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Background: Functional dyspepsia (FD) is a common functional gastrointestinal disorder characterized by chronic digestive symptoms without identifiable structural abnormalities. FD affects approximately 8-46% of the population, leading to significant socioeconomic burdens due to reduced quality of life and productivity. Traditional medicine utilizes differential diagnosis through comprehensive examinations, which include observing and questioning, abdominal examination, and pulse diagnosis for functional gastrointestinal disorders. However, challenges persist in the standardization and objectivity of diagnostic protocols. Methods: This study aims to develop an artificial intelligence-based algorithm to predict identified patterns in patients with functional dyspepsia by integrating brain-body bio-signals, including brain activity measured by functional near-infrared spectroscopy, pulse wave, skin conductance response, and electrocardiography. We will conduct an observational cross-sectional study comprising 100 patients diagnosed according to the Rome IV criteria, collecting bio-signal data alongside differential diagnoses performed by licensed Korean medicine doctors. The study protocol was reviewed and approved by the Institutional Review Board of Kyung Hee University Hospital at Gangdong on 25 January 2024 (IRB no. KHNMCOH 2023-12-003-003) and was registered in the Korean Clinical Trial Registry (KCT0009275). Results: By creating AI algorithms based on bio-signals and integrating them into clinical practice, the objectivity and reliability of traditional diagnostics are expected to be enhanced. Conclusions: The integration of bio-signal analysis into the diagnostic process for patients with FD will improve clinical practices and support the broader acceptance of traditional-medicine diagnostic processes in healthcare.

Background: The validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population., Objectives: This study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT., Methods: This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE)., Results: 199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population., Conclusions: This study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Azman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3-month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population., Methods: Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. Patients were stratified into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI., Results: Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients., Conclusion: Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and MI and a moderately elevated risk of bleeding., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We evaluated the in vitro activity of rifamycin derivatives, including rifampin, rifapentine, rifaximin, and rifabutin, against clinical nontuberculous mycobacteria (NTM) isolates. Of the rifamycin derivatives, rifabutin showed the lowest MICs against all NTM species, including Mycobacterium avium complex, M. abscessus , and M. kansasii Rifabutin also had effective in vitro activity against macrolide- and aminoglycoside-resistant NTM isolates. Rifabutin could be worth considering as a therapeutic option for NTM disease, particularly drug-resistant disease., (Copyright © 2021 American Society for Microbiology.)

A core component of NCCN's mission is to improve and facilitate equitable cancer care. Inclusion and representation of diverse populations are essential toward this goal of equity. Within NCCN's professional content, inclusivity increases the likelihood that clinicians are prepared to provide optimal oncology care to all patients; within NCCN's patient-facing content, it helps ensure that cancer information is relevant and accessible for all individuals. This article describes changes that have been made in the language and images used in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Guidelines for Patients to promote justice, respect, and inclusion for all patients with cancer. The goals are to use language that is person-first, nonstigmatizing, inclusive of individuals of all sexual orientations and gender identities, and anti-racist, anti-classist, anti-misogynist, anti-ageist, anti-ableist, and anti-fat-biased. NCCN also seeks to incorporate multifaceted diversity in images and illustrations. NCCN is committed to continued and expanding efforts to ensure its publications are inclusive, respectful, and trustworthy, and that they advance just, equitable, high-quality, and effective cancer care for all.

Objectives: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS., Methods: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS)., Results: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR)., Conclusions: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Inferior alveolar nerve (IAN) can be subjected to iatrogenic injury during implant surgical procedures. The purpose of this retrospective study was to identify the buccolingual orientation of IAN in posterior mandible as adjunct information for implant planning and to estimate ethnicity-, sex-, and side-related variations in Malaysian population. Material and Methods . A total of 121 CBCT images were viewed with eXamVision software. The buccolingual position of IAN was identified in the posterior region. Buccal bone width (B), canal thickness (C), and lingual bone width (L) were measured at the horizontal canal levels. Kruskal-Wallis H test and Friedman test were used to analyze the buccolingual position. One-way ANOVA was performed to evaluate the variations in B, C, and L values., Results: Overall, most of the IANs were located on the lingual sides of the second molar regions (left: 71.9%; right: 71.1%) and at the centers of the first molar regions (left: 57.9%; right: 47.10%) and exited through the mental foramen before the second premolar regions. There was statistically significant difference in the buccolingual position of the IAN between the sexes in the left second premolar regions ( P = 0.03). There was variation in B between the sexes in the left first molar regions ( P = 0.01). Statistically significant differences in C and L were also found between different ethnic groups ( P = 0.04). Between both sides, there were variations in C in the first molar regions ( P < 0.001) and the second molar regions ( P = 0.03)., Conclusion: From the second molar to the second premolar, the buccal bone width decreased while the lingual bone width increased. There were variations between ethnicities, sexes, and sides among Malaysians., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Michelle Kher Wei Chua et al.)

