Rationale: Use of Xpert MTB/RIF assay as a substitute for smear microscopy in routine clinical practice remains unexplored in an intermediate tuberculosis-burden setting. Objectives: To compare the diagnostic performance of Xpert and smear microscopy, based on sampling time and location, correlation of Xpert semiquantitative category with smear grade and time-to-culture positivity, and compliance of reporting time with defined standard time. Methods: Consecutive sputum samples collected from 2,952 suspected pulmonary tuberculosis patients over a 3-year-period were tested by Xpert, smear microscopy, and liquid culture as part of routine diagnostics in South Korea. Measurements and Main Results: Based on the analysis of a single-sputum-specimen per patient, of 2,952 samples, 263 (8.9%) were culture-confirmed tuberculosis and 265 (9.0%) were nontuberculous mycobacteria. The overall sensitivity and specificity were 74.1% and 97.5% for Xpert versus 38.8% and 96.7% for smear microscopy, respectively (P0.05). Of 82 smear-positive nontuberculous mycobacteria, 81 (98.8%) were accurately excluded by Xpert. Sampling time and location significantly affected the performance of smear microscopy, but not that of Xpert. Xpert semiquantitative category strongly correlated with smear grade (γ_{Goodman-Kruskal}=0.982, P<0.0001) and time-to-culture positivity (γ_{Goodman-Kruskal}=-0.962, P<0.0001). Median reporting time and its compliance rate within 24h were 3.1h and 96.3% for Xpert versus 19.1h and 88.7% for smear microscopy, respectively (P<0.0001; P<0.05). Conclusions: Xpert provides faster, more stable, and superior results compared to smear microscopy, in addition to its strong correlation with smear grade. Xpert might replace smear microscopy as the first-line diagnostic test for pulmonary tuberculosis in routine clinical practice in an intermediate-burden setting.

Whole-genome sequencing (WGS) was used to determine the molecular mechanisms of multidrug resistance for 10 serial Candida glabrata bloodstream isolates obtained from a neutropenic patient during 82 days of amphotericin B (AMB) or echinocandin therapy. For WGS, a library was prepared and sequenced using a Nextera DNA Flex Kit (Illumina) and the MiseqDx (Illumina) instrument. All isolates harbored the same Msh2p substitution, V239L, associated with multilocus sequence type 7 and a Pdr1p substitution, L825P, that caused azole resistance. Of six isolates with increased AMB MICs (≥2 mg/L), three harboring the Erg6p A158fs mutation had AMB MICs ≥ 8 mg/L, and three harboring the Erg6p R314K, Erg3p G236D, or Erg3p F226fs mutation had AMB MICs of 2–3 mg/L. Four isolates harboring the Erg6p A158fs or R314K mutation had fluconazole MICs of 4–8 mg/L while the remaining six had fluconazole MICs ≥ 256 mg/L. Two isolates with micafungin MICs > 8 mg/L harbored Fks2p (I661_L662insF) and Fks1p (C499fs) mutations, while six isolates with micafungin MICs of 0.25–2 mg/L harbored an Fks2p K1357E substitution. Using WGS, we detected novel mechanisms of AMB and echinocandin resistance; we explored mechanisms that may explain the complex relationship between AMB and azole resistance.

Ju Hyeon Shin, M.D., Soo Hyun Kim, M.D., Dain Lee, M.S., Seung Yeob Lee, M.D., Sejong Chun, M.D., Jun Hyung Lee, M.D., Eun Jeong Won, M.D., Hyun Jung Choi, M.D., Hyun Woo Choi, M.D., Seung Jung Kee, M.D., Myung Geun Shin, M.D., and Jong Hee Shin, M.D.. Ann Lab Med 2021;41:214-20. https://doi.org/10.3343/alm.2021.41.2.214

This paper examines whether material weakness in internal accounting control is negatively associated with investment efficiency in Korea. Since internal accounting control weakness drives poor accounting quality and poor accounting quality exacerbates information asymmetry between firms and outside capital suppliers, managerial investment cannot be monitored effectively which result in over- and/or under- investment. Since internal accounting system is closely related to corporate governance, weak internal accounting control is often associated with poor corporate governance, and this control environment makes it hard to monitor managerial opportunistic behavior, causing abnormal investment such as over- and/or under- investment. We find that firms with internal accounting control weakness tend to make over- and under- investment. We also find the number of weakness in internal accounting control is negatively related to investment efficiency. In addition, three types of qualified review opinion - overall company level weakness, account-specific weakness and disclaimer review opinion due to scope limitation - are differentially affected to investment efficiency; disclaimer review opinion is present the most severe problem in internal accounting control that drives over- and under- investment. Our findings suggest weak internal accounting control provides poor monitoring to manager and cannot restrain managerial inefficient investment decision.

Jo YG, et al. J Korean Med Sci. 2017 May;32(5):750-756. https://doi.org/10.3346/jkms.2017.32.5.750