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BackgroundThis study assessed longitudinal national data on mortality due to nontuberculous mycobacteriosis (NTMosis) and bronchiectasis and the association between the two diseases.MethodsWe analysed the national death statistics of Japan from 1970 to 2015. The International Classification of Disease (ICD) codes were used to extract the relevant data. Crude mortality, age-adjusted mortality and standardised mortality rates were calculated using vital statistics and the population in 2000. We also identified domestic publications related to NTMosis and bronchiectasis with an internet-based search system.ResultsThe total number of bronchiectasis-related deaths remained at the same level, which was approximately 1000, for 45 years, although the number of deaths has consistently decreased in males but increased in females since the mid-1990s. A substantial increasing trend in females was also observed for NTMosis in the same period. The age-adjusted mortality data showed an increase in mortality in women due to NTMosis and confirmed the trend in bronchiectasis in women. The patterns in the number of domestic reports showed a recent slight increase in bronchiectasis and a marked increase in NTMosis.ConclusionsThe trends in bronchiectasis-related mortality differed by sex. The epidemiological trends in the two diseases were associated, especially in elderly females since the mid-1990s. It is suggested that pulmonary NTMosis without pre-existing bronchiectasis might be a leading cause of postinfectious bronchiectasis in Japan.

Probability of cure is important for patients with lung metastasis who must decide whether to undergo metastasectomy. Although progression-free survival (PFS) is thought to reflect this, it does not include curative effects by repeat metastasectomy. Thus, the authors developed a new indicator, time to incurable recurrence (TTIR), in which only incurable recurrence was set as an event that included death, with incurable recurrence defined as recurrence not treated by definitive local therapy (DLT), recurrence treated by DLT but with PFS maintained less than 2 years, or recurrence followed by re-recurrence.This multi-institutional study included 339 patients who underwent lung metastasectomy for colorectal cancer between 1990 and 2008.Among the 339 patients, 191 experienced recurrence, 77 received DLT for recurrence, 38 had a PFS of 2 years or longer after the treatment, and 33 had maintained a PFS at the last follow-up date. The patients had PFS ranging from 39 to 212 months (median, 101 months). The 5-year OS, PFS, and TTIR rates were respectively 63.4%, 42.2%, and 51.9%. The TTIR curve was similar to the OS curve 7 years after the initial metastasectomy. The difference between TTIR and PFS at 7 years was 9.7%, indicating probability of cure by repeat DLT. Multivariable analysis showed different prognostic factors among OS, PFS, and TTIR.At the initial metastasectomy, TTIR may reflect probability of a cure, including cure by repeat DLT, and can be used to analyze prognostic factors associated with cure.

A 48-year-old woman with extensive clarithromycin-resistant Mycobacterium avium complex pulmonary disease (MAC-PD) was successfully treated by left lower lobectomy and lingulectomy following combination treatment of intravenous/inhaled amikacin plus bronchial occlusion by Endobronchial Watanabe Spigots (EWSs). A left pneumonectomy was initially indicated for removing all the lesions, but the procedure would have been barely tolerated by the patient. However, her preoperative combination treatment sufficiently reduced the lesions requiring resection to allow surgical preservation of the left upper division. This novel approach might be promising for patients with Mycobacterium avium complex lung disease whose pulmonary reserve will not allow an extensive parenchymal resection.

Clofazimine (CFZ) is used to treat pulmonary non-tuberculous mycobacterial (NTM) infection; however, its pharmacokinetics remain unexplored in patients with pulmonary NTM, and the relationship between CFZ serum concentration and adverse effects has not been investigated. The objectives of this study were to characterize the pharmacokinetics of CFZ in pulmonary NTM disease treatment and to investigate the relationship between the steady-state CFZ serum concentration and adverse effects. A prospective observational study was conducted on 45 patients with pulmonary NTM treated with CFZ (UMIN000041053). A maximum of five serum samples per patient were taken at the CFZ trough, and serum concentration was measured using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The pharmacokinetics of CFZ were analyzed using a nonlinear mixed effect model. The relationships among steady-state CFZ serum concentration and adverse effects, pigmentation, and heart rate-corrected QT (QTc) interval were investigated. Twenty-six patients had M. avium or M. intracellulare infection and nineteen had M. abscessus infection. The primary CFZ dosage was 50 mg/day. The estimated apparent CFZ clearance, apparent volume of distribution, and half-life were 2.4 L/h, 2,960 L, and 36 days, respectively. The combined use of rifampicin and CFZ significantly reduced CFZ exposure by 22%. Although there was no relationship between CFZ serum concentration and pigmentation intensity, the QTc interval was significantly correlated with CFZ serum concentration. The estimation of accurate pharmacokinetics for CFZ required approximately 5 months of monitoring. The relationship between the serum concentration and specific adverse effects of CFZ confirmed that CFZ serum concentration was not associated with pigmentation but did affect the QTc interval.

