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Stenotrophomonas maltophilia is an important pathogen in healthcare-associated infections. S. maltophilia may contain Smqnr, a quinolone resistance gene encoding the pentapeptide repeat protein, which confers low-level quinolone resistance upon expression in a heterologous host. We investigated the prevalence of Smqnr and plasmid-mediated quinolone resistance (PMQR) determinants in S. maltophilia isolates from Japan. A total of 181 consecutive and nonduplicate clinical isolates of S. maltophilia were collected from four areas of Japan. The antimicrobial susceptibility profiles for these strains were determined. PCR was conducted for Smqnr and PMQR genes, including qnrA, qnrB, qnrC, qnrS, aac(6′)-Ib and qepA. PCR products for Smqnr and aac(6′)-Ib were sequenced. For the S. maltophilia isolates containing Smqnr, pulsed-field gel electrophoresis (PFGE) was performed using XbaI. Resistance rates to ceftazidime, levofloxacin, trimethoprim–sulfamethoxazole, chloramphenicol and minocycline were 67.4%, 6.1%, 17.7%, 8.8% and 0%, respectively. The minimum inhibitory concentration required to inhibit the growth of 50% and 90% of organisms were 0.5 and 2 mg/L for moxifloxacin but 1 and 4 mg/L for levofloxacin, respectively. Smqnr was detected in 104 of the 181 S. maltophilia isolates (57.5%), and the most frequent was Smqnr6, followed by Smqnr8 and Smqnr11. Eleven novel variants from Smqnr48 to Smqnr58 were detected. The 24 Smqnr-containing S. maltophilia isolates were typed by PFGE and divided into 21 unique types. Nine S. maltophilia isolates (5.0%) carried aac(6′)-Ib-cr. No qnr or qepA genes were detected. This study describes a high prevalence of Smqnr and novel variants of Smqnr among S. maltophilia from Japan. Continuous antimicrobial surveillance and further molecular epidemiological studies on quinolone resistance in S. maltophilia are needed.

Introduction: Staphylococcus aureus bacteremia (SAB), especially when caused by methicillin-resistant S. aureus (MRSA), is of considerable clinical importance. In recent years, the proportion of MRSA among S. aureus has decreased, and a relative increase in the proportion of methicillin-susceptible S. aureus (MSSA) has been observed. It is therefore necessary to consider both MRSA and MSSA when assessing the microbiological and clinical significance of SAB., Materials and Methods: We included SAB cases from the Nara Medical University Hospital between January 2015 and February 2017. We performed drug susceptibility testing, toxicity gene analysis, multilocus sequence typing (MLST), and polymerase chain reaction-based open reading frame typing (POT) of stored strains to integrate clinical and bacteriological characteristics., Results: There were 90 cases during the experimental period (42 MRSA and 48 MSSA), with 30-day mortality rates of 19 % for MRSA and 10.4 % for MSSA. Deaths were more frequently complicated by septic shock and disseminated intravascular coagulation. MLST studies showed that ST8, ST764, ST1, and ST15 were prevalent in the MRSA group, whereas ST5, ST188, and ST12 were prevalent in MSSA. Infective endocarditis cases had a long time from onset to the initiation of effective antimicrobials and were all MSSA. MLST and POT results correlated well, and POT appeared to have better discriminatory power., Conclusions: The severity and mortality of SAB, along with the microbiological characteristics of causative isolates, vary by location and time. Continued studies integrating clinical and microbiological investigations are thus needed., Competing Interests: Declarations of interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

To measure α-glucosidase activity, rat intestinal acetone powder is commonly used as a source of α-glucosidase, and the mutarotase-glucose oxidase (GOD) methods commonly used to quantitate glucose produced by enzymatic hydrolysis of the substrates. In this study, we compared human Caco-2 cell extracts with rat intestinal acetone powder extracts. We also compared high-performance anion-exchange chromatography with pulsed amperometric detection (HPAE-PAD) with the mutarotase-GOD method. The sensitivity of HPAE-PAD was higher than that of mutarotase-GOD. The glucose concentration quantified by HPAE-PAD was similar to that quantified using the mutarotase-GOD method. In the maltase reaction, 1-deoxynojirimycin (1-DNJ) exerted a more potent inhibitory effect on human enzymes than on rat enzymes. This order was reversed during the sucrase reaction. These results suggested that the combined use of Caco-2 cell extracts and HPAE-PAD is advantageous for use in α-glucosidase-related basic research., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the clinical state of posttraumatic epilepsy (PTE) in patients with chronic disorders of consciousness (CDC) due to severe traumatic brain injury (STBI) after traffic accidents and clarify the risk factors for seizure occurrence in such patients., Methods: Two hundred ninety-three patients with CDC due to STBI (mean age at admission [±standard deviation]: 36.4 ± 17.9 years; men: 71.7 %; mean duration of injury to admission: 416 ± 732 days; mean hospitalization time: 899 ± 319 days) were enrolled in this study. We retrospectively investigated the relationship between seizure conditions (type and frequency) and clinical data, including age, sex, pathological types of brain injury, with/without surgical intervention, degree of CDC, and administration of antiseizure medications (ASMs)., Results: Overall, 52.9 % (n = 155/293) and 64.2 % of the patients (n = 183/of 285 patients surviving at discharge) were administered ASMs at admission and discharge, respectively. One hundred thirty-two patients (45.1 %) experienced epileptic seizures during hospitalization, and the mean seizure frequency was 4.0 ± 0.4 times per year. In multivariate analysis, significant and independent risk factors of seizure occurrence were revealed to be male sex, high National Agency for Automotive Safety and Victims' Aid score, hypoxic encephalopathy, and history of the neurosurgical operations., Conclusion: The high prevalence of PTE in patients with CDC due to STBI, and the significant and independent risk factors for seizure occurrence in the chronic clinical phase were revealed. We expect that this study will aid toward improving clinical assessment and management of epileptic seizures in the population., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Introduction: An increased incidence of metabolic syndrome has been observed in human immunodeficiency virus (HIV)-infected individuals. In contrast, gut