Efficacy and safety of video-assisted thoracoscopic surgery for pulmonary TB.

OBJECTIVE: Compared with thoracotomy, video-assisted thoracoscopic surgery (VATS) has the advantage of post-operative recovery for patients undergoing surgery. However, studies comparing the efficacy of VATS with conventional traditional thoracotomy for treating patients with pulmonary TB (PTB) are inconsistent.METHODS: Five electronic databases were used to search studies on VATS and conventional thoracotomy for PTB up to 15 March 2022. Standardised mean differences (SMDs) and odds ratios (ORs) were calculated for comparison.RESULTS: A total of 14 were included. Compared with traditional thoracotomy, patients with drug-resistant TB treated using VATS had shorter operative time, less intra-operative bleeding, faster post-operative recovery and fewer post-operative complications (operation time: SMD -0.87, 95% CI -1.29 to -0.45; blood loss: SMD -1.31, 95% CI -1.71 to -0.92; duration of hospital stay: SMD -1.68, 95% CI -2.46 to -0.90; catheterisation time: SMD -1.56, 95% CI -2.39 to -0.73; post-operative complication: OR 0.40, 95% CI 0.27 to 0.60).CONCLUSION: Compared with conventional thoracotomy, VATS for patients with multidrug-resistant PTB undergoing lobectomy and wedge resection has the advantages of minor bleeding, shorter operative time, shorter hospital stay and post-operative pleural cavity drainage duration, and fewer post-operative complications, which can accelerate the post-operative recovery of patients.

Pulmonary tuberculosis associated with immune checkpoint inhibitors: a pharmacovigilance study.

We examined case reports of immune checkpoint inhibitors (ICIs) associated pulmonary tuberculosis (PT) using data from the Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis was performed by using the reporting OR (ROR) with relevant 95% CI. A total of 74 cases of PT related to ICIs therapy were identified. ICIs were significantly associated with over-reporting frequencies of PT (ROR=3.16, 95% CI: 2.51 to 3.98), while the signal was differed between anti-programmed death-1/ligand-1 and anti-cytotoxic T lymphocyte antigen-4 agents. Most indications were lung cancer (64.9%), the median onset age was 70 years, the median time to onset of PT was 70 days, ICIs were discontinued in most cases (85.2%).

Combination of Xpert® MTB/RIF and DetermineTM TB-LAM Ag improves the diagnosis of extrapulmonary tuberculosis at Jimma University Medical Center, Oromia, Ethiopia.

BACKGROUND: Ethiopia is one of the high burden countries for extrapulmonary tuberculosis (EPTB); however, the prompt diagnosis of EPTB remains challenging. This study is aimed to evaluate the diagnostic performance of Xpert MTB/RIF and DetermineTM TB-LAM Ag (TB-LAM) for the prompt diagnosis of EPTB in Ethiopia. METHODS: A total of 147 presumptive EPTB patients, including 23 HIV- positive participants were enrolled. Extra-pulmonary samples were collected from all presumptive EPTB cases and tested for Mycobacterium tuberculosis complex (MTBC) using fluorescent microscopy, Xpert MTB/RIF, and culture. Additionally, urine samples were also collected from 126 participants and were tested by DetermineTM TB-LAM Ag (Alere Inc, Waltham, USA). The Sensitivity and specificity of Xpert and TB- LAM tests were calculated by comparing with a composite reference standard (CRS), which comprises smear microscopy, culture and response to empirical anti-TB treatment. RESULTS: Of 147 patients, 23 (15.6%) were confirmed EPTB cases (culture-positive), 14 (9.5%) were probable EPTB (clinically, radiologically or cytologically positive and received anti-TB treatment with good response), and 110 (74.8%) were classified as "non- TB" cases. Compared to the composite reference standard (CRS), the overall sensitivity and specificity of Xpert MTB/RIF were 43.2% and 100%, respectively with the highest sensitivity for Lymph node aspirate (85.7%) and lower sensitivity for pleural fluid (14.3%) and 100% specificity for all specimen types. The sensitivity and specificity of TB-LAM were 33.3% and 94.4% respectively with the highest sensitivity for HIV co-infected participants (83.3%). The sensitivity of the combination of Xpert MTB/RIF and TB-LAM tests regardless of HIV status was 61.1% whereas the sensitivity was improved to 83.3% for HIV-positive cases. CONCLUSION: TB-LAM alone has low sensitivity for EPTB diagnosis; however, the combination of TB-LAM and Xpert MTB/RIF improves the diagnosis of EPTB particularly for countries with high EPTB and HIV cases.

