The epidemiology of pulmonary Mycobacterium abscessus species in Japanese population.

BACKGROUND: Mycobacterium abscessus species (MABS) is now a most virulent rapidly growing mycobacteria (RGM), and the rapid increase of MABS was recently observed worldwide, including in Japan. Thus, we gathered evidences of the presence of pulmonary MABS in Japanese population from Japanese articles. METHODS: we searched studies that addressed the isolation of pulmonary non-tuberculous Mycobacteria (NTM) or MABS from clinical respiratory specimens in Japan. RESULTS: the ratio of MABS to NTM was 3.04% (95% confidence interval [CI]: 2.51-3.68), found using the meta-analysis of single proportions. The estimated mean age of patients infected with MABS was 67.72 years (95% CI: 65.41-70.02), found using the meta-analysis of single means. The estimated proportion of females, never smoker, and the co-infection with Mycobacterium avium complex (MAC) was 66.75% (95% CI: 59.23-73.50), 67.57% (95% CI: 62.43-72.32), and 36.74% (95% CI: 25.30-49.90), respectively. The characteristics of MABS in Japan were considerably different from that in Europe and United States from the perspective of age, gender, and complications, wherein the patients in these countries tended to be younger, had lower number of females, and had more occurrences of hereditary diseases, including cystic fibrosis (CF). CONCLUSION: we hypothesized that the characteristics of MABS in the Japanese were involved in those of non-CF MABS, and the distribution of gender and age of MABS were similar to that of MAC in the Japanese.

Association between hospital-acquired functional decline and 2-year readmission or mortality after cardiac surgery in older patients: a multicenter, prospective cohort study.

BACKGROUND: Hospital-acquired functional decline (HAFD) is a new predictor of poor prognosis in hospitalized older patients. AIMS: We aimed to assess the impact of HAFD on the prognosis of older cardiac surgical patients 2 years after discharge. METHODS: This multicenter prospective cohort study assessed 293 patients with cardiac disease aged ≥ 65 years who underwent cardiac surgery at 7 Japanese hospitals between June 2017 and June 2018. The primary endpoint was the composite outcome of cardiovascular-related readmission and all-cause mortality 2 years after discharge. HAFD was assessed using the total Short Physical Performance Battery at hospital discharge. RESULTS: The primary outcome was observed in 17.3% of the 254 included patients, and HAFD was significantly associated with the primary outcome. Female sex (hazard ratio [HR], 2.451; 95% confidence interval [CI] 1.232-4.878; P = 0.011), hemoglobin level (HR, 0.839; 95% CI 0.705-0.997; P = 0.046), preoperative frailty (HR, 2.391; 95% CI 1.029-5.556; P = 0.043), and HAFD (HR, 2.589; 95% CI 1.122-5.976; P = 0.026) were independently associated with the primary outcome. The incidence rate of HAFD was 22%, with female sex (odds ratio [OR], 1.912; 95% CI 1.049-3.485; P = 0.034), chronic obstructive pulmonary disease (OR, 3.958; 95% CI 1.413-11.086; P = 0.009), and the time interval (days) between surgery and the start of ambulation (OR, 1.260, 95% CI 1.057-1.502; P = 0.010) identified as significant factors. DISCUSSION: HAFD was found to be an independent prognostic determinant of the primary outcome 2 years after discharge. CONCLUSION: HAFD prevention should be prioritized in the hospital care of older cardiac surgery patients.

Echo Intensity of Gastrocnemius Is Independently Associated with 6-Minute Walking Distance in Male Patients with Peripheral Arterial Disease.

Background and Objectives: This study aimed to examine the differences in the thickness and echo intensity (EI) of the gastrocnemius muscle measured via ultrasonography between healthy adults and patients with peripheral arterial disease (PAD) and to determine the associations of gastrocnemius thickness (GT) and EI within a 6 min walking distance (6MD) in patients with PAD. Materials and Methods: This cross-sectional study targeted 35 male patients with PAD (mean age, 73.7 years; mean body mass index [BMI], 23.5 kg/m2) and age- and gender-matched 73 male healthy adults (mean age, 73.2 years; mean BMI, 23.3 kg/m2). The gastrocnemius thickness (GT) and EI were measured using ultrasound. Both legs of patients with PAD were classified based on higher and lower ankle brachial pressure index (ABI), and the GTs and EIs with higher and lower ABI were compared with those of healthy adults. Multiple regression analysis incorporated 6MD as a dependent variable and each GT and EI with higher and lower ABI, age, and BMI as independent variables. Results: This study showed that GT was considerably greater in healthy adults than in both legs with higher and lower ABI (median values, 13.3 vs. 11.3 vs. 10.7, p < 0.01), whereas EI was lower in healthy adults than in the lower ABI leg (72.0 vs. 80.8 vs. 83.6, p < 0.05). The 6MD was shown to be substantially related to EI in both legs with higher and lower ABIs (p < 0.01) but not in the GT. Conclusions: In patients with PAD, the GT was lower, and EI was higher than in healthy adults. In addition, EIs in both legs with higher and lower ABIs were independently associated with 6MD in male PAD patients. This study showed that the EI measured via ultrasonography could become an important indicator for treatments for patients with PAD.