dysbiosis is involved in various pathogeneses, including vascular endothelial disorders. Organic acids, including short-chain fatty acids (SCFAs), are essential for maintaining gut homeostasis. Therefore, this study aimed to explore the gut microbiome profile and organic acids in a Japanese population infected with HIV., Methods: Forty-nine patients with HIV infection on combination antiretroviral therapy (cART) were enrolled and divided into the high and low CD4 groups based on a CD4 cutoff of 350 cells/μL. Stool samples were analyzed by 16S ribosomal RNA next-generation sequencing and high-performance liquid chromatography. The association between the gut microbiome, including bacterial taxa and organic acids, was statistically analyzed., Results: The fecal microbial community composition was significantly different between HIV patients with CD4 counts above and below 350 cells/μL. The relative abundance of Roseburia, Prevotella, Prevotella_9, and [Clostridium]_methylpentosum_group were significantly enriched in the high CD4 group. Fecal succinic acid tended to be more abundant in the low CD4 group, and acetic, propionic, and butyric acids tended to be more abundant in the high CD4 group. Roseburia was positively correlated with butyric acid levels. Prevotella_9 and Prevotella were negatively correlated with succinic acid levels and positively correlated with acetic and propionic acid levels., Conclusions: This study showed intestinal dysbiosis bordering on a CD4 count of 350 in patients with HIV infection undergoing cART. These findings might help in understanding intestinal damage and systemic inflammation in HIV infection., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Bromovalerylurea (BU), an acyl urea derivative, was originally developed as a hypnotic/sedative. We recently reported that BU at a dose of 50 mg/kg ameliorates sepsis, Parkinson's disease, and traumatic brain injury in Wistar rat models through its anti-inflammatory actions on microglia and macrophages. However, since BU was developed more than 100 years ago, its hypnotic mechanism and characteristics are poorly understood. Herein, we conducted an electroencephalogram (EEG) study and found that BU, when administered at a dose of more than 125 mg/kg but not at a dose of 50 mg/kg in Wistar rats, significantly increased non-rapid eye movement (NREM) sleep duration and dose-dependently decreased rapid eye movement (REM) sleep duration. This characteristic of sleep induced by BU is similar to the effect of compounds such as barbiturate, benzodiazepine, and z-drugs, all of which require γ-aminobutyric acid A receptors (GABA A R) for hypnotic/sedative activity. To investigate whether BU could potentiate GABA A ergic neurotransmission, we conducted a whole-cell patch-clamp recording from pyramidal neurons in rat cortical slices to detect spontaneous GABA A R-mediated inhibitory postsynaptic currents (IPSCs). We found that BU dose-dependently prolonged IPSCs. Importantly, the prolonged IPSCs were not attenuated by flumazenil, a benzodiazepine receptor antagonist, suggesting that modulation of IPSCs by BU is mediated by different mechanisms from that of benzodiazepine. Taken together, these data elucidate the basic characteristics of the hypnotic effects of BU and suggest that the enhancement of GABA A R-mediated Cl - flux may be a possible mechanism that contributes to its hypnotic/sedative activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The prognosis of patients with chronic limb-threatening ischemia (CLTI) is unacceptably poor, and risk factors are unknown. Serum remnant lipoprotein has been associated with cardiovascular events. The aim of our study was to test the hypothesis that remnant lipoprotein is associated with the prognosis of patients with CLTI., Methods: This retrospective study included 67 patients with CLTI who had received endovascular therapy (EVT) for de novo below-the-knee lesions. Patients were divided into 2 groups using fasting preoperative value of remnant-like particle cholesterol (RLP-C) with a cutoff value of 5.1 mg/dL into LOW RLP-C (n = 46) and HIGH RLP-C (n = 21). We assessed the differences between the 2 groups in the prevalence of major adverse limb events (MALE), composed of target lesion revascularization and major amputation., Results: At a median follow-up period of 12 months, MALE had occurred in 11 LOW RLP-C patients (23.9%) and 11 HIGH RLP-C patients (52.4%; P = 0.03). Kaplan-Meier analysis showed the prevalence of MALE was significantly higher in HIGH RLP-C than LOW RLP-C (log-rank χ 2  = 5.2, P = 0.02). Multivariate analysis found HIGH RLP-C to be an independent predictor for MALE (hazard ratio, 2.6; 95% confidence interval, 1.1-6.1; P = 0.02) along with history of coronary artery disease., Conclusions: Preoperative remnant lipoprotein was associated with the prognosis of patients with CLTI who had received EVT for de novo below-the-knee lesions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The immune system and the peripheral nervous system are distributed throughout the body and surveil vital organs utilizing various sensory mechanisms. Previous studies have demonstrated that tissue-resident innate lymphoid cells (ILCs) and neurons are heavily enriched in the body's barrier surfaces, where it is critical to detect and rapidly adapt to the changes in dietary, microbial and other environmental stimuli. However, our understanding of how these two sensory systems cooperatively integrate these diverse signals to orchestrate host responses remains incomplete. Recent research has provided insights into how neurotrophic and neuronally derived factors regulate the functions of ILCs, establishing the neuro-ILC axis as a crucial component of broader neuro-immune interactions. Further, neurons express receptors for many cytokines produced by ILCs, opening the possibility for bidirectional neuro-immune interactions in regulating tissue homeostasis and inflammation. This review highlights recent advances in the cellular and molecular mechanisms of neuro-ILC interactions and their potential therapeutic implications., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We previously reported that glioma stemlike cells (GSCs) exist in the area of the tumor periphery showing no gadolinium enhancement on magnetic resonance imaging. In the present work, we analyzed glucose metabolism to investigate whether lactate could be predictive of tumor invasiveness and of use in detection of the tumor invasion area in glioblastoma multiforme (GBM)., Methods: The expression of lactate dehydrogenase A (LDH-A) and pyruvate dehydrogenase (PDH) was