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Interstitial lung abnormalities (ILAs) are immune checkpoint inhibitor (ICI)-related pneumonitis (ICI-P) risk factors. However, the relationship between imaging patterns and immunotherapy outcomes, and treatment strategies remain unclear in patients with non-small cell lung cancer (NSCLC) and ILAs. We retrospectively evaluated patients with ILAs-complicated NSCLC who received ICI therapy. ILAs were subcategorized as non-subpleural, subpleural non-fibrotic, and subpleural fibrotic (SF) based on the 2020 position paper by the Fleischner Society. We investigated ICI-P incidence, ICI-P risk factors, lung cancer prognosis, and ILAs radiological progression. Of the 481 ICI-treated patients, 79 (16.4%) had ILAs (45 non-SF and 34 SF). The ICI-P cumulative incidence (hazard ratio, 4.57; 95% confidence interval [CI], 1.90–10.98; p = 0.001) and any grade and grade ≥ 3 ICI-P incidences were higher in patients with SF-ILAs than in those with non-SF-ILAs (all grades: 7/45 [15.6%)] vs. 18/34 [52.9%]; p < 0.001; grade ≥ 3: 1/45 [2.2%] vs. 10/34 [29.4%]; p = 0.001). According to multivariate analysis, SF-ILAs independently predicted ICI-P (odds ratio, 5.35; 95% CI 1.62–17.61; p = 0.006). Patients with SF-ILAs had shorter progression-free and overall survival and higher ICI-P-related respiratory failure death rates than those with non-SF-ILAs. Approximately 2.5 times more patients with SF-ILAs showed progression by the 2-year follow-up than those with non-SF-ILAs. SF-ILAs is an independent strong predictor of ICI-P development in patients with NSCLC, may increase ICI-P severity, worsen prognosis, and accelerate ILAs progression. ILAs subcategorization is an important treatment strategy for patients with lung cancer treated with ICIs. [ABSTRACT FROM AUTHOR]

Background: The number of adult patients with childhood-onset chronic diseases is increasing. However, the process of transitioning these patients from child- to adult-centered medical services faces many difficulties. Despite the key role that doctors in the pediatric field are considered to play in transition, few fact-finding surveys about transition have been conducted among these doctors. Objective: The aim of this study was to demonstrate the current status and challenges in the transition of patients with childhood-onset chronic diseases by a fact-finding survey of pediatricians and pediatric surgeons at a university hospital. Methods: A cross-sectional survey was performed using an anonymous self-administered questionnaire. Seventy-six doctors of pediatrics and pediatric surgery (excluding junior residents) in a university hospital were asked to answer an anonymous self-report questionnaire. A multidisciplinary research team selected items related to the transitional process. Results: Sixty (79%) doctors participated, of whom 52 (87%) showed awareness of transition. No doctor answered that "Transition is conducted smoothly." Doctors with shorter pediatric department experience had lower awareness and poorer experience with transition. In contrast to pediatric surgeons, pediatricians explained "job-seeking activities" and "contraceptive methods" to the patient, and reported a higher patient age at which to initiate explanation of transition to the patient and his/her family. Among factors inhibiting transition, 39 (65%) respondents selected "The patient's family members do not desire transition" and 34 (57%) selected "Although a relevant adult healthcare department is available, it will not accept the patient." The medical providers most frequently considered to have responsibility for playing a central role in the transition process were "pediatrician/pediatric surgeon," "medical social worker," and "regional medical liaison office." Discussion: To promote transition, pediatric and adult healthcare departments should share concerns about and cooperate in the establishment of more effective methods of transition, and provide multidisciplinary collaboration to support patients and their families. [ABSTRACT FROM AUTHOR]

Background: Predicting the incidence of chemotherapy‐triggered acute exacerbation of interstitial lung disease (AE‐ILD) in patients with lung cancer is important because AE‐ILD confers a poor prognosis. The Glasgow prognostic score (GPS), which is an inflammation‐based index composed of serum levels of C‐reactive protein and albumin, predicts prognosis in patients with small cell lung cancer (SCLC) without ILD. In this study, we investigated AE‐ILD and survival outcome based on the GPS in patients with ILD associated with SCLC who were receiving chemotherapy. Methods: Medical records of patients who received platinum‐based first‐line chemotherapy between June 2010 and May 2019 were retrospectively reviewed to compare the incidence of AE‐ILD and overall survival (OS) between GPS 0, 1, and 2. Results: Among our cohort of 31 patients, six (19.3%) experienced chemotherapy‐triggered AE‐ILD. The AE‐ILD incidence increased from 9.5% to 25.0% and 50.0% with increase in GPS of 0, 1, and 2, respectively. Univariate and multivariate analyses revealed remarkable associations between GPS 2 and both AE‐ILD (odds ratio for GPS 2, 18.69; p = 0.046) and prognosis (hazard ratio of GPS 2, 13.52; p = 0.002). Furthermore, median OS in the GPS 0, 1, and 2 groups was 16.2, 9.8, and 7.1 months, respectively (p < 0.001). Conclusions: Our results suggest that GPS 2 is both a predictor of risk of chemotherapy‐triggered AE‐ILD and a prognostic indicator in patients with ILD associated with SCLC. We propose that GPS may be used as a guide to distinguish chemotherapy‐tolerant patients from those at high risk of AE‐ILD. [ABSTRACT FROM AUTHOR]