Cardiovascular disease constitutes the leading cause of mortality worldwide, irrespective of race/ethnicity. Previous studies have shown that minority patients with acute coronary syndrome have distinct clinical, anatomic, and socioeconomic characteristics which may affect clinical outcomes. We included patients who underwent percutaneous coronary intervention with drug-eluting stents for ST-segment elevation myocardial infarction (STEMI), non-STEMI, or unstable angina in a single center. Patients were stratified into Caucasian, African-American, Hispanic, and Asian. Caucasians were the reference group. The primary end point was major adverse cardiac and cerebrovascular events, composite of death, spontaneous myocardial infarction, or stroke at 1 year. Of 6,800 patients included, 49.7% were Caucasian, 20.7% Hispanic, 17.0% Asian and 12.6% African-American. Caucasians were the oldest, Hispanics and Asians had the highest prevalence of diabetes mellitus whereas African-Americans had more chronic kidney disease. Hispanics and African-Americans had the highest STEMI rates, whereas Asians were more likely to present with unstable angina. Compared with Caucasians, Asians had a lower rate of major adverse cardiac and cerebrovascular events at 1 year (3.9% vs 7.1%; p <0.01) whereas Hispanics (6.2% vs 7.1%; p = 0.17) and African-Americans (8.0% vs 7.1%; p = 0.38) had comparable outcomes. Differences were driven by mortality. Findings remained unchanged after adjustment. In conclusion, in acute coronary syndrome patients who underwent percutaneous coronary intervention, Asian race/ethnicity was associated with favorable cardiovascular outcomes compared with Caucasians. No significant differences were observed for Hispanics and African-Americans., Competing Interests: Disclosures The other authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Incidental fish bone ingestion may penetrate the upper aerodigestive tract and cause extraluminal migration due to late presentation or missed diagnosis. The migrated fish bone exhibits a wide spectrum of clinical manifestations, ranging from mild symptoms to potentially fatal complications., Presentation of Case: We report three cases of extraluminal fish bone migration with diverse clinical presentations and complications. The first patient had mild throat symptoms and a fish bone that travelled through the neck and migrated towards the subcutaneous tissue without causing complications. The second patient developed deep neck abscess and thoracic complications as a result of the migrated foreign body, but recovered after surgical exploration and foreign body removal. The third patient presented late in sepsis and upper airway obstruction, subsequently succumbed to multiorgan failure before any surgical intervention., Discussion: Thorough physical and endoscopy examinations are essential in patients with fish bone ingestion. Normal endoscopic findings in a symptomatic patient should always raise the suspicion of a migrated fish bone. A radiographic imaging study is often helpful in locating the foreign body and potential complications. The migrated fish bone that acts as the source of infection in the neck should be traced and removed surgically. The resulting abscess, if present, must be drained. The management of a migrated fish bone can be challenging and often require multi-discipline collaboration., Conclusion: The migration of the ingested fish bone outside the upper aerodigestive tract can cause serious complications and death in some cases. Clinicians should always maintain a high level of suspicion towards extraluminal migration in a patient with a history of fish bone ingestions but normal endoscopic findings. We emphasize the importance of early recognition and prompt surgical intervention to remove the migrated fish bone to minimise the potential morbidity and mortality., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A detailed examination in an older adult presenting with chronic hoarseness is mandatory to exclude an upper aerodigestive tract malignancy. We describe a 71-year-old chronic smoker with essential hypertension who presented with hoarseness and vocal fatigue for 5 months. Laryngoscopic examination showed left vocal fold paralysis with phonation gap. No growth was seen at all laryngeal and hypopharyngeal subsites. The rest of the head and neck, chest, upper limbs and neurovascular examination were unremarkable. A plain chest radiograph demonstrated a cause for the left recurrent laryngeal nerve palsy. The diagnosis, complications and definitive management of the underlying cause and resultant voice problem will be discussed., (© Academy of Family Physicians of Malaysia.)

Prostate cancer is the third most common cancer in Malaysia with the lifetime risk of 1 in 117 men. Here, we initiated a longitudinal Malaysia Prostate Cancer (M-CaP) Study to investigate the clinical and tumour characteristics, treatment patterns as well as disease outcomes of multi-ethnic Asian men at real-world setting. The M-CaP database consisted of 1839 new patients with prostate cancer diagnosed between 2016 and 2018 from nine public urology referral centres across Malaysia. Basic demographic and clinical parameters, tumour characteristics, primary treatment, follow-up and vital status data were retrieved prospectively from the hospital-based patients' case notes or electronic medical records. Primary endpoints were overall survival (OS) and biochemical progression-free survival (bPFS). The median age at diagnosis of M-CaP patients was 70 years (interquartile range, IQR 65-75). Majority of patients were Chinese (831, 45.2%), followed by Malays (704, 38.3%), Indians (124, 6.7%) and other races (181, 9.8%). The median follow-up for all patients was 23.5 months (IQR 15.9-33.6). Although 58.1% presented with late-stage cancer, we observed ethnic and geographic disparities in late-stage prostate cancer diagnosis. Curative radiotherapy and primary androgen deprivation therapy were the most common treatment for stage III and stage IV diseases, respectively. The median OS and bPFS of stage IV patients were 40.1 months and 19.2 months (95% CI 17.6-20.8), respectively. Late stage at presentation remains a challenge in multi-ethnic Asian men. Early detection is imperative to improve treatment outcome and survival of patients with prostate cancer., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Limited data are available regarding the in vitro activity of clofazimine against nontuberculous mycobacteria (NTM) or on outcomes of clofazimine-containing regimens in NTM-pulmonary disease (PD). Therefore, we evaluated the in vitro activity of clofazimine and the clinical outcomes of clofazimine-containing regimens. We evaluated clofazimine in vitro activity for 303 NTM isolates from NTM-PD patients. Fifty-seven clarithromycin-resistant and 35 amikacin-resistant isolates were also analyzed. Culture conversion after a 12-month treatment regimen containing clofazimine was evaluated in 58 NTM-PD patients, including 20 patients with drug-resistant isolates. Most of the 303 isolates (238/303) had minimum inhibitory concentrations (MICs) ≤ 0.25 µg/mL for clofazimine (57/63 Mycobacterium avium , 53/57 M. intracellulare , 49/52 M. kansasii , 22/64 M. abscessus , and 57/67 M. massiliense ). For the 57 clarithromycin-resistant and 35 amikacin-resistant isolates, most had MICs ≤ 0.25 µg/mL (47/57 and 32/35, respectively). Among the 38 NTM-PD patients without resistance to clarithromycin or amikacin, 47% achieved culture conversion (8/27 M. abscessus , 9/9 M. massiliense , 0/1 M. avium , and 1/1 M. intracellulare ). The conversion rate was higher in the MIC ≤ 0.25 µg/mL group than in the MIC = 0.5 µg/mL group (13/18 vs. 5/20, p = 0.004), and an MIC ≤ 0.25 µg/mL remained a significant factor in multivariable analysis. Culture conversion was achieved in 20% of 20 patients with clarithromycin- or amikacin-resistant isolates. However, a clofazimine MIC ≤ 0.25 µg/mL was not significant for culture conversion in the 58 NTM-PD patients, regardless of the drug resistance pattern. Clofazimine was effective in vitro against NTM species. Some patients on clofazimine-containing regimens achieved culture conversion.