investigated in 20 patients. In GSC lines, LDH-A and PDH expression also was examined in parallel to assessments of mitochondrial respiration. We then investigated the relationship between lactate/creatine ratios in the tumor periphery measured by magnetic resonance spectroscopy, using learning-compression-model algorithms and phenotypes of GBMs., Results: In 20 GBMs, high-invasive GBM expressed LDH-A at significantly higher expression than did low-invasive GBM, whereas low-invasive GBM showed significantly higher expression of PDH than did high-invasive GBM. The highly invasive GSC line showed higher expression of LDH-A and lower expression of PDH compared with low-invasive GSC lines. The highly invasive GSC line also showed the lowest consumption of oxygen and the lowest production of adenosine triphosphate. Lactate levels, as measured by magnetic resonance spectroscopy, showed a significant positive correlation with LDH-A transcript levels, permitting classification of the GBMs into high-invasive and low-invasive phenotypes based on a cutoff value of 0.66 in the lactate/creatine ratio., Conclusions: In the tumor periphery area of the highly invasive GBM, aerobic glycolysis was the predominant pathway for glucose metabolism, resulting in the accumulation of lactate. The level of lactate may facilitate prediction of the tumor-infiltrating area on GBM., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The abilities to invade surrounding tissues and metastasize to distant organs are the most outstanding features that distinguish malignant from benign tumors. However, the mechanisms preventing the invasion and metastasis of benign tumor cells remain unclear. By using our own rat distant metastasis model, gene expression of cells in primary tumors was compared with that in metastasized tumors. Among many distinct gene expressions, we have focused on chloride intracellular channel protein 2 (CLIC2), an ion channel protein of as-yet unknown function, which was predominantly expressed in the primary tumors. We created CLIC2 overexpressing rat glioma cell line and utilized benign human meningioma cells with naturally high CLIC2 expression. CLIC2 was expressed at higher levels in benign human brain tumors than in their malignant counterparts. Moreover, its high expression was associated with prolonged survival in the rat metastasis and brain tumor models as well as with progression-free survival in patients with brain tumors. CLIC2 was also correlated with the decreased blood vessel permeability likely by increased contents of cell adhesion molecules. We found that CLIC2 was secreted extracellularly, and bound to matrix metalloproteinase (MMP) 14. Furthermore, CLIC2 prevented the localization of MMP14 in the plasma membrane, and inhibited its enzymatic activity. Indeed, overexpressing CLIC2 and recombinant CLIC2 protein effectively suppressed malignant cell invasion, whereas CLIC2 knockdown reversed these effects. Thus, CLIC2 suppress invasion and metastasis of benign tumors at least partly by inhibiting MMP14 activity., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Knowledge is limited on the virologic course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, particularly the time taken for viral clearance and the optimal time to discontinue isolation. This study aims to identify the clinical and demographic factors influencing the time taken for viral clearance in patients with COVID-19 to determine the optimal isolation period., Methods: This two-center retrospective observational cohort study was conducted between March 1 and June 31, 2020. Patients with COVID-19, which was confirmed by real-time reverse transcription polymerase chain reaction, were included. Data were extracted from medical records. The positive duration, which was defined as the period from the day of symptom onset to the negative conversion day, was assessed using a generalized linear model., Results: We included 63 patients. The mean positive duration was 20 days. The positive duration was significantly shorter for patients younger than 30 years of age and those between 30 and 60 years of age than for patients older than 60 years of age. We observed a more scattered distribution of the positive duration in older patients than in younger patients., Conclusions: Younger patients who recovered from COVID-19 took less time to clear SARS-CoV-2 than older patients; thus, a classification of the isolation periods based on age could be considered. A uniform viral clearance period for older patients may be difficult to determine because of biases such as underlying medical conditions. Further surveillance measures are recommended to determine the viral clearance time and the optimal isolation period., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Bordetella trematum and Kerstersia gyiorum are rare gram-negative bacilli that are not frequently detected in human infections. In this report, we describe a case of a 48-year-old man who presented to our hospital with an infected wound on his leg. Discharges from the cracks of the granulation were collected and evaluated in our microbiology laboratory. Gram staining of the specimen showed polymorphonuclear leukocytes and abundant gram-negative bacilli. Three types of colonies were isolated on blood agar and were identified as B. trematum and Alcaligenes faecalis using VITEK MS. Moreover, K. gyiorum and B. trematum were identified and confirmed via 16S ribosomal RNA (rRNA) gene sequencing. The patient successfully recovered following application of meropenem antibacterial therapy and surgical debridement. This is the first reported case of complex wound infection caused by both B. trematum and K. gyiorum. Identification of B. trematum has recently been made possible by routine bacterial identification using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). However, K. gyiorum isolation is still rare, and species identification requires 16S rRNA sequencing. Thus, this case highlighted the importance of using multiple methods, such as MALDI-TOF MS and 16S rRNA gene sequencing, for identification of rarely isolated species from clinical specimens., Competing Interests: Declarations of competing interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Chronic infection with Helicobacter pylori, specifically cagA-positive strains, is associated with gastric cancer. Thus, measures to prevent H. pylori infection are required. This study was conducted to clarify the prevalence of H. pylori in the community to identify the infection source and comprehensively assess the risk of H. pylori infection., Methods: We collected 90 human