The child ecosystem and childhood pulmonary tuberculosis: A South African perspective.

INTRODUCTION: This study investigates drivers of childhood pulmonary tuberculosis (PTB) using a childhood ecosystem approach in South Africa. An ecosystem approach toward identifying risk factors for PTB may identify targeted interventions. METHODS: Data were collected as part of a prospective cohort study of children presenting at a primary care facility or tertiary hospital with possible TB. Characterization of the childhood ecosystem included proximal, medial, and distal determinants. Proximal determinants included child characteristics that could impact PTB outcomes. Medial determinants included relational factors, such as caregiver health, which might impact interactions with the child. Distal determinants included macro-level determinants of disease, such as socioeconomic status and food insecurity. Children who started on TB treatment were followed for up to 6 months. Multivariate regression models tested independent associations between factors associated with PTB in children. RESULTS: Of 1202 children enrolled, 242 (20%) of children had confirmed PTB, 756 (63%) were started on TB treatment, and 444 (37%) had respiratory conditions other than TB. In univariate analyses, childhood malnutrition and caregiver smoking were associated with treated or confirmed PTB. In multivariate analyses, proximal factors, such as male gender and hospitalization, as well as low socioeconomic status as a distal factor, were associated with PTB. CONCLUSIONS: Interventions may need to target subgroups of children and families with elevated proximal, medial, and distal risk factors for PTB. Screening for risk factors, such as caregiver's health, may guide targeting. The provision of social protection programs to bolster economic security may be an important intervention for attenuating childhood exposure to risk factors.

Tuberculosis pulmonar asociada a Infliximab: a propósito del primer caso reportado en Cuba / Infliximab-associated pulmonary tuberculosis: regarding the first case reported in Cuba

La terapia con fármacos antagonistas del factor de necrosis tumoral alfa ha sido beneficiosa en el tratamiento de varias enfermedades como las del tejido conectivo e inflamatorias del intestino, pero no está exenta de riesgos. Las principales complicaciones de estas drogas inmunosupresoras son las infecciones, y la tuberculosis pulmonar es una de las principales afecciones, que se pueden observar en los pacientes con este tipo de tratamiento.Se presentó una mujer de 31 años, atendida en el Hospital Clínico Quirúrgico Hermanos Ameijeiras, La Habana, Cuba, con antecedentes de colitis ulcerativa, que hace 3 meses recibe terapia con Infliximab. Acude al hospital por referir 4 días previos al ingreso, fiebre de 390 C dos veces al día, acompañándose de cefalea, pérdida del apetito y dolor en la región perineal. Se le realizó radiografía de tórax, donde se describe radiopacidad heterogénea que va desde el cuerno superior del hilio derecho hasta planos axilares, en la tomografía axial de tórax reportan consolidación en segmento anterior del lóbulo superior derecho con presencia de broncograma aéreo y en el lavado bronquial microbiológico para bacilos ácido-alcohol resistentes se informó codificación 8, positivo a Mycobacterium tuberculosis. El diagnóstico preciso de tuberculosis relacionada con el uso de fármacos antagonistas del factor de necrosis tumoral alfa requiere un alto índice de sospecha y una investigación detallada. Existe un alto grado de complejidad diagnóstica, por la existencia de un amplio espectro clínico y la necesidad de excluir otras enfermedades.