Objectives: Limited data exist on the optimal treatment duration for chronic pulmonary aspergillosis (CPA). We investigated the treatment outcome and recurrence rate according to treatment duration in CPA patients., Methods: A total of 196 patients who completed at least 6 months of antifungal therapy (99% oral itraconazole) and achieved favorable treatment responses were analyzed. A Cox's proportional hazards regression model was used to adjust for potential confounding factors in the association between the duration of antifungal therapy (6-12 months vs. ≥ 12 months) and recurrence., Results: All patients were treated with antifungal agents for at least 6 months (median: 12.5, interquartile range: 8.5-18.4 months) and categorized into 6-12 months group (79/196, 40%) and ≥ 12 months group (117/196, 60%). The 6-12 months group had significantly higher recurrence rates owing to CPA aggravation after the completion of treatment compared with the ≥ 12 months group (51% vs. 25%, P  =  0.003). In a Cox's proportional hazards regression model, treatment duration ≥ 12 months was independently associated with a lower risk of recurrence (adjusted hazard ratio: 0.48, 95% confidence interval: 0.28-0.80)., Conclusions: Our data suggest that prolonging antifungal therapy beyond 12 months could reduce the recurrence rate in CPA patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Rationale: Nontuberculous mycobacteria (NTM) are environmental mycobacteria that can cause a chronic progressive lung disease. Although epidemiological data indicate potential genetic predisposition, its nature remains unclear., Objectives: We aimed to identify host susceptibility loci for Mycobacterium avium complex (MAC), the most common NTM pathogen., Methods: This genome-wide association study (GWAS) was conducted in Japanese patients with pulmonary MAC and healthy controls, followed by genotyping of candidate single-nucleotide polymorphisms (SNPs) in another Japanese cohort. For verification by Korean and European ancestry, we performed SNP genotyping., Results: The GWAS discovery set included 475 pulmonary MAC cases and 417 controls. Both GWAS and replication analysis of 591 pulmonary MAC cases and 718 controls revealed the strongest association with chromosome 16p21, particularly with rs109592 (p=1.64×10 -13 , OR 0.54), which is in an intronic region of the calcineurin-like EF-hand protein 2 ( CHP2 ). Expression quantitative trait loci analysis demonstrated an association with lung CHP2 expression. CHP2 was expressed in the lung tissue in pulmonary MAC disease. This SNP was associated with the nodular bronchiectasis subtype. Additionally, this SNP was significantly associated with the disease in patients of Korean (p=2.18×10 -12 , OR 0.54) and European (p=5.12×10 -03 , OR 0.63) ancestry., Conclusions: We identified rs109592 in the CHP2 locus as a susceptibility marker for pulmonary MAC disease., Competing Interests: Conflict of interest: H. Namkoong reports grants from JSPS (JSPS KAKENHI grant number 15H06590), AMED (2019 US-Japan Collaborative Proposal 28863) and NIAID/CBER Intramural Tuberculosis Research Initiative (FY19 Start-up support from CAN 8020315), during the conduct of the study. Conflict of interest: Y. Omae reports grants from JSPS KAKENHI (18K15041), during the conduct of the study. Conflict of interest: T. Asakura reports grants from JSPS, outside the submitted work. Conflict of interest: M. Ishii reports grants from JSPS KAKENHI (18H02821, 18K19566), outside the submitted work. Conflict of interest: S. Suzuki reports grants from JSPS, outside the submitted work. Conflict of interest: K. Morimoto reports grants from AMED (2019 US-Japan Collaborative Proposal 28863), during the conduct of the study; personal fees for consultancy from INSMED, outside the submitted work. Conflict of interest: Y. Kawai has nothing to disclose. Conflict of interest: K. Emoto has nothing to disclose. Conflict of interest: A.J. Oler has nothing to disclose. Conflict of interest: E.P. Szymanski has nothing to disclose. Conflict of interest: M. Yoshida reports grants from JSPS (grant-in-aid for young scientists (B), JSPS KAKENHI grant number 17K16066), during the conduct of the study. Conflict of interest: S. Matsuda has nothing to disclose. Conflict of interest: K. Yagi has nothing to disclose. Conflict of interest: I. Hase has nothing to disclose. Conflict of interest: T. Nishimura reports grants from JSPS KAKENHI (16K09942), outside the submitted work. Conflict of interest: Y. Sasaki reports grants from JSPS (JSPS KAKENHI grant number 15H06590), during the conduct of the study. Conflict of interest: T. Asami has nothing to disclose. Conflict of interest: T. Shiomi has nothing to disclose. Conflict of interest: H. Matsubara has nothing to disclose. Conflict of interest: H. Shimada has nothing to disclose. Conflict of interest: J. Hamamoto reports grants from JSPS KAKENHI (19K08610), outside the submitted work. Conflict of interest: B.W. Jhun reports grants from AMED (2019 US-Japan Collaborative Proposal 28863), during the conduct of the study. Conflict of interest: S-Y. Kim has nothing to disclose. Conflict of interest: H.J. Huh has nothing to disclose. Conflict of interest: H-H. Won has nothing to disclose. Conflict of interest: M. Ato reports grants from Japan Agency for Medical Research and Development, during the conduct of the study. Conflict of interest: K. Kosaki reports grants from Japan Agency for Medical Research and Development (AMED), outside the submitted work. Conflict of interest: T. Betsuyaku reports grants from JSPS KAKENHI and Japan Agency for Medical Research and Development (AMED), outside the submitted work. Conflict of interest: K. Fukunaga reports grants from JSPS KAKENHI and Japan Agency for Medical Research and Development (AMED), outside the submitted work. Conflict of interest: A. Kurashima reports personal fees for consultancy from Insmed, during the conduct of the study. Conflict of interest: H. Tettelin reports grants from NIAID (contract number HHSN272200900009CJSPS), during the conduct of the study. Conflict of interest: H. Yanai has nothing to disclose. Conflict of interest: S. Mahasirimongkol has nothing to disclose. Conflict of interest: K.N. Olivier reports non-financial support from AIT Therapeutics, non-financial support from Insmed, outside the submitted work. Conflict of interest: Y. Hoshino reports grants from The Japan Agency for Medical Research and Development/Japan International Cooperation Agency (AMED), during the conduct of the study (JP18fk0108043 and JP18fk0108075). Conflict of interest: W-J. Koh reports grants from National Research Foundation of Korea (grant number NRF-2018R1A2A1A05018309), during the conduct of the study. Conflict of interest: S.M. Holland has nothing to disclose. Conflict of interest: K. Tokunaga reports grants from Japan Agency for Medical Research and Development (grant-in-aid for research JP17km0405205h0002), during the conduct of the study. Conflict of interest: N. Hasegawa reports grants from Japan Agency for Medical Research and Development(AMED), during the conduct of the study; grants from JSPS KAKENHI, personal fees for consultancy from INSMED, outside the submitted work., (The content of this work is not subject to copyright. Design and branding are copyright ©ERS 2021. For commercial reproduction rights and permissions contact permissions@ersnet.org.)