faecal samples and 73 environmental samples (water, vegetable, and animal faecal samples) from the residents in an area with a high incidence of gastric cancer in Japan. Polymerase chain reaction assay was performed to detect the glmM housekeeping gene and the cagA virulence gene of H. pylori. A questionnaire survey was conducted, and the responses were analyzed statistically., Results: The glmM gene was detected in 18 of 90 (20%) faecal samples obtained from residents; among them, the cagA gene was detected in 33.3% (6/18), and in all who had undergone eradication therapy. H. pylori was not detected in environmental samples. However, contact with dogs (OR 3.89, 95% CI 1.15-13.15, P < 0.05) was associated with higher odds for glmM gene positivity in the questionnaire survey., Conclusions: The prevalence of H. pylori and cagA-positive strains among the residents was low. However, the study results suggest a correlation between recurrent infection and cagA-positive H. pylori strains. Although H. pylori genes were not detected in living environments, an association between contact with dogs and a glmM positive status was revealed. Further investigations targeting community-dwelling healthy people and their living environments would be required for H. pylori infection control., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Non-typhoidal Salmonellae are Gram negative bacilli commonly causing self-limiting gastroenteritis, representing a public health issue particularly in tropical countries. Further, the epidemiology of invasive infection by non-typhoidal Salmonella species is poorly understood. Herein, we presented a case of an unusual Salmonella enterica subsp. enterica serovar Altona epidural abscess that cause osteomyelitis and psoas abscess in a 52-year-old Japanese man. To ensure adequate antibiotics penetration into the epidural space, the patient was treated with antibiotics in doses similar to those administered for meningitis. We also reviewed the literature on patients who developed non-typhoidal Salmonella epidural abscesses, and we found 10 other previously reported cases. Salmonella Enteritidis was the pathogen most commonly identified, similar to gastroenteritis. More surveillance of non-typhoidal Salmonella serovars, especially in cases of severe infection, and investigation of antibiotic penetration rate into the epidural space are warranted to decide the best treatment course., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To provide data on the molecular characteristics of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae clinical isolates in Japan., Methods: A total of 100 clinical isolates of ESBL-producing K. pneumoniae collected throughout Japan between June and July 2018 were studied. ESBL genes were analyzed using PCR and DNA sequencing. Transferability of ESBL genes was investigated by conjugation experiments. Plasmid replicon types, virulence genes (rmpA, rmpA2, iucA, iroB, and peg-344) associated with hypervirulent K. pneumoniae (hvKp), and capsule types were detected using PCR. Genotyping was performed using multilocus sequence typing., Results: All ESBL-producing isolates carried bla CTX-M genes. The most predominant CTX-M-type identified was CTX-M-15 (n=55). We identified 24 sequence types (STs) among the CTX-M-15 producers, with ST25 (n=8) being the most common. Most of the transconjugants carrying bla CTX-M-15 contained the FIIk replicon. Of the 100 ESBL-producing isolates, 31 were hvKp defined by the presence of the virulence genes. These ESBL-producing hvKp isolates belonged to eight STs (STs 23, 25, 36, 65, 86, 268, 412, and 4492), with five capsule types (K1, K2, K20, K57, and undefined)., Conclusions: CTX-M-15 was the predominant ESBL among K. pneumoniae isolates from Japan. This study shows that ESBL-producing hvKp strains comprising various clones are emerging in Japan., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee conducted a nationwide surveillance on six otorhinolaryngological diseases and investigated the antimicrobial susceptibility patterns and isolation rates of the causative pathogens. The surveillance program was conducted in the otorhinolaryngological departments of 12 universities, and 36 affiliated hospitals and clinics. Patients with acute otitis media (children under six years old), chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess (over 20 years old) between December 2015 and June 2017 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the antimicrobial susceptibility of the detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa), and three anaerobic bacteria (anaerobic gram-positive cocci, Prevotella spp., Porphyromonas spp., and Fusobacterium spp.). Bacterial susceptibility to 40 antimicrobial agents was investigated. We were unable to completely mitigate the rise in the occurrence of resistant bacteria, such as methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, penicillin-intermediate resistant S. pneumoniae, beta-lactamase non-producing ampicillin-resistant H. influenzae, and beta-lactamase producing ampicillin-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial agents to prevent the spread of these bacteria. We also suggested that immunization with pneumococcal vaccines is useful for decreasing the occurrence of otorhinolaryngological infectious diseases caused by pneumococci., Competing Interests: Declaration of Competing Interest Kenji Suzuki has received speaker's honorarium from KYORIN Pharm. Co., Ltd., FUJIFILM Toyama Chemical Co., Ltd., Meiji Seika Pharma Co., Ltd., and Dainippon Sumitomo Pharm. Co., Ltd. Akira Watanabe has received speaker's honorarium from MSD Co., Ltd., and Shionogi Pharma Co., Ltd., and a technical guidance fee from FUJIFILM Toyama Chemical Co., Ltd. Tetsuya Matsumoto has received speaker's honorarium from Merck Sharp and Dohme (MSD). Co., Ltd., and Pfizer Co., Ltd. Yoshisaburo Takahashi is employed by Meiji Seika Pharma Co., Ltd. The other authors declare that they have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Patients experiencing out-of-hospital cardiac arrest (OHCA) and subsequent post-cardiac arrest syndrome are often compromised by multi-organ failure. The Sequential Organ Failure Assessment (SOFA) score has been used to predict clinical outcome of patients requiring intensive care for multi-organ failure. Thus, the assessment of SOFA score is recommended as a criterion for sepsis. Although post-cardiac arrest patients frequently develop sepsis-like status in ICU, there are limited reports evaluating the SOFA score in post-cardiac arrest patients. We investigated the predictive value of the