Aim: To verify the reliability and validity of a Japanese translation of the Satter eating competence Inventory‐2.0™ (ecSI‐2.0™) for parents of fifth and sixth grade elementary school students. Methods: Participants were parents who prepared meals for their children aged 10–12 years. A preliminary study was conducted with 11 parents using semi‐structured interviews and questionnaires, followed by a main study of 2,825 parents. Internal consistency and test–retest methods were used to verify reliability. Face and content validity were confirmed in the preliminary study, and feasibility was examined by the valid response rate and response time. Construct validity was verified using factor validity and known population validity. Results: Of the 2,825 persons surveyed, 626 returned valid responses, and among the 60 persons who received the re‐survey, 48 returned valid responses. The average score of the Japanese translation of the ecSI‐2.0™ was 33.1 (SD ± 7.8) points. Cronbach's alpha coefficient for the whole scale was.87 and ranged from.67–.79 for the four subscales. The test–retest method confirmed the scale's stability. Factor analysis confirmed that reproducibility of the four factors was similar to the original version. In the examination of known population validity, the same correlation as the original edition was confirmed. Conclusions: The Japanese translation of the ecSI‐2.0™ may be reliable and valid for understanding eating competence related to behavior of parents of school‐age children. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) in patients with non‐small cell lung cancer (NSCLC) worsens the prognosis for overall survival (OS) due to chemotherapy‐triggered acute exacerbation (AE)‐ILD. The Glasgow Prognostic Score (GPS), which is based on serum C‐reactive protein and albumin levels, has been suggested as a reliable prognostic tool for mortality in cancer patients, including NSCLC. In this study, we investigated whether GPS is a predictor for chemotherapy‐triggered AE‐ILD and the prognosis in patients with NSCLC and pre‐existing ILD. Methods: We conducted a retrospective review on 56 NSCLC and ILD patients at our hospital who received platinum agent‐based treatment as first‐line chemotherapy between June 2010 and May 2019. We categorized these patients according to their GPS (0–2) and compared the incidence of chemotherapy‐triggered AE‐ILD and OS. Results: The GPS 0, 1, and 2 groups included 31, 16, and nine patients, respectively, out of 56. A total of 12 (21.4%) patients showed chemotherapy‐triggered AE‐ILD. The median OS was at 11.5 months (95% confidence interval: 8.0–15.1). The incidence of chemotherapy‐triggered AE‐ILD within the first year of chemotherapy in the GPS 0, 1, and 2 groups was three (9.6%), four (25.0%), and five (55.5%), and the median OS time was 16.9, 9.8 and 7.6 months, respectively. Univariate and multivariate analyses indicated that only GPS 2 could predict both chemotherapy‐triggered AE‐ILD and OS (P < 0.05). Conclusions: GPS assessment of patients with NSCLC and pre‐existing ILD is a valuable prognostic tool for predicting chemotherapy‐triggered AE‐ILD and OS. Key points: Significant findings of the study: We found that GPS 2 was an independent risk factor for chemotherapy‐triggered AE‐ILD and prognosis in patients with ILD associated with NSCLC. What this study adds: GPS may potentially enable the discrimination of patients tolerant of chemotherapy from those at an increased risk of AE‐ILD and predict the prognosis in patients with NSCLC and ILD receiving chemotherapy. [ABSTRACT FROM AUTHOR]

Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 are involved in the disposition of a variety of commonly prescribed drugs. The evaluation of OATP1B1/1B3 inhibition potential by investigational drugs is of interest during clinical drug development due to various adverse events associated with increased exposures of their substrates. Regulatory guidance documents on the in vitro assessment of OATP1B1/1B3 inhibition potential are conservative with up to a third of predictions resulting in false positives. This work investigated the utility of OATP1B1/1B3 endogenous biomarkers, coproporphyrin (CP)‐I and CP‐III, to assess clinical inhibition of OATP1B1/1B3 and potentially eliminate the need for prospective clinical drug‐drug interaction (DDI) studies. Correlations between CP‐I exposures and various OATP1B1 static DDI predictions were also evaluated. Glecaprevir/pibrentasvir (GLE/PIB) 300/120 mg fixed‐dose combination is known to cause clinical inhibition of OATP1B1/1B3. In a clinical study evaluating the relative bioavailability of various formulations of GLE/PIB regimen, CP‐I peak plasma concentration (Cmax) ratio and 0–16‐hour area under the concentration‐time curve (AUC0–16) ratio relative to baseline increased with increasing GLE exposures, whereas there was a modest correlation between GLE exposure and CP‐III Cmax ratio but no correlation with CP‐III AUC0–16 ratio. This suggests that CP‐I is superior to CP‐III as an endogenous biomarker for evaluation of OATP1B1 inhibition. There was a significant correlation between CP‐I and GLE Cmax (R2 = 0.65; P < 0.001) across individual subjects. Correlation analysis between GLE OATP1B1 R values and CP‐I exposures (Cmax ratio and AUC0–16 ratio) suggests that an R value of > 3 can predict a biologically meaningful inhibition of OATP1B1 when the inhibitor clinical pharmacokinetic parameters are available. [ABSTRACT FROM AUTHOR]

As part of control techniques, gust-alleviation systems using airborne Doppler lidar technology are expected to enhance aviation safety by significantly reducing the risk of turbulence-related accidents. Accurate measurement and estimation of the vertical wind velocity are very important in the successful implementation of such systems. An estimation algorithm for the airflow vector based on data from airborne lidars is proposed and investigated for preview control to prevent turbulence-induced aircraft accidents in flight. An existing technique – simple vector conversion – assumes that the wind field between the lidars is homogeneous, but this assumption fails when turbulence occurs due to a large wind-velocity fluctuation. The proposed algorithm stores the line-of-sight (LOS) wind data at every moment and uses recent and past LOS wind data to estimate the airflow vector and to extrapolate the wind field between the airborne twin lidars without the assumption of homogeneity. Two numerical experiments – using the ideal vortex model and numerical weather prediction, respectively – were conducted to evaluate the estimation performance of the proposed method. The proposed method has much better performance than simple vector conversion in both experiments, and it can estimate accurate two-dimensional wind-field distributions, unlike simple vector conversion. The estimation performance and the computational cost of the proposed method can satisfy the performance demand for preview control. [ABSTRACT FROM AUTHOR]

The control technique in a gust alleviation system by using the airborne Doppler Lidar technology is expected to enhance aviation safety to minimize the risks of turbulence-related accidents. Accurate measurement and estimation of the vertical wind velocity are very important in the successful implementation of a gust alleviation system by using the airborne Doppler Lidar technology. An estimation algorithm of airflow vector based on the airborne Lidars is proposed and investigated for preview control to prevent turbulence-induced aircraft accidents in flight. The use of the simple vector conversion method, which is an existing technique, assumes that the wind field between the Lidars is homogeneous. The assumption of a homogeneous field would be wrong when turbulence occurs due to large wind velocity fluctuation. The proposed algorithm stores the line-of-sight (LOS) wind data with each passing moment and uses recent and past LOS wind data in order to estimate the airflow vector. The recent and past LOS wind data are used to extrapolate the wind field between the airborne twin Lidars. Two numerical experiments - ideal vortex model and numerical weather prediction - were conducted to evaluate the estimation performance of the proposed method. The proposed method has much better performance than simple vector conversion in the two numerical experiments, and it can estimate accurate two-dimensional wind field distributions unlike simple vector conversion. The estimation performance and the computational cost of the proposed method can satisfy the performance demand for preview control. [ABSTRACT FROM AUTHOR]

