), are unclear. In the present study, we genotyped xCT polymorphisms in a large Chinese cohort and found that the single-nucleotide polymorphism (SNP) rs13120371 was associated with susceptibility to TB. The rs13120371 AA genotype was strongly associated with an increased risk of TB and increased xCT mRNA expression levels compared to those with the GG or AG genotype. rs13120371 is located on the 3' untranslated (UTR) region of the xCT gene, in the putative binding site for miR-142-3p, and the results of luciferase reporter assays indicated that the rs13120371 AA genotype inhibited the binding of miR-42-3p to xCT. Bacterial burden was also significantly higher in cells with the AA genotype than in those with the GG genotype. Furthermore, pretreatment with SASP alleviated this burden in cells with the AA genotype but conferred no benefit in cells with the GG phenotype. In summary, we identified a functional SNP (rs13120371) in the xCT 3' UTR region that increases susceptibility to TB through interacting with miR-142-3p. IMPORTANCE Tuberculosis (TB) is the leading cause of death from a single infectious agent globally, and the development of multidrug resistance represents a serious health concern, particularly in the developing world. Novel effective treatments are urgently required. xCT expression is known to increase susceptibility to TB, and certain polymorphisms in the gene encoding this protein interrupt the binding of microRNA and prevent its suppression. Taking advantage of the FDA approval for the use of sulfasalazine (SASP), which inhibits xCT-mediated cystine transport in humans, we demonstrate how host genotype-specific therapies tailored to the xCT genotype can improve TB outcomes., (Copyright © 2020 Wang et al.)

The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18-24 months and has a poor cure rate of 50-60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB.We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment success rate was measured in the propensity-matched cohort as the primary outcome.Patients in the optimised group achieved a higher treatment success rate than those in the regular group (76.3% versus 55.3%, p=0.006). Of 51 patients with isolates that were susceptible to PZA and who were receiving a 12-month regimen, 42 (82.4%) were treated successfully. The optimised group showed faster culture conversion than the regular group (p=0.024). After exclusion of pre-extensively drug-resistant TB (pre-XDR-TB), the treatment outcome in the optimised group was still better than the regular group (83.1% versus 62.1%, p=0.009).Introducing molecular susceptibility testing for PZA improved the treatment outcomes for MDR-TB without the use of new drugs. Introducing PZA for patients with PZA-susceptible (PZA-S) MDR-TB allows the current regimen to be shortened to 12 months with comparable success rates to the World Health Organization (WHO) recommended shorter regimen., Competing Interests: Conflict of interest: F. Sun has nothing to disclose. Conflict of interest: Y. Li has nothing to disclose. Conflict of interest: Y. Chen has nothing to disclose. Conflict of interest: W. Guan has nothing to disclose. Conflict of interest: X. Jiang has nothing to disclose. Conflict of interest: X. Wang has nothing to disclose. Conflict of interest: P. Ren has nothing to disclose. Conflict of interest: J. Li has nothing to disclose. Conflict of interest: J. Shi has nothing to disclose. Conflict of interest: G. He has nothing to disclose. Conflict of interest: M. Wu has nothing to disclose. Conflict of interest: P. Tang has nothing to disclose. Conflict of interest: F. Wang has nothing to disclose. Conflict of interest: Y. Sheng has nothing to disclose. Conflict of interest: F. Huang has nothing to disclose. Conflict of interest: Z. Zhou has nothing to disclose. Conflict of interest: H. Huang has nothing to disclose. Conflict of interest: L. Hong has nothing to disclose. Conflict of interest: Q. Liu has nothing to disclose. Conflict of interest: Y. Zhang has nothing to disclose. Conflict of interest: W. Zhang has nothing to disclose., (Copyright ©ERS 2019.)

We compared the positive rates of T-SPOT.TB and bacterial culture in the smear-negative PTB, and analyzed the factors affecting the results of negative T-SPOT.TB and bacterial culture. Retrospective evaluation of data from smear-negative PTB patients who underwent T-SPOT.TB and bacterial culture were done. The agreement and concordance were analyzed between T-SPOT.TB and bacterial culture. Multivariable logistic regression analysis was used to explore the factors associated with positive results of T-SPOT.TB and bacterial culture in smear-negative PTB. 858 eligible smear-negative PTB patients were included in the study. The agreement rate was 25.6% (22.7~28.5%) between T-SPOT.TB and bacterial culture in smear- negative PTB patients. The positive rate of T-SPOT.TB was higher than that of bacterial culture in smear-negative PTB patients (p < 0.001). There were nearly no concordance between T-SPOT.TB and bacterial culture (p > 0.05). Using multivariable logistic regression analysis we found that older age ≥ 60 years (OR = 0.469, 95% CI: 0.287-0.768) and decreased albumin (OR = 0.614, 95% CI: 0.380-0.992) were associated with negative diagnostic results of T-SPOT.TB in smear-negative PTB patients. Female (OR = 0.654, 95% CI: 0.431-0.992) were associated with negative diagnostic results of bacteria culture in smear-negative PTB patients. Our results indicated that the older age and decreased albumin were independently associated with negative T-SPOT.TB responses.

Background: Clofazimine (Cfz) has shown activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to treat MDR tuberculosis in China., Methods: We enrolled 105 patients who had sputum culture-positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in China. Patients were randomly assigned to either the Cfz therapy group (n = 53) or control group (n = 52). Patients in the 2 groups were given 21 months of individual-based chemotherapy regimens based on medication history and drug susceptibility test results. The Cfz therapy group regimens incorporated 100 mg of Cfz once daily for 21 months., Results: Three patients in each group discontinued therapy because of side effects or other reasons. Sputum culture conversion to negative was earlier in patients who received Cfz compared with controls (P = .042 by log-rank test). Chest computed tomography showed cavitary changes in 46 patients in the Cfz therapy group and 45 in the control group. Cavity closure was earlier in patient who received Cfz compared with controls (P = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%, higher than that in control group (53.8%; P = .035). Side effects in skin only occurred in the Cfz group. The rates of skin discoloration and ichthyosis were 94.3% and 47.2%, respectively., Conclusions: Using Cfz to treat MDR tuberculosis promotes cavity closure, accelerates sputum culture conversion, and improves treatment success rates., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Linezolid may be effective in treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. We conducted a prospective, multicentre, randomised study to further evaluate the efficacy, safety and tolerability of linezolid in patients with extensively drug-resistant tuberculosis in China. 65 patients who had culture-positive sputum for extensively drug-resistant tuberculosis were randomly assigned to a linezolid therapy group or a control group. Patients in the two groups adopted a 2-year individually based chemotherapy regimen. The linezolid therapy group was given linezolid at a start dose of 1200 mg per day for a period of 4-6 weeks and this was then followed by a dose of 300-600 mg per day. The proportion of sputum culture conversions in the linezolid therapy group was 78.8% by 24 months, significantly higher than that in the control group (37.6%, p<0.001). The treatment success rate in linezolid therapy group was 69.7%, significantly higher than that in the control group (34.4%, p=0.004). 27 (81.8%) patients had clinically significant adverse events in the linezolid group, of whom 25 (93%) patients had events that were possibly or probably related to linezolid. Most adverse events resolved after reducing the dosage of linezolid or temporarily discontinuing linezolid. Linezolid containing chemotherapy for treatment of extensively drug-resistant tuberculosis may significantly promote cavity closure, increase sputum culture-conversion rate and improve treatment success rate., (Copyright ©ERS 2015.)