Background:The diagnosis of tuberculous pleurisy(TP)presents a significant challenge due to the low bacterial load in pleural effusion(PE)samples.Cell-free Mycobacterium tuberculosis DNA(cf-TB)in PE samples is conside...Background:The diagnosis of tuberculous pleurisy(TP)presents a significant challenge due to the low bacterial load in pleural effusion(PE)samples.Cell-free Mycobacterium tuberculosis DNA(cf-TB)in PE samples is considered an optimal biomarker for diagnosing TP.This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size.Methods:Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022.Following centrifugation,sediments obtained from PE were used for Xpert MTB/RIF(Xpert)and mycobacterial culture,while the supernatants were subjected to cf-TB testing.This study employed a composite reference standard to definite TP,which was characterized by any positive result for Mycobacterium tuberculosis(MTB)through either PE culture,PE Xpert,or pleural biopsy.Results:A total of 1412 participants underwent screening,and 1344(95.2%)were subsequently enrolled in this study.Data from 1241(92.3%)participants were included,comprising 284 with definite TP,677 with clinically diagnosed TP,and 280 without TP.The sensitivity of cf-TB testing in definite TP was 73.6%(95%CI 68.2%-78.4%),significantly higher than both Xpert(40.8%,95%CI 35.3%-46.7%,P<0.001)and mycobacterial culture(54.2%,95%CI 48.4%-59.9%,P<0.001).When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis,cf-TB testing showed a sensitivity of 46.8%(450/961,95%CI 43.7%-50.0%),significantly higher than both Xpert(12.1%,116/961,95%CI 10.2%-14.3%,P<0.001)and mycobacterial culture(16.0%,154/961,95%CI 13.8%-18.5%,P<0.001).The specificities of cf-TB testing,Xpert,and mycobacterial culture were all 100.0%.Conclusions:The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods,indicating that it can be considered as the primary diagnostic approach for improving TP detection.Trial registration:The trial was registered on Chictr.org.cn(ChiCTR2000031680,https://www.chictr.org.cn/showproj.html?proj=49316).展开更多
BACKGROUND Bronchopleural fistula(BPF)is a relatively rare,but severe complication of pulmonary tuberculosis.It is associated with significant mortality;however,its management remains a major therapeutic challenge.CAS...BACKGROUND Bronchopleural fistula(BPF)is a relatively rare,but severe complication of pulmonary tuberculosis.It is associated with significant mortality;however,its management remains a major therapeutic challenge.CASE SUMMARY We present a 24-year-old man with BPF resulting from severe pulmonary tuberculosis combined with mixed infections.The damaged right upper lobe and concomitant empyema were demonstrated via computed tomography.After undergoing open-window thoracostomy and tuberculosis treatment for 4 mo,decortication and right upper lobectomy were subsequently performed,leading to the resolution of tuberculosis and other concurrent pulmonary infections.Followup,6 mo after surgery,failed to reveal any evidence of infection recurrence resulting in a good prognosis.CONCLUSION The disease course of tuberculous BPF is particularly challenging.Surgical intervention serves as an effective and safe therapeutic strategy for BPF.展开更多
Introduction: Pleural effusion (PF) is a common clinical presentation in several diseases. Tuberculosis is one of the most frequent causes of exudative pleural effusions in immunocompetent patients. Tuberculosis is th...Introduction: Pleural effusion (PF) is a common clinical presentation in several diseases. Tuberculosis is one of the most frequent causes of exudative pleural effusions in immunocompetent patients. Tuberculosis is the leading cause of morbidity and mortality from an infectious disease in developing countries. Pakistan is ranked fifth in the world in terms of tuberculosis high-burden countries. Various pleural fluid parameters have been used to identify the cause of pleural effusion. It has been discovered that tuberculous pleural effusions had a greater alkaline phosphatase (ALP) concentration than transudative effusions. This study used pleural fluid alkaline phosphatase levels to distinguish between tuberculous pleural effusion and malignant pleural effusion because there is little information from tuberculosis-high burden nations like Pakistan. Study Design: A descriptive cross-sectional study conducted at the Jinnah Postgraduate Medical Center in Karachi between October 2016 and October 2017. Material and Methods: The study