Cobicistat has been reported to increase serum creatinine clinically without affecting glomerular filtration. This was ascribed to transient inhibition of MATE1-mediated renal creatinine secretion. Interestingly, a structurally similar drug, ritonavir, has not been associated with serum creatinine increases at the pharmacoenhancer dose. The present study was aimed to investigate the translation of in vitro MATE1/2K inhibition to clinical creatinine increase (cobicistat) and lack of it (ritonavir) considering their intracellular concentrations in renal proximal tubules. Uptake studies showed ritonavir and cobicistat are unlikely substrates for OCT2. The steady-state unbound concentration in the cytosol of human renal proximal tubule epithelial cells was comparable with the extracellular unbound concentration, suggesting that the entry of these compounds is predominantly mediated by passive diffusion. Ritonavir and cobicistat are MATE1 and MATE2K inhibitors with IC 50 values of 3.1 and 90 μM (ritonavir), and 4.4 and 3.2 μM (cobicistat), respectively. However, the unbound cytosolic concentrations (C u,cytosol) of ritonavir and cobicistat in human renal proximal tubule epithelial cells, 0.065 and 0.10 μM, respectively, after incubation with the clinical maximum total plasma concentrations at pharmacoenhancer doses does not support inhibition in vivo ; C u,cytosol >30 fold lower than IC 50 s. These results demonstrate that MATE1/2K inhibition is unlikely the mechanism of the clinical creatinine elevations with cobicistat. [ABSTRACT FROM AUTHOR]

The tumor microenvironment has previously been reported to be hypercapnic (as high as ~84 mmHg), although its effect on tumor cell behaviors is unknown. In this study, high CO 2 levels, ranging from 5% to 15%, protected lung cancer cells from anticancer agents, such as cisplatin, carboplatin and etoposide, by suppressing apoptosis. The cytoprotective effect of a high CO 2 level was independent of acidosis and was due to mitochondrial metabolic reprogramming that reduced mitochondrial respiration, as assessed by oxygen consumption, oxidative phosphorylation, mitochondrial membrane and oxidative potentials, eventually leading to reduced reactive oxidant species production. In contrast, high CO 2 levels did not affect cisplatin-mediated DNA damage responses or the expression of Bcl-2 family proteins. Although high CO 2 levels inhibited glycolysis, this inhibition was not mechanistically involved in high CO 2 -mediated reductions in mitochondrial respiration, because a high CO 2 concentration inhibited isolated mitochondria. A cytoprotective effect of high CO 2 levels on mitochondria DNA-depleted cells was not noted, lending support to our conclusion that high CO 2 levels act on mitochondria to reduce the cytotoxicity of anticancer agents. High CO 2 -mediated cytoprotection was also noted in a 3D culture system. In conclusion, the hypercapnic tumor microenvironment reprograms mitochondrial respiratory metabolism causing chemoresistance in lung cancer cells. Thus, tumor hypercapnia may represent a novel target to improve chemosensitivity. fx1 • Tumor microenvironment is hypercapnic. • Hypercapnia reprograms mitochondrial metabolism, reducing ROS and chemosensitivity. • Reduced chemosensitivity induced by hypercapnia is independent of acidosis. • Tumor hypercapnia represents a novel target to improve cancer chemosensitivity. [ABSTRACT FROM AUTHOR]

We investigated element composition ratios in two sets of sequentially collected airborne particulate matter (PM) samples obtained through the automatic sampler of the Atmospheric Environmental Regional Observation System (AEROS). A series of micro-PIXE analyses and imaging were performed on a PTFE (Polytetrafluoroethylene) membrane tape filter corresponding to two hourly time slots through a high-concentration air pollution event from 26th to 27th March 2020 sampled at Ota, Japan (36.290° N, 139.381° E) by utilizing an external 3 MeV proton microprobe. Latent variables of sequentially collected PM samples were analyzed by the non-linear least square method and classified by those clustering driven by house-made data analysis software. Micro-PIXE imaging effectively confirmed the presence of large elemental agglomerations on the PTFE membrane tape filter of AEROS that often appeared as outliners in data analysis. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study proposes an algorithm that combines ensemble numerical weather‐prediction model data and aircraft flight data in a wind nowcasting system for safe and efficient aircraft operation. It uses an ensemble‐weighted average method based on sequential importance sampling (SIS), which is a particle filter method for forecasting the wind field in real time. SIS is applied to the ensemble forecast data and control run data of the European Centre for Medium‐Range Weather Forecasts (ECMWF), Japan Meteorological Agency (JMA), Korea Meteorological Administration (KMA), National Centers for Environmental Prediction (NCEP) and United Kingdom Met Office (UKMO) for the two case studies that use flight data from 72 commercial aircraft flights. The results show that SIS can forecast better than the other four methods: direct ensemble average (DEA), elite strategy (ES), and selective ensemble average (SEAV) and weighted average (SEWE), with average improvements in forecast performance of about 10–15%, even at 300 min ahead. In addition, the overall forecast performance between the forecast wind and observation of the radiosonde of SIS was slightly better than DEA. In both cases, the forecast performance was significantly improved on points along the flight path of the aircraft used for this study. Case analyses and the impact of differences in the hyper‐parameters of SIS on forecast performance are also presented in this study. [ABSTRACT FROM AUTHOR]

Abstract: Background: Health‐related quality of life (HRQOL) is an important outcome in solid organ transplantation. This study evaluated and explored the factors of generic and transplant‐specific HRQOL in Japanese pediatric and adolescent patients with biliary atresia (BA) after living donor liver transplant (LDLT). Methods: A cross‐sectional survey using anonymous questionnaires was completed between April and July 2015. Patient medical records were accessed. The Japanese version of Pediatric Quality of Life InventoryTM Generic Core Scales and Transplant Modules (child self‐report and parent proxy‐report) was administered. Results: Participants consisted of 75 patients (mean age at survey, 9.6 years) and 74 parents. Japanese patients reported higher generic and transplant‐specific HRQOL (total score) than that reported by US patients with BA after LT (US I; age at survey, 7.2 years) and by US patients after solid organ transplant (US II; age at survey, 11.3 years; LT, 53.8%; effect size, 0.55–0.96). Japanese parents, however, rated their children's generic HRQOL (total score) similar to that rated by the US I and II parents (0.13 and 0.30, respectively) and reported lower transplant‐specific HRQOL (total score) than that reported by US II (0.26). Although the number of types of prescribed drugs was a common factor in HRQOL, most demographic and medical factors (e.g. child's age at survey and consultation frequency) varied with reporter (i.e. patients and parents). Conclusions: The levels and factors of generic and transplant‐specific HRQOL of Japanese pediatric and adolescent patients with BA after LDLT varied with reporter (i.e. patients or parents). [ABSTRACT FROM AUTHOR]