Tumor necrosis factor alpha antagonist drug therapy has been beneficial in the treatment of several diseases such as connective tissue and inflammatory bowel diseases, but it is not without risks. The main complications of these immunosuppressive drugs are infections, and pulmonary tuberculosis is one of the main conditions, which can be observed in patients with this type of treatment. A 31-year-old woman, treated at the Hermanos Ameijeiras Clinical Surgical Hospital, Havana, Cuba, with a history of ulcerative colitis, who has been receiving Infliximab therapy for 3 months, presented. He went to the hospital for referring 4 days prior to admission, a fever of 390 C twice a day, accompanied by headache, loss of appetite and pain in the perineal region. A chest X-ray was performed, which described heterogeneous radiopacity that goes from the upper horn of the right hilum to axillary planes, in the chest axial tomography they report consolidation in the anterior segment of the right upper lobe with the presence of air bronchogram and in the bronchial lavage microbiological for acid-fast bacilli coding 8, positive for mycobacterium tuberculosis was reported. Accurate diagnosis of tuberculosis related to the use of tumor necrosis factor alpha antagonist drugs requires a high index of suspicion and detailed investigation. There is a high degree of diagnostic complexity, due to the existence of a wide clinical spectrum and the need to exclude other diseases.

Unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe endobronchial ultrasound.

BACKGROUND: Bronchoscopy using radial probe endobronchial ultrasound (EBUS) is performed when a peripheral lung lesion (PLL) is suspected to be malignant. However, pulmonary tuberculosis is diagnosed in some patients, and healthcare workers could therefore be exposed to tuberculosis if sufficient precautions are not taken. In this study, we examined the proportion of and factors associated with unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe EBUS. METHODS: This retrospective study included 970 patients who received bronchoscopy using radial probe EBUS between December 2015 and November 2018. Clinical, histological, radiological, and microbiological data were reviewed. RESULTS: Pulmonary tuberculosis was diagnosed in 31 patients (3.2%) during bronchoscopy using radial probe EBUS. Patients with a lower age were significantly more likely to be diagnosed with tuberculosis than elderly patients (odds ratio [OR], 0.951; 95% confidence interval [CI], 0.924-0.978; P = 0.001). Among the various CT findings, a low HUs difference between pre- and post-enhanced CT (OR, 0.976; 95% CI, 0.955-0.996; P = 0.022), the presence of concentric cavitation (OR, 5.211; 95% CI, 1.447-18.759; P = 0.012), and the presence of satellite centrilobular nodules (OR, 22.925; 95% CI, 10.556-49.785; P < 0.001) were independently associated with diagnosis of tuberculosis. CONCLUSIONS: The proportion of unexpected exposure to Mycobacterium tuberculosis during bronchoscopy using radial probe EBUS was 3.2%. A higher risk was independently associated with a younger age and CT findings of a small difference in HUs between pre- and post-enhancement images, concentric cavitation, and the presence of a satellite centrilobular nodule.

S100A2: A potential biomarker to differentiate malignant from tuberculous pleural effusion.

BACKGROUND: S100 calcium binding protein A2 (S100A2)-which has been testified to have an abnormal expression in non-small cell lung cancer (NSCLC)-is considered as an effective biomarker in the diagnosis and prognosis of this malignancy. In this study, we detected the S100A2 levels in pleural effusion, aiming to evaluate its potential value in differentiating malignant pleural effusion (MPE) from tuberculous pleural effusion (TPE). METHODS: We collected pleural effusion from 104 NSCLC patients with MPE and 96 tubercular pleurisy cases. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of S100A2 in these samples. Meanwhile, the serum S100A2 levels were also examined in same subjects. The data concerning the expression of those commonly-used markers, including CEA, CYFRA211 and NSE, were obtained from medical records. RESULTS: Like other classified biomarkers, S100A2 had an over-expression in both pleural effusion and sera of the NSCLC patients compared with controls (P = 0.000), though having a lower P value. Receiver operating characteristic (ROC) analysis showed that the levels of S100A2 in pleural effusion (PE) could distinguish MPE from tuberculous pleurisy (Area Under the Receiver Operating Characteristic Curve (AUC) = 0.887), and its diagnostic value in hydrothorax was obviously higher than in serum (AUC = 0.709). CONCLUSION: Our results indicate that levels of S100A2 are significantly elevated in MPE, and that S100A2 may serve as a diagnostic biomarker for NSCLC patients with MPE. In further studies, we will validate our findings with a larger sample population.