Background: Mycobacterium abscessus pulmonary disease (M abscessus-PD) is challenging to treat because of its resistance to antibiotics., Research Question: What are the outcomes of treatment-naive patients with M abscessus-PD treated with inhaled amikacin-containing multidrug regimens?, Study Design and Methods: We identified 82 treatment-naive patients with M abscessus-PD from a prospective observational cohort treated with regimens containing inhaled amikacin with or without clofazimine between March 2015 and June 2018 (ClinicalTrials.gov identifier: NCT00970801). During the initial phase, all patients received IV amikacin, imipenem (or cefoxitin), and oral azithromycin. Oral clofazimine was added in cases of (1) M abscessus subspecies abscessus (here M abscessus) or (2) M abscessus subspecies massiliense (here M massiliense) with cavitary lesions. During the continuation phase, amikacin was changed from an injectional to inhalational form., Results: Of 82 patients, 46 (56%) had M massiliense-PD and 36 (44%) had M abscessus-PD. Among 59 patients with nodular bronchiectatic disease (72%), 23 of 59 had a concurrent cavitary lesion. The remaining 23 patients (28%) had fibrocavitary disease. Twelve months after treatment initiation, cure was achieved in 53 patients (65%): 42 of 46 patients (91%) with M massiliense-PD and 11 of 36 patients (31%) with M abscessus-PD (P < .001). Symptomatic and radiologic improvements were observed in 72 patients (88%) and 64 patients (78%), respectively, with significantly greater improvement in patients with M massiliense-PD (symptom improvement, 96% vs 78% [P = .047]; improvement on CT scanning, 93% vs 61% [P = .002])., Interpretation: Inhaled amikacin with or without clofazimine in the regimen provides favorable treatment outcomes in M massiliense-PD. However, more effective treatments are needed for M abscessus-PD., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

We evaluated the in vitro activities of oxazolidinone antibiotics, including linezolid, sutezolid, and delpazolid, against clinical nontuberculous mycobacteria (NTM) isolates. Regardless of macrolide resistance, for Mycobacterium avium, Mycobacterium intracellulare, and Mycobacterium kansasii, sutezolid showed the lowest MIC and minimal bactericidal concentration (MBC) values among oxazolidinone antibiotics. However, for Mycobacterium abscessus and Mycobacterium massiliense, the MIC and MBC for all oxazolidinone antibiotics showed similar values. Oxazolidinone antibiotics warrant further investigation as potential treatment for NTM.

We evaluated the association between 16S rRNA gene (rrs) mutations and susceptibility in clinical isolates of amikacin-resistant nontuberculous mycobacteria (NTM) in NTM-pulmonary disease (PD) patients. Susceptibility was retested for 134 amikacin-resistant isolates (minimum inhibitory concentration [MIC] ≥ 64 µg/ml) from 86 patients. Amikacin resistance was reconfirmed in 102 NTM isolates from 62 patients with either Mycobacterium avium complex-PD (MAC-PD) (n = 54) or M. abscessus-PD (n = 8). MICs and rrs mutations were evaluated for 318 single colonies from these isolates. For the 54 MAC-PD patients, rrs mutations were present in 34 isolates (63%), comprising all 31 isolates with amikacin MICs ≥ 128 µg/ml, but only three of 23 isolates with an MIC = 64 µg/ml. For the eight M. abscessus-PD patients, all amikacin-resistant (MIC ≥ 64 µg/ml) isolates had rrs mutations. In amikacin-resistant isolates, the A1408G mutation (n = 29) was most common. Two novel mutations, C1496T and T1498A, were also identified. The culture conversion rate did not differ by amikacin MIC. Overall, all high-level and 13% (3/23) of low-level amikacin-resistant MAC isolates had rrs mutations whereas mutations were present in all amikacin-resistant M. abscessus isolates. These findings are valuable for managing MAC- and M. abscessus-PD and suggest the importance of phenotypic and genotypic susceptibility testing.