comprised all patients who were admitted to the department of chest medicine at Jinnah post graduate medical centre (JPMC) of either gender between the ages of 18 and 70 who had exudative lymphocytic pleural effusions lasting two weeks or more included in the study. Non probability consecutive sampling was used to collect data. Patients who have tonsillitis, pharyngitis, pneumonia, asthma, Chronic obstructive pulmonary disease (COPD), or a history of hemoptysis, Bleeding disorders like, platelet function disorder, thrombocytopenia, Liver cirrhosis and Pregnant women were excluded. Parents’ informed consent was obtained after being informed of the study’s protocol, hazards, and advantages. Each patient had their level of pleural fluid alkaline phosphate (PALP) assessed. In order to evaluate the patient’s pleural effusion, a pre-made questionnaire was used. All the collected data were entered into the SPSS 20. An independent sample t-test was used to recognize alkaline phosphate levels association with pleural fluid secondary to tuberculosis or malignancy. Results: In this Descriptive Cross-Sectional Study, the total of 156 patients with age Mean ± SD of was 41.96 ± 17.05 years. The majority of patients 110 (70.5%) were male and 46 (29.5%) were female. Advanced age was associated with raised pleural fluid alkaline phosphatase. The difference of pleural fluid alkaline phosphate level between tuberculous v/s malignant group was found to be (38.03 ± 45.97) v/s (82.77 ± 61.80) respectively with P-value (P = 0.0001). Conclusion: Malignant pleural effusions had elevated PALP when compared to tuberculous pleural effusions in exudative lymphocytic pleural effusions;better differences are seen in older ages and shorter disease durations.展开更多
Introduction: The objective of this study was the comparison of the results of T-SPOT.TB using pleural effusion (PE) with those of IGRAs using peripheral blood (PB) or other diagnostic methods for the diagnosis of tub...Introduction: The objective of this study was the comparison of the results of T-SPOT.TB using pleural effusion (PE) with those of IGRAs using peripheral blood (PB) or other diagnostic methods for the diagnosis of tuberculous (TB) pleurisy. Methods: We measured adenosine deaminase (ADA) in PE, QuantiFERON TB-Gold In-Tube (QFT), and T-SPOT.TB using PB, and T-SPOT.TB using PE. The definite group of TB pleurisy included 12 patients and other disease group 33 patients. Main find-ings: Sensitivity for QFT using PB was 83% and specificity was 85%, sensitivity for T-SPOT.TB using PB was 92% and specificity was 82%, while sensitivity for ADA in PE was 83% and specificity was 76%. When we adopted the same cut-off level of a positive response for T-SPOT.TB as PB using PE, sensitivity for T-SPOT.TB using PE was 100% and specificity was 82%, respectively. Although there were no significant differences among the four diagnostic methods, sensitivity for T-SPOT.TB using PE gave the most accurate diagnosis of TB-definite patients compared to ADA in PE or QFT using PB. Conclusions: If we performed T-SPOT.TB using a local specimen from the infection site, we could obtain a higher sensitivity than IGRAs using PB or ADA in PE and the numbers of ESAT-6 and CFP-10-positive SFCs were 3 to 5 fold higher in PEMCs than in PBMCs. T-SPOT.TB using PE may become a useful diagnostic method for TB pleurisy.展开更多
Objective: To report a case of Endometriosis associated with Pleural effusion. Design: Case report. Setting: Tertiary care center. Patient(s): A 30-year old woman presented with a right pleural effusion complicated wi...Objective: To report a case of Endometriosis associated with Pleural effusion. Design: Case report. Setting: Tertiary care center. Patient(s): A 30-year old woman presented with a right pleural effusion complicated with pneumothorax-mimicking TB. Intervention(s): Thoracentesis, pleural biopsy by a video-assisted thoracic surgery, pleurodesis, thoracic wedge resection, CT chest, CT Abdomen, and diagnostic Laparoscopy. Main Outcome Measure(s): After taking a GnRH analog, there was no recurrence of pleural effusion nor ascites. Result(s): Thoracentesis and wedge resection of lung ruled out malignancy. An omental mass biopsy obtained from diagnostic laparoscopy after the patient returned with drug-induced hepatitis, and ascites revealed endometriosis. Conclusion(s): Thoracic endometriosis is rare;however, it should be considered in the differential diagnosis by unknown causes of pleural effusion in reproductive age timeframe in women.展开更多