Logistic regression analysis of environmental and other variables and incidences of tuberculosis in respiratory patients.

The objective of this study was to examine the association of 14 variables with TB in respiratory patients. The variables included: urban/rural, persons in 1200 sqft area, TB in family, crowding, smoking (family member), gender, age, education, smoking, workplace, kitchen location, cooking fuel, ventilation, and kerosene uses. Eight hundred respiratory patients were tested for sputum positive pulmonary TB; 500 had TB and 300 did not. An analysis of the unadjusted odds ratio (UOR) and adjusted OR (AOR) was undertaken using logistic regression to link the probability of TB incidences with the variables. There was an inconsistency in the significance of variables using UOR and AOR. A subset model of 4 variables (kerosene uses, ventilation, workplace, and gender) based on significant AOR was adjudged acceptable for estimating the probability of TB incidences. Uses of kerosene (AOR 2.62 (1.95, 3.54)) consistently related to incidences of TB. It was estimated that 50% reduction in kerosene uses could reduce the probability of TB by 13.29% in respiratory patients. The major recommendation was to replace kerosene uses from households with a supply of clean fuel like liquid petroleum or natural gas and rural electrification.

Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.

Type 2 diabetes mellitus (T2DM) is a risk factor for pulmonary tuberculosis (PTB) and increased mortality. This work focused on the functions of phosphorylated STAT3 in lung injury in mouse with T2DM-associated PTB and the molecules involved. A mouse model with T2DM-PTB was induced by administrations of streptozotocin, nicotinamide and mycobacterium tuberculosis (Mtb). A pSTAT3-specific inhibitor AG-490 was given into mice and then the lung injury in mice was observed. The molecules involved in AG-490-mediated events were screened out. Altered expression of miR-19b, miR-1281 and NFAT5 was introduced to identify their involvements and roles in lung injury and PTB severity in the mouse model. Consequently, pSTAT3 expression in mice with T2DM-associated PTB was increased. Down-regulation of pSTAT3 by AG-490 prolonged the lifetime of mice and improved the histopathologic conditions, and inhibited the fibrosis, inflammation, Mtb content and number of apoptotic epithelial cells in mouse lung tissues. pSTAT3 transcriptionally suppressed miR-19b/1281 expression to up-regulate NFAT5. Inhibition of miR-19b/1281 or up-regulation of NFAT5 blocked the protective roles of AG-490 in mouse lung tissues. To conclude, this study evidenced that pSTAT3 promotes NFAT5 expression by suppressing miR-19b/1281 transcription, leading to lung injury aggravation and severity in mice with T2DM-associated PTB.

Use of steroids to treat anti-tumor necrosis factor α induced tuberculosis-associated immune reconstitution inflammatory syndrome: Case report and literature review.