Key message: If a double‐ring sign is found in contrast‐enhanced computed tomography, this should raise concern not only for Takayasu arteritis, but also for granulocyte colony‐stimulating factor‐induced vasculitis. [ABSTRACT FROM AUTHOR]

1. Accurate predictions of clinical transporter-mediated drug–drug interactions (DDI) fromin vitrodata can be challenging when compounds have poor solubility and/or high nonspecific binding. Additionally, current DDI predictions for compounds with high plasma–protein binding assume that the unbound fraction in plasma is 0.01, if the experimental value is less than 0.01 or cannot be determined. This approach may result in an overestimation of DDI risk. To overcome these challenges, it may be beneficial to conduct inhibition studies under physiologically relevant conditions. 2. Here, IC50values, determined in the presence of 4% bovine serum albumin approximating human plasma albumin concentrations, were successfully used to predict DDI for uptake transporters, OATP1B1/1B3, OCT1/2, OAT1/3 and MATE1/2K. 3. The IC50values of reference inhibitors with 4% bovine serum albumin, considered total IC50, were comparable to the predicted values based on nominal IC50values determined under protein-free conditions and unbound fraction in plasma. Calculation of R-total andCmax/IC50,totalvalues using total plasma exposure and total IC50values explained the clinical DDI or absence of it for these inhibitors. 4. These results suggest that IC50determinations in the presence of 4% albumin can be used, in the context of clinical total exposure, to predict DDI involving uptake transporters. [ABSTRACT FROM PUBLISHER]

The aim of this article is to understand the bereavement of a family as a unit from multiple perspectives. Using qualitative metasynthesis, we described family members’ bereavement experiences from multiple perspectives. The most common perspectives reported were those of parents who had lost their children. No studies reported the perspectives of husbands. Every article explicitly or implicitly referred to a continued connection with the deceased and the effect of this connection on family relationships. This article addresses the importance of focusing on more than one relationship within a family, which should be investigated further in future research. [ABSTRACT FROM PUBLISHER]

Background Health-related quality of life ( HRQOL) is an important outcome in pediatric solid organ transplantation. Considering the emerging problems after transplantation, an evaluation of transplant-specific aspects of HRQOL is essential, but no validated HRQOL measure is available in Japan. The aim of this study was therefore to develop the Japanese version of the Pediatric Quality of Life Inventory™ (Peds QL) Transplant Module Child Self-Report and to investigate its feasibility, reliability, and validity. Methods Based on the Peds QL linguistic validation process, the Japanese version of the Peds QL Transplant Module was developed through translation and cognitive interviews (patient testing). The scale's reliability and validity were investigated, using statistical analyses of field tests of the target population. Results Eighty-seven pairs of pediatric liver-transplant recipients and their parents participated in the field test. The pediatric patients completed the measure in 3-7 min, and the rate of missing items was low (0.27%). Excellent internal consistency and test-retest reliability were confirmed. Known-groups validity, concurrent validity, and convergent and discriminant validity also were confirmed. Conclusions Excellent feasibility, reliability, and validity of this Japanese self-report version of the Peds QL Transplant Module Child Self-Report were verified. As a measure of transplant-specific aspects of HRQOL in Japanese pediatric patients who have undergone organ transplants, the Japanese version of the Peds QL Transplant Module is appropriate for use in clinical and research settings. [ABSTRACT FROM AUTHOR]

Key message: In lung cancer patients, brain metastasis is often suspected when neurological symptoms appear; however, if ptosis, ocular motility disorder or optic nerve disorder is observed, it is important to identify and treat the orbital apex syndrome. [ABSTRACT FROM AUTHOR]

An integrated method consisting of a proper orthogonal decomposition (POD)-based reduced-order model (ROM) and a particle filter (PF) is proposed for real-time prediction of an unsteady flow field. The proposed method is validated using identical twin experiments of an unsteady flow field around a circular cylinder for Reynolds numbers of 100 and 1000. In this study, a PF is employed (ROM-PF) to modify the temporal coefficient of the ROM based on observation data because the prediction capability of the ROM alone is limited due to the stability issue. The proposed method reproduces the unsteady flow field several orders faster than a reference numerical simulation based on Navier–Stokes equations. Furthermore, the effects of parameters, related to observation and simulation, on the prediction accuracy are studied. Most of the energy modes of the unsteady flow field are captured, and it is possible to stably predict the long-term evolution with ROM-PF. [ABSTRACT FROM AUTHOR]

Few studies have examined HRQOL in pediatric Tx recipients' parents. This study investigated HRQOL in these parents and relationships between HRQOL and perceived burden of nurturing, family functioning, and social support. Self-report anonymous questionnaires and a survey of medical records were completed between September and December 2013. The SF-36v2, which evaluates physical, psychological, and social health, was used to measure HRQOL. While values for physical and psychological health were higher than standard values (Cohen's d = 0.34 and 0.17, respectively), social health scores were lower ( d = 0.21). 'Parental consultation unrelated to donation' (standardized partial regression coefficient: β = −0.52) was associated with physical health. 'Family functioning' and 'Commuting time between home and primary follow-up hospital' (β = 0.57 and −0.31) were related to psychological health. 'Total score for perceived burden of nurturing' (β = −0.31) was related to social health. Regarding parental HRQOL, while physical and psychological health was favorable, social health was impaired. In clinical practice, interventions targeting parents' physical conditions and facilitation of community and family understanding and support to share recipients' nurturing are important in improving parental HRQOL. [ABSTRACT FROM AUTHOR]

Veliparib ( ABT-888) is largely eliminated as parent drug in human urine (70% of the dose). Renal unbound clearance exceeds glomerular filtration rate, suggesting the involvement of transporter-mediated active secretion. Clinically relevant pharmacokinetic interactions in the kidney have been associated with OAT1, OAT3, OCT2, MATE1, and MATE2 K. In the present study, interactions of veliparib with these transporters were investigated. Veliparib inhibited OAT1, OAT3, OCT2, MATE1, and MATE2 K with IC50 values of 1371, 505, 3913, 69.9, and 69.5 μM, respectively. The clinical unbound maximum plasma concentration of veliparib after single oral dose of 50 mg (0.45 μM) is manyfold lower than IC50 values for OAT1, OAT3, OCT2, MATE1, or MATE2 K. These results indicate a low potential for drug-drug interaction ( DDI) with OAT1/3, OCT2, or MATE1/2 K. Additional studies demonstrated that veliparib is a substrate of OCT2. In Oct1/ Oct2 double-knockout mice, the plasma exposure of veliparib was increased by 1.5-fold, and the renal clearance was decreased by 1.8-fold as compared with wild-type mice, demonstrating that organic cation transporters contribute to the renal elimination in vivo. In summary, the in vitro transporter data for veliparib predicts minimal potential for an OAT1/3-, OCT2-, and MATE1/2 K-mediated DDI given the clinical exposure after single oral dose of 50 mg. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4426-4432, 2013 [ABSTRACT FROM AUTHOR]

