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Background and Purpose: Population study on relationship between nontuberculous mycobacterial (NTM) infection and respiratory failure (RF) is limited. This study evaluated the RF risk, including acute respiratory failure (ARF), chronic respiratory failure (CRF) and ARF on CRF, in patients with NTM infection in Taiwan., Methods: We used the National Health Insurance Research Database of Taiwan to identify 3864 newly diagnosed NTM patients (NTM cohort) from 1999 to 2009, and 15456 non-NTM patients (non-NTM cohort), frequency matched by demographic status for comparison. Incidence and hazard of developing RF were measured by the end of 2010., Results: The incidence rate of RF was 4.31-fold higher in the NTM cohort than in the non-NTM cohort (44.0 vs.10.2 per 1000 person-years), with an adjusted hazard ratio (HR) of 3.11 (95% CI: 2.73-3.54). The cumulative proportional incidence of RF was 10% higher in the NTM cohort than in the non-NTM cohort (P<0.0001). The RF risk was much greater within 6 months after the diagnosis of NTM infection with a HR of 7.45 (95% CI = 5.50-10.09). Age-specific comparison showed that the younger NTM patients had a higher HR of RF than the elderly NTM patients (HR: 4.42, 95% CI: 3.28-5.96 vs. HR: 2.52, 95% CI: 2.17-2.92). Comorbidity increased the risk of RF in both cohorts, particularly in those with chronic obstructive pulmonary disease., Conclusion: Our study suggests patients with NTM infection are at a high risk of RF. The risk appears much greater soon after patients diagnosed with NTM infection.

The use of focused ultrasound (FUS) with microbubbles has been proven to induce transient blood-brain barrier opening (BBB-opening). However, FUS-induced inertial cavitation of microbubbles can also result in erythrocyte extravasations. Here we investigated whether induction of submicron bubbles to oscillate at their resonant frequency would reduce inertial cavitation during BBB-opening and thereby eliminate erythrocyte extravasations in a rat brain model. FUS was delivered with acoustic pressures of 0.1-4.5 MPa using either in-house manufactured submicron bubbles or standard SonoVue microbubbles. Wideband and subharmonic emissions from bubbles were used to quantify inertial and stable cavitation, respectively. Erythrocyte extravasations were evaluated by in vivo post-treatment magnetic resonance susceptibility-weighted imaging, and finally by histological confirmation. We found that excitation of submicron bubbles with resonant frequency-matched FUS (10 MHz) can greatly limit inertial cavitation while enhancing stable cavitation. The BBB-opening was mainly caused by stable cavitation, whereas the erythrocyte extravasation was closely correlated with inertial cavitation. Our technique allows extensive reduction of inertial cavitation to induce safe BBB-opening. Furthermore, the safety issue of BBB-opening was not compromised by prolonging FUS exposure time, and the local drug concentrations in the brain tissues were significantly improved to 60 times (BCNU; 18.6 µg versus 0.3 µg) by using chemotherapeutic agent-loaded submicron bubbles with FUS. This study provides important information towards the goal of successfully translating FUS brain drug delivery into clinical use.

This study evaluated the use of high-resolution computed tomography (HRCT) to predict the presence of culture-positive pulmonary tuberculosis (PTB) in adult patients with pulmonary lesions in the emergency department (ED). The study included a derivation phase and validation phase with a total of 8,245 patients with pulmonary disease. There were 132 patients with culture-positive PTB in the derivation phase and 147 patients with culture-positive PTB in the validation phase. Imaging evaluation of pulmonary lesions included morphology and segmental distribution. The post-test probability ratios between both phases in three prevalence areas were analyzed. In the derivation phase, a multivariate analysis model identified cavitation, consolidation, and clusters/nodules in right or left upper lobe (except anterior segment) and consolidation of the superior segment of the right or left lower lobe as independent positive factors for culture-positive PTB, while consolidation of the right or left lower lobe (except superior segment) were independent negative factors. An ideal cutoff point based on the receiver operating characteristic (ROC) curve analysis was obtained at a score of 1. The sensitivity, specificity, positivity predictive value, and negative predictive value from derivation phase were 98.5% (130/132), 99.7% (3997/4008), 92.2% (130/141), and 99.9% (3997/3999). Based on the predicted positive likelihood ratio value of 328.33 in derivation phase, the post-test probability was observed to be 91.5% in the derivation phase, 92.5% in the validation phase, 94.5% in a high TB prevalence area, 91.0% in a moderate prevalence area, and 76.8% in moderate-to-low prevalence area. Our model using HRCT, which is feasible to perform in the ED, can promptly diagnose culture-positive PTB in moderate and moderate-to-low prevalence areas.