The incidence of nontuberculous mycobacterial lung disease (NTMLD) is increasing worldwide, the number of lung surgeries is increasing accordingly. The disease is progressive and is characterized by exertional intolerance, respiratory dysfunctions, and impaired health-related quality of life (HRQOL). Treatment comprises multidrug antibiotic treatment combined with lung resection. The incremental shuttle walk distance (ISWD) is a standard tool for assessing the patients' tolerance to lung resection. The exertional tolerance, physical functions and HRQOL among pre-surgical patients with NTMLD are clinically important, but not fully studied yet from the viewpoint of physiotherapy. The purpose of this study was to explore the clinical significance of ISWD for assessing the exercise capacity of pre-surgical patients with NTMLD. For peripheral muscle evaluation, the strength of the quadriceps femoris muscle was measured. HRQOL was evaluated using scores of the St. George's Respiratory Questionnaire (SGRQ). Thirty-three patients (mean age 54.9 ± 13 years) were enrolled. The mean ISWD was 505 ± 134 m, shorter than the reference values (ISWD %predicted: 96 ± 27%). Regression analysis showed significant associations between ISWD and percent-predicted vital capacity (r = 0.38, p = 0.03) and percent quadriceps force/body weight (r = 0.54, p = 0.001). HRQOL assessed by SGRQ scores was correlated with ISWD (r < -0.4, p < 0.05). Multiple regression analysis showed that ISWD was significantly associated with leg muscle strength and with HRQOL. In conclusion, ISWD is useful to evaluate the exercise capacity among pre-surgical patients with NTMLD, The Tohoku journal of experimental medicine, 250(1), pp.43-48; 2020

Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes.Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage.Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07).An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Two types of re-operations for inflammatory lung diseases are presented:thoracoplasty and cavernostomy. Thoracoplasty is used to obliterate a residual pleural space after upper lung resection with prolonged air leak. Usually, the 2nd to the 6th ribs are resected, according to the extent of the space. Posteriorly the ribs should be removed to the costotransverse joint to achieve sufficient space obliteration. The tip of the scapula is resected in case of the resection of the 6th rib, otherwise the scapula would impinge on the 7th rib. The resection of the 1st rib should be avoided because of a subsequent severe scoliosis. Cavernostomy is a procedure to open the infected cavity of the residual lung. Aspergillus and non-tuberculous mycobacteria are the most frequent pathogens. The site of skin incision depends on the location of the cavity:midaxially incision for an anterior cavity and paravertebral incision for a posterior cavity. Cutting "septum" in the cavity makes it a single space, contributing to sufficient drainage by gauze. The closure of the cavity will be considered after several months or years when the cavity is sterilized and the patient's nutritional status becomes well. These 2 procedures are effective in treating refractory lung inflammation after lung resection, although they are quite traditional.

Purpose: To investigate the exercise capacity and health-related quality of life (HRQOL) of surgical patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) preoperatively versus 6 months postoperatively. Methods: This prospective observational study included patients with NTM-PD and was conducted at a single center. The intervention was surgical resection plus perioperative and post-discharge physical therapy. The physical function was assessed preoperatively and 6 months postoperatively using the 6-minute walk test (6MWT). HRQOL was assessed preoperatively and 6 months postoperatively using the Short-Form 36 (SF-36) health survey questionnaire and St. George’s Respiratory Questionnaire. The postoperative HRQOL was compared between patients with and without preoperative clinical symptoms. Results: In total, 35 patients were analyzed. The preoperatively symptomatic group had significantly lower preoperative HRQOL than the preoperatively asymptomatic group (p, Annals of Thoracic and Cardiovascular Surgery, 28(2), pp. 103-110; 2022