SOFA score in survival and neurological outcomes in patients with post-cardiac arrest syndrome., Methods: A total of 231 cardiovascular arrest patients achieving return of spontaneous circulation (ROSC) were finally extracted from the institutional consecutive database comprised of 1218 OHCA patients transferred to the institution between January 2015 and July 2018. The SOFA score was calculated on admission and after 48h. Predictors of survival and neurological outcome defined as having cerebral-performance-category (CPC) 1 or 2 at 30 days were determined., Results: SOFA score was lower in survived patients (5.0 vs 10.0, p<0.001) and those with favorable neurological outcome (5.0 vs 8.0, p<0.001) as compared with the counterparts. The SOFA score on admission was an independent predictor of survival (OR 0.68, 95% confidence interval [CI] 0.59-0.78; p<0.001) and favorable neurological performance (OR 0.79; 95% CI 0.69-0.90; p<0.001) at 30 days. Furthermore, a change in SOFA score (48-0h) was predictive of favorable 30-day neurological outcome (OR 0.71, 95% CI 0.60-0.85; p<0.001)., Conclusions: Evaluation of the SOFA score in the ICU is useful to predict survival and neurological outcome in post-cardiac arrest patients., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The escalating problem of the dissemination of carbapenemase-producing bacteria (CPB) has gained worldwide attention. The prompt diagnosis of CPB and precise identification of carbapenemases are imperative to enable specific antibiotic therapy and control the spread of these bacteria. The present study was designed to assess the performance of five important assays for the detection of carbapenemases. The modified carbapenem inactivation method (mCIM), CARBA-5, GeneXpert Carba-R, BD MAX Check-Points CPO, and GeneFields CPE assays were evaluated with an international collection of 159 bacterial isolates, including 93 CPB and 66 non-CPB isolates. The overall accuracy/sensitivity/specificity for carbapenemase detection were 100% (95% CI, 97.7%-100%)/100% (95% CI, 96.1%-100%)/100% (95% CI, 94.6%-100%) for mCIM, 98.7% (95% CI, 95.5%-99.9%)/97.9% (95% CI, 92.5%-99.7%)/100% (95% CI, 94.6%-100%) for CARBA-5, 96.9% (95% CI, 92.8%-99%)/95.7% (95% CI, 89.4%-98.8%)/98.5% (95% CI, 91.8%-99.9%) for GeneXpert Carba-R, 94.3% (95% CI, 89.5%-97.4%)/90.3% (95% CI, 82.4%-95.5%)/100% (95% CI, 94.6%-100%) for BD MAX Check-Points CPO, and 86.2% (95% CI, 79.8%-91.1%)/77.4% (95% CI, 67.6%-85.5%)/98.5% (95% CI, 91.8%-100%) for GeneFields CPE. Interestingly, mCIM and CARBA-5 assays showed 100% accuracy/sensitivity/specificity for detection of the target genes. Furthermore, all the other assays showed comparable high accuracy (96.9% to 100%), sensitivity (100%), and specificity (96.4% to 100%) for the detection of the target genes. On the basis of these results, a new scheme was proposed for their efficient application. These results confirmed the high sensitivity of the evaluated assays, and the proposed scheme is reliable and improves the overall sensitivity and specificity of the assays., (Copyright © 2020 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: The increasing number of carbapenemase-producing Enterobacteriaceae (CPE) has become a global problem. Most carbapenemases detected in Japan are imipenemase, which is an imipenem-degrading enzyme with low ability; thus, CPE could have been overlooked. Therefore, this study aimed to detect and analyze CPE, without overlooking CPE showing the low minimum inhibitory concentration phenotype., Methods: CPE screening was conducted on 531 ceftazidime-resistant Enterobacteriaceae isolated from Kitasato University Hospital during 2006-2015. We confirmed the presence of the carbapenemase genes (bla IMP , bla VIM , bla KPC , bla NDM , and bla OXA-48 ) by multiplex polymerase chain reaction. The detected CPE strains were analyzed by antimicrobial susceptibility testing, multilocus sequence typing, conjugal experiments, replicon typing, and plasmid profiling by restriction enzyme treatment., Results: The CPE detection rate in Kitasato University Hospital within the past 10 years was 0.0003% (nine CPE strains). These nine CPE strains were identified to harbor 8 bla IMP-1 or 1 bla NDM-5 . The CPE strains consisted of five species including Klebsiella pneumoniae and Citrobacter freundii. Six of eight bla IMP-1 were coded by IncHI2 plasmid, and the other two were coded by IncA/C plasmid. Plasmid profiling revealed that K. pneumoniae and C. freundii isolated from the same patient harbored the same plasmid., Conclusion: The CPE detection rate in this study was significantly lower than those previously reported in Japan. In one case, IncA/C plasmid transmission through different bacterial species within the body was speculated. Although the number of CPE detected was low, these results indicated that the resistance plasmid could spread to other bacterial species., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, evolocumab, to statin therapy produced incremental regression of atherosclerotic plaques and a collaborative prevention of cardiovascular events in patients with coronary artery disease. The effect on fibrous-cup thickness, or extension of the atherosclerotic plaque with PCSK9-inhibitor, for several weeks after onset of acute coronary syndrome (ACS) has never been reported., Methods: This study aimed to examine the effect of evolocumab on fibrous-cap thickness, as well as the extent of the atherosclerotic plaque, by serial optical coherence tomography (OCT) analysis in patients with ACS. All patients received rosuvastatin 5 mg/day from at least 24 h after onset of ACS. Patients received evolocumab (140 mg every 2 weeks) 1 week after the onset of ACS in the statin plus evolocumab group. Patients took only rosuvastatin in the statin monotherapy group. OCT was performed to assess intermediate, non-culprit lesions just 4 and 12 weeks after emergent percutaneous coronary intervention., Results: OCT analysis revealed that the increase in fibrous-cap thickness and decrease in macrophage grade were greater with a narrower lipid arc and shorter lipid length, which were associated with lower low-density lipoprotein cholesterol (LDL-C) in the statin plus evolocumab group than in the statin alone treatments, even for a short term after ACS onset., Conclusions: Addition of the PCSK9-inhibitor evolocumab to statin therapy might produce incremental growth in fibrous-cap thickness and regression of the lipid-rich plaque, which were associated with greater reduction of LDL-C even for a short term in the early phase of ACS., (Copyright © 2019. Published by Elsevier Ltd.)