Purpose: Nontuberculous mycobacteria (NTM) is ubiquitous in the environment, but NTM lung disease (NTM-LD) is uncommon. Since exposure to NTM is inevitable, patients who develop NTM-LD are likely to have specific susceptibility factors, such as primary ciliary dyskinesia (PCD). PCD is a genetically heterogeneous disorder of motile cilia and is characterized by chronic respiratory tract infection, organ laterality defect, and infertility. In this study, we performed whole exome sequencing (WES) and investigated the genetic characteristics of adult NTM patients with suspected PCD., Materials and Methods: WES was performed in 13 NTM-LD patients who were suspected of having PCD by clinical symptoms and/or ultrastructural ciliary defect observed by transmission electron microscopy. A total of 45 PCD-causing genes, 23 PCD-candidate genes, and 990 ciliome genes were analyzed., Results: Four patients were found to have biallelic loss-of-function (LoF) variants in the following PCD-causing genes: CCDC114 , DNAH5 , HYDIN , and NME5 . In four other patients, only one LoF variant was identified, while the remaining five patients did not have any LoF variants., Conclusion: At least 30.8% of NTM-LD patients who were suspected of having PCD had biallelic LoF variants, and an additional 30.8% of patients had one LoF variant. Therefore, PCD should be considered in patients with NTM-LD with symptoms or signs suspicious of PCD., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Mycobacterium abscessus complex (MABC) is a taxonomic group of rapidly growing, nontuberculous mycobacteria that are found as etiologic agents of various types of infections. They are considered as emerging human pathogens. MABC consists of 3 subspecies-M. abscessus subsp. bolletti, M. abscessus subsp. massiliense and M. abscessus subsp. abscessus. Here we present a novel method for subspecies differentiation of M. abscessus named Subspecies-Specific Sequence Detection (SSSD). This method is based on the presence of signature sequences present within the genomes of each subspecies of MABC. We tested this method against a virtual database of 1505 genome sequences of MABC. Further, we detected signature sequences of MABC in 45 microbiological samples through DNA hybridization. SSSD showed high levels of sensitivity and specificity for differentiation of subspecies of MABC, comparable to those obtained by rpoB sequence typing.

Purpose: Standard treatment guidelines improve patient outcomes, including disease-specific survival, in cancer care. The African Cancer Coalition was formed in 2016 to harmonize cancer treatment guidelines for sub-Saharan Africa., Methods: The African Cancer Coalition collaborated with the National Comprehensive Cancer Network (NCCN) and the American Cancer Society to harmonize 46 cancer treatment guidelines for use in sub-Saharan Africa. Harmonization for each guideline was completed by a group of approximately 6-10 African cancer experts from a range of specialties and with representation across resource levels. Each working group was chaired by an African oncologist and included a member of the appropriate NCCN guidelines panel. Treatment recommendations from the parent guidelines were distinguished as options that are generally available and should be considered standard care in most of the region or as highly advanced options for which cost or other resources may limit widespread availability. Additional recommendations specific to sub-Saharan Africa were added., Results: The NCCN Harmonized Guidelines for sub-Saharan Africa, available for download on the NCCN website and mobile application, provide flexible recommendations appropriate for the range of resources seen in African cancer programs, from private comprehensive cancer centers to resource-constrained public hospitals. IBM (Armonk, NY) has developed a digital interface-the Cancer Guidelines Navigator-that allows oncologists to access the treatment recommendations for the first five guidelines through an interactive web-based application., Conclusion: Harmonized guidelines that reflect the diversity of resource levels that characterize the current state of clinical care for cancer in Africa have the potential to fill a crucial gap in efforts to standardize and improve cancer care in Africa.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by defects in the function or structure of motitle cilia. In most cases, causative variants result in axonemal dynein arm anomalies, however, PCD due to radial spoke (RS) and central pair (CP) of microtubules has been rarely reported. To identify the molecular basis of PCD characterized by RS/CP defects, we performed whole exome sequencing in PCD patients with RS/CP defects. We identified a homozygous nonsense variant (c.572G>A; p.Trp191*) in NME5, which encodes a protein component of the RS neck, in one PCD patient with situs solitus. Morpholino knockdown of nme5 in zebrafish embryos resulted in motile cilia defects with phenotypes compatible with ciliopathy. This is the first study to show NME5 as a PCD-causative gene in humans. Our findings indicate that NME5 screening should be considered for PCD patients with RS/CP defects., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Clinical practice guidelines in oncology lead to improved outcomes in care. However, the most frequently used guidelines are developed for highly resourced systems. Recognizing the significant and increasing burden of cancer in low- and middle-income countries, the National Comprehensive Cancer Network (NCCN) has developed resource-stratified framework and harmonization processes that allow the NCCN Guidelines to be tailored and optimized for specific geographical areas, resource levels, and settings. The critical need for local expertise and involvement in successful development and uptake is emphasized, and the promise of this collaboration for advancement in oncology programs is illustrated., (© 2020 American Cancer Society.)

Background: Several studies suggest that systemic magnesium reduces postoperative opioid consumption and the intensity of pain, but others report conflicting results. The efficacy and safety profile of intravenous magnesium in noncardiac surgery remain uncertain., Objectives: The aim of this review was to investigate the effect of intravenous magnesium on the consumption of postoperative morphine in the first 24 h in adults undergoing noncardiac surgery., Design: Systematic review and meta-analysis with trial sequential analysis., Data Sources: MEDLINE, EMBASE, CENTRAL from their inception until January 2019., Eligibility Criteria: All randomised clinical trials comparing intravenous magnesium versus placebo in noncardiac surgery were systematically searched in the databases. Observational studies, case reports, case series and nonsystematic reviews were excluded., Results: Fifty-one trials (n=3311) were included for quantitative meta-analysis. In comparison with placebo, postoperative morphine consumption at 24-h was significantly reduced in the magnesium group, with a mean difference [95% confidence interval (CI)] of -5.6 mg (-7.54 to -3.66, P < 0.001, I = 92%, level of evidence low). The trial sequential analysis for the effect of magnesium on postoperative morphine consumption was conclusive. Patients who received magnesium had a longer time to the first analgesia request [143 (103 to 183) min, P < 0.001, I = 99%, level of evidence low] and a lower incidence of shivering [0.26 (0.15 to 0.44), P < 0.001, I = 35%, level of evidence very low]. However, no significance differences were demonstrated in postoperative pain scores in the first 24 h (mean difference, 95% CI) -0.30 (-0.69 to 0.09, P = 0.13, I = 91%, level of evidence low), bradycardia (odds ratio, 95% CI) 1.13 (0.43 to 2.98, P = 0.80, I = 35%, level of evidence very low) and postoperative nausea and vomiting (odds ratio, 95% CI) 0.90 (0.67 to 1.22, P = 0.49, I = 25%, level of evidence moderate)., Conclusion: The current meta-analysis demonstrates that the use of intravenous magnesium as part of multimodal analgesia may reduce morphine consumption in the first 24 h after surgery and delay the time to the first request for analgesia in patients undergoing noncardiac surgery. However, the included studies were of low-quality with substantial heterogeneity., Trial Registration: CRD42018086846.