A 48-year-old woman with extensive clarithromycin-resistant Mycobacterium avium complex pulmonary disease (MAC-PD) was successfully treated by left lower lobectomy and lingulectomy following combination treatment of intravenous/inhaled amikacin plus bronchial occlusion by Endobronchial Watanabe Spigots (EWSs). A left pneumonectomy was initially indicated for removing all the lesions, but the procedure would have been barely tolerated by the patient. However, her preoperative combination treatment sufficiently reduced the lesions requiring resection to allow surgical preservation of the left upper division. This novel approach might be promising for patients with Mycobacterium avium complex lung disease whose pulmonary reserve will not allow an extensive parenchymal resection.

Background: Nontuberculous mycobacterium pulmonary disease (NTM-PD) is a progressive condition characterized by exercise intolerance and impaired health-related quality of life (HRQOL). NTM-PD is sometimes treated with surgery in combination with medication, but little is known about the postoperative physical function and HRQOL. This study aimed to investigate the exercise capacity and HRQOL of patients with NTM-PD preoperatively and 6 months postoperatively.Methods: This prospective observational study included patients with NTM-PD and was conducted at Fukujuji Hospital. The intervention was surgical resection plus perioperative and post-discharge physical therapy. The physical function was assessed preoperatively and 6 months postoperatively using the 6-minute walk test (6MWT). HRQOL was assessed preoperatively and 6 months postoperatively using the Short-Form 36 Health Survey (SF-36) and St. George’s Respiratory Questionnaire. The postoperative HRQOL was compared between patients with and without preoperative clinical symptoms.Results: In total, 35 patients were analyzed. Preoperative clinical symptoms were present in 20 of 35 patients (57%), and the preoperatively symptomatic group had significantly lower preoperative HRQOL than the preoperatively asymptomatic group (p < 0.05). Thirty-two patients completed the 6-month follow-up. Compared with preoperatively, there were significant improvements at 6 months postoperatively in the 6MWT (p < 0.01) and HRQOL, mainly in the SF-36 mental component summary (p < 0.01). The SF-36 mental component summary in the preoperatively symptomatic group was very significantly improved from preoperatively to 6 months postoperatively (p < 0.05).Conclusions: The combination of surgical treatment and physical therapy for NTM-PD contributes to improvements in physical function and HRQOL.

Background Mycobacterium abscessus complex pulmonary disease is notoriously difficult to treat by medication alone. We report our experience with resectional surgery combined with preoperative and postoperative multidrug chemotherapy for the treatment of patients with M. abscessus complex pulmonary disease. Methods This is a retrospective review of 33 patients undergoing lung resection for M. abscessus complex pulmonary disease at a single center in Japan between January 2008 and December 2019. Results The median age of patients was 54.0 (interquartile range [IQR], 49.0-66.0) years; 27 (81.8%) were female. Nodular-bronchiectatic was the most common disease type (n = 24, 72.7%). Disease was limited in 18 (54.5%) patients and extensive in 15 (45.5%). The median duration of preoperative multidrug chemotherapy employing oral and parenteral antibiotics was 10.0 (IQR, 3.0-18.0) months. A total of 34 anatomical lung resections were performed as follows: 22 lobectomies, 5 segmentectomies, 4 combined resections, 2 bilobectomies, and 1 pneumonectomy. No operative mortalities and 4 (13.3%) morbidities occurred. The median duration of multidrug chemotherapy after the surgery was 18.0 (IQR, 12.0-31.0) months. Postoperative sputum-negative status was achieved in 31 (93.9%) patients; all 23 patients obtaining preoperative negative conversion remained negative, and 8 (80.0%) of 10 patients with preoperative positive sputum became negative postoperatively. Recurrence was observed in 2 (6.5%) patients. The recurrence-free probabilities were 96.3%, 96.3%, and 80.2% at 1 year, 3 years, and 5 years, respectively. Conclusions Combined with preoperative and postoperative multidrug chemotherapy, resectional surgery can be performed safely and achieve favorable outcomes for patients with M. abscessus complex pulmonary disease.