Sepsis is a leading cause of mortality in intensive care units due to multi-organ failure caused by dysregulated immune reactions. In this study, kinetic changes in the immune system were analyzed for 72 h in cecal ligation and puncture (CLP)-induced septic mice while preventing animal death by keeping body temperature. Increase of myeloid cells and decrease of B cells in circulation at 6 h after CLP were markedly observed. At the same time point, interleukin (IL)-10 expressing CD5 + regulatory B cells (Bregs) appeared. IL-10 and programmed death-ligand 1 (PD-L1) mRNA as well as IL-1β, IL-6 and interferon γ (IFNγ) mRNA was increased in the spleen at 6 h. A gradual decrease in Bcl-2 and abrupt increase of Bim expression in the spleen at the late phase were also found. These results showed that B lymphocytopenia with the appearance of Bregs is the earliest event, likely leading to immunoparalysis in sepsis., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We report a clinical case of Filifactor alocis brain abscess in an 85-year-old man who had decayed teeth 1 week prior. In this case, the abscess was surgically drained after empirical antibiotics had been initiated. Although the causative organism could not be identified by culture, F. alocis was detected via 16S ribosomal RNA (16S rRNA) gene sequencing of the pus isolated from the abscess. The patient recovered without serious sequelae after surgical drainage and prolonged antibiotic treatment, including metronidazole, ceftriaxone and meropenem for 8 weeks. The findings in this case emphasize that 16S rRNA gene sequencing allows bacterial diagnosis of brain abscess when phenotypic identification fails, such as in cases where patients are undergoing antimicrobial treatment at the time of sampling or where patients are infected with fastidious organisms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A-26-year-old man was admitted to our hospital with diffuse abdominal pain, nausea, and vomiting. He had a history of malignant nephrosclerosis, for which he had been receiving peritoneal dialysis (PD) for the past 14 months. His PD effluent was cloudy and turbid (white blood cell count, 10,528/μL; neutrophils 95.2%). A Gram-negative coccobacillus was isolated from peritoneal fluid culture. However, the organism could not be identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS, bioMérieux), but was identified as Moraxella osloensis by the 16S rRNA gene sequencing. He was successfully treated with intraperitoneal cefazolin therapy for 3 weeks without removing the intra-abdominal catheter. A literature review revealed three previous case reports all of which were diagnosed by MALDI Biotyper (Bruker Daltonics), suggesting that the identification of M. osloensis may vary depending on the type of MALDI-TOF MS system. In conclusion, we experienced a case of M. osloensis infection in a PD patient, which was successfully treated by antibiotic treatment, without removing the PD catheter., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Use of the everolimus-eluting stent (EES) instead of the sirolimus-eluting stent (SES) has been shown to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) out to 3 years. However, it is not known whether the differences in efficacy and safety outcomes remain constant throughout 5 years., Methods: This was a retrospective, non-randomized, observational study. We followed 1460 consecutive patients undergoing PCI in our institutions from April 2005 to March 2012. There were 718 cases in patients with SES (SES group) and 742 with EES (EES group). Ten-month angiographic follow-up results and 5-year clinical follow-up outcomes were compared between the EES and SES groups. The primary outcome of this study was major adverse cardiac events (MACE), defined as the composite of cardiac death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis (ST)., Results: At 5 years, the rates of target lesion revascularization (TLR), TVR, recurrent MI and ST were significantly lower in the EES group compared to the SES group (TLR: 4.6% vs. 8.2%, p<0.05; TVR: 5.0% vs. 9.0%, p<0.05; recurrent MI: 1.5% vs. 4.4%, p<0.05; ST: 1.2% vs. 3.9%, p<0.05). Thus, MACE were significantly lesser in the EES group compared to the SES group (8.8% vs. 12.8%, p=0.006)., Conclusions: EES improved clinical outcomes compared to SES, and specifically, was associated with reductions in TVR, ST, and recurrent MI out to 5 years., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Neutrophil elastase (NE) is necessary for effective sterilization of phagocytosed bacterial and fungal pathogens; however, NE increases alveolocapillary permeability and induces proinflammatory cytokine production in sepsis-induced acute respiratory distress syndrome. Under septic conditions, the pulmonary endothelial glycocalyx covering on the healthy endothelium surface is injured, but the contribution of NE to this injury remains unknown. Our aim was to examine whether NE-induced pulmonary endothelial injury is associated with endotoxemia. Lipopolysaccharide (LPS; 20 mg/kg) was injected intraperitoneally into 9- to 12-week-old granulocyte colony-stimulating factor knockout (G-CSFKO) mice, which harbor few neutrophils, and littermate control mice; in a second assay, mice were injected with the NE-inhibitor sivelestat (0.2 mg/kg) at 3, 6, 9, and 12 hours after LPS administration. Subsequently, vascular endothelial injury was evaluated through ultrastructural analysis. At 48 hours after LPS injection, survival rate was more than threefold higher among G-CSFKO than control mice, and degradation of both thrombomodulin and syndecan-1 was markedly attenuated in G-CSFKO compared with control mice. Ultrastructural analysis revealed attenuated vascular endothelial injury and clear preservation of the endothelial glycocalyx in G-CSFKO mice. Moreover, after LPS exposure, survival rate was approximately ninefold higher among sivelestat-injected mice than control mice, and sivelestat treatment potently preserved vascular endothelial structures and the endothelial glycocalyx. In conclusion, NE is associated with pulmonary endothelial injury under LPS-induced endotoxemic conditions., (Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The aims of the present study were to compare the longitudinal changes of glioblastoma multiforme after radiotherapy (RT) between 11C-methionine positron emission tomography (MET-PET) and gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) and to clarify whether these changes were predictive of survival. We included 30 patients, who had undergone MET-PET and Gd-MRI before and every 3 months after RT. The lesion/normal brain uptake (L/N) ratio and contrast-enhancing lesion volume were examined. The L/N ratio was decreased until 9 months after RT with significance until 3 months. The contrast-enhancing lesion volume was decreased until 3 months and thereafter increased until 9 months with significance. The variation rates of the L/N ratio between pre-RT and 3 months differentiated survival of >23 months from ≤23 months. A dissociation could exist in the longitudinal changes of GBM after RT between MET-PET and Gd-MRI. The variation rate of the L/N ratio could be related to survival., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Tumefactive demyelinating lesion (TDL) is often reported as a rare variation of multiple sclerosis (MS). TDL is difficult to diagnose solely by magnetic resonance imaging (MRI) in patients with no history of MS. This is because the lesion often shows ring enhancement with perifocal brain edema on gadolinium MRI, thus mimicking glioblastoma multiforme (GBM)., Case Description: A 54-year-old healthy woman complained of headache 1 month before admission. She developed a