Database-assisted global metabolomics has received growing attention due to its capability for unbiased identification of metabolites in various biological samples.Herein,we established a mass spectrometry(MS)-based d...Database-assisted global metabolomics has received growing attention due to its capability for unbiased identification of metabolites in various biological samples.Herein,we established a mass spectrometry(MS)-based database-assisted global metabolomics method and investigated metabolic distance between pleural effusion induced by tuberculosis and malignancy,which are difficult to be distinguished due to their similar clinical symptoms.The present method utilized a liquid chromatography(LC) system coupled with high resolution mass spectrometry(MS) working on full scan and data dependent mode for data acquisition.Unbiased identification of metabolites was performed through mass spectral searching and then confirmed by using authentic standards.As a result,a total of 194 endogenous metabolites were identified and 33 metabolites were found to be differentiated between tuberculous and malignant pleural effusions.These metabolites involved in tryptophan catabolism,bile acid biosynthesis,and β-oxidation of fatty acids,provided non-invasive biomarkers for differentiation of the pleural effusion samples with high sensitivity and specificity.展开更多
Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level b...Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.展开更多
BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and...Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.展开更多
Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinic...Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.展开更多
Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients...Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.展开更多
Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This...Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.展开更多
Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have bee...Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.展开更多
Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.展开更多
Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the...Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.展开更多
This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishi...This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.展开更多
Pleural effusion,characterized by the accumulation of fluid in the pleural space,poses significant challenges in clinical practice,especially in determining whether it belongs to the inflammatory exudates or non-infla...Pleural effusion,characterized by the accumulation of fluid in the pleural space,poses significant challenges in clinical practice,especially in determining whether it belongs to the inflammatory exudates or non-inflammatory transudates.Adenosine deaminase(ADA),an enzyme primarily produced by immune cells,particularly lymphocytes,increase in response to inflammatory conditions,including tuberculosis and malignancies.Elevated ADA levels in pleural have been shown to correlate with inflammatory exudates,making it a valuable biomarker for dif-ferentiating between inflammatory and non-inflammatory effusions.Moreover,numerous studies have demonstrated the treatment function of ADA in inflammation-related pleural effusion syndrome.Recently,research has established the values for the implication of ADA in diagnosing and managing pleural disease.Based on these findings,ADA becomes a reliable,non-invasive marker for early diagnosis and the appropriate treatment for pleural inflammation,ultimately improving patient outcomes.展开更多
Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively aff...Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively affect prognosis.COPD and tuberculosis share a number of common risk factors and pathogenetic mechanisms involving various immune and non-immune cells.Inflammation,hypoxia,oxidative stress,and lung tissue remodeling play an important role in the comorbid course of COPD and respiratory tuberculosis.These mechanisms are of diagnostic interest and are promising therapeutic targets.Thus,the aim of the current review is to discuss the mechanisms of the comorbid course of chronic obstructive pulmonary disease and respiratory tuberculosis.展开更多
基金supported by the Beijing Municipal Science and Technology Project(Z191100006619079)the General Program of the National Natural Science Foundation of China(82072381).
