Visualizing the dynamics of tuberculosis pathology using molecular imaging.

Nearly 140 years after Robert Koch discovered Mycobacterium tuberculosis, tuberculosis (TB) remains a global threat and a deadly human pathogen. M. tuberculosis is notable for complex host-pathogen interactions that lead to poorly understood disease states ranging from latent infection to active disease. Additionally, multiple pathologies with a distinct local milieu (bacterial burden, antibiotic exposure, and host response) can coexist simultaneously within the same subject and change independently over time. Current tools cannot optimally measure these distinct pathologies or the spatiotemporal changes. Next-generation molecular imaging affords unparalleled opportunities to visualize infection by providing holistic, 3D spatial characterization and noninvasive, temporal monitoring within the same subject. This rapidly evolving technology could powerfully augment TB research by advancing fundamental knowledge and accelerating the development of novel diagnostics, biomarkers, and therapeutics.

Tuberculosis

This guideline covers preventing, identifying and managing latent and active tuberculosis (TB) in children, young people and adults. It aims to improve ways of finding people who have TB in the community and recommends that everyone under 65 with latent TB should be treated. It describes how TB services should be organised, including the role of the TB control board.

Outcome of incidentally detected airway nodules.

Low-dose chest computed tomography (LDCT) screening increased detection of airway nodules. Most nodules appear to be secretions, but pathological lesions may show similar findings. The National Comprehensive Cancer Network (NCCN) recommends repeating LDCT after 1 month and proceeding to bronchoscopy if the nodules persist. However, no reports exist about incidentally detected airway nodules. We investigated the significance of airway nodules detected by LDCT screening.We screened patients with incidental airway nodules detected by LDCT in the Seoul National University Hospital group. The characteristics of computed tomography, bronchoscopy, pathology and clinical findings were analysed.Among 53 036 individuals who underwent LDCT screening, 313 (0.6%) had airway nodules. Of these, 186 (59.4%) were followed-up with chest computed tomography and/or bronchoscopy. Seven (3.8%) cases had significant lesions, including leiomyoma (n=2), endobronchial tuberculosis (n=2), chronic inflammation (n=1), hamartoma (n=1) and benign granuloma (n=1). The remaining 179 lesions were transient, suggesting that they were secretions.The use of LDCT for lung cancer screening demonstrated the low incidence of airway lesions. Most lesions were transient secretions. True pathological lesions were rare, and no malignant lesion was found. The current recommendation of the NCCN guideline is a reasonable approach that can avoid unnecessary bronchoscopy.

Detecting Disease in Radiographs with Intuitive Confidence.

This paper argues in favor of a specific type of confidence for use in computer-aided diagnosis and disease classification, namely, sine/cosine values of angles represented by points on the unit circle. The paper shows how this confidence is motivated by Chinese medicine and how sine/cosine values are directly related with the two forces Yin and Yang. The angle for which sine and cosine are equal (45°) represents the state of equilibrium between Yin and Yang, which is a state of nonduality that indicates neither normality nor abnormality in terms of disease classification. The paper claims that the proposed confidence is intuitive and can be readily understood by physicians. The paper underpins this thesis with theoretical results in neural signal processing, stating that a sine/cosine relationship between the actual input signal and the perceived (learned) input is key to neural learning processes. As a practical example, the paper shows how to use the proposed confidence values to highlight manifestations of tuberculosis in frontal chest X-rays.

Risk factors for tuberculosis in dialysis patients: a prospective multi-center clinical trial.

BACKGROUND: Profound alterations in immune responses associated with uraemia and exacerbated by dialysis increase the risk of developing active tuberculosis (TB) in chronic haemodialysis patients (HDPs). In the current study, was determined the impact of various risk factors on TB development. Our aim was to identify which HDPs need anti-TB preventive therapy. METHODS: Prospective study of 272 HDPs admitted, through a 36-month period, to our institutions. Specific Relative Risk (RR) for TB was estimated, considering age matched subjects from the general population as reference group. Entering the study all patients were tested with tuberculin (TST). Using Cox's proportional hazard model the independent effect of various risk factors associated with TB development was estimated. RESULTS: History of TB, dialysis efficiency, use of Vitamin D supplements, serum albumin and zinc levels were not proved to influence significantly the risk for TB, in contrast to: advanced age (>65 years), BMI, diabetes mellitus, tuberculin reactivity, healed TB lesions on chest X-ray and time on dialysis. Elderly (>70 years old) HDPs (Adjusted RR 25.3, 95%CI 20.4-28.4, P < 0.02), diabetics (Adj.RR 25.3, 95%CI 17.2-21.1, P < 0.03), underweighted (Adj.RR 72.3, 95%CI 65.2-79.8 P < 0.001), tuberculin responders (Adj.RR 41.4, 95%CI 37.9-44.8, P < 0.03), HDPs with fibrotic lesions on chest x-ray (Adj.RR 82.3, 95%CI 51.3-95.5, P < 0.03) and those treated with haemodialysis for < 12 months (Adj.RR 110.0, 95%CI 97.4-135.3, P < 0.001), presented significantly higher specific RR for TB even after adjusting for the effect of the remaining studied risk factors. CONCLUSION: The above mentioned factors have to be considered by the clinicians, evaluating for TB in HDPs. Positive TST, the existence of predisposing risk factors and/or old TB lesions on chest X-ray, will guide the diagnosis of latent TB infection and the selection of those HDPs who need preventive chemoprophylaxis.

