Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Gene Polymorphisms of NLRP3 Associated With Plasma Levels of 4ß-Hydroxycholesterol, an Endogenous Marker of CYP3A Activity, in Patients With Asthma.

Inflammation decreases the activity of cytochrome P450 3A (CYP3A). Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) is responsible for regulating the inflammatory response, and its genetic polymorphisms have been linked to inflammatory diseases such as asthma. However, there have been few studies on the effect of NLRP3 on CYP3A activity. We aimed to investigate the association between polymorphisms in the NLRP3 gene and plasma 4ß-hydroxycholesterol (4ßOHC), an endogenous marker of CYP3A activity, in patients with asthma. In this observational study including 152 adult asthma patients, we analyzed 10 NLRP3 gene single-nucleotide polymorphisms (SNPs). Plasma 4ßOHC levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The results showed that five SNPs were associated with significantly lower plasma 4ßOHC concentrations. Among these SNPs, rs3806265, rs4612666, rs1539019, and rs10733112 contributed to a significant increase in plasma IL-6 concentrations. Moreover, a multivariate regression model showed that the rs3806265 TT, rs4612666 CC, rs1539019 AA, and rs10733112 TT genotypes were significant factors for decreased plasma 4ßOHC, even after including patient background factors and CYP3A5*3 (rs776746) gene polymorphisms as covariates. These results were also observed when plasma 4ßOHC concentrations were corrected for cholesterol levels. We conclude that NLRP3 gene polymorphisms are involved in increasing plasma IL-6 concentrations and decreasing plasma 4ßOHC concentrations in patients with asthma. Therefore, NLRP3 gene polymorphisms may be a predictive marker of CYP3A activity in inflammatory diseases such as asthma.

Association of the predicted free blood concentration of teicoplanin with the development of renal dysfunction.

PURPOSE: In clinical practice, teicoplanin (TEIC) is typically administered at a trough concentration of 15-40 µg/mL. TEIC has a protein binding rate of approximately 90%, and its concentration rarely exceeds 40 µg/ml. Nevertheless, an increase in the free blood trough concentration may result in renal dysfunction. However, the relationship between the free blood trough concentration and the occurrence of renal dysfunction remains unclear. This study aimed to examine the impact of the predicted free blood concentration on the development of renal dysfunction. METHODS: This retrospective study included patients who underwent TEIC and had at least one trough concentration measurement. The association between the frequency of renal dysfunction occurrence and the predicted free blood concentration was evaluated using the following equation: free TEIC concentration = total TEIC concentration/(1 + 1.78 × serum albumin level). RESULTS: Of the 170 patients included in this study, 18% (31/170) developed renal dysfunction. The predicted free trough concentration was significantly higher in the renal dysfunction onset group than in the nononset group. However, the total trough concentration was not significantly associated with the development of renal dysfunction. The odds ratio for developing renal dysfunction was 4.5 (95% confidence interval, 1.9-10.5; P < 0.001) when the predicted free trough concentration was > 4.0 µg/mL. CONCLUSION: Elevated free trough concentrations of TEIC were associated with an increased risk of renal dysfunction. Controlling the increase in the predicted free blood concentration may effectively prevent the development of renal dysfunction.

[Developing Biomarkers in Precision Medicine for Asthma and COPD].

There is a growing demand for the implementation of precision medicine. There is an urgent need to move away from one-size-fits-all medicine, in which the treatment is based on the disease name alone, and to implement a precision-medicine approach. Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) require a precision-medicine approach. Asthma and COPD are heterogeneous disorders with various phenotypes. In order to characterize the pathological features of a patient, it is important to analyze not only the phenotype, but also the molecular mechanisms underlying the clinical features, called endotypes. It is crucial to customize the treatment of the disease according to both the phenotype and endotype. Therefore, developing biomarkers enabling treatment stratification is essential to the practice of precision medicine. This approach of finding optimal treatment by identifying patient features using biomarkers is known as a treatable-traits approach. We conducted clinical and basic studies to identify patients with COPD who could be treated with asthma medications and to identify the pathological features of patients with COPD and asthma (asthma-COPD overlap: ACO). We identified several blood proteins and microRNAs that have potential for be clinically useful as biomarkers for customizing treatment in patients with ACO.

Impaired cough-related quality of life in patients with nontuberculous mycobacteriosis.