文摘Background:The diagnosis of tuberculous pleurisy(TP)presents a significant challenge due to the low bacterial load in pleural effusion(PE)samples.Cell-free Mycobacterium tuberculosis DNA(cf-TB)in PE samples is considered an optimal biomarker for diagnosing TP.This study aimed to evaluate the applicability of cf-TB testing across diverse research sites with a relatively large sample size.Methods:Patients suspected of TP and presenting with clinical symptoms and radiological evidence of PE were consecutively enrolled by treating physicians from 11 research sites across 6 provinces in China between April 2020 and August 2022.Following centrifugation,sediments obtained from PE were used for Xpert MTB/RIF(Xpert)and mycobacterial culture,while the supernatants were subjected to cf-TB testing.This study employed a composite reference standard to definite TP,which was characterized by any positive result for Mycobacterium tuberculosis(MTB)through either PE culture,PE Xpert,or pleural biopsy.Results:A total of 1412 participants underwent screening,and 1344(95.2%)were subsequently enrolled in this study.Data from 1241(92.3%)participants were included,comprising 284 with definite TP,677 with clinically diagnosed TP,and 280 without TP.The sensitivity of cf-TB testing in definite TP was 73.6%(95%CI 68.2%-78.4%),significantly higher than both Xpert(40.8%,95%CI 35.3%-46.7%,P<0.001)and mycobacterial culture(54.2%,95%CI 48.4%-59.9%,P<0.001).When clinically diagnosed TP was incorporated into the composite reference standard for sensitivity analysis,cf-TB testing showed a sensitivity of 46.8%(450/961,95%CI 43.7%-50.0%),significantly higher than both Xpert(12.1%,116/961,95%CI 10.2%-14.3%,P<0.001)and mycobacterial culture(16.0%,154/961,95%CI 13.8%-18.5%,P<0.001).The specificities of cf-TB testing,Xpert,and mycobacterial culture were all 100.0%.Conclusions:The performance of cf-TB testing is significantly superior to that of Xpert and mycobacterial culture methods,indicating that it can be considered as the primary diagnostic approach for improving TP detection.Trial registration:The trial was registered on Chictr.org.cn(ChiCTR2000031680,https://www.chictr.org.cn/showproj.html?proj=49316).
基金Supported by grants of Wuhan Municipal Health Commission,No.WX20Z30.
文摘BACKGROUND Bronchopleural fistula(BPF)is a relatively rare,but severe complication of pulmonary tuberculosis.It is associated with significant mortality;however,its management remains a major therapeutic challenge.CASE SUMMARY We present a 24-year-old man with BPF resulting from severe pulmonary tuberculosis combined with mixed infections.The damaged right upper lobe and concomitant empyema were demonstrated via computed tomography.After undergoing open-window thoracostomy and tuberculosis treatment for 4 mo,decortication and right upper lobectomy were subsequently performed,leading to the resolution of tuberculosis and other concurrent pulmonary infections.Followup,6 mo after surgery,failed to reveal any evidence of infection recurrence resulting in a good prognosis.CONCLUSION The disease course of tuberculous BPF is particularly challenging.Surgical intervention serves as an effective and safe therapeutic strategy for BPF.
文摘Introduction: Pleural effusion (PF) is a common clinical presentation in several diseases. Tuberculosis is one of the most frequent causes of exudative pleural effusions in immunocompetent patients. Tuberculosis is the leading cause of morbidity and mortality from an infectious disease in developing countries. Pakistan is ranked fifth in the world in terms of tuberculosis high-burden countries. Various pleural fluid parameters have been used to identify the cause of pleural effusion. It has been discovered that tuberculous pleural effusions had a greater alkaline phosphatase (ALP) concentration than transudative effusions. This study used pleural fluid alkaline phosphatase levels to distinguish between tuberculous pleural effusion and malignant pleural effusion because there is little information from tuberculosis-high burden nations like Pakistan. Study Design: A descriptive cross-sectional study conducted at the Jinnah Postgraduate Medical Center in Karachi between October 2016 and October 2017. Material and Methods: The study comprised all patients who were admitted to the department of chest medicine at Jinnah post graduate medical centre (JPMC) of either gender between the ages of 18 and 70 who had exudative lymphocytic pleural effusions lasting two weeks or more included in the study. Non probability consecutive sampling was used to collect data. Patients who have tonsillitis, pharyngitis, pneumonia, asthma, Chronic obstructive pulmonary disease (COPD), or a history of hemoptysis, Bleeding disorders like, platelet function disorder, thrombocytopenia, Liver cirrhosis and Pregnant women were excluded. Parents’ informed consent was obtained after being informed of the study’s protocol, hazards, and advantages. Each patient had their level of pleural fluid alkaline phosphate (PALP) assessed. In order to evaluate the patient’s pleural effusion, a pre-made questionnaire was used. All the collected data were entered into the SPSS 20. An independent sample t-test was used to recognize alkaline phosphate levels association with pleural fluid secondary to tuberculosis or malignancy. Results: In this Descriptive Cross-Sectional Study, the total of 156 patients with age Mean ± SD of was 41.96 ± 17.05 years. The majority of patients 110 (70.5%) were male and 46 (29.5%) were female. Advanced age was associated with raised pleural fluid alkaline phosphatase. The difference of pleural fluid alkaline phosphate level between tuberculous v/s malignant group was found to be (38.03 ± 45.97) v/s (82.77 ± 61.80) respectively with P-value (P = 0.0001). Conclusion: Malignant pleural effusions had elevated PALP when compared to tuberculous pleural effusions in exudative lymphocytic pleural effusions;better differences are seen in older ages and shorter disease durations.