The clinical importance of Mycobacterium abscessus subsp. abscessus (M. abscessus) lung disease has been increasing, but few studies have assessed the clinical characteristics associated with the treatment outcome. We retrospectively analyzed 75 consecutive patients with M. abscessus lung disease diagnosed at a tertiary hospital from January 2004 to April 2018. Among 52 patients with sufficient clinical data, 19 patients (42.2%) achieved treatment success. Compared with 26 (57.8%) patients in the treatment failure group, body mass index (BMI) (19.8 vs 17.5 kg/m2, P = 0.022), previous nontuberculous mycobacterial (NTM) lung disease (26.3% vs 61.5%, P = 0.034), the presence of cavitary lesions (31.6% vs 69.2%, P = 0.017), and the bronchiectasis score (3.0 vs 5.0, P = 0.003) were significantly different in the treatment success group. Multivariate analysis showed that age (adjusted hazard ratio (aHR), 0.94; 95% confidence interval (CI), 0.90 to 0.99; P = 0.010), the presence of cavitary lesions (aHR, 0.34; 95% CI, 0.12 to 0.94; P = 0.039), and previous NTM lung disease (aHR, 0.28; 95% CI, 0.09 to 0.86; P = 0.026) were negatively associated with treatment success. This is the first study to show that previous NTM lung disease might be a clinically important factor related to unfavorable treatment outcomes in M. abscessus lung disease patients. To increase our understanding the characteristics of M. abscessus lung disease, this factor should be independently analyzed in future research.

Tuberculosis (TB) and Mycobacterium avium complex lung disease (MAC-LD) are both characterized pathologically by granuloma lesions, which are typically composed of a necrotic caseum at the center surrounded by fibrotic cells and lymphocytes. Although the histological characterization of TB and MAC-LD granulomas has been well-documented, their molecular signatures have not been fully evaluated. In this research we applied mass spectrometry-based proteomics combined with laser microdissection to investigate the unique protein markers in human mycobacterial granulomatous lesions. Comparing the protein abundance between caseous and cellular sub-compartments of mycobacterial granulomas, we found distinct differences. Proteins involved in cellular metabolism in transcription and translation were abundant in cellular regions, while in caseous regions proteins related to antimicrobial response accumulated. To investigate the determinants of their heterogeneity, we compared the protein abundance in caseous regions between TB and MAC-LD granulomas. We found that several proteins were significantly abundant in the MAC-LD caseum of which proteomic profiles were different from those of the TB caseum. Immunohistochemistry demonstrated that one of these proteins, Angiogenin, specifically localized to the caseous regions of selected MAC-LD granulomas. We also detected peptides derived from mycobacterial proteins in the granulomas of both diseases. This study provides new insights into the architecture of granulomatous lesions in TB and MAC-LD.

Single crystal growth of ScAlMgO4 boules with 10 mm up to 4 in. (c.a. 101.6 mm) in diameter by Czochralski technique was demonstrated. Some high quality ScAlMgO4 single crystal boules with 2-inches (c.a. 50.8 mm) in diameter were successfully grown without dislocation, which was revealed by X-ray rocking curve and X-ray topography measurements for the c-plane wafers. After a GaN template was formed on a substrate cut out from a grown ScAlMgO4 boule by using metalorganic vapor phase epitaxy, a thick GaN film was epitaxially grown on the template using hydride vapor phase epitaxy (HVPE). At the cooling stage after the growth in the HVPE process, the thick grown GaN film was separated by itself from the ScAlMgO4 substrate due to high cleavability of ScAlMgO4, which makes it possible the reuse of the substrate. The free-standing GaN grown on the reused ScAlMgO4 substrate showed the same quality as a GaN fabricated on a fresh ScAlMgO4 substrate. The reuse of ScAlMgO4 substrates is beneficial for saving the GaN films fabrication cost. The fabrication of a free-standing GaN substrate with 2 in. in diameter and 1 mm in thickness on ScAlMgO4 substrates was demonstrated to be more high-yield than the fabrication on a sapphire substrate. The growth method shown in this study is very promising, and it opens an efficient way to obtain GaN free-standing wafers and to reduce the production cost of GaN wafers.