BACKGROUND: Cough and sputum are the significant symptoms of nontuberculous mycobacteriosis (NTM) and impair quality of life (QOL). However, the relationship between these symptoms and clinical features is not fully understood. This study aimed to investigate cough-related QOL in NTM patients. METHODS: The study subjects included 78 patients with NTM at our hospital from October to December 2015. They completed the Leicester Cough Questionnaire (LCQ) and the Cough and Sputum Assessment Questionnaire (CASA-Q) (both questionnaires: the higher, the better); the Frequency Scale for the Symptoms of gastroesophageal reflux disease (GERD) (FSSG), a validated Japanese questionnaire for GERD (the higher, the worse), was also assessed. The FSSG consists of 12 items, including the reflux-related symptoms and dysmotility symptoms domains, each of which is quantified on a scale of 0-4 points, and the cut-off score for GERD is set at 8 points. Associations between these scores and clinical parameters were assessed. RESULTS: The total LCQ score was reduced-the physical domain was dominant. The total LCQ and CASA-Q scores were reduced, with dominance in the physical and symptoms domains, respectively. The reflux-related symptoms score was higher than the dysmotility symptoms score. A multivariate linear regression analysis revealed that the mean total LCQ score was independently associated with current smoking, fibrocavitary type, bilateral cavitary lesion, and FSSG total score. CONCLUSIONS: Cough-related QOL was impaired in NTM patients who currently smoked, had radiological characteristics, and had GERD.

Evaluating the Influence of ipRGCs on Color Discrimination.

To investigate the influence of intrinsically photosensitive retinal ganglion cells (ipRGCs) on color discrimination, it is necessary to create two metameric light stimuli (metameric ipRGC stimuli) with the same amount of cone and rod stimulation, but different amounts of ipRGC stimulation. However, since the spectral sensitivity functions of cones and rods overlap with those of ipRGCs in a wavelength band, it has been difficult to independently control the amount of stimulation of ipRGCs only. In this study, we first propose a method for calculating metameric ipRGC stimulation based on the orthogonal basis functions of human photoreceptor cells. Then, we clarify the controllable range of metameric ipRGC stimulation within a color gamut. Finally, to investigate the color discrimination by metameric ipRGC stimuli, we conduct subjective evaluation experiments on 24 chromaticity coordinates using a multispectral projector. The results reveal a correlation between differences in the amount of ipRGC stimulation and differences in color appearance, indicating that ipRGCs may influence color discrimination.

Fabrication of a Human Skin Mockup with a Multilayered Concentration Map of Pigment Components Using a UV Printer.

In this paper, we propose a pipeline that reproduces human skin mockups using a UV printer by obtaining the spatial concentration map of pigments from an RGB image of human skin. The pigment concentration distributions were obtained by a separating method of skin pigment components with independent component analysis from the skin image. This method can extract the concentration of melanin and hemoglobin components, which are the main pigments that make up skin tone. Based on this concentration, we developed a procedure to reproduce a skin mockup with a multi-layered structure that is determined by mapping the absorbance of melanin and hemoglobin to CMYK (Cyan, Magenta, Yellow, Black) subtractive color mixing. In our proposed method, the multi-layered structure with different pigments in each layer contributes greatly to the accurate reproduction of skin tones. We use a UV printer because the printer is capable of layered fabrication by using UV-curable inks. As the result, subjective evaluation showed that the artificial skin reproduced by our method has a more skin-like appearance than that produced using conventional printing.

Mucus Plugs and Small Airway Dysfunction in Asthma, COPD, and Asthma-COPD Overlap.

PURPOSE: There are reports concerning mucus plugs detected on high-resolution computed tomography images and airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). However, little is known about the associations between mucus plugs and small airway dysfunction (SAD). We evaluated the relationship between mucus plugs and pulmonary function in patients with asthma, COPD, and asthma-COPD overlap (ACO), and investigated the relevance to SAD and type 2 inflammation in a retrospective study. METHODS: Subjects included 49 asthmatic, 40 ACO, and 41 COPD patients. ACO was diagnosed based on the Japanese Respiratory Society ACO guidelines. Clinical and laboratory parameters, including blood eosinophil count, serum total IgE levels, fractional exhaled nitric oxide (FeNO), spirometry, and forced oscillation technique (FOT), were compared between patients with and without mucus plugs. RESULTS: Mucus plugs were found in 29 (59%) asthmatic, 25 (65%) ACO, 17 (41%) COPD patients. Patients with mucus plugs had reduced spirometry and larger FOT parameters, especially in COPD patients. Mucus scores correlated positively with IgE in ACO and FeNO in asthmatic patients, but not in COPD patients. Multivariate logistic regression analysis revealed that SAD parameters, including forced vital capacity and resonant frequency, a respiratory reactance parameter, were significantly associated with the presence of mucus plugs in the whole studied population. CONCLUSIONS: SAD, rather than large airway dysfunction, was associated with mucus plugs in asthma, ACO, and COPD patients.

Forced oscillatory parameters as predictors of COPD assessment test improvement in untreated COPD patients.