文摘Introduction: The objective of this study was the comparison of the results of T-SPOT.TB using pleural effusion (PE) with those of IGRAs using peripheral blood (PB) or other diagnostic methods for the diagnosis of tuberculous (TB) pleurisy. Methods: We measured adenosine deaminase (ADA) in PE, QuantiFERON TB-Gold In-Tube (QFT), and T-SPOT.TB using PB, and T-SPOT.TB using PE. The definite group of TB pleurisy included 12 patients and other disease group 33 patients. Main find-ings: Sensitivity for QFT using PB was 83% and specificity was 85%, sensitivity for T-SPOT.TB using PB was 92% and specificity was 82%, while sensitivity for ADA in PE was 83% and specificity was 76%. When we adopted the same cut-off level of a positive response for T-SPOT.TB as PB using PE, sensitivity for T-SPOT.TB using PE was 100% and specificity was 82%, respectively. Although there were no significant differences among the four diagnostic methods, sensitivity for T-SPOT.TB using PE gave the most accurate diagnosis of TB-definite patients compared to ADA in PE or QFT using PB. Conclusions: If we performed T-SPOT.TB using a local specimen from the infection site, we could obtain a higher sensitivity than IGRAs using PB or ADA in PE and the numbers of ESAT-6 and CFP-10-positive SFCs were 3 to 5 fold higher in PEMCs than in PBMCs. T-SPOT.TB using PE may become a useful diagnostic method for TB pleurisy.
文摘Objective: To report a case of Endometriosis associated with Pleural effusion. Design: Case report. Setting: Tertiary care center. Patient(s): A 30-year old woman presented with a right pleural effusion complicated with pneumothorax-mimicking TB. Intervention(s): Thoracentesis, pleural biopsy by a video-assisted thoracic surgery, pleurodesis, thoracic wedge resection, CT chest, CT Abdomen, and diagnostic Laparoscopy. Main Outcome Measure(s): After taking a GnRH analog, there was no recurrence of pleural effusion nor ascites. Result(s): Thoracentesis and wedge resection of lung ruled out malignancy. An omental mass biopsy obtained from diagnostic laparoscopy after the patient returned with drug-induced hepatitis, and ascites revealed endometriosis. Conclusion(s): Thoracic endometriosis is rare;however, it should be considered in the differential diagnosis by unknown causes of pleural effusion in reproductive age timeframe in women.
基金supported by grants from National Key Research and Development Program of China (No.2017YFC1600500)National Nature Science Foundation of China (Nos.21575120and 21707112)Hong Kong General Research Fund (No.12302317)。
文摘Database-assisted global metabolomics has received growing attention due to its capability for unbiased identification of metabolites in various biological samples.Herein,we established a mass spectrometry(MS)-based database-assisted global metabolomics method and investigated metabolic distance between pleural effusion induced by tuberculosis and malignancy,which are difficult to be distinguished due to their similar clinical symptoms.The present method utilized a liquid chromatography(LC) system coupled with high resolution mass spectrometry(MS) working on full scan and data dependent mode for data acquisition.Unbiased identification of metabolites was performed through mass spectral searching and then confirmed by using authentic standards.As a result,a total of 194 endogenous metabolites were identified and 33 metabolites were found to be differentiated between tuberculous and malignant pleural effusions.These metabolites involved in tryptophan catabolism,bile acid biosynthesis,and β-oxidation of fatty acids,provided non-invasive biomarkers for differentiation of the pleural effusion samples with high sensitivity and specificity.