INTRODUCTION: Individuals with tuberculosis (TB) who are being treated with anti-tumor necrosis factor α (anti-TNFα) for coexisting conditions may experience unexpected exacerbations of TB after the initiation of antituberculous therapy, so-called anti-TNFα-induced TB-immune reconstitution inflammatory syndrome (anti-TNFα-induced TB-IRIS). Anti-TNFα-induced TB-IRIS is often treated empirically with corticosteroids; however, the evidence of the effectiveness of corticosteroids is lacking and the management can be a challenge. PATIENT CONCERNS: A 32-year-old man on long-term infliximab therapy for Crohn disease visited a clinic complaining of persistent fever and cough that had started 1 week previously. His most recent infliximab injection had been administered 14 days before the visit. A chest X-ray revealed a left pleural effusion, and he was admitted to a local hospital. DIAGNOSIS: A chest computed tomography (CT) scan revealed miliary pulmonary nodules; acid-fast bacilli were found in a sputum smear and a urine sediment sample; and polymerase chain reaction confirmed the presence of Mycobacterium tuberculosis in both his sputum and the pleural effusion. He was diagnosed with miliary TB. INTERVENTIONS: Antituberculous therapy was started and he was transferred to our hospital for further management. His symptoms initially improved after the initiation of antituberculous therapy, but 2 weeks later, his symptoms recurred and shadows on chest X-ray worsened. A repeat chest CT scan revealed enlarged miliary pulmonary nodules, extensive ground-glass opacities, and an increased volume of his pleural effusion. This paradoxical exacerbation was diagnosed as TB-IRIS associated with infliximab. A moderate-dose of systemic corticosteroid was initiated [prednisolone 25 mg/day (0.5 mg/kg/day)]. OUTCOMES: After starting corticosteroid treatment, his radiological findings improved immediately, and his fever and cough disappeared within a few days. After discharge, prednisolone was tapered off over the course of 10 weeks, and he completed a 9-month course of antituberculous therapy uneventfully. He had not restarted infliximab at his most recent follow-up 14 months later. CONCLUSION: We successfully managed a patient with anti-TNFα-induced TB-IRIS using moderate-dose corticosteroids. Due to the limited evidence currently available, physicians should consider the necessity, dosage, and duration of corticosteroids for each case of anti-TNFα-induced TB-IRIS on an individual patient-by-patient basis.

A descriptive study of smear negative pulmonary tuberculosis in a high HIV burden patient's population in North Central Nigeria.

Tuberculosis (TB) is a serious disease of public health concern, mainly in low- and middle-income countries. Most of these countries have challenges in diagnosis and treatment of TB in people with smear-negative pulmonary tuberculosis (SNPTB), which remains a significant public health challenge because of the global burden of the disease. We evaluated the epidemiology and clinical presentation of SNPTB in a cohort of patients with high HIV burden. The study was a cross-sectional study among patients with SNPTB in four major hospitals that care for TB/HIV patients in north-central Nigeria. All patients 18 years and above who were newly diagnosed as SNPTB, or patients with SNPTB who had not taken TB drugs for up to 2 weeks irrespective of their HIV status were recruited. Demographic data (sex, age), smoking status, and medical history (clinical form of TB, symptoms at admission, diagnostic methods, presence of comorbidities, prior TB treatment) were obtained using a semi-structured questionnaire. Detailed clinical examination was also done on all the study subjects. Baseline results of packed cell volume, HIV test and sputum acid fast bacilli done during TB screening were retrieved from the patients' case notes and recorded. Also, the base line Chest X-ray films taken during TB screening were reviewed and reported by two radiologists blinded to each other's reports. The Xpert MTB/RIF tests and sputum culture (using LJ medium) were done in a TB reference laboratory. A total of 150 patients with SNPTB were studied. Majority of the patients were female 93 (62%). The median age of the patients was 36.5 years with greater percentage of the patients within the ages of 25-44 years 92 (61.3%). Twenty-two (14.7%) of the patients had previous TB treatment. History of cigarette smoking was obtained in only 7(4.7%) of the patients while 82 (64.1%) were HIV positive. All the patients had a history of cough for over a period of at least three weeks, while, 27 (18%) reported having hemoptysis. About 87 (58%) had fever and 110 (73.7%) had anemia, while weight loss and night sweat were reported in 98(65.3%) and 82 (54.7%) of the patients respectively. Chest x rays were reported as typical of TB in only 24 (16%) of the patients. Of the 150 sputa sample analyzed, 21/150 (14.0%) and 22/150 (14.7%) where Gene Xpert and sputum culture positive respectively. The sensitivity and specificity of Gene Xpert assay were 81.8% (18/22; 95% CI 61.5 to 92.7%) and 97.4% (112/115; 95% CI 92.6 to 99.1%), respectively. The study found cough, fever and anemia to be the commonest presentation in patient with SNPTB in a high HIV burden patient's population. There is also relatively high culture positivity among the patients. This underscores the need to expand the facilities for culture and confirmation in TB centers across the country.

