Molecular Analysis for Potential Hospital-Acquired Infection Caused by Aspergillus Tubingensis Through the Environment.

The identification of Aspergillus species has been performed mainly by morphological classification. In recent years, however, the revelation of the existence of cryptic species has required genetic analysis for accurate identification. The purpose of this study was to investigate five Aspergillus section Nigri strains isolated from a patient and the environment in a university hospital. Species identification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry identified all five black Aspergillus strains as Aspergillus niger. However, calmodulin gene sequence analysis revealed that all five strains were cryptic species, four of which, including the clinical strain, were Aspergillus tubingensis. Hospital-acquired infection of the patient with the A. tubingensis strain introduced from the environment was suspected, but sequencing of six genes from four A. tubingensis strains revealed no environmental strain that completely matched the patient strain. The amount of in vitro biofilm formation of the four examples of the A. tubingensis strain was comparable to that of Aspergillus fumigatus. An extracellular matrix was observed by electron microscopy of the biofilm of the clinical strain. This study suggests that various types of biofilm-forming A. tubingensis exist in the hospital environment and that appropriate environmental management is required.

Atezolizumab for EGFR-mutated Non-small Cell Lung Cancer Patients: An Observation Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab, an anti-programed death-ligand 1 monoclonal antibody, targets programed death-ligand 1 expressed on cancer cells and antigen-presenting cells and is now commonly used in combination with chemotherapy. We conducted a study to clarify the efficacy of atezolizumab in epidermal growth factor receptor (EGFR)-mutated patients who are considered less responsive to immune checkpoint inhibitors. PATIENTS AND METHODS: A retrospective review of patients with advanced non-small cell lung cancer (NSCLC) who received atezolizumab-containing therapy at 11 hospitals from April 2018 to March 2023 was performed. RESULTS: Median progression-free survival and overall survival in 33 EGFR-mutated patients treated with atezolizumab monotherapy were 2.0 and 9.0 months, respectively, and those in 19 patients who received combined atezolizumab plus chemotherapy were 12.0 and 17.0 months, respectively. When comparing EGFR-mutated and EGFR-negative patients after propensity score matching, there were no significant differences in progression-free survival and overall survival between the two groups, whether atezolizumab monotherapy or combined atezolizumab plus chemotherapy. Among EGFR-mutated patients, being male was a significant favorable factor in both atezolizumab treatment groups. None of the EGFR-mutated patients had grade 5 immune-related adverse events. CONCLUSION: Efficacy of atezolizumab in EGFR-mutated NSCLC patients could be comparable to that for EGFR-negative patients. To prolong the survival of EGFR-mutated NSCLC patients, appropriate selection and sequencing of EGFR for tyrosine kinase inhibitors, as well as immune checkpoint inhibitors, anti-tumor agents, and anti-angiogenic agents are important.

Atezolizumab Monotherapy for Non-small Cell Lung Cancer Patients: An Observational Study in Ibaraki Group (ATTENTION-IBARAKI).

BACKGROUND/AIM: Atezolizumab is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) expressed on cancer cells derived from various organs and antigen-presenting cells and is currently commonly used in combination with chemotherapy. We conducted a study to clarify the current status of response to atezolizumab monotherapy in clinical practice and clarify the factors that contribute to long-term response and survival. PATIENTS AND METHODS: We conducted a retrospective review of patients with advanced non-small cell lung cancer (NSCLC) treated with atezolizumab monotherapy from April 2018 to March 2023 at 11 Hospitals. RESULTS: The 147 patients evaluated had a progression-free survival (PFS) of 3.0 months and an overall survival of 7.0 months. Immune-related adverse events of any grade were observed in 13 patients (8.8%), grade 3 or higher in nine patients (6.1%), and grade 5 with pulmonary toxicity in one patient (0.7%). Favorable factors related to PFS were 'types of NSCLC other than adenocarcinoma'. Favorable factors for overall survival were 'performance status 0-1' and 'treatment lines up to 3'. There were 16 patients (10.9%) with PFS >1 year. No characteristic clinical findings were found in these 16 patients compared to the remaining 131 patients. CONCLUSION: Efficacy and immune-related adverse events of NSCLC patients associated with atezolizumab monotherapy were comparable to those of previous clinical trial results. Knowledge of characteristics of patients who are most likely to benefit from atezolizumab monotherapy is a crucial step towards implementing appropriate prescribing.

