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.
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.
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 < .001).
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.
We may encounter patients with chronic empyema for whom open-window thoracostomy is unavoidable. However, patients with chronic empyema are sometimes at high-risk for surgery under general ...anesthesia. We, herein, present our surgical experience with three chronic empyema cases who underwent open-window thoracostomy under local anesthesia. Indications for open-window thoracostomy under local anesthesia were raised PaCO2 in Case 1, old age and poor performance status in Case 2, and a history of esophageal reconstruction and vocal cordoplasty in Case 3. All patients were well during the surgery. Case 1 developed type 2 respiratory failure postoperatively and had to be put on a ventilator, but finally recuperated. The sedatives used could have exacerbated raised PaCO2 in this patient, and careful selection of anesthetic agents is mandatory. Considering pain and stress that patients suffer during open-window thoracostomy under local anesthesia, case selection is necessary. Nevertheless, we believe that open-window thoracostomy under local anesthesia is an effective option for high-risk patients.
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.
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.
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%).
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.
Tuberculosis (TB) and
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.
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.
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.
In total, 35 patients were analyzed. The preoperatively symptomatic group had significantly lower preoperative HRQOL than the preoperatively asymptomatic group (p <0.05). 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).
The combination of surgical treatment and physical therapy for NTM-PD contributes to improvements in physical function and HRQOL.
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 <0.05). 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).Conclusion: The combination of surgical treatment and physical therapy for NTM-PD contributes to improvements in physical function and HRQOL.
Pyrethroid insecticides have been shown to possess thyroid hormone disrupting properties in previous animal studies. In this study, the relationship between maternal exposure to pyrethroid ...insecticides during pregnancy and neonatal thyroid hormone status (free thyroxine (fT4) and thyroid stimulating hormone (TSH) in whole blood) and birth sizes were explored in 147 mother–neonate pairs in Tokyo. The concentration of 3-phenoxybenzoic acid (3-PBA) in maternal urine, sampled in the first trimester of gestation, was used for pyrethroid exposure assessment. Neonatal fT4 and TSH were within the normal range except for one elevated TSH (but normal fT4) in a neonate. Multiple regression analyses with stepwise variable selection did not extract maternal 3-PBA as significant for neonatal fT4 and TSH, indicating that maternal pyrethroid exposure had no apparent effect on the neonatal thyroid hormone status of the neonate subjects. For birth weight and head circumference, maternal 3-PBA was selected as significant with a positive partial regression coefficient along with other factors known to increase birth sizes of neonates (gestational weeks or maternal BMI). It was not clear if this was causal because no biological mechanism was apparent.
•We examined relationship between neonatal fT4 and TSH and maternal pyrethroid exposure.•The relationship between pyrethroid exposure and neonatal body size was also exploired.•Urinary metabolite (3-PBA) level was used as a biomarker of pyrethroid exposure.•Multiple regression analysis did not extract urinary 3-PBA as significant for neonatal fT4 and TSH.•Maternal urinary 3-PBA was a significant predictor of birth size and head circumference.
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.
Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10–12 gestational weeks recruited at a ...university hospital in Tokyo during 2009–2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06)μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83–3.41ng/dL, 0.01–27.4μIU/mL and 16.4–54.4μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected.
•Pyrethroid exposure and thyroid hormone status was examined in pregnant women.•Urinary 3-phenoxybenzoic acid was used as a biomarker of exposure.•Iodine nutrition, age and other covariates were included in statistical models.•No association was found between levels of thyroid hormone and pyrethroid exposure.•The result may be ascribed to lower exposure level.
Abstract
We report on multi-wavelength monitoring observations of an M-dwarf flare star AD Leonis with the Seimei Telescope (6150–7930 Å), SCAT (Spectroscopic Chuo-university Astronomical Telescope; ...3700–7500 Å), and NICER (Neutron Star Interior Composition Explorer; 0.2–12.0 keV), with the collaboration of the OISTER (Optical and Infrared Synergetic Telescopes for Education and Research) program. Twelve flares are detected in total, including ten Hα, four X-ray, and four optical-continuum flares; one of them is a superflare with a total energy of ∼2.0 × 1033 erg. We found that: (1) during the superflare, the Hα emission line full width at 1/8 maximum dramatically increases to 14 Å from 8 Å in the low-resolution spectra (R ∼ 2000) accompanied by large white-light flares, (2) some weak Hα/X-ray flares are not accompanied by white-light emissions, and (3) the non-flaring emissions show clear rotational modulations in X-ray and Hα intensity in the same phase. To understand these observational features, one-dimensional hydrodynamic flare simulations are performed using the RADYN code. We find the simulated Hα line profiles with hard and high-energy non-thermal electron beams to be consistent with the initial phase line profiles of the superflares, while those with a softer and/or weak-energy beam are consistent with those in decay phases, indicating the changes in the energy fluxes injected to the lower atmosphere. Also, we find that the relation between the optical continuum and Hα intensity is nonlinear, which can be one cause of the non-white-light flares. The flare energy budget exhibits diversity in the observations and models, and more observations of stellar flares are necessary for constraining the occurrence of various emission line phenomena in stellar flares.
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