基金Southwest Hospital Boqing Innovation Fund,Grant/Award Number:2024BQCXJJ-9Fundings for Young Investigators of PLA,Grant/Award Number:2022-JCJQ-QT-004+3 种基金NSFC Key Projects of the Regional Innovation and Development Joint Fund,Grant/Award Number:U23A20413China Postdoctoral Science Foundation,Grant/Award Number:2023M744280National Natural Science Foundation of China,Grant/Award Number:82103778,82172449 and 82172489Southwest Hospital Postdoctoral Starting Fund,Grant/Award Number:5175ZA36BP。
文摘Background:Skeletal tuberculosis(TB)remains a persistent clinical and research chal-lenge due to its chronic course,osteolytic destruction,and the limitations of existing animal models,which often require high-level biosafety containment or fail to repli-cate human skeletal pathology.Methods:This study developed a biosafe,accessible,and versatile murine model of skeletal TB using Mycobacterium smegmatis,a fast-growing,nonpathogenic myco-bacterial species with high genomic homology to Mycobacterium tuberculosis.Three infection routes-subperiosteal calvarial injection,intratibial injection,and intra-cardiac inoculation-were systematically evaluated for their ability to induce lo-calized versus disseminated bone infection under standard biosafety level(BSL)-1 conditions.Results:Subperiosteal calvarial and intratibial injection of M.smegmatis induced local-ized bone lesions characterized by osteolysis,sequestrum formation,granulomatous inflammation,and increased osteoclast activity.Intratibial infection additionally trig-gered compartment-specific immune responses,including neutrophil and macrophage expansion,transient B-cell depletion,and activation of interferon-γ^(+)(IFN-γ^(+))T cells,reflecting active immune remodeling at the infection site.Systemic dissemination via intracardiac injection reproducibly generated progressive vertebral and tibial bone destruction with organized granuloma formation and immune cell infiltration but without prominent sequestrum formation.Compared to intratibial infection,intracar-diac delivery exhibited lower intragroup variability and more closely recapitulated the diffuse progression of extrapulmonary skeletal tuberculosis.Conclusions:This M.smegmatis-based murine model provides a straightforward,reliable,and immunopathologically relevant platform for exploring host-pathogen dynamics,immune-driven bone destruction,and early-stage therapeutic testing in skeletal TB,all within standard BSL-1 laboratories.This model fills a critical gap by enabling BSL-1 research into skeletal TB mechanisms and drug development.
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金supported by the National Natural Science Foundation of China(82574173,82003516)Jiangsu Provincial Natural Science Foundation(BK20251958)+2 种基金Jiangsu Provincial Medical Key Discipline(ZDXK202250)Top Talent Awards Project Fund(RDF-TP-0023,RDF-TP-0030)Postgraduate Research Fund(PGRS2112022)at Xi'an Jiaotong-Liverpool University.
文摘Tuberculosis(TB),one of the oldest infectious diseases caused by Mycobacterium tuberculosis,poses a considerable challenge to global public health.There are approximately 10 million new TB cases worldwide annually,and TB claims the lives of nearly 3 million people each year,making it one of the leading causes of death from a single infectious disease[1].China ranks third globally in terms of TB burden,with approximately 733,000 TB cases reported in 2023[2].Based on the ecological model of health determinants developed by Whitehead and Dahlgren,health determinants can be classified into direct causes.
基金financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-I2M-1-038 and 2023-I2M-2-001)the Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310029 and 2023-PT310-04).
文摘Tuberculosis(TB)continues to pose a significant threat to global public health,necessitating rapid and precise diagnostic methods and comprehensive detection of antimicrobial resistance(AMR)to facilitate timely clinical management.Traditional diagnostic techniques suffer from extended turnaround times and limited ability to comprehensively profile AMR,often resulting in delayed therapeutic interventions.Highthroughput sequencing(HTS)technologies have revolutionized pathogen research by significantly improving diagnostic speed and accuracy.In the context of TB,diverse sequencing strategies and platforms are being employed to fulfill specific research goals,ranging from elucidating the molecular mechanisms underlying AMR to characterizing the genomic diversity among clinical isolates.This review systematically examines current progress in the application of HTS for rapid pathogen identification,comprehensive AMR profiling,epidemiological studies,advances in novel drugs,and vaccine development.Furthermore,we address existing technological limitations and bioinformatics challenges and explore the future directions necessary for effectively integrating HTS-based methodologies into global TB control efforts.