The GENEDIA MTB/NTM Detection Kit (GENEDIA MTB/NTM; Green Cross Medical Science Corp., Chungbuk, Korea) is a multiplex real-time PCR assay used for differential identification of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM). While the importance of differential identification of MTB/NTM is recognized, there is limited data on the performance of GENEDIA MTB/NTM assay to date. A total of 687 consecutive sputum specimens were cultured and analyzed with the GENEDIA MTB/NTM and GENEDIA MTB assays. Nineteen specimens (2.8%) were MTBC-positive, and 69 (10.0%) were NTM-positive based on mycobacterial culture. All specimens showed concordant results for MTBC using both assays, with a kappa value of 1.00, overall sensitivity of 63.2% (12/19), and specificity of 100% (668/668). The overall NTM sensitivity and specificity were 23.2% (16/69) and 99.7% (616/618) for GENEDIA MTB/NTM. The association between NTM-positivity using GENEDIA MTB/NTM and the diagnosis of NTM pulmonary disease was not statistically significant. In conclusion, the two real-time PCR assays showed similar diagnostic performance for MTBC detection. However, the sensitivity for NTM detection was lower than that for MTBC detection., Competing Interests: None declared., (© The Korean Society for Laboratory Medicine.)

Although oncology care has evolved, outcome assessment remains a key challenge. Outcome measurement requires identification and adoption of a succinct list of metrics indicative of high-quality cancer care for use within and across healthcare systems. NCCN established an advisory committee, the NCCN Quality and Outcomes Committee, consisting of provider experts from NCCN Member Institutions and other stakeholders, including payers and patient advocacy, community oncology, and health information technology representatives, to review the existing quality landscape and identify contemporary, relevant cancer quality and outcomes measures by reevaluating validated measures for endorsement and proposing new measure concepts to fill crucial gaps. This manuscript reports on 22 measures and concepts; 15 that align with existing measures and 7 that are new.

Pulmonary disease (PD) due to nontuberculous mycobacteria (NTM) is increasing globally, but specific biomarkers for NTM-PD have not been established. As circulating miRNAs are promising biomarkers for various diseases, we investigated whether miRNAs have potential as NTM-PD biomarkers. Sera from 12 NTM-PD patients due to Mycobacterium avium, M. intracellulare, M. abscessus, or M. massiliense and three healthy controls were initially evaluated via small RNA sequencing. Multiple miRNAs showed significant differences in expression in patients compared to in healthy controls, with some expression differences unique to PD caused by a specific mycobacterial species. Notably, 14 miRNAs exhibited significant expression differences in PD associated with all four mycobacteria. Validation by quantitative reverse-transcription-PCR in an additional 40 patients with NTM-PD and 40 healthy controls confirmed that four differentially expressed miRNAs (hsa-miR-484, hsa-miR-584-5p, hsa-miR-625-3p, and hsa-miR-4732-5p) showed significantly higher serum expressions in NTM-PD patients than in controls. Receiver operating characteristic curve analysis of these four miRNAs supported the discriminative potential for NTM-PD and their combination provided an improved diagnostic value for NTM-PD. Furthermore, bioinformatics analysis revealed their 125 target genes, which were mostly associated with immune responses. Collectively, this study identified four miRNAs as potential biomarkers for NTM-PD and provided insight into NTM-PD pathophysiology.

Background: Macrophages play a key role in the infection process, and alternatively activated macrophages (M2 polarization) play important roles in persistent infection via the immune escape of pathogens. This suggests that immune escape of pathogens from host immunity is an important factor to consider in treatment failure and multidrug-resistant tuberculosis (MDR-TB)/extensively drug-resistant tuberculosis (XDR-TB). In this study, we investigated the association between macrophage polarization and MDR-TB/XDR-TB and the association between macrophage polarization and the anti-TB drugs used., Methods: iNOS and arginase-1, a surface marker of polarized macrophages, were quantified by immunohistochemical staining and imaging analysis of lung tissues of patients who underwent surgical treatment for pulmonary TB. Drug susceptibility/resistance and the type and timing of anti-tuberculosis drugs used were investigated., Results: The M2-like polarization rate and the ratio of the M2-like polarization rate to the M1-like polarization rate were significantly higher in the MDR-TB/XDR-TB group than in the DS-TB group. The association between a high M2-like polarization rate and MDR-TB/XDR-TB was more pronounced in patients with a low M1-like polarization rate. Younger age and a higher M2-like polarization rate were independent associated factors for MDR-TB/XDR-TB. The M2-like polarization rate was significantly higher in patients who received anti-TB drugs containing pyrazinamide continuously for 4 or 6 weeks than in those who received anti-TB drugs not containing pyrazinamide., Conclusions: The M2-like polarization of macrophages is associated with MDR-TB/XDR-TB and anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.

There is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus Here, we report that rifabutin is as active as clarithromycin against M. abscessus K21 in NOD.CB17-Prkdc scid /NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with M. abscessus disease., (Copyright © 2020 Dick et al.)