Intra-Axial Metastatic Angiosarcoma of the Central Nervous System Associated with Anemia, Pulmonary Tuberculosis and Short Survival

Introduction Angiosarcoma (AG) is a malignant mesenchymal neoplasm that predominantly affects the soft tissues and, to variable degrees, expresses themorphological and functional characteristics of the endothelium. The incidence of sarcomas of the central nervous system(CNS) is low (0.5% to 2.7%), and AGs involving the brain are even rarer. Case Description A 45-year-old male patient presented with complaints of headache, nausea, and vomiting. An examination showed bilateral papilledema and a right lung pleurotomy. The patient's previous history included drug addiction, pulmonary tuberculosis, lung abscess, pleural empyema, and pulmonary artery embolization for severe hemoptysis. Computed tomography/magnetic resonance imaging scans revealed a large intra-axial lesion extending into the right parietal and temporal lobes, with hemorrhagic zones. The patient underwent surgical resection of the lesion. Microscopy showed a poorly-differentiated, high-grade malignant tumor composed of plump/epithelioid cells forming small vascular spaces and solid nests, compatible with AG.In the postoperative period, the patient developed recurrent hemoptysis. A biopsy of the tissues adjacent to the pleurotomy determined the diagnosis of pulmonary AG. At 30 days after the resection, the patient died from hemoptysis, hemothorax, lung atelectasis, and intracranial hypertension related to the recurrence of the brain tumor. Conclusion Angiosarcoma is a rare neoplasia related to short survival due to the high proliferative index, which must be considered in patients presenting hemorrhagic tumors. No specific genetic abnormalities have been described for this neoplasia.

Caracterización de la tuberculosis pulmonar en mayores de 15 años. Hospital de Día "Dr. Efrén Jurado López" / Characterization of pulmonary tuberculosis in over 15 years. "Dr. Efrén Jurado López Day Hospital"

La tuberculosis pulmonar constituye una enfermedad de salud pública en el territorio ecuatoriano en expansión que provoca muerte y sufrimiento para la población. El objetivo del estudio es caracterizar la tuberculosis pulmonar en individuos mayores de 15 años que asisten al Hospital de Día "Dr. Efrén Jurado López" de la ciudad de Guayaquil. Se realizó una investigación cuantitativa, descriptiva, retrospectiva. La muestra de estudio quedó conformada por 58 pacientes de ambos géneros mayores de 15 años, diagnosticados con tuberculosis en todas sus formas, atendidos en el contexto de estudio entre enero 2017 y enero de 2018. En la recolección de la información se aplicó una ficha de observación validada por expertos con previo consentimiento informado de los pacientes estudiados. Como resultados se obtuvo que el 72,4% eran del sexo masculino y el 27,6% femenino. El predominio de diagnóstico presentado fue sintomático TBP BK+ en un 100%. Por otra parte para el diagnóstico por TBP cultivo + fue 87,9% (51/58) y TBP cultivo- de 12,1% (7/58). Por otra parte la TB EP fue de 25,9% (15/58) con predominio en el sexo masculino 80%, las formas de tuberculosis y la comorbilidad asociada al al Virus de Inmunodeficiencia Humana (VIH), se observó una frecuencia de 6,9% (4/58) de personas con TB que tenían VIH, de las cuales el 5,2% correspondían a casos de VIH con tuberculosis extra pulmonar y 1,7% a casos de TBP BK+/VIH. Se debe continuar trabajando en la búsqueda de TB en pacientes sintomáticos respiratorios para un diagnóstico oportuno(AU)