Objectives Thoracoscopic surgery for lung metastasectomy remains controversial. The study aimed at determining the efficacy of thoracoscopic surgery for lung metastasectomy. Methods This was a multi-institutional, retrospective study that included 1047 patients who underwent lung metastasectomy for colorectal cancer between 1999 and 2014. Prognostic factors of overall survival were compared between the thoracoscopic and open thoracotomy groups using the multivariate Cox proportional hazard model. The propensity score, calculated using the preoperative covariates, included the era of lung surgery as a covariate. A stepwise backward elimination method, with a probability level of 0.15, was used to select the most powerful sets of outcome predictors. The difference between the radiological tumour number and the resected tumour number (delta_num) was also evaluated. Results The c -statistics and the P -value of the Hosmer-Lemeshow Chi-square of the propensity score model were 0.7149 and 0.1579, respectively. After adjusting for the propensity score, the thoracoscopy group had a better survival rate than the open group (stratified log-rank test: P = 0.0353). After adjusting for the propensity score, the most powerful predictive model for overall survival was that which combined thoracoscopy [hazard ratio (HR): 0.468, 95% CI: 0.262-0.838, P = 0.011] and anatomical resection (HR: 1.49, 95% CI: 1.134-1.953, P = 0.004). Before adjusting for the propensity score, the delta_num was significantly greater in the open group than in the thoracoscopy group (thoracoscopy: 0.06, open: 0.33, P = 0.001); however, after adjustment, there was no difference in the delta_num (thoracoscopy: 0.04, open: 0.19, P = 0.114). Conclusions Thoracoscopic metastasectomy showed better overall survival than the open approach in this analysis. The thoracoscopic approach may be an acceptable option for resection of pulmonary metastases in terms of tumour identification and survival outcome in the current era.

Linezolid (LZD) is classified as a WHO group 5 drug used in the treatment of tuberculosis (TB). Although its efficacy and long-term safety have not yet been established, it is being increasingly used in the treatment of multidrug resistant tuberculosis (MDR-TB) and extensive multidrug-resistant tuberculosis (XDR-TB). The current study is a single-center retrospective clinical analysis of hospitalized M/XDR-TB patients in Fukujuji Hospital involving 26 patients (18 men and 8 women) consecutively treated with combinations of anti-TB drugs including LZD from 2009 to 2015. The sputum culture results were negative after using LZD for an average period of 28.0 ± 12.0 (average ± SD) days. LZD was reduced or withdrawn in 11 cases due to adverse effects. Nineteen cases including 3 XDR-TB patients were operated on, and their TB was treated following surgery. The average time from the initiation of LZD therapy to surgery was 87.6 ± 38.7 (average ± SD) days. Favorable clinical outcome was maintained in 23 surviving patients, while 3 patients died during treatment because of end stage cancer and aspiration pneumonia. Our study showed that LZD might be clinically effective in the treatment of M/XDR-TB patients in Japan.

Background Successful surgical treatment of patients with Mycobacterium avium complex pulmonary disease is thought to require complete removal of parenchymal destructive lesions. This study aimed to evaluate the short-term and long-term outcomes and the predictors of microbiological recurrence after surgery for M avium complex pulmonary disease. Methods We conducted a retrospective review of 184 patients undergoing unilateral lung resection for M avium complex pulmonary disease at a single center in Japan between January 2008 and December 2017. Results Median age of the 184 patients was 55.5 years; 133 were female (72.3%). All but 2 patients had anatomical lung resection. A total of 116 patients had limited disease and underwent complete resection (63.0%); the remaining 68 patients had extensive disease and underwent debulking surgery (37.0%). No operative mortalities occurred. In 18 of 184 patients, 21 morbidities occurred (9.8%), including 3 bronchopleural fistulas (1.6%). Postoperative sputum-negative status was achieved in 183 patients (99.5%). Microbiological recurrences occurred in 15 patients (8.2%). By multivariate analysis, extensive disease was an independent risk factor for recurrence (hazard ratio, 5.432; 95% confidence interval, 1.372-21.50; P = .016). Recurrence-free rates were significantly higher in patients with limited disease compared with those with extensive disease (99.0%, 97.4%, and 95.0% versus 93.0%, 89.2%, and 75.1% at 1, 3, and 5 years, respectively; P Conclusions Complete resection of parenchymal destructive lesions can achieve excellent microbiological control for patients with limited M avium complex pulmonary disease. The efficacy of debulking surgery in patients with extensive disease needs further investigation.