Limited data are available regarding the prognostic factors for patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the prognostic factors associated with long-term mortality in NTM-PD patients after adjusting for individual confounders, including aetiological organism and radiological form.A total of 1445 patients with treatment-naïve NTM-PD who were newly diagnosed between July 1997 and December 2013 were included. The aetiological organisms were as follows: Mycobacterium avium (n=655), M. intracellulare (n=487), M. abscessus (n=129) and M. massiliense (n=174). The factors associated with mortality in NTM-PD patients were analysed using a multivariable Cox model after adjusting for demographic, radiological and aetiological data.The overall 5-, 10- and 15-year cumulative mortality rates for the NTM-PD patients were 12.4%, 24.0% and 36.4%, respectively. On multivariable analysis, the following factors were significantly associated with mortality in NTM-PD patients: old age, male sex, low body mass index, chronic pulmonary aspergillosis, pulmonary or extrapulmonary malignancy, chronic heart or liver disease and erythrocyte sedimentation rate. The aetiological organism was also significantly associated with mortality: M. intracellulare had an adjusted hazard ratio (aHR) of 1.40, 95% CI 1.03-1.91; M. abscessus had an aHR of 2.19, 95% CI 1.36-3.51; and M. massiliense had an aHR of 0.99, 95% CI 0.61-1.64, compared to M. avium Mortality was also significantly associated with the radiological form of NTM-PD for the cavitary nodular bronchiectatic form (aHR 1.70, 95% CI 1.12-2.59) and the fibrocavitary form (aHR 2.12, 95% CI 1.57-3.08), compared to the non-cavitary nodular bronchiectatic form.Long-term mortality in patients with NTM-PD was significantly associated with the aetiological NTM organism, cavitary disease and certain demographic characteristics., Competing Interests: Conflict of interest: B.W. Jhun has nothing to disclose. Conflict of interest: S.M. Moon has nothing to disclose. Conflict of interest: K. Jeon has nothing to disclose. Conflict of interest: O.J. Kwon has nothing to disclose. Conflict of interest: H. Yoo has nothing to disclose. Conflict of interest: K.C. Carriere has nothing to disclose. Conflict of interest: H.J. Huh has nothing to disclose. Conflict of interest: N.Y. Lee has nothing to disclose. Conflict of interest: S.J. Shin has nothing to disclose. Conflict of interest: C.L. Daley reports grants from Insmed Inc., and has served on advisory boards for Insmed, Johnson & Johnson, Spero and Horizon, outside the submitted work. Conflict of interest: W-J. Koh reports personal fees for consultancy from Insmed, outside the submitted work., (Copyright ©ERS 2020.)

Tuberculosis (TB) remains a threat to public health and is the leading cause of death globally. Isoniazid (INH) is an important first-line agent for the treatment of TB considering its early bactericidal activity. Resistance to INH is now the most common type of resistance. Resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other first-line drugs such as rifampicin (RIF), thereby increasing the risk of multidrug-resistant-TB. Studies in the 1970s and 1980s showed high success rates for INH-resistant TB cases receiving regimens comprised of first-line drugs. However, recent data have indicated that INH-resistant TB patients treated with only first-line drugs have poor outcomes. Fortunately, based on recent systematic meta-analyses, the World Health Organization published consolidated guidelines on drug-resistant TB in 2019. Their key recommendations are treatment with RIF-ethambutol (EMB)-pyrazinamide (PZA)-levofloxacin (LFX) for 6 months and no addition of injectable agents to the treatment regimen. The guidelines also emphasize the importance of excluding resistance to RIF before starting RIF-EMB-PZA-LFX regimen. Additionally, when the diagnosis of INH-resistant TB is confirmed long after starting the first-line TB treatment, the clinician must decide whether to start a 6-month course of RIF-EMB-PZA-LFX based on the patient's condition. However, these recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty of the effect estimates. Therefore, further work is needed to optimize the treatment of INH-resistant TB., Competing Interests: Dr. Won-Jung Koh served on Advisory Boards for Johnson and Johnson and Insmed, not associated with the submitted work. Dr. Byung Woo Jhun has no conflicts of interest., (Copyright©2020. The Korean Academy of Tuberculosis and Respiratory Diseases.)

Background: Limited data exist on the development of tuberculosis (TB) in cancer patients receiving immune checkpoint inhibitors (ICIs)., Method: s: We evaluated the development of TB in 1144 solid-cancer patients who started ICIs (pembrolizumab, nivolumab, or atezolizumab) between July 2014 and December 2018., Results: A total of 1144 cancer patients were treated with ICIs. The median age of the patients at the start of ICI treatment was 62 years (interquartile range [IQR]; 53-69 years). Lung cancer (n = 796, 69.6%) was the most common cancer followed by melanoma (n = 115, 10.1%), and lymphoma (n = 85, 7.4%). Pembrolizumab (n = 612, 53.5%) was the most common treatment, followed by nivolumab (n = 474, 41.4%) and atezolizumab (n = 58, 5.1%). The median treatment duration with ICIs was 42 days (IQR; 18-154 days), and the median follow-up duration after initiating ICIs was 187 days (IQR; 70-342 days). Overall, three patients developed TB, two of whom received nivolumab and one who received pembrolizumab., Conclusions: Our data showed that TB can develop in cancer patients receiving ICIs. However, due to the small number of study population, it is insufficient to draw accurate conclusions about the role of ICIs in the development of TB. Moreover, it is unclear whether the incidence of TB would be comparable with the incidence of TB in elderly cancer patients. Further studies are needed to evaluate whether diagnosis and treatment of latent TB infections before starting ICIs could be helpful in preventing the development of TB in these patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Se-Hoon Lee received grants and personal fees from Merck Sharp & Dohme Corp (MSD), and personal fees from Novartis, AstraZeneca, Bristol-Myers Squibb (BMS), and Roche, not associated with the submitted work. Dr. Won-Jung Koh has served on Advisory Boards for Insmed Inc. and Johnson and Johnson, not associated with the submitted work. The authors have no additional conflicts of interest to declare., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction : The incidence and prevalence rates of nontuberculous mycobacterial (NTM) pulmonary disease have been continuously increasing worldwide. However, the rate of successful treatment of this disease greatly needs improving, particularly when intrinsic (natural) drug resistance and acquired drug resistance in NTM pulmonary disease are associated with poor outcomes for patients. Areas covered : This review covers the major pathogens that cause NTM pulmonary disease caused by Mycobacterium avium complex, Mycobacterium abscessus , and Mycobacterium kansasii ; the key drugs and recommended regimens used in the treatment of NTM pulmonary disease; the factors that contribute to resistance to the key drugs, including genetic factors and monotherapy; and the treatment strategies, including revised antibiotic regimens and surgery, that can be used to treat drug-resistant NTM pulmonary disease. Expert opinion : To avoid and overcome drug resistance in NTM pulmonary disease, the appropriate guideline-based treatments are essential, and clinical studies to evaluate new or repurposed drugs are urgently needed.