基金funded by the National Key Research and Development Program of China(grant number 2022YFC2305204).
文摘Objective To determine the proportions of drug-resistant tuberculosis(TB),its trends,and the drug resistance-conferring mutations among patients with pulmonary TB aged 10-24 years in China.Methods The data of patients with pulmonary TB were retrieved from a national drug-resistant TB survey for analysis.Joinpoint regression software was used to analyze time trends.We also used whole genome sequencing to analyze the lineages and drug resistance-conferring mutations of 621 isolates.Results Among 4,235 patients with pulmonary TB,the proportion of new cases of multidrug-resistant tuberculosis(MDR-TB)was 3.18%(95%confidence interval[CI]:2.37-4.15)for adolescents and 3.76%(95%CI:3.03-4.60)for young adults;for previously treated patients,MDR-TB accounted for 11.25%(95%CI:5.28-20.28)of adolescents and 11.05%(95%CI:6.88-16.55)of young adults.The proportion of patients with MDR-TB remained stable among both new and previously treated patients aged 10-24 years during the study period.Through whole genome sequencing,we found that the most common mutations in the MDR-TB strains were Ser315Thr in the katG gene(71.74%)and Ser450Leu in the rpoB gene(50.00%).Conclusion This study revealed a high proportion of MDR-TB among adolescents and young adults,indicating that urgent and comprehensive measures are needed to reduce the emergence and transmission of drug-resistant TB among this population in China.
基金supported by the National Science and Technology Major Project for the Prevention and Control of Emerging and Major Infectious Diseases[2025ZD01908702]Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological innovation[BMU2024YFJHP014]supported by Fundamental Research Funds for the Central Universities+1 种基金Key Clinical Projects of Peking University Third Hospital[BYSYZD2022014]Peking University Third Hospital[2025024].
文摘Objective Post tuberculosis lung disease(PTLD)manifests in various forms,including tuberculosisassociated chronic obstructive pulmonary disease(TB-COPD),yet the clinical features of PTLD remain undercharacterized.This study aimed to assess longitudinal changes in lung function over a 5-year period and to identify predictors of airflow obstruction in a cohort of patients treated for active pulmonary TB.Methods Patients with active pulmonary TB were enrolled in this study and were followed during treatment,at treatment completion and five years post-treatment.Assessments included lung function and chest CT,analyzing longitudinal trends and airflow obstruction risk factors.Results Among 53 patients(mean age 36.9±13.9 years;64.2%male),7 patients(13.2%)exhibited airflow obstruction.At the 5-year follow-up,the mean FEV_(1)/FVC declined significantly(76.27%±12.04%vs.80.23%±11.02%,P<0.001)and 9 patients(17.0%)exhibited airflow obstruction.Seven of these patients predominantly showed air trapping consistent with small airway disease on chest CT,aligning with TB-COPD phenotype.Notably,four young-to-middle-aged patients(<60 years old)had persistent obstruction over the five years.Conclusion The initial test revealed that 13.2%of patients presented with airflow obstruction.By the 5-year follow-up,this proportion had increased to 17.0%,with most cases demonstrating imaging findings aligning with TB-COPD,even among younger,non-smoking individuals.These findings emphasize the importance of long-term follow-up and routine lung function assessments in TB survivors.