Nontuberculous mycobacteriosis (NTM) has been increasing recently. The treatment of choice of NTM is chemotherapy. Surgical treatment is sometimes indicated for patients with refractory NTM. When NTM lesion is enlarging despite of chemotherapy, there are 2 possibilities:intractable NTM and co-existing lung cancer. A 67-year-old male had been treated for fibro-cavitary NTM in the right upper lobe with chemotherapy. The cavitary lesion, however, was growing in spite of 6 months treatment. We suspected of a co-existing lung cancer because SCC level and standardized uptake value (SUV) in positron emission tomography (PET)-computed tomography (CT) were high. Bronchoscopy was performed but revealed no malignancy. He underwent a right upper lobectomy and the intraoperative pathology indicated NTM with no malignancy. After the operation, SCC levels decreased. This is a rare case with preoperative high SCC level which seemed to be related to NTM lesion.

A symposium entitled "Legacies of surgery for tuberculosis and succession to the next generation" was held at the 89th annual meeting of The Japanese Society for Tuberculosis in Gifu. The purpose of the symposium was to look back at the history of surgery for tuberculosis and development of surgical techniques. The contribution of those techniques to the next generation was also discussed. Many unique and universal techniques such as segmentectomy, thoracoplasty, muscle flap plombage, greater omental plom- bage, open window thoracotomy, cavernostomy, and decortication have matured during a long history. Based on the development of antituberculous drugs, surgery seems to have a less important role. However, surgical techniques are still required for multi-drug resistant tuberculosis and non- tuberculous mycobacteriosis. Core techniques are apjlied in the surgery for many thoracic diseases, such as lung cancer, mycosis, pyothorax, and mesothelioma. This manuscript summarizes the presentations.

The management of macrolide-resistant Mycobacterium avium complex (MR-MAC) pulmonary disease is difficult and is thought to be analogous to that of multidrug-resistant tuberculosis (MDR-TB).This study aimed to clarify the cause of MR-MAC, to see how its management affected outcome, and to compare its prognosis with that of MDR-TB.The medical records of 102 consecutive cases with MR-MAC pulmonary disease at three tertiary hospitals for mycobacteriosis in metropolitan Tokyo and one in Aichi prefecture from 2005 to 2014 were reviewed. The data of 311 consecutive cases with MDR-TB were extracted from the medical data at Fukujuji Hospital.Of the 90 patients who met the criteria, 53 (58.9%) received inappropriate first-line treatment, and 28 (31.1%) deviated from the standard treatment because of the adverse effects of ethambutol. The survival rates for MR-MAC disease and MDR-TB were not significantly different (P = 0.6). Multivariate analysis showed that the combination of aminoglycoside and surgery resulted in the best treatment outcome (P = 0.02), although neither of the two factors reached significance by themselves. The continuation of clarithromycin and the addition of fluoroquinolones did not improve the outcome for the treatment of disease caused by MR-MAC.Inappropriate prescription patterns and deviations from the standard treatment because of adverse drug reactions appeared to be the main causes of macrolide resistance in this patient series. Drug sensitivity testing should be performed at diagnosis to identify macrolide resistance and patients who may benefit from other therapy.

The incidence of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, while that of tuberculosis (TB) is decreasing in many industrialized countries, including Japan. However, the long-term evaluation of clinico-epidemiological features of NTM-PD in relation to TB are limited. We aimed to clarify the long-term changes in the epidemiology and clinical features of NTM-PD in relation to those of TB at a nationally-designated TB center in Japan.We reviewed all mycobacterial examination records at Fukujuji Hospital between 2006 and 2016. Cases of NTM-PD were defined according to the 2007 American Thoracic Society/Infectious Disease Society of America microbiologic criteria. The current characteristics of Mycobacterium avium complex pulmonary disease (MAC-PD) were compared with those in the 1980s and circa 2000.We identified a total of 3,546 pulmonary TB cases and 2,155 NTM-PD cases. While the annual number of incident pulmonary TB cases remained stable over the study period (P = 0.59), that of NTM-PD cases increased significantly from 165 to 278 (P 0.01). The mean age of pulmonary TB cases increased from 59.7 ± 16.3 to 66.2 ± 21.7 years, whereas that of NTM-PD cases remained unchanged. Regarding the age distribution, the greatest increases were observed in patients over 75 years for TB and in patients 50-74 years for NTM. The most common causative organism for NTM was Mycobacterium avium complex (87.3%), M. abscessus complex (5.5%) and M. kansasii (3.9%). Among patients with MAC-PD, the proportion of the nodular bronchiectatic (NB) form increased significantly from 60.0% to 84.4% between circa 2000 and 2016 (P 0.01). Significant increases in the NB form were observed in both males (33.3%-70.7%, P 0.01) and females (71.3%-89.2%, P 0.01).The annual number of incident NTM-PD cases increased markedly. In contrast to patients with TB, the mean age of new NTM-PD patients did not increase in the last 10 years. Among MAC-PD patients, the proportions accounted for by the NB form increased significantly in both sexes.