The purpose of this study was to present the computed tomographic (CT) findings of lung abnormalities in macrolide-resistant Mycobacterium massiliense pulmonary disease and its changes in follow-up CT after antibiotic treatment.Chest CT scans of patients with macrolide-resistant M massiliense pulmonary disease (n = 19) were retrospectively reviewed. Patients were treated with multidrug therapy, and sputum examinations were performed. Follow-up CT scans obtained during antibiotic treatment after detection of macrolide resistance were also reviewed, if available (n = 13). The CT scores at detection of macrolide resistance and at the last follow-up periods were also compared.Of all patients with macrolide-resistant M massiliense pulmonary disease, 2 (11%) patients achieved sputum culture conversion during the follow-up period. The most common CT findings of M massiliense pulmonary disease at detection of macrolide resistance were bronchiectasis and bronchiolitis (n = 19, 100%), followed by consolidation (n = 16, 84%), cavities (n = 11, 58%), and nodules (n = 6, 32%). On the last follow-up CT, overall CT scores were increased in 8 (62%) of 13 patients, and total mean CT score was significantly increased (P = .021). For each CT pattern, the cavity showed the greatest increase in CT score (P = .027), followed by bronchiectasis (P = .038).Common CT findings of macrolide-resistant M massiliense pulmonary disease were similar to those of pulmonary disease caused by other species of nontuberculous mycobacteria at presentation. However, in macrolide-resistant M massiliense pulmonary disease, serial CT scans showed deterioration with cavitary and bronchiectatic change in most patients despite multidrug antibiotic therapy.

Accumulating evidence suggests that human infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, indicating that NTM disease is no longer uncommon in many countries. As a result of an increasing emphasis on the importance of differential identification of NTM species, several molecular tools have recently been introduced in clinical and experimental settings. These advances have led to a much better understanding of the diversity of NTM species with regard to clinical aspects and the potential factors responsible for drug resistance that influence the different outcomes of NTM disease. In this paper, we review currently available molecular diagnostics for identification and differentiation of NTM species by summarizing data from recently applied methods, including commercially available assays, and their relevant strengths and weaknesses. We also highlight drug resistance-associated genes in clinically important NTM species. Understanding the basis for different treatment outcomes with different causative species and drug-resistance mechanisms will eventually improve current treatment regimens and facilitate the development of better control measures for NTM diseases., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We evaluated the GenoType NTM-DR (NTM-DR) line probe assay for identifying Mycobacterium avium complex (MAC) species and Mycobacterium abscessus subspecies and for determining clarithromycin and amikacin resistance. Thirty-eight reference strains and 145 clinical isolates (58 MAC and 87 M. abscessus isolates), including 54 clarithromycin- and/or amikacin-resistant strains, were involved. The performance of the NTM-DR assay in rapid identification was evaluated by comparison with results of multigene sequence-based typing, whereas performance in rapid detection of clarithromycin and amikacin resistance was evaluated by comparison with sequencing of the erm (41), rrl , and rrs genes and drug susceptibility testing (DST). The accuracies of MAC and M. abscessus (sub)species identification were 92.1% (35/38) and 100% (145/145) for the 38 reference strains and 145 clinical isolates, respectively. Three MAC strains other than M. intracellulare were found to cross-react with the M. intracellulare probe in the assay. Regarding clarithromycin resistance, NTM-DR detected rrl mutations in 52 isolates and yielded 99.3% (144/145) and 98.6% (143/145) concordant results with sequencing and DST, respectively. NTM-DR sensitivity and specificity in the detection of clarithromycin resistance were 96.3% (52/54) and 100% (91/91), respectively. The NTM-DR yielded accurate erm (41) genotype results for all 87 M. abscessus isolates. Regarding amikacin resistance, NTM-DR detected rrs mutations in five isolates and yielded 99.3% (144/145) and 97.9% (142/145) concordant results with sequencing and DST, respectively. Our results indicate that the NTM-DR assay is a straightforward and accurate approach for discriminating MAC and M. abscessus (sub)species and for detecting clarithromycin and amikacin resistance mutations and that it is a useful tool in the clinical setting., (Copyright © 2019 American Society for Microbiology.)

We evaluated the in vitro activities of the antimicrobial drugs bedaquiline and delamanid against the major pathogenic nontuberculous mycobacteria (NTM). Delamanid showed high MIC values for all NTM except Mycobacterium kansasii However, bedaquiline showed low MIC values for the major pathogenic NTM, including Mycobacterium avium complex, Mycobacterium abscessus subsp. abscessus , M. abscessus subsp. massiliense , and M. kansasii Bedaquiline also had low MIC values with macrolide-resistant NTM strains and warrants further investigation as a potential antibiotic for NTM treatment., (Copyright © 2019 American Society for Microbiology.)