decline in cognitive function, decreased attention, and executive function disorder 10 days before admission. Gadolinium magnetic resonance imaging showed a ring-shaped enhancement accompanied by massive brain edema in the left frontal lobe. This suggested GBM, but methionine positron emission tomography (MET PET), surprisingly, showed no uptake with a tumor-to-normal brain ratio of 1.18. Accordingly, we eliminated GBM and suspected brain abscess because diffusion-weighted images showed high signal intensity in the lesion. Although we performed drainage, we could not demonstrate the presence of pus. Pathologic analysis of a specimen obtained by needle biopsy revealed broad necrosis and a small number of inflammatory cells. We therefore prescribed steroid therapy, by which symptoms gradually improved. No relapse occurred for 2 years. We finally diagnosed the patient as having TDL., Conclusions: MET PET is considered a possible diagnostic modality for demyelinating disease as it can appropriately reflect pathologic findings. MET PET will facilitate decision making regarding surgery in patients with TDL., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: In renal cell carcinoma (RCC), several prognostic biomarkers have been identified and are under investigation. Several reports have shown that the expression of programmed death 1 (PD-1) and its ligand PD-L1 is associated with poor outcome for patients with RCC. The present study is aimed at evaluating the expression of PD-1 and PD-L1 and to investigate their clinical and prognostic significance in patients with clear cell RCC (CCRCC) having received molecular targeted therapies. In addition, we also evaluated the relationship between the expression of PD-1 and PD-L1 and intratumoral tumor infiltrating lymphocytes (TILs)., Methods: A total of 33 patients with metastatic CCRCC who underwent surgery and received molecular targeted therapies from March 2008 to April 2016 were retrospectively reviewed and analyzed. Tissue specimens from the patients were analyzed for PD-1 and PD-L1 expression by immunohistochemistry., Results: The median patient age was 64 years old (range=53-78). The majority of patients were male (81.8%). All Memorial Sloan Kettering Cancer Center risk groups were represented among the patients with 39.4% with favorable-, 51.5% with intermediate- and 9.1% with poor-risk. The expression of PD-1 and PD-L1 was observed in 16 (48.5%) and 9 (27.3%) patients, respectively. The expression of PD-1 and PD-L1 was associated with a larger primary renal tumor size, higher nuclear grade and sarcomatoid feature. Kaplan-Meier analysis revealed that no significant difference in progression free survival of first line molecular targeted therapy was found for PD-1 (P=0.2396) and PD-L1 (P=0.5919) expression. However, PD-1 expression has a significant worse impact on overall survival (OS) (P=0.0385), while for PD-L1 expression only a trend is seen for OS (P=0.1542). The patients with PD-1 and PD-L1 expression showed higher infiltration of CD4 (P<0.0001 and P<0.0001, respectively), CD8 (P=0.0328 and P=0.0044, respectively) and FOXP3 (P<0.0001 and P=0.0033, respectively) positive TILs., Conclusion: PD-1 and PD-L1 expression is significantly associated with adverse clinicopathological features in CCRCC. Furthermore, PD-1 expression could be one of the biomarkers suggesting poor outcome in patients with metastatic CCRCC receiving molecular targeted therapies., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The most recent diagnostic criteria for sepsis include organ failure. Microvascular endothelial injury is believed to lead to the multiple organ failure seen in sepsis, although the precise mechanism is still controversial. ARDS is the primary complication during the sequential development of multiple organ dysfunction in sepsis, and endothelial injury is deeply involved. Sugar-protein glycocalyx coats all healthy vascular endothelium, and its disruption is one factor believed to contribute to microvascular endothelial dysfunction during sepsis. The goal of this study was to observe the three-dimensional ultrastructural alterations in the pulmonary capillary endothelium, including the glycocalyx, during sepsis-induced pulmonary vasculitis., Methods: This study investigated the three-dimensional ultrastructure of pulmonary vascular endothelial glycocalyx in a mouse lipopolysaccharide-induced endotoxemia model. Lungs were fixed with lanthanum-containing alkaline fixative to preserve the glycocalyx., Results: On both scanning and transmission electron microscopic imaging, the capillary endothelial glycocalyx appeared as a moss-like structure entirely covering the endothelial cell surface in normal mice. In the septic lung following liposaccharide injection, however, this structure was severely disrupted; it appeared to be peeling away and coagulated. In addition, syndecan-1 levels were significantly reduced in the septic lung, and numerous spherical structures containing glycocalyx were observed on the endothelial surface., Conclusions: It appears that endothelial glycocalyx in the lung is markedly disrupted under experimental endotoxemia conditions. This finding supports the notion that disruption of the glycocalyx is causally related to the microvascular endothelial dysfunction that is characteristic of sepsis-induced ARDS., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The semidry dot-blot method is a diagnostic procedure for detecting lymph node (LN) metastases using the presence of cytokeratin (CK) in lavage fluid from sectioned LNs. We evaluated 2 novel kits that use newly developed anti-CK-19 antibodies to diagnose LN metastases in breast cancer., Patients and Methods: We examined 159 LNs dissected that we sliced at 2-mm intervals and washed with phosphate-buffered saline. The suspended cells in the lavage were centrifuged and lysed to extract protein. This extracted protein was used with a low-power and a high-power kit to diagnose LN metastasis. Diagnoses on the basis of the kits were compared with pathological diagnoses., Results: Of the 159 LNs, 68 were assessed as positive and 91 as negative in permanent section examination. Sensitivity, specificity, and accuracy of the low-power kit for detecting LN metastases was 83.8%, 100%, and 93.1%, respectively. Those of the high-power kit were 92.6%, 92.3%, and 92.5%, respectively. Combining the low- and high-power kit results, those for distinguishing macrometastases were 94.5%, 95.2%, and 95.0%, respectively. Diagnosis was achieved in approximately 20 minutes, at a cost of less than $30 USD., Conclusion: The kits were accurate, fast, and cost-effective in diagnosing LN metastases without the loss of LN tissue., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Even though longer stented lengths may increase the risk of restenosis, full coverage of diffuse long lesions with longer stents seems to be the optimal strategy for percutaneous coronary intervention (PCI) in the new drug-eluting stent (DES) era. However, it remains unclear whether this strategy will indicate favorable outcome or not. This study evaluated the impact of stent length on two-year clinical outcomes after PCI with the XIENCE Alpine everolimus-eluting stent., Methods: This was a retrospective, non-randomized, observational study. Four patient groups were classified according to implanted overall total stent length (short, <15mm; middle, 15-23mm; long, 24-32mm; and ultra-long, >32mm). The primary outcome of this study was major adverse cardiac events (MACE), defined as the composite of cardiac death, recurrent myocardial infarction (MI), target vessel revascularization (TVR), and stent thrombosis (ST). Angiographic restenosis by quantitative coronary angiography was