High lymphocyte population-related predictive factors for a long-term response in non-small cell lung cancer patients treated with pemetrexed: a retrospective observational study.

BACKGROUND: Regimens combining pemetrexed (PEM) and immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are widely used for the treatment of advanced non-squamous non-small-cell lung cancer (NSq-NSCLC). Recently, PEM was shown to induce immunogenic cell death (ICD) and to enhance immune-regulatory genes. Some patients demonstrate an extremely long-term response to PEM. It is possible that the continued response in these patients is dependent on not only the pharmacological induction of cytotoxic cell death but also antitumor immunity. However, factors that can predict outcomes associated with long-term PEM administration using blood test results have not yet been elucidated. We investigated the clinical characteristics and predictive factors in patients with advanced NSq-NSCLC who underwent long-term PEM maintenance therapy. METHODS: In total, 504 patients with advanced NSq-NSCLC who received PEM combination therapy/monotherapy (n = 414) or paclitaxel (PTX) combination therapy (n = 90) between January 2010 and November 2019 were recruited; 381 patients were retained for the final analysis. Patients treated with PEM (n = 301) were divided into subgroups according to the total cycles of PEM (≥ 17 [n = 25] for the long-term administration group and ≤ 16 [n = 276] for the intermediate/short-term group) and compared with another population (n = 80) treated with PTX combination regimen. We investigated clinical features and predictive biomarkers, focusing on immune-regulatory factors, absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), and PD-1 and PD-L1 expression, to predict long-term response to PEM. RESULTS: The long-term PEM administration group exhibited a higher ALC and a lower NLR than the shorter-term group did. Both these markers displayed greater association with progression-free survival and overall survival in the PEM combination therapy group than in the PTX combination therapy group. Increased PD-1 lymphocytes were associated with the long-term PEM response group, as PD-L1 expression in tumors was associated with a high incidence of immune-related adverse effects following ICI administration. CONCLUSIONS: ALC, NLR, and PD-1 expression are PEM-mediated predictive biomarkers that are indirectly related to tumor immunity and can provide useful predictive information on the long-term response to PEM in patients with NSq-NSCLC.

Formulation of objective indices to quantify machine failure risk analysis for interruptions in radiotherapy.

OBJECTIVES: To evaluate the effect of interruption in radiotherapy due to machine failure in patients and medical institutions using machine failure risk analysis (MFRA). MATERIAL AND METHODS: The risk of machine failure during treatment is assigned to three scores (biological effect, B; occurrence, O; and cost of labor and repair parts, C) for each type of machine failure. The biological patient risk (BPR) and the economic institution risk (EIR) are calculated as the product of B and O ( B × O ) and C and O ( C × O ), respectively. The MFRA is performed in two linear accelerators (linacs). RESULT: The multileaf collimator (MLC) fault has the highest BPR and second highest EIR. In particular, TrueBeam has a higher BPR and EIR for MLC failures. The total EIR in TrueBeam was significantly higher than that in Clinac iX. The minor interlock had the second highest BPR, whereas a smaller EIR. Meanwhile, the EIR for the LaserGuard fault was the highest, and that for the monitor chamber fault was the second highest. These machine failures occurred in TrueBeam. The BPR and EIR should be evaluated for each linac. Further, the sensitivity of the BPR, it decreased with higher T 1 / 2 and α/ß values. No relative difference is observed in the BPR for each machine failure when T 1 / 2 and α/ß were varied. CONCLUSION: The risk faced by patients and institutions in machine failure may be reduced using MFRA. ADVANCES IN KNOWLEDGE: For clinical radiotherapy, interruption can occur from unscheduled downtime with machine failures. Interruption causes sublethal damage repair. The current study evaluated the effect of interruption in radiotherapy owing to machine failure on patients and medical institutions using a new method, that is, machine failure risk analysis.

The synergetic effect of Imipenem-clarithromycin combination in the Mycobacteroides abscessus complex.