[Linear endobronchial ultrasound as the initial diagnostic tool in patients with indications of mediastinal disease]. / La ultrasonografía endobronquial lineal como instrumento de diagnóstico inicial en el paciente con ocupación mediastínica.

BACKGROUND AND OBJECTIVE: Linear endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven useful for sampling mediastinal masses and nodes and for staging lung cancer. The aim of this study was to assess the usefulness of this diagnostic tool in patients with indications of mediastinal disease that could not be diagnosed by noninvasive methods or white light bronchoscopy. PATIENTS AND METHODS: All patients undergoing linear EBUS-TBNA for the diagnosis of mediastinal masses and/or adenopathy at our endoscopy unit were included in the study. Diagnoses obtained by linear EBUS-TBNA or any surgical technique performed after a nondiagnostic EBUS-TBNA were considered as final. RESULTS: In the study population of 128 patients with a mean (SD) age of 62.0 (11.2) years, a total of 294 TBNAs were performed on 12 masses and 282 nodes. Satisfactory samples were obtained in 11 cases (91.7%) from masses and in 233 cases (82.6%) from nodes. Linear EBUS-TBNA was diagnostic, obviating the need for mediastinoscopy in 115 patients (diagnostic sensitivity, 89.8%). The technique confirmed the diagnosis in 85 of the 94 patients with cancer (90.4%), in 8 of the 10 patients with tuberculosis (80.0%), and in the 5 patients with sarcoidosis. CONCLUSIONS: Linear EBUS-TBNA is a useful diagnostic tool in patients with mediastinal disease for whom a pathologic diagnosis is not achieved by noninvasive methods or white light bronchoscopy.

From contact investigation to tuberculosis screening of drug addicts and homeless persons in Rotterdam.

BACKGROUND: In early 2001 there were indications that tuberculosis (TB) was increasingly becoming a problem among drug addicts and homeless persons in Rotterdam, after a periodical screening was discontinued in 1997. A contact investigation around a homeless drug addicted man in Rotterdam with infectious pulmonary TB is described. Contact investigation: A total of 507 drug addicts, homeless persons, and staff of facilities for these risk groups were examined with tuberculin skin testing (TST) and chest radiography. DNA fingerprinting of mycobacteriological cultures through Restricted Fragment Length Polymorphism methodology and molecular epidemiology investigation through cluster analysis were performed. OUTCOME: TST showed an infection prevalence of 29%, especially among staff of services for drug addicts and homeless persons. Six persons with active intrathoracic TB were identified. Cluster analysis demonstrated no relation with the initial case but showed intense transmission of TB among drug addicts and homeless persons in Rotterdam by multiple sources. As a consequence of the findings, a proposal to the Council of the City of Rotterdam resulted in the re-introduction of a comprehensive TB screening programme among these risk groups with mobile digital X-ray units (MXUs). CONCLUSION: This contact investigation gradually obtained the characteristics of a screening of drug addicts and homeless persons. Novel technologies, such as MXUs, facilitate appropriate and efficient outreach approaches to TB control among difficult-to-reach groups. This method and knowledge of individual fingerprints and clusters of TB patients are indispensable for underpinning proposals for change of local TB control strategies and convincing local authorities of the rationale.

Tuberculosis of the foot.

In 44 patients with tuberculosis of the foot we identified five radiological patterns of lesions; cystic, rheumatoid, subperiosteal, kissing and spina ventosa. Cystic destruction had the best outcome and rheumatoid the poorest. All the patients were cured after antituberculous treatment for 18 months, and none required surgery.