defined as >50% diameter stenosis at 10 months after PCI., Results: A total of 730 patients who received intravascular ultrasound (IVUS)-guided PCI were enrolled. The short, middle, long, and ultra-long stent groups included 138 patients (149 lesions), 210 patients (235 lesions), 190 patients (209 lesions), and 192 patients (208 lesions), respectively. The primary outcome at two years did not differ among the four groups (MACE: 4.4% in short, 3.3% in middle, 4.7% in long, and 4.7% in ultra-long groups, p=0.402); TVR, ST, MI, and cardiac mortality also did not differ among groups., Conclusions: Long stenting using the XIENCE stent which was guided by IVUS for diffuse, long lesions was associated with favorable clinical outcomes at two years in daily clinical practice., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Introduction: Nonadherence to adjuvant endocrine therapy has been poorly studied in Asian patients with breast cancer. We therefore assessed adherence to endocrine therapy among women with breast cancer in Japan., Patients and Methods: We conducted a prospective observational study among Japanese women with hormone receptor-positive breast cancer. Patients brought their pill packets to visits for 1 year and answered a questionnaire. We also examined prescription records during the study period. Adherence to endocrine therapy was defined as patients who had taken > 80% of the pills according to the packets during the study. Clinicopathologic features and questionnaires were compared between adherent and nonadherent patients., Results: A total of 234 patients completed the trial, of whom 85% demonstrated adherence based on pill packets, and 98% demonstrated adherence based on prescription records. Mastectomy, higher stage, nodal metastasis and adjuvant chemotherapy were correlated with adherence based on pill packets. Adjuvant chemotherapy was an independent factor associated with adherence. According to the questionnaire, adherent patients were more likely to consult a nurse when they had trouble with their medication. These patients also emphasized the efficacy rather than the side effects of the medication. Nonadherent patients were aware that they were being nonadherent., Conclusion: The results of this study revealed that 85% of patients were adherent to endocrine therapy, but physicians were unaware of the nonadherent patients. Raised awareness of nonadherence and information sharing between patients and medical teams might increase adherence to endocrine therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ischemic brain injuries caused release of damage-associated molecular patterns (DAMPs) that activate microglia/macrophages (MG/MPs) by binding to Toll-like receptors. Using middle cerebral artery transiently occluded rats, we confirmed that MG/MPs expressed inducible nitric oxide synthase (iNOS) on 3days after reperfusion (dpr) in ischemic rat brain. iNOS expression almost disappeared on 7dpr when transforming growth factor-β1 (TGF-β1) expression was robustly increased. After transient incubation with TGF-β1 for 24h, rat primary microglial cells were incubated with lipopolysaccharide (LPS) and released NO level was measured. The NO release was persistently suppressed even 72h after removal of TGF-β1. The sustained TGF-β1 effects were not attributable to microglia-derived endogenous TGF-β1, as revealed by TGF-β1 knockdown and in vitro quantification studies. Then, boiled supernatants prepared from ischemic brain tissues showed the similar sustained inhibitory effects on LPS-treated microglial cells that were prevented by the TGF-β1 receptor-selective blocker SB525334. After incubation with TGF-β1 for 24h and its subsequent removal, LPS-induced phosphorylation of IκB kinases (IKKs), IκB degradation, and NFκB nuclear translocation were inhibited in a sustained manner. SB525334 abolished all these effects of TGF-β1. In consistent with the in vitro results, phosphorylated IKK-immunoreactivity was abundant in MG/MPs in ischemic brain lesion on 3dpr, whereas it was almost disappeared on 7dpr. The findings suggest that abundantly produced TGF-β1 in ischemic brain displays sustained anti-inflammatory effects on microglial cells by persistently inhibiting endogenous Toll-like receptor ligand-induced IκB degradation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

CD200 mediates immunosuppression in immune cells that express its receptor, CD200R. There are two CD200 variants; truncated CD200 that lacks the part of N-terminal sequence necessary for CD200R binding (CD200S) and full-length CD200 (CD200L). We established a novel lung metastasis model by subcutaneously transplanting C6 glioma cells into the backs of neonatal Wistar rats. All transplanted rats developed large back tumors, nearly 90% of which bore lung metastases. To compare the effects of CD200S and CD200L on tumor immunity, CD200L (C6-L)- or CD200S (C6-S)-expressing C6 cells were similarly transplanted. The results showed that 100% of rats with C6-L tumors developed lung metastases, while metastases were found in only 44% of rats with C6-S tumors (n = 25). Tumors disappeared in approximately 20% of the C6-S-bearing rats, and these animals evaded death 180 d after transplantation, while all C6-L tumor-bearing rats died after 45 d. Next generation sequencing revealed that C6-S tumors expressed chemokines and granzyme B at much higher levels than C6-L tumors. Flow cytometry revealed that C6-S tumors contained more dead cells and more CD45 + cells, including natural killer cells and CD8 + lymphocytes. In particular, multiple subsets of dendritic cells expressing CD11c, MHC class II, CD8, and/or CD103 were more abundant in C6-S than in C6-L tumors. These results suggested that CD200S induced the accumulation of multiple dendritic cell subsets that activated cytotoxic T lymphocytes, leading to the elimination of metastasizing tumor cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Commercially available fibrin glue (Com-FG), which is used commonly worldwide, is produced with pooled human plasma from multiple donors. However, it has added bovine aprotinin, which involves the risk of infection, allogenic immunity, and allergic reactions. We evaluate the efficacy, reliability, and safety of completely autologous fibrin glue (CAFG)., Methods: From August 2014 to February 2016, prospective data were collected and analyzed from 153 patients. CAFG was prepared with the CryoSeal System using autologous blood and was applied during neurosurgical procedures. Using CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets, we performed a pinpoint hemostasis, transposed the offending vessels in a microvascular decompression, and covered the dural incision to prevent cerebrospinal fluid leakage., Results: The CryoSeal System had generated up to a mean of 4.51 mL (range, 3.0-8.4 mL) of CAFG from 400 mL autologous blood. Com-FG products were not used in our procedures. Only 6 patients required an additional allogeneic blood transfusion. The hemostatic effective rate was 96.1% (147 of 153 patients). Only 1 patient who received transsphenoidal surgery for a pituitary adenoma presented with the complication of delayed postoperative cerebrospinal fluid leakage (0.65%). No patient developed allergic reactions or systemic complications associated with the use of CAFG., Conclusions: CAFG effectively provides hemostatic, adhesive, and safety performance. The timing and three-dimensional shape of CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets solidification can be controlled with slow fibrin formation. The cost to prepare CAFG is similar compared with Com-FG products, and it can therefore be easily used at most institutions., (Copyright © 2017 Elsevier Inc. All rights reserved.)