BACKGROUND: Nontuberculous mycobacteria (NTM) are ubiquitous organisms and the incidence of NTM infections has been increasing in recent years. Mycobacteroides abscessus (M. abscessus) is one of the most antimicrobial-resistant NTM; however, no reliable antibiotic regimen can be officially advocated. We evaluated the efficacy of clarithromycin in combination with various antimicrobial agents against the M. abscessus complex. RESULTS: Twenty-nine clinical strains of M. abscessus were isolated from various clinical samples. Of the isolates, 10 (34.5%) were of M. abscessus subsp. abscessus, 18 (62.1%) of M. abscessus subsp. massiliense, and 1 (3.4%) of M. abscessus subsp. bolletii. MICs of three antimicrobial agents (amikacin, imipenem, and moxifloxacin) were measured with or without clarithromycin. The imipenem-clarithromycin combination significantly reduced MICs compared to clarithromycin and imipenem monotherapies, including against resistant strains. The association between susceptibility of the M. abscessus complex and each combination of agents was significant (p = 0.001). Adjusted residuals indicated that the imipenem-clarithromycin combination had the synergistic effect (adjusted residual = 3.1) and suppressed the antagonistic effect (adjusted residual = - 3.1). In subspecies of M. abscessus complex, the association with susceptibility of M. abscessus subsp. massiliense was similarly statistically significant (p = 0.036: adjusted residuals of synergistic and antagonistic effect respectively: 2.6 and - 2.6). The association with susceptibility of M. abscessus subsp. abscessus also showed a similar trend but did not reach statistical significance. CONCLUSION: Our data suggest that the imipenem-clarithromycin combination could be the recommended therapeutic choice for the treatment of M. abscessus complex owing to its ability to restore antimicrobial susceptibility.

Prognostic differences among patients with idiopathic interstitial pneumonias with acute exacerbation of varying pathogenesis: a retrospective study.

BACKGROUND: Acute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs. METHODS: We retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs. RESULTS: Among the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death. CONCLUSIONS: Our findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.

Tolerance levels of mass density for CT number calibration in photon radiation therapy.

Computed tomography (CT) data are required to calculate the dose distribution in a patient's body. Generally, there are two CT number calibration methods for commercial radiotherapy treatment planning system (RTPS), namely CT number-relative electron density calibration (CT-RED calibration) and CT number-mass density calibration (CT-MD calibration). In a previous study, the tolerance levels of CT-RED calibration were established for each tissue type. The tolerance levels were established when the relative dose error to local dose reached 2%. However, the tolerance levels of CT-MD calibration are not established yet. We established the tolerance levels of CT-MD calibration based on the tolerance levels of CT-RED calibration. In order to convert mass density (MD) to relative electron density (RED), the conversion factors were determined with adult reference computational phantom data available in the International Commission on Radiological Protection publication 110 (ICRP-110). In order to validate the practicability of the conversion factor, the relative dose error and the dose linearity were validated with multiple RTPSes and dose calculation algorithms for two groups, namely, CT-RED calibration and CT-MD calibration. The tolerance levels of CT-MD calibration were determined from the tolerance levels of CT-RED calibration with conversion factors. The converted RED from MD was compared with actual RED calculated from ICRP-110. The conversion error was within ±0.01 for most standard organs. It was assumed that the conversion error was sufficiently small. The relative dose error difference for two groups was less than 0.3% for each tissue type. Therefore, the tolerance levels for CT-MD calibration were determined from the tolerance levels of CT-RED calibration with the conversion factors. The MD tolerance levels for lung, adipose/muscle, and cartilage/spongy-bone corresponded to ±0.044, ±0.022, and ±0.045 g/cm3 , respectively. The tolerance levels were useful in terms of approving the CT-MD calibration table for clinical use.

Synthesis and Photophysical Properties of λ5-Phosphinines as a Tunable Fluorophore.

A practical synthesis of a variety of λ5-phosphinines, which show distinct fluorescence both in solution and solid state, is described. Both C4-selective electrophilic substitutions and the following conversions realized an easy preparation of a wide range of derivatives having several substituents for electronic modification, which provides the potential for fine-tuning of the photophysical properties.

Tolerance levels of CT number to electron density table for photon beam in radiotherapy treatment planning system.

The accuracy of computed tomography number to electron density (CT-ED) calibration is a key component for dose calculations in an inhomogeneous medium. In a previous work, it was shown that the tolerance levels of CT-ED calibration became stricter with an increase in tissue thickness and decrease in the effective energy of a photon beam. For the last decade, a low effective energy photon beam (e.g., flattening-filter-free (FFF)) has been used in clinical sites. However, its tolerance level has not been established yet. We established a relative electron density (ED) tolerance level for each tissue type with an FFF beam. The tolerance levels were calculated using the tissue maximum ratio (TMR) and each corresponding maximum tissue thickness. To determine the relative ED tolerance level, TMR data from a Varian accelerator and the adult reference computational phantom data in the International Commission on Radiological Protection publication 110 (ICRP-110 phantom) were used in this study. The 52 tissue components of the ICRP-110 phantom were classified by mass density as five tissues groups including lung, adipose/muscle, cartilage/spongy-bone, cortical bone, and tooth tissue. In addition, the relative ED tolerance level of each tissue group was calculated when the relative dose error to local dose reached 2%. The relative ED tolerances of a 6 MVFFF beam for lung, adipose/muscle, and cartilage/spongy-bone were ±0.044, ±0.022, and ±0.044, respectively. The thicknesses of the cortical bone and tooth groups were too small to define the tolerance levels. Because the tolerance levels of CT-ED calibration are stricter with a decrease in the effective energy of the photon beam, the tolerance levels are determined by the lowest effective energy in useable beams for radiotherapy treatment planning systems.