Non-cystic fibrosis bronchiectasis (bronchiectasis) is an abnormal dilatation of the bronchi and bronchioles, resulting from a prolonged recurrent infectious process due to various causes and predisposing factors. This disease has several etiologies and affects a heterogeneous population of patients. The most important viewpoint for the surgical management of bronchiectasis is to select appropriate candidates for surgery and conduct suitable anatomic lung resections at the right time under appropriate conditions. The ideal candidates for lung resection are symptomatic patients with focal disease due to truly localized bronchial pathology regardless of optimal and absolute medical management.

BACKGROUND Although Mycobacterium gordonae isolation from respiratory samples is usually regarded as contamination, M. gordonae can cause definite pulmonary disease. The establishment of a standard diagnostic criteria of pulmonary disease that is caused by this low virulence mycobacterium is obviously necessary. METHODS We performed clinical research on over 200 cases in which M. gordonae was isolated over an 8-year period, focusing on the M. gordonae subtype. Sequence analysis of rpoB was performed to identify the genotypes. RESULTS A total of 287 respiratory samples (209 cases) were positive for M. gordonae. Twenty-seven cases (12.9%) had a positive culture more than twice and 11 of these cases (5.3%) had more than three positive cultures. Ultimately, three cases (1.4%) were newly diagnosed as M. gordonae pulmonary disease using our own diagnostic criteria. In all of the identified M. gordonae cases, the cultures tested positive with a Mycobacteria Growth Indicator Tube test at 24 days; however, in patients with definitive pulmonary disease, the cultures were positive at 9 days. A subtype analysis revealed that all of the definitive disease cases had subtype C. CONCLUSION The time taken to detect a positive culture and subtype of the isolates could be used as the diagnostic criteria for definite M. gordonae pulmonary disease.

OBJECTIVE Body weight loss in patients with Mycobacterium avium complex (MAC) pulmonary disease can be fatal. The administration of nutritional supplements should be an important component in the treatment of this disease. Objective data regarding the association between the nutritional status and disease severity have not been reported. This cross-sectional study aimed to compare the nutritional status and radiological severity scores in MAC pulmonary disease patients. METHODS We retrospectively reviewed the records of 40 patients who were admitted to our institution for the treatment of MAC pulmonary disease between July 2008 and July 2010. Nutritional indices, including the ideal body weight ratio, triceps skinfold, mid-upper arm muscle circumference, and percentage of predicted resting energy expenditure, were compared with the radiological severity scores. Quantitative values of the extent of nodules, infiltration shadows, cavities, and bronchiectasis on the computed tomography scans were used to evaluate the radiological severity scores. RESULTS The patients suffered from a significantly decreased percentage of ideal body weight, body fat and muscle mass. The average radiological score was 17.6±8.4 points. The percentage of ideal body weight (p

Background According to the 2007 American Thoracic Society/Infectious Diseases Society of America statement on nontuberculous mycobacterial diseases, more evidence for the benefits of adjuvant nontuberculous mycobacterial lung disease surgical intervention is needed before its wide application can be recommended. Methods A retrospective review was conducted of 60 consecutive patients who met American Thoracic Society/Infectious Diseases Society of America diagnostic criteria and underwent pulmonary resection for localized nontuberculous mycobacterial lung disease between January 2007 and December 2011. All patients were receiving chemotherapy before resection. Results Included were 41 women (68%) and 19 men (32%), with a median age of 50 years (range, 20 to 72 years). Of these, 55 patients (92%) had Mycobacterium avium complex disease. Bronchiectatic disease was noted in 29 patients, cavitary disease in 25, both in 4, and nodular disease in 2. The indications for resection were a poor response to drug therapy in 52 patients, hemoptysis in 6, and a secondary infection in 2. Sixty-five pulmonary resections were performed: 1 pneumonectomy, 3 bilobectomies, 39 lobectomies, 17 segmentectomies, 3 lobectomies plus segmentectomies, and 2 wedge resections. There were no operative deaths, and all patients attained sputum-negative status postoperatively. Eleven postoperative complications occurred in 8 patients (12%); relapse was observed in only 2 (3%). Conclusions Pulmonary resection combined with chemotherapy is safe, with favorable treatment outcomes, for patients with localized nontuberculous mycobacterial lung disease. Our results support the liberal use of operations for nontuberculous mycobacterial lung disease whenever indicated.