文摘Detection and treatment of drug resistance in extrapulmonary tuberculosis(EPTB)is a major challenge worldwide.Drug resistance in EPTB has not been studied extensively.However,patients with drug-resistant EPTB have been reported to have poor outcomes[1].Rifampicin and isoniazid are the cornerstone drugs in the management of EPTB.Resistance in Mycobacterium(M.)tuberculosis to these drugs commonly arises due to mutations in the‘rpoB’gene and‘katG&inhA’genes,which confer resistance to rifampicin and isoniazid,respectively.Treatment outcomes are affected by the presence of these mutations.In addition,anatomical and physiological barriers impede the effective delivery of drugs to the affected extrapulmonary site[1].An analysis of the frequency of mutations in drug resistant M.tuberculosis strains causing EPTB in our region can help identify patterns of drug resistance.This,in turn,can provide inputs that may be used for modifying standard treatment regimens to make them more effective.The present study aims to identify the frequency and pattern of mutations in the‘rpoB’gene and‘katG&inhA’genes in M.tuberculosis strains isolated from EPTB samples.
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
基金Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
文摘Among critically ill patients,severe pulmonary and extrapulmonary tuberculosis has high morbidity and mortality.Yet,it is a diagnostic challenge given its nonspecific clinical symptoms and signs in early stages of the disease.In addition,management of severe pulmonary and extrapulmonary tuberculosis is complicated given the high risk of drug-drug interactions,drug-disease interactions,and adverse drug reactions.To help clinicians acquire an up-to-date approach to severe tuberculosis,this paper will provide a narrative review of contemporary diagnosis and management of severe pulmonary and extrapulmonary tuberculosis in critically ill patients.
文摘This editorial underscores the importance of Maranhão et al’s study,which investigates pleural adenosine deaminase(P-ADA)as a biomarker for inflammatory pleural effusions.Despite advances in imaging,distinguishing between inflammatory and non-inflammatory causes of pleural effusion remains a diagnostic challenge.The authors conducted a rigorous retrospective cohort analysis of 157 patients(124 with inflammatory exudates and 33 with non-inflammatory transudates),establishing a robust cutoff value of P-ADA≥9.00 U/L for diagnosing inflammatory diseases using receiver operating characteristic curve analysis and internal statistical calibration.This is the first study to define a standardized PADA threshold in a Brazilian cohort,addressing previous inconsistencies in cutoff values.Furthermore,the authors delved into the pathophysiological mechanisms underlying elevated P-ADA,linking it to purinergic signaling pathways and immune cell activation,particularly emphasizing the role of ADA2 isoforms in macrophages and lymphocytes.Their findings support P-ADA as a non-invasive,cost-effective biomarker for early diagnosis,treatment stratification,and minimizing the need for invasive procedures such as thoracentesis.This has particular relevance in resource-limited settings,where streamlined diagnostics can reduce healthcare costs and improve patient outcomes.Future studies must prioritize global validation,explore the integration of adenosine deaminase with additional biomarkers(e.g.,interleukin 6,C-reactive protein),and support the development of point-of-care technologies.
文摘Pleural effusion,characterized by the accumulation of fluid in the pleural space,poses significant challenges in clinical practice,especially in determining whether it belongs to the inflammatory exudates or non-inflammatory transudates.Adenosine deaminase(ADA),an enzyme primarily produced by immune cells,particularly lymphocytes,increase in response to inflammatory conditions,including tuberculosis and malignancies.Elevated ADA levels in pleural have been shown to correlate with inflammatory exudates,making it a valuable biomarker for dif-ferentiating between inflammatory and non-inflammatory effusions.Moreover,numerous studies have demonstrated the treatment function of ADA in inflammation-related pleural effusion syndrome.Recently,research has established the values for the implication of ADA in diagnosing and managing pleural disease.Based on these findings,ADA becomes a reliable,non-invasive marker for early diagnosis and the appropriate treatment for pleural inflammation,ultimately improving patient outcomes.
文摘Chronic obstructive pulmonary disease(COPD)and respiratory tuberculosis are important respiratory problems.Meeting together,these diseases can mutually worsen the severity of clinical manifestations and negatively affect prognosis.COPD and tuberculosis share a number of common risk factors and pathogenetic mechanisms involving various immune and non-immune cells.Inflammation,hypoxia,oxidative stress,and lung tissue remodeling play an important role in the comorbid course of COPD and respiratory tuberculosis.These mechanisms are of diagnostic interest and are promising therapeutic targets.Thus,the aim of the current review is to discuss the mechanisms of the comorbid course of chronic obstructive pulmonary disease and respiratory tuberculosis.