Risk Factors and Clinical Characteristics of Patients with Ocular Candidiasis.

Ocular candidiasis is a critical and challenging complication of candidemia. The purpose of this study was to investigate the appropriate timing for ophthalmologic examinations, risk factors for complications of ocular lesions, and their association with mortality. This retrospective cohort study applied, using multiple logistic regression analysis and Cox regression models, to cases of candidemia (age ≥ 18 years) for patients who underwent ophthalmologic consultation. Of the 108 candidemia patients who underwent ophthalmologic examination, 27 (25%) contracted patients had ocular candidiasis, and 7 experienced the more severe condition of endophthalmitis, which included subjective ocular symptoms. In most cases, the initial ophthalmologic examination was performed within one week of the onset of candidiasis with a diagnosis of ocular candidiasis, but in three cases, the findings became apparent only after a second examination within 7−14 days after onset of candidiasis. The independent risk factor extracted for the development of ocular candidiasis was the isolation of C. albicans (OR, 4.85; 95% CI, 1.58−14.90), unremoved CVC (OR, 10.40; 95% CI, 1.74−62.16), and a high ßDG value (>108.2 pg/mL) (HR, 2.83; 95% CI = 1.24−6.27). Continuous ophthalmologic examination is recommended in cases of candidemia with the above risk factors with an initial examination within 7 days of onset and a second examination 7−14 days after onset.

Reducing the urine collection rate could prevent hospital-acquired horizontal transmission of multidrug-resistant Pseudomonasaeruginosa.

INTRODUCTION: Multidrug-resistant Pseudomonas aeruginosa (MDRP) is a waterborne pathogen that occasionally causes hospital-acquired infection in immunocompromised or critically ill patients. Urine is frequently collected to evaluate renal function or to perform hormonal examinations, but the procedure involves risk due to the possibility of healthcare workers with contaminated hands. Our objective was to evaluate the association between the urine collection and hospital-acquired horizontal transmission of MDRP. METHODS: We monitored the urine collection rate from 2011 to 2017, as part of ongoing efforts to reduce the need to collect urine. The urine collection rate and the frequency of isolation of MDRP, Methicillin resistant S. aureus (MRSA) and extended spectrum ß-lactamases (ESBL)-producing E. coli were analyzed during the same period. PFGE and MLST were also performed to analyze the identity of 5 MDRP strains detected on the same ward in 2014-2015. RESULTS: The urine collection rate was dramatically decreased from 4.8% in 2011 to less than 0.5% in 2017, because the isolation rate of MDRP was significantly positively associated (RR = 1.72, 95%CI:1.03-2.85) with the urine collection rate. Isolations of MRSA and ESBL-producing E. coli showed no significant. Molecular typing showed the PFGE patterns of 3 of 5 MDRP strains were closely related as did MLST (ST17), and the remaining 2 MDRP strains had different PFGE and MLST patterns (ST14, ST655). Our data implicated the urine collection as one of the causes of hospital-acquired MDRP infections. CONCLUSIONS: We concluded that a reducing the urine collection rate could contribute to preventing hospital-acquired horizontal transmission of MDRP.

Small-Cell Lung Cancer Treatment of Newly Diagnosed Patients with Poor Performance Status.