Purpose: The expression of a multispecific organic anion transporter, OATP1B3/ SLCO1B3, is associated with clinical prognosis and survival of cancer cells. The aims of present study were to investigate the involvement of epigenetic regulation in mRNA expression of a cancer-type variant of OATP1B3 (Ct-OATP1B3) in cancer cell lines. Methods: The membrane localization and transport functions of Ct-OATP1B3 were investigated in HEK293 cells transiently expressing Ct-OATP1B3. DNA methylation profiles around the transcriptional start site of Ct-OATP1B3 in cancer cell lines were determined. The effects of a DNA methyltransferase inhibitor and siRNA knockdown of methyl-DNA binding proteins (MBDs) on the expression of Ct-OATP1B3 mRNA were investigated. Results: 5′-RACE identified the TSS of Ct- OATP1B3 in PK-8 cells. Ct-OATP1B3 was localized on the plasma membrane, and showed the transport activities of E17βG, fluvastatin, rifampicin, and Gd-EOB-DTPA. The CpG dinucleotides were hypomethylated in Ct-OATP1B3-positive cell lines (DLD-1, TFK-1, PK-8, and PK-45P) but were hypermethylated in Ct-OATP1B3-negative cell lines (HepG2 and Caco-2). Treatment with a DNA methyltransferase inhibitor and siRNA knockdown of MBD2 significantly increased the expression of Ct-OATP1B3 mRNA in HepG2 and Caco-2. Conclusions: Ct-OATP1B3 is capable of transporting its substrates into cancer cells. Its mRNA expression is regulated by DNA methylation-dependent gene silencing involving MBD2. [ABSTRACT FROM AUTHOR]

DNA methylation-dependent gene silencing is one of the most characterized mechanisms in epigenetic regulation of gene expression. This process is thought to influence the ability of hepatocyte nuclear factor 1 (HNF1) to transactivate organic anion transporter expression in the liver and kidney. To evaluate this further we profiled 282 mouse solute carrier transporters by examining regions near their transcription start sites for tissue-dependent differentially methylated regions (T-DMR) using restriction tag-mediated amplification to determine T-DMR disparity between the liver and kidney. Forty-two of these were associated with T-DMR tags hypomethylated in the kidney but hypermethylated in the liver. Computational analysis found a canonical HNF1-binding motif within 1 kbp of the promoter region of 13 carriers including the amino acid transporters Slc6a19, Slc6a20, Slc7a8 and Slc7a9; all expressed predominantly in the kidney. Bisulfite genomic sequencing found that CpG dinucleotides neighboring the T-DMR tags were hypomethylated in the kidney compared with the liver. The Hnf1α promoter region itself contained a T-DMR hypomethylated in the liver and kidney but hypermethylated in the cerebrum, consistent with the tissue distribution of Hnf1α. Taken together, our results show a central role of DNA methylation in the kidney-specific expression of amino acid transporters thus determining both the tissue distribution of their master regulator, Hnf1α, and its interaction with downstream genes. [ABSTRACT FROM AUTHOR]

Multispecific organic anion transporter, OATP1B3/ SLCO1B3, is expressed in several cancer cell lines as well as tumor tissues, and its expression sensitizes the cells to some anti-cancer agents. The present study was aimed to characterize the DNA methylation profiles around the transcriptional start site (TSS) of OATP1B3 and correlate them with the mRNA expression in cancer and immortalized cell lines. The mRNA expression and DNA methylation profiles of OATP1B3 were determined by RT-PCR and bisulfite sequencing, respectively. The expression of OATP1B3 mRNA was detected in DLD-1, TFK-1, PK-8, and PK-45P cells, but below the limit of detection in HepG2, Caco-2, and HEK293 cells. Bisulfite sequencing demonstrated that CpG dinucleotides around the TSS are differentially methylated among cell lines and partly associated with the mRNA expression profile of OATP1B3. Furthermore, treatment with 5-aza-2′-deoxycytidine, an inhibitor of DNA methyltransferase, significantly increased the mRNA expression of OATP1B3 in HepG2 and Caco-2 cells by 18- and 14-fold, respectively, but not in DLD-1 and TFK-1 cells. DNA methylation-dependent gene silencing is at least partly involved in the regulation of OATP1B3 expression in cancer/immortalized cell lines. [ABSTRACT FROM AUTHOR]