Characterization of pulmonary tuberculosis in teenagers older than 15 years in thedr.Efrénjuradolópez day time hospital. Pulmonary tuberculosis is a public health disease in the expanding Ecuadorian territory that causes death and suffering for the population. The objective of the study is to characterize pulmonary tuberculosis in individuals over 15 years of age attending the "Dr. Efrén Jurado López" Day Hospital in the city of Guayaquil. A quantitative, descriptive, retrospective investigation was carried out. The study sample consisted of 58 patients of both genders over 15 years of age, diagnosed with tuberculosis in all its forms, treated in the context of the study between January 2017 and January 2018. A data sheet was applied in the collection of information observation validated by experts with prior informed consent of the patients studied. As a result, it was obtained that 72.4% were male and 27.6% female. The prevalence of diagnosis presented was symptomatic TBP BK + in 100%. On the other hand for the diagnosis by TBP culture + it was 87.9% (51/58) and TBP culture- of 12.1% (7/58). On the other hand, the TB TB was 25.9% (15/58) with a predominance in the male sex 80%, the forms of tuberculosis and the comorbidity associated with the Human Immunodeficiency Virus (HIV), a frequency of 6 was observed, 9% (4/58) of people with TB who had HIV, of which 5.2% corresponded to HIV cases with extra pulmonary tuberculosis and 1.7% to cases of BK + / HIV TBP. Work should continue in the search for TB in symptomatic respiratory patients for a timely diagnosis(AU)

Clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy for pulmonary tuberculosis with Yin-deficiency and Fire-hyperactivity syndrome.

OBJECTIVE: To evaluate the clinical efficacy of Baihe Gujin decoction combined with anti-tuberculosis therapy in mitigating the symptoms of pulmonary tuberculosis and to measure the effect on the CD4+ CD25+ regulatory T cell (Treg) ratio. METHODS: This randomized study enrolled patients with pulmonary tuberculosis and randomly assigned them to one of two treatment groups: an anti-tuberculosis treatment group and a combined treatment group. Bronchoalveolar lavage was performed before and 2 weeks after treatment. The ratio of CD4+ CD25+ Treg cells and the levels of tumour necrosis factor (TNF)-α, interleukin (IL)-4, IL-6 and IL-12 in peripheral blood and bronchoalveolar lavage fluid were measured. Symptoms were recorded before and after treatment. RESULTS: A total of 100 patients were enrolled and assigned to the anti-tuberculosis (n = 58) and combined treatment groups (n = 42). In the combined treatment group, Leicester Cough Questionnaire score, erythrocyte sedimentation rate, CD4+ CD25+ Treg cell ratio in bronchoalveolar lavage fluid, cytokine levels, chest pain score and sleep disorder score were significantly decreased compared with the anti-tuberculosis treatment group after treatment. The leukocyte count, haemoglobin level, platelet and alanine aminotransferase levels did not differ significantly between the two groups after treatment. The creatinine level in the combined treatment group was significantly lower than that in the anti-tuberculosis treatment group. CONCLUSION: Baihe Gujin decoction combined with anti-tuberculosis treatment can effectively alleviate the symptoms of pulmonary tuberculosis, enhance the host immune function and protect renal function.

A Unique Spectrum of Tuberculosis Flare Up Related to Cardiothoracic Surgery.

Three cases of tuberculosis (TB) related to or complicating cardiothoracic surgery are presented in this paper. The aim of this article is to alert cardiothoracic surgeons about the presence or rebound of TB, which can complicate cardiothoracic surgeries even in the immediate postoperative course.

Tuberculosis associated with Triplet therapy for lung cancer.

We report the first case of TB associated with triplet therapy (chemotherapy and immunotherapy concurrently) for lung cancer, developing just 44 days after treatment initiation. We feel that several important learning points arise from the discussion that are likely to be very relevant to the broad readership of Thorax, and have important clinical and scientific implications. In the three discussion paragraphs, we highlight that: 1) Triplet therapy is now standard first-line treatment for inoperable lung cancer. 2) TB reactivation is increasingly recognised as an adverse effect of immune checkpoint inhibition, but sending diagnostic samples is critical to avoid a missed diagnosis. 3) These insights from novel cancer immunotherapies are challenging the traditional views of the host-pathogen interaction in TB, with wide implications for future control strategies. We propose that the cases reported in the literature are likely to be the tip of the iceberg as most people with lung cancer managed with antiprogrammed death-1 agents who develop new lung lesions will be treated with standard antibiotics and then palliated when they do not respond.