BACKGROUND: Few studies have examined whether baseline spirometry and the forced oscillation technique (FOT) would predict The COPD Assessment Test (CAT) score improvement after treatment of untreated COPD patients. METHODS: The study subjects included 65 untreated COPD patients. They underwent the CAT, spirometry, and FOT (MostGraph) before and after treatment for more than 2 months. In addition, recursive partitioning analysis was performed using spirometry and the FOT parameters to identify the predictors of CAT improvement (CAT score ≥2). RESULTS: CAT scores and lung function significantly improved after treatment. Recursive partitioning analysis identified 3 improved classes, defined by Rrs at 20 Hz (R20), Xrs at 5 Hz (X5), and ΔX5, but not by spirometry. The accuracy of predicting CAT improvement was as follows: odds ratio, 25.3; 95 % confidence interval, 6.1 to 104.1; sensitivity, 91.2 %; specificity, 71.0 %; positive likelihood ratio, 3.14; and negative likelihood ratio, 0.12. CONCLUSIONS: FOT helps predict improved health status in untreated COPD patients.

Blood eosinophil count and FeNO to predict benralizumab effectiveness in real-life severe asthma patients.

OBJECTIVE: Benralizumab is a promising drug for severe uncontrolled asthma. This study aimed to clarify the effectiveness of benralizumab in a real-life setting. METHODS: Subjects included 24 patients with severe type 2 asthma who received benralizumab between April 2018 and July 2019. Changes in parameters, exacerbation frequency, and oral corticosteroid (OCS) use after 4 and 24 weeks of administration were examined. The parameters included the Global Evaluation of Treatment Effectiveness (GETE) scale, Asthma Control Questionnaire (ACQ), Asthma Control Test (ACT), blood eosinophils, fractional exhaled nitric oxide (FeNO), and spirometry. The response to treatment was defined as follows: for patients with exacerbations or OCS use before treatment initiation, a reduction of ≥50% in exacerbation frequency or OCS use; and for patients without exacerbations or OCS use, an improvement of ≥0.5 in ACQ scores and ≥3 in ACT scores, or of ≥10.38% in FEV1. RESULTS: Twenty-one patients completed the treatment for 24 weeks. Excellent and good GETE scales and ACQ and ACT improvement were found in 67% of the patients at 4 weeks, and the effect continued until 24 weeks. The patients' rate with exacerbations was significantly reduced compared to the previous 24 weeks before administration. In 17 patients receiving OCS, the use could be reduced or quit in 14 patients. Overall, 16 patients (76.2%) met the responder definition and could be predicted by the baseline eosinophil count and FeNO levels with the best cutoff values of 100/µL and 40 ppb, respectively. CONCLUSIONS: Blood eosinophil and FeNO could predict benralizumab effectiveness.

Predicting individual emotion from perception-based non-contact sensor big data.

This study proposes a system for estimating individual emotions based on collected indoor environment data for human participants. At the first step, we develop wireless sensor nodes, which collect indoor environment data regarding human perception, for monitoring working environments. The developed system collects indoor environment data obtained from the developed sensor nodes and the emotions data obtained from pulse and skin temperatures as big data. Then, the proposed system estimates individual emotions from collected indoor environment data. This study also investigates whether sensory data are effective for estimating individual emotions. Indoor environmental data obtained by developed sensors and emotions data obtained from vital data were logged over a period of 60 days. Emotions were estimated from indoor environmental data by machine learning method. The experimental results show that the proposed system achieves about 80% or more estimation correspondence by using multiple types of sensors, thereby demonstrating the effectiveness of the proposed system. Our obtained result that emotions can be determined with high accuracy from environmental data is a useful finding for future research approaches.

Circulating microRNA-15b-5p as a biomarker for asthma-COPD overlap.

BACKGROUND: It remains unclear how to characterize different subtypes of asthma and chronic obstructive pulmonary disease (COPD). We previously described serum periostin and chitinase-3-like protein 1 (YKL-40) as useful markers for asthma-COPD overlap (ACO). MicroRNAs (miRNAs) are now recognized as markers for identifying the pathophysiological features in several diseases. This study aimed to identify circulating miRNAs that could discriminate patients with ACO from patients with asthma or COPD. METHODS: This study included two independent cohorts. First, we screened 84 miRNAs for expression levels in patients with ACO (n = 6) or asthma (n = 6) using a quantitative real-time PCR array. The miRNAs showing at least a 2-fold difference in the discovery phase were analyzed in 30 patients each with asthma, COPD, or ACO in the replication phase. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: Nine miRNAs were identified in the discovery phase. Five of these miRNAs (miR-148a-3p, miR-15b-5p, miR-223-3p, miR-23a-3p, and miR-26b-5p) had lower levels in ACO patients and could discriminate between ACO patients and patients with either asthma or COPD. miR-15b-5p was the most accurate miRNA for the discrimination of patients with ACO (AUROC, 0.71). Moreover, the combined assessment of miR-15b-5p, serum periostin, and YKL-40 (AUROC, 0.80) improved diagnostic accuracy for ACO compared with the combined model of periostin and YKL-40 (AUROC, 0.69). CONCLUSIONS: Circulating miR-15b-5p is a potential marker for identifying patients with ACO. By elucidating the molecular pathways controlled by miRNAs, we may better understand the pathophysiology of ACO.