This study introduced a data screening method for comparing the reflectances in middle latitude forest regions collected by a Geostationary Earth Observing (GEO) satellite and a Low Earth Orbit (LEO) satellite. This method attempts to reduce the differences between the relative azimuth angles of the GEO and LEO observations. The method, called relative azimuthal-angle matching (RAM), takes advantage of the high temporal resolution of the GEO satellites, which enables collection of a wide range of relative azimuth angles within a day. The performance of the RAM method was evaluated using data in the visible and near-infrared bands collected by the Himawari-8/Advanced Himawari Imager (AHI) and the Terra/Moderate Resolution Imaging Spectroradiometer (MODIS). The consistency of the reflectance pairs of MODIS and AHI selected by the RAM method was compared with the consistency of the reflectance pairs acquired simultaneously by the two sensors. The data were matched pixel-by-pixel after applying atmospheric corrections and cloud screening. The results show that RAM improved the reflectance ratio by approximately 10% for the red and NIR bands on average relative to the simultaneous observations. Significant improvements in the two bands were observed (20%), especially among data collected in the fall and winter. Performance of RAM depends largely on season. Especially in summer, the reflectance pair chosen by RAM showed less consistency than solar zenith-angle matching (SZM). The results also indicated the relatively large influence of the spectral response functions on the green and red bands of the two sensors. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Discharge particle flowability increased with decreasing MP and AP diameters. • Mechanisms for improving particle flowability are dependent on the operation. • Multi-point contact via APs affords the maximum discharge particle flowability. Abstract Particle flowability can be improved by admixing with particles smaller than the main particles. However, the mechanism by which this technique improves flowability is not yet fully understood. In this study, we focused on vibrating discharge particle flowability as one type of flowability and investigated the influence of the main particle roughness created by the adhesion of the admixed particles on improving the flowability. The diameters of the main and admixed particles (MPs and APs) were 41.4 or 60.8 μm and 8 or 104 nm, respectively. The main and admixed particles were mixed in various mass ratios, and the discharge particle flow rates of the mixed particles were measured. Scanning electron microscopy images were acquired from two different angles to determine the three-dimensional surface roughness using image analysis software. We then calculated the coating structure parameters from the obtained three-dimensional surface roughness. The observed trends for improving the vibrating discharge particle flowability were found to differ from those reported for compression particle flowability. Furthermore, the main particle roughness conditions that led to the greatest improvement involved the presence of several admixed particle agglomerations between the main particles. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is often associated with co-morbidities. Metabolic disorders like hyperlipidemia and diabetes occur also in underweight COPD patients, although the mechanism is uncertain. Subcutaneous adipose tissue (SAT) plays an important role in energy homeostasis, since restricted capacity to increase fat cell number with increase in fat cell size occurring instead, is associated with lipotoxicity and metabolic disorders. The aim of this study is to show the protective role of SAT for the metabolic disorders in pulmonary emphysema of a murine model. We found ectopic fat accumulation and impaired glucose homeostasis with wasting of SAT in a murine model of elastase-induced pulmonary emphysema (EIE mice) reared on a high-fat diet. ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, improved angiogenesis and subsequently adipogenesis, and finally improved ectopic fat accumulation and glucose homeostasis with restoration of the capacity for storage of surplus energy in SAT. These results suggest that metabolic disorders like hyperlipidemia and diabetes occured in underweight COPD is partially due to the less capacity for storage of surplus energy in SAT, though the precise mechanism is uncertained. Our data pave the way for the development of therapeutic interventions for metabolic disorders in emphysema patients, e.g., use of pro-angiogenic agents targeting the capacity for storage of surplus energy in the subcutaneous adipose tissue. [ABSTRACT FROM AUTHOR]

A high sugar concentration is used as a starting condition in alcoholic fermentation by budding yeast, which shows changes in intracellular state and cell morphology under conditions of high-sugar stress. In this study, we developed artificial intelligence (AI) models to predict ethanol yields in yeast fermentation cultures under conditions of high-sugar stress using cell morphological data. Our method involves the extraction of high-dimensional morphological data from phase contrast images using image processing software, and predicting ethanol yields by supervised machine learning. The neural network algorithm produced the best performance, with a coefficient of determination (R 2) of 0.95, and could predict ethanol yields well even 60 min in the future. Morphological data from cells cultured in low-glucose medium could not be used for accurate prediction under conditions of high-glucose stress. Cells cultured in high-concentration glucose medium were similar in terms of morphology to cells cultured under high osmotic pressure. Feeding experiments revealed that morphological changes differed depending on the fermentation phase. By monitoring the morphology of yeast under stress, it was possible to understand the intracellular physiological conditions, suggesting that analysis of cell morphology can aid the management and stable production of desired biocommodities. [ABSTRACT FROM AUTHOR]

The phased-array weather radar (PAWR) is a new-generation weather radar that can make a 100-m-resolution three-dimensional (3D) volume scan every 30 s for 100 vertical levels, producing ~100 times more data than the conventional parabolic-antenna radar with a volume scan typically made every 5 min for 15 scan levels. This study takes advantage of orders of magnitude more rapid and dense observations by PAWR and explores high-precision nowcasting of 3D evolution at 1-10-km scales up to several minutes, which are compared with conventional horizontal two-dimensional (2D) nowcasting typically at O(100) km scales up to 1-6 h. A new 3D precipitation extrapolation system was designed to enhance a conventional algorithm for dense and rapid PAWR volume scans. Experiments show that the 3D extrapolation successfully captured vertical motions of convective precipitation cores and outperformed 2D nowcasting with both simulated and real PAWR data. [ABSTRACT FROM AUTHOR]

The pour-plate method, a conventional approach to the evaluation of food microbial contamination, is costly and time-consuming. We have developed a novel and efficient system to evaluate microbial growth on the surfaces of foods using a membrane filter and microscope followed by image analysis. While Wickerhamomyces anomalus cells directly inoculated onto loin ham were undetectable because of the complex surface structure of the food, the placement of a hydrophilic polytetrafluoroethylene membrane filter on the loin ham enabled us to clearly observe the yeast cells on the filter by microscopy without affecting their growth. Under microscopic observation, cells on the membrane filter as well as those on the agar plate were always observed with surrounding annular dark regions, which were separated from the background by clear boundaries. We defined the areas inside the boundaries, including the cells and the annular dark regions, as the "bounded areas". In image analysis, the numbers of pixels in the bounded areas increased exponentially in parallel with the viable cell count (CFU/g), suggesting that the pixel numbers were proportional to the viable cell numbers. We applied this system to investigate the adverse effects of sorbic acid preparation (SAP), a common food preservative, on yeast growth. The yeast was incubated on filter-overlaid agar medium in the presence or absence of SAP, resulting in a dose-dependent reduction in the specific pixel increase rate (k [/h]) determined by image analysis as well as in the specific growth rate (μ [/h]) estimated by the agar-plate-based conventional method. Regression analysis revealed a strong correlation between the k and μ values (R2, 0.985) normalized to the corresponding values without SAP. Our system could be applied to estimate the growth rate of microbes on foods and to examine the effects of environmental factors on microbial growth by using the k value as an index. Furthermore, this system would contribute to enhancing food safety, extending shelf life, and solving the important global problem of food loss. • An efficient system for evaluating microbial growth on food surfaces was developed. • Key features are use of a membrane filter on the food and microscopic image analysis. • Characteristic bounded areas around the cells enabled quantitative image analysis. • The system can be used to evaluate cell growth rate and food preservative effects. • The system contributes to research on food preservation and reduce food loss. [ABSTRACT FROM AUTHOR]