Reactivation of TB during administration of durvalumab after chemoradiotherapy for non-small-cell lung cancer: a case report.

Background: Tuberculosis (TB) is considered to be an adverse effect of treatment with immune checkpoint inhibitors. Methodology & results: Our case was a 75-year-old woman diagnosed with unresectable stage III non-small-cell lung cancer. After radical chemoradiotherapy was completed, durvalumab was initiated as a consolidation therapy. However, since chest CT showed appearances of infiltration shadows scattered in the periphery of the lungs after five doses of immunotherapy, duruvalumab was discontinued. 6 weeks later, the patient was aware of intermittent fever. Chest CT scan showed the appearance of a tree-in-bud pattern in the right lung. Acid-fast bacilli stain of sputum was positive and the PCR test was positive for Mycobacterium tuberculosis. Conclusion: Duruvalumab as PD-L1 blockade may activate TB.

Silico-tuberculosis, silicosis and other respiratory morbidities among sandstone mine workers in Rajasthan- a cross-sectional study.

BACKGROUND: Exposures to respirable crystalline silica causes silicosis, pulmonary tuberculosis, chronic obstructive pulmonary disease, lung cancer, autoimmune disorders and chronic renal disease. The aim of this study was to find out the prevalence of silico-tuberculosis, silicosis and other respiratory morbidities in sandstone mine workers in Jodhpur district of Rajasthan. METHODS: It was a cross-sectional study done in sandstone mines in Jodhpur. A total of 15 mines were selected. The sample size was calculated and fixed to 174 mine workers. Chi-square and t-test were applied to draw inferences. RESULTS: The mean age of the mine workers was 39.13 ± 11.09 years. Three fourth (75.3%) of the workers were working for more than ten years in mines. Around 30.0% had a history of tuberculosis. Abnormal spirometry was found in 89.2% of workers. Around 42% of mine workers were found with abnormal chest x-rays. Prevalence of silicosis was 37.3%, silico-tuberculosis was 7.4%, tuberculosis was 10.0%, and other respiratory diseases like emphysema and pleural effusion were diagnosed among 4.3% workers. CONCLUSION: Prevalence of silico-tuberculosis, silicosis and other respiratory morbidities are high among sandstone mine workers.

Hydrogen sulfide dysregulates the immune response by suppressing central carbon metabolism to promote tuberculosis.

The ubiquitous gasotransmitter hydrogen sulfide (H2S) has been recognized to play a crucial role in human health. Using cystathionine γ-lyase (CSE)-deficient mice, we demonstrate an unexpected role of H2S in Mycobacterium tuberculosis (Mtb) pathogenesis. We showed that Mtb-infected CSE-/- mice survive longer than WT mice, and support reduced pathology and lower bacterial burdens in the lung, spleen, and liver. Similarly, in vitro Mtb infection of macrophages resulted in reduced colony forming units in CSE-/- cells. Chemical complementation of infected WT and CSE-/- macrophages using the slow H2S releaser GYY3147 and the CSE inhibitor DL-propargylglycine demonstrated that H2S is the effector molecule regulating Mtb survival in macrophages. Furthermore, we demonstrate that CSE promotes an excessive innate immune response, suppresses the adaptive immune response, and reduces circulating IL-1ß, IL-6, TNF-α, and IFN-γ levels in response to Mtb infection. Notably, Mtb infected CSE-/- macrophages show increased flux through glycolysis and the pentose phosphate pathway, thereby establishing a critical link between H2S and central metabolism. Our data suggest that excessive H2S produced by the infected WT mice reduce HIF-1α levels, thereby suppressing glycolysis and production of IL-1ß, IL-6, and IL-12, and increasing bacterial burden. Clinical relevance was demonstrated by the spatial distribution of H2S-producing enzymes in human necrotic, nonnecrotic, and cavitary pulmonary tuberculosis (TB) lesions. In summary, CSE exacerbates TB pathogenesis by altering immunometabolism in mice and inhibiting CSE or modulating glycolysis are potential targets for host-directed TB control.