The role of so-called “group 5” second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB.Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death.Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1–6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study.The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Human urotensin II (U-II), the most potent vasoconstrictor undecapeptide identified to date, and its receptor (UT) are involved in the pathogenesis of systemic and pulmonary hypertension. Here, we review recent advances in our understanding of the pathophysiology of U-II with particular reference to its role in atherosclerotic cardiovascular diseases. Single-nucleotide polymorphisms of U-II gene (S89N) are associated with onset of essential hypertension, type II diabetes mellitus, and insulin resistance in the Asian population. Plasma U-II levels are elevated in patients with vascular endothelial dysfunction-related diseases such as essential hypertension, diabetes mellitus, atherosclerosis, ischemic heart disease, and heart failure. Chronic infusion of U-II enhances atherosclerotic lesions in the aorta in apolipoprotein E-knockout mice. In human atherosclerotic plaques from the aorta and coronary and carotid arteries, U-II is expressed at high levels in endothelial cells (ECs) and lymphocytes, whereas UT is expressed at high levels in vascular smooth muscle cells (VSMCs), ECs, monocytes, and macrophages. U-II stimulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in human ECs as chemoattractant for monocytes, and accelerates foam cell formation by up-regulation of acyl-coenzyme A:cholesterol acyltransferase-1 in human monocyte-derived macrophages. U-II produces reactive oxygen species (ROS) via nicotinamide adenine dinucleotide phosphate oxidase activation in human VSMCs, and stimulates VSMC proliferation with synergistic effects when combined with ROS, oxidized LDL, and serotonin. Clinical studies demonstrated increased plasma U-II levels in accordance with the severity of carotid atherosclerosis in patients with essential hypertension and that of coronary artery lesions in patients with ischemic heart disease. Here, we summarize the key roles of U-II in progression of hypertension and atherosclerotic cardiovascular diseases.

Objective Our recent studies have indicated that urotensin II, the most potent vasoconstrictor peptide identified to date, potentiates human macrophage foam cell formation and vascular smooth muscle cell proliferation, and its levels are increased in the plasma of hypertensive patients with carotid atherosclerotic plaques. In the present study, we investigated the enhancing effect of urotensin II on atherosclerosis in apolipoprotein E-knockout mice and its suppression by 4-aminoquinoline, an urotensin II receptor-selective antagonist. Methods Urotensin II, urotensin II + 4-aminoquinoline, or vehicle was infused for 4 weeks through an osmotic mini-pump into 9-week-old apolipoprotein E-knockout mice on a high-fat diet. Aortic atherosclerosis and foam cell formation in exudate peritoneal macrophages were examined. Results Atherosclerotic lesions as well as plasma levels of urotensin II, reactive oxygen species, and oxidized low-density lipoprotein and oxidized low-density lipoprotein-induced foam cell formation were significantly greater in urotensin II-infused mice than vehicle-infused controls. Western blotting analysis showed increased expression of scavenger receptors (CD36 and scavenger receptor class A) and acyl-CoA:cholesterol acyltransferase-1 in these macrophages. Increases in these parameters were significantly reduced by addition of 4-aminoquinoline. In apolipoprotein E-knockout mice even without urotensin II infusion, the treatment with 4-aminoquinoline for 8 weeks significantly prevented the development of atherosclerotic lesions. Conclusion Our results provide the first evidence that increased plasma urotensin II level stimulates oxidized low-density lipoprotein and reactive oxygen species production and macrophage foam cell formation via increased expression of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1, contributing to the development of atherosclerosis in apolipoprotein E-deficient mice. Urotensin II receptor antagonism may be a promising therapeutic strategy against atherosclerosis.