On behalf of the team I am pleased to present the second annual 'novel insights into drug transporter sciences review' focused on peer-reviewed articles that were published in the year 2021. In compiling the articles for inclusion, preprints available in 2021 but officially published in 2022 were considered to be in scope. To support this review the contributing authors independently selected one or two articles that were thought to be impactful and of interest to the broader research community. A similar approach as published last year was adopted whereby key observations, methods and analysis of each paper is concisely summarized in the synopsis followed by a commentary highlighting the impact of the paper in understanding drug transporters' role in drug disposition. As the goal of this review is not to provide a comprehensive overview of each paper but rather highlight important findings that are well supported by the data, the reader is encouraged to consult the original articles for additional information. Further, and keeping in line with the goals of this review, it should be noted that all authors actively contributed by writing synopsis and commentary for individual papers and no attempt was made to standardize language or writing styles. In this way, the review article is reflective of not only the diversity of the articles but also that of the contributors. I extend my thanks to the authors for their continued support and also welcome Diane Ramsden and Pallabi Mitra as contributing authors for this issue (Table 1). Table 1. Selected articles for this review. Title Area Authors Source 1. Atorvastatin-associated rhabdomyolysis in a patient with a novel variant of the SLCO1B1 gene: a case report Polymorphism Kiage et al. J Clin Lipidol. 2022;16(1):23–27 2. Quantitation of plasma membrane drug transporters in kidney tissue and cell lines using a novel proteomic approach enabled a prospective prediction of metformin disposition Proteomics Kikuchi et al. Drug Metab Dispos. 2021;49(10):938–946 3. Proteomics-informed prediction of rosuvastatin plasma profiles in patients with a wide range of body weight Proteomics Wegler et al. Clin Pharmacol Ther. 2021;109(3):762–771 4. Performance of plasma coproporphyrin I and III as OATP1B1 biomarkers in humans Biomarker Neuvonen et al. Clin Pharmacol Ther. 2021 Dec;110(6):1622–1632 5. Identification of appropriate endogenous biomarker for risk assessment of multidrug and toxin extrusion protein-mediated drug-drug interactions in healthy volunteers Biomarker Miyake et al. Clin Pharmacol Ther. 2021;109(2):507–516 6. Population pharmacokinetic modeling and simulation to support qualification of pyridoxic acid as endogenous biomarker of OAT1/3 renal transporters Biomarker Ahmad et al. CPT Pharmacometrics Syst Pharmacol. 2021 May;10(5):467–477 7. Acute and chronic effects of rifampin on letermovir suggest transporter inhibition and induction contribute to letermovir Pharmacokinetics Induction/Biomarkers Robbins et al. Clin Pharmacol Ther. 2022;111(3):664–675 8. Exploring the use of serum-derived small extracellular vesicles as liquid biopsy to study the induction of hepatic cytochromes P450 and organic anion transporting polypeptides Induction/Biomarkers Rodrigues et al. Clin Pharmacol Ther. 2021;110(1):248–258 9. Unraveling pleiotropic effects of rifampicin by using physiologically based pharmacokinetic modeling: assessing the induction magnitude of P-glycoprotein-cytochrome P450 3A4 dual substrates Induction Pan et al. CPT Pharmacometrics Syst Pharmacol. 2021;10:1485–1496. 10. Quantification of CYP3A and Drug transporters activity in healthy young, healthy elderly and chronic kidney disease elderly patients by a microdose cocktail approach Clinical pharmacology Rattanacheeworn et al. Front Pharmacol. 2021;12:726669. 11. Quantitative prediction of P-glycoprotein-mediated drug–drug interactions and intestinal absorption using humanized mice DDI Miyake et al. Br J Pharmacol. 2021;178(21):4335–4351. 12. Regulation of OATP1B1 function by tyrosine kinase-mediated phosphorylation Regulation Hayden et al. Clin Cancer Res. 2021;27(15):4301–4310. [ABSTRACT FROM AUTHOR]

Body weight loss is a common manifestation in patients with chronic obstructive pulmonary disease (COPD), particularly those with severe emphysema. Adipose angiogenesis is a key mediator of adipogenesis and use of pro-angiogenic agents may serve as a therapeutic option for lean COPD patients. Since angiogenesis is stimulated by PGE 2 , we examined whether ONO-AE1-259, a selective E-prostanoid (EP) 2 receptor agonist, might promote adipose angiogenesis and adipogenesis in a murine model of elastase-induced pulmonary emphysema (EIE mice). Mice were intratracheally instilled with elastase or saline, followed after 4 weeks by intraperitoneal administration of ONO-AE1-259 for 4 weeks. The subcutaneous adipose tissue (SAT) weight decreased in the EIE mice, whereas in the EIE mice treated with ONO-AE1-259, the SAT weight was largely restored, which was associated with significant increases in SAT adipogenesis, angiogenesis, and VEGF protein production. In contrast, ONO-AE1-259 administration induced no alteration in the weight of the visceral adipose tissue. These results suggest that in EIE mice, ONO-AE1-259 stimulated adipose angiogenesis possibly via VEGF production, and thence, adipogenesis. Our data pave the way for the development of therapeutic interventions for weight loss in emphysema patients, e.g., use of pro-angiogenic agents targeting the adipose tissue vascular component. [ABSTRACT FROM AUTHOR]

1. Transient benign unconjugated hyperbilirubinemia has been observed clinically with several drugs including indinavir, cyclosporine, and rifamycin SV. Genome-wide association studies have shown significant association of OATP1B1 and UGT1A1 with elevations of unconjugated bilirubin, and OATP1B1 inhibition data correlated with clinical unconjugated hyperbilirubinemia for several compounds. 2. In this study, inhibition of OATP1B3 and UGT1A1, in addition to OATP1B1, was explored to determine whether one measure offers value over the other as a potential prospective tool to predict unconjugated hyperbilirubinemia. OATP1B1 and OATP1B3-mediated transport of bilirubin was confirmed and inhibition was determined for atazanavir, rifampicin, indinavir, amprenavir, cyclosporine, rifamycin SV and saquinavir. To investigate the intrinsic inhibition by the drugs, both in vivo Fi (fraction of intrinsic inhibition) and R-value (estimated maximum in vivo inhibition) for OATP1B1, OATP1B3 and UGT1A1 were calculated. 3. The results indicated that in vivo Fi values >0.2 or R-values >1.5 for OATP1B1 or OATP1B3, but not UGT1A1, are associated with previously reported clinical cases of drug-induced unconjugated hyperbilirubinemia. 4. In conclusion, inhibition of OATP1B1 and/or OATP1B3 along with predicted human pharmacokinetic data could be used pre-clinically to predict potential drug-induced benign unconjugated hyperbilirubinemia in the clinic. [ABSTRACT FROM AUTHOR]