Small-cell lung cancer (SCLC) is highly sensitive to platinum-based chemotherapy. However, its indication in patients with a poor performance status (PS) at initial diagnosis is controversial. We retrospectively reviewed all clinical courses of pathologically diagnosed SCLC patients with poor PS, Eastern Cooperative Oncology Group PS 3 and 4. Among 18 patients, 12 were treated with chemotherapy and 6 with supportive care alone. During the chemotherapy courses, PS improved in 7 (58.3%, including the PS 4 cases), remained stable in 2 (16.7%), and deteriorated in 3 (25%) patients. Moreover, 5 patients showed partial responses to chemotherapy (response rate of 41.7%). Grade 3-4 neutropenia developed in 10 (83.3%) patients and grade 3 febrile neutropenia occurred in 5 (41.7%) patients, but no grade 4 non-hematological toxicity was noted. Mortality associated with lung toxicity (grade 5) due to treatment occurred in a 77-year-old-male patient with PS 3. No substantial difference in survival was observed between patients with PS 3 and 4, even when including those treated with supportive care alone. Treatment had a positive effect on survival: after chemotherapy, the 6-month survival rate of PS 3 and 4 patients was 66.7%. In contrast, all patients treated with supportive care alone died within 5 months. These findings suggest that chemotherapy is indicated in selected SCLC patients not only with PS 3, but also with PS 4.

Influence of MILR1 promoter polymorphism on expression levels and the phenotype of atopy.

The recently identified cell surface immunoreceptor MILR1 (mast cell immunoglobulin-like receptor 1; synonyms, Allergin-1) has been shown to suppress immunoglobulin E (IgE)-mediated, mast cell-dependent responses in both mice and humans. We performed a mutation search of MILR1 together with a genetic association study to determine whether polymorphisms in MILR1 are associated with atopy in human. Mutation screening of MILR1 was performed using DNA from 146 unrelated Japanese. Genotyping of the identified polymorphisms was done with 1505 individuals from the general Japanese adult population. Atopy, as defined by positive responses for specific IgEs against at least one of the 26 common allergens, was evaluated using MAST-26. Five polymorphisms (rs6504230, c.-170_-166delAGGAA, rs8071835, rs143526766 and rs12936887) and two rare missense variants (Val273Ala and Leu311Val) were identified by mutation screening. The C allele of rs6504230 had protective effects against atopy (P=0.002). A luciferase reporter assay using the promoter region of MILR1 revealed that the C allele of rs6504230 was associated with increased expression of MILR1, which was in accordance with the results of expression quantitative trait loci analysis using human leukocytes. Our data indicates that the rs6504230 polymorphism affects MILR1 expression levels in humans, leading to a susceptibility to producing specific IgE antibodies against common allergens.

Genome-wide association study identifies HLA-DP as a susceptibility gene for pediatric asthma in Asian populations.

Asthma is a complex phenotype influenced by genetic and environmental factors. We conducted a genome-wide association study (GWAS) with 938 Japanese pediatric asthma patients and 2,376 controls. Single-nucleotide polymorphisms (SNPs) showing strong associations (P<1×10(-8)) in GWAS were further genotyped in an independent Japanese samples (818 cases and 1,032 controls) and in Korean samples (835 cases and 421 controls). SNP rs987870, located between HLA-DPA1 and HLA-DPB1, was consistently associated with pediatric asthma in 3 independent populations (P(combined) = 2.3×10(-10), odds ratio [OR] = 1.40). HLA-DP allele analysis showed that DPA1*0201 and DPB1*0901, which were in strong linkage disequilibrium, were strongly associated with pediatric asthma (DPA1*0201: P = 5.5×10(-10), OR = 1.52, and DPB1*0901: P = 2.0×10(-7), OR = 1.49). Our findings show that genetic variants in the HLA-DP locus are associated with the risk of pediatric asthma in Asian populations.

Synthetic Applications of the Carbanion with a Fluoroalkyl Group Generated by Palladium(0) Catalyst under Neutral Conditions.

The generation and synthetic application of stable carbanions situated in the beta position from fluorine atom(s) are described. Palladium(0)-catalyzed allylation reactions under neutral conditions proceeded smoothly in the system where a methylene group is activated by fluoroalkyl and carbonyl groups. In the above systems, the 2,2,2-trifluoroethyl moiety has been introduced onto the allylic position without the release of fluoride. Further, palladium(0)-catalyzed heterocyclization was achieved from the reaction of vinyl epoxide with 2-(trifluoromethyl)acrylate and/or 2,3,3,3-tetrafluoropropionate.