Appropriate drug treatment for smoking asthmatics is uncertain because most smokers with asthma are less sensitive to treatment with glucocorticoids compared with non-smokers with asthma. We hypothesized that roflumilast (Rof), a selective phosphodiesterases-4 inhibitor regarded as an add-on therapy for chronic obstructive pulmonary disease, might be more effective than glucocorticoids for improving asthma in smokers. To investigate this hypothesis, we compared the therapeutic effects of dexamethasone (Dex) and Rof in a mouse model of ovalbumin-induced asthma with or without concurrent cigarette smoke (CS) exposure for 2 weeks. We found that recurrent asthma attacks increased lung tissue resistance. CS exposure in asthmatic mice decreased the central airway resistance, increased lung compliance, and attenuated airway hyper-responsiveness (AHR). CS exposure in asthmatic mice also increased the number of neutrophils and macrophages in the bronchoalveolar fluid. Treatment with Dex in asthmatic mice without CS exposure reduced airway resistance, AHR and airway eosinophilia. In asthmatic mice with CS exposure, however, Dex treatment unexpectedly increased lung tissue resistance and restored AHR that had been otherwise suppressed. Dex treatment in asthmatic mice with CS exposure inhibited eosinophilic inflammation but conversely exacerbated neutrophilic inflammation. On the other hand, treatment with Rof in asthmatic mice without CS exposure reduced airway resistance and airway eosinophilia, although the inhibitory effect of Rof on AHR was unremarkable. In asthmatic mice with CS exposure, Rof treatment did not exacerbate lung tissue resistance but modestly restored AHR, without any significant effects on airway inflammation. These results suggest that CS exposure mitigates sensitivity to both Dex and Rof. In asthmatic mice with CS exposure, Dex is still effective in reducing eosinophilic inflammation but increases lung tissue resistance, AHR and neutrophilic inflammation. Rof is ineffective in improving lung function and inflammation in asthmatic mice with CS exposure. This study did not support our initial hypothesis that Rof might be more effective than glucocorticoids for improving asthma in smokers. However, glucocorticoids may have a detrimental effect on smoking asthmatics. [ABSTRACT FROM AUTHOR]

Hepatic uptake clearance has been measured in suspended human hepatocytes (SHH). Plated human hepatocytes (PHH) after short-term culturing are increasingly employed to study hepatic transport driven mainly by its higher throughput. To know pros/cons of both systems, the hepatic uptake clearances of several organic anion transporting polypeptide 1B substrates were compared between PHH and SHH by determining the initial uptake velocities or through dynamic model-based analyses. For cerivastatin, pitavastatin and rosuvastatin, initial uptake clearances (PS inf) obtained using PHH were comparable to those using SHH, while cell-to-medium concentration (C/M) ratios were 2.7- to 5.4-fold higher. For pravastatin and dehydropravastatin, hydrophilic compounds with low uptake/cellular binding, their PS inf and C/M ratio in PHH were 1.8- to 3.2-fold lower than those in SHH. These hydrophilic substrates are more prone to wash-off during the uptake study using PHH, which may explain the apparently lower uptake than SHH. The C/M ratios obtained using PHH were stable over an extended time, making PHH suitable to estimate the C/M ratios and hepatocyte-to-medium unbound concentration ratios (K p,uu). In conclusion, PHH is useful in evaluating hepatic uptake/efflux clearances and K p,uu of OATP1B substrates in a high-throughput manner, however, a caution is warranted for hydrophilic drugs with low uptake/cellular binding. [ABSTRACT FROM AUTHOR]

Aim: Nurses are expected to have a role in the transition of care from pediatric to adult medical practices for adolescents and young adults with childhood‐onset chronic diseases. This study compares the experience, knowledge, and perceptions regarding the ideal care among adult unit and pediatric nurses regarding the transition to adult care for those with childhood‐onset chronic diseases. Methods: A cross‐sectional study using self‐report questionnaires was conducted with nurses in a tertiary hospital in Tokyo. Questions were generated based on a literature review and expert discussion. Data from 1,064 participants were analyzed (adult unit nurses: n = 959, 90.1%; pediatric nurses: n = 105, 9.9%). Results: Among 623 adult unit nurses who had care experience for adult patients with a childhood‐onset chronic disease, 458 nurses (73.6%) were unaware of the concept of transitional care. As the obstructive factors for transition, pediatric nurses recognized problems in healthcare providers' attitudes and lack of transitional care coordinators, while the adult unit nurses emphasized the patients' wishes to continue to receive pediatric healthcare. Most adult unit nurses expected pediatric nurses to function as transitional care coordinators. Conclusion: Adult unit and pediatric nurses had different perceptions of the barriers in transitioning children with chronic diseases to adult care. It is important to have educational programs focusing on transitional care for all nurses, both to enable pediatric nurses to improve transition readiness of children with chronic diseases and to offer adult patients with a childhood‐onset chronic disease continuing support through adult unit nurses. [ABSTRACT FROM AUTHOR]

A 69‐year‐old man with a history of type 2 diabetes and high blood pressure was diagnosed with coronavirus disease 2019 (COVID‐19). He had hyperferritinaemia and respiratory failure. Despite the initiation of favipiravir and high‐dose corticosteroid and ceftriaxone, his respiratory failure progressed and serum ferritin levels increased. After polymyxin B‐immobilized fibre column direct haemoperfusion (PMX‐DHP) therapy, there was improvement of the respiratory failure and hyperferritinaemia. We report the first case of COVID‐19‐induced hyperferritinaemia and severe respiratory failure successfully treated by PMX‐DHP. [ABSTRACT FROM AUTHOR]

Objective: This study investigated clinical factors associated with negative urinary antigen tests (UAT) implemented for the diagnosis of pneumococcal community-acquired pneumonia (CAP) in adult patients. Subjects and Methods: We reviewed the medical records of 755 adult patients who completed the UAT in our hospital between 2009 and 2012. Of these, we evaluated 63 patients with bacteriologically confirmed definite pneumococcal CAP (33 were UAT-positive, and 30 were UAT-negative). Results: There was no significant difference between the UAT-positive and the UAT-negative patients regarding age, dehydration, respiratory failure, orientation, blood pressure (ADROP) score (the CAP severity score proposed by the Japanese Respiratory Society), gender, white blood cell counts, liver/kidney function tests, or urinalysis. However, serum C-reactive protein (CRP) concentrations were 31% lower in the UAT-negative patients than in the UAT-positive patients (p = 0.02). Furthermore, the prothrombin time-international normalized ratio was 50% higher in the UAT-negative patients than in the UAT-positive patients, although the difference did not reach statistical significance (p = 0.06). The prevalence of comorbidities was similar in both UAT-positive and UAT-negative patients. However, warfarin had been prescribed in 8 (27%) of the UAT-negative patients compared to only 1 (3%) of the UAT-positive patients (odds ratio = 11.6; p = 0.01). Conclusions: These results suggested that low serum CRP concentrations and the use of warfarin increased the possibility with which false-negative UAT results occurred in these patients with pneumococcal CAP. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]