Association of early antibiotic therapy and in-hospital mortality in adult mild-to-moderate acute aspiration pneumonitis: a cohort study.

BACKGROUND: Patients with aspiration pneumonitis often receive empiric antibiotic therapy despite it being due to a non-infectious, inflammatory response. OBJECTIVE: To study the benefits of early antibiotic therapy in patients with suspected aspiration pneumonitis in an acute care hospital. DESIGN: Retrospective cohort study using electronic medical records from Teine Keijinkai Hospital. PARTICIPANTS: Adults aged over 18 years admitted with a diagnosis of aspiration pneumonitis to the Department of General Internal Medicine or Emergency Department between January 1, 2008, and May 31, 2019. A diagnosis of aspiration pneumonitis was defined as a documented macro-aspiration event and a chest radiograph demonstrating new radiographic infiltrates. MAIN MEASURES: Patients were classified into the "early antibiotic treatment" group and the "no or late treatment" group depending on whether they received antibiotic therapy for respiratory bacterial pathogens within 8 h of arrival. The primary outcome was in-hospital all-cause mortality. Secondary outcomes included length of hospital stay, antibiotic-free days, duration of fever, readmission within one month, and incidence of complications. KEY RESULTS: Of the 146 patients enrolled, 52 (35.6%) did not receive early antibiotic therapy, while the remaining 94 (64.4%) did. There was no difference in in-hospital mortality rates between the groups after adjustment for potential confounding variables using Cox proportional hazards analysis (hazard ratio 2.78; 95% confidence interval, 0.57-13.50, p = 0.20). Patients in the no or late treatment group had more antibiotic-free days (p < 0.001) and a shorter length of hospital stay among survivors (p = 0.040) than did those in the early antibiotic treatment group. There were no statistically significant differences between the groups with respect to other secondary outcomes. CONCLUSIONS: Early antibiotic therapy for acute aspiration pneumonitis was not associated with in-hospital mortality, but was associated with a longer hospital stay and prolonged use of antibiotics.

Recent progress in production of amino acid-derived chemicals using Corynebacterium glutamicum.

Green chemical production by microbial processes is critical for the development of a sustainable society in the twenty-first century. Among the important industrial microorganisms, the gram-positive bacterium Corynebacterium glutamicum has been utilized for amino acid fermentation, which is one of the largest microbial-based industries. To date, several amino acids, including L-glutamic acid, L-lysine, and L-threonine, have been produced by C. glutamicum. The capability to produce substantial amounts of amino acids has gained immense attention because the amino acids can be used as a precursor to produce other high-value-added chemicals. Recent developments in metabolic engineering and synthetic biology technologies have enabled the extension of metabolic pathways from amino acids. The present review provides an overview of the recent progress in the microbial production of amino acid-derived bio-based monomers such as 1,4-diaminobutane, 1,5-diaminopentane, glutaric acid, 5-aminolevulinic acid, L-pipecolic acid, 4-amino-1-butanol, and 5-aminolevulinic acid, as well as building blocks for healthcare products and pharmaceuticals such as ectoine, L-theanine, and gamma-aminobutyric acid by metabolically engineered C. glutamicum.

Anaerobic glucose consumption is accelerated at non-proliferating elevated temperatures through upregulation of a glucose transporter gene in Corynebacterium glutamicum.

Cell proliferation is achieved through numerous enzyme reactions. Temperature governs the activity of each enzyme, ultimately determining the optimal growth temperature. The synthesis of useful chemicals and fuels utilizes a fraction of available metabolic pathways, primarily central metabolic pathways including glycolysis and the tricarboxylic acid cycle. However, it remains unclear whether the optimal temperature for these pathways is correlated with that for cell proliferation. Here, we found that wild-type Corynebacterium glutamicum displayed increased glycolytic activity under non-growing anaerobic conditions at 42.5 °C, at which cells do not proliferate under aerobic conditions. At this temperature, glucose consumption was not inhibited and increased by 28% compared with that at the optimal growth temperature of 30 °C. Transcriptional analysis revealed that a gene encoding glucose transporter (iolT2) was upregulated by 12.3-fold compared with that at 30 °C, with concomitant upregulation of NCgl2954 encoding the iolT2-regulating transcription factor. Deletion of iolT2 decreased glucose consumption rate at 42.5 °C by 28%. Complementation of iolT2 restored glucose consumption rate, highlighting the involvement of iolT2 in the accelerating glucose consumption at an elevated temperature. This study shows that the optimal temperature for glucose metabolism in C. glutamicum under anaerobic conditions differs greatly from that for cell growth under aerobic conditions, being beyond the upper limit of the growth temperature. This is beneficial for fuel and chemical production not only in terms of increasing productivity but also for saving cooling costs. KEY POINTS: • C. glutamicum accelerated anaerobic glucose consumption at elevated temperature. • The optimal temperature for glucose consumption was above the upper limit for growth. • Gene expression involved in glucose transport was upregulated at elevated temperature. Graphical abstract.

Gatekeeping function of primary care physicians under Japan's free-access system: a prospective open cohort study involving 14 isolated islands.

BACKGROUND: Gatekeeping is important for strong primary care and cost containment. Under Japan's free-access system, patients can access any medical institution without referral, which makes it difficult to evaluate the gatekeeping function of primary care physicians (PCPs). OBJECTIVES: To examine the gatekeeping function of PCPs in Japan, we compared the frequencies of visits to primary care clinics, referrals to advanced care and hospitalizations between 14 remote islands and a nationwide survey. METHODS: This study was a prospective, open cohort study involving 14 isolated islands (12 238 inhabitants) in Okinawa, Japan. Participants were all patients who visited the clinics on these islands in 1 year. Main outcome measures were the incidence of on-island clinic visits and referrals to off-island advanced care. RESULTS: There were 54 741 visits to the islands' clinics with 2045 referrals to off-island medical facilities, including 549 visits to emergency departments and 705 hospitalizations. The age- and sex-standardized incidences of healthcare use per 1000 inhabitants per month were: 360.0 (95% confidence interval: 359.9 to 360.1) visits to primary care clinics, 11.6 (11.0 to 12.2) referrals to off-island hospital-based outpatient clinics, 3.3 (2.8 to 5.2) visits to emergency departments and 4.2 (3.1 to 5.2) hospitalizations. Comparison with the nationwide survey revealed a lower incidence of visits to hospital-based outpatient clinics in this study, while more patients had visited PCPs. CONCLUSIONS: The lower incidence of visits to secondary care facilities in this study might suggest that introduction of a gatekeeping system to Japan would reduce the incidence of referral to advanced care.

Associations of Patient Experience in Primary Care With Hospitalizations and Emergency Department Visits on Isolated Islands: A Prospective Cohort Study.

PURPOSE: In rural areas, the management of hospitalizations and emergency department (ED) visits is an important issue, and it is compounded by factors such as the long distance to secondary care facilities, funding difficulties in many rural medical institutions, and shortage of medical staff. While better patient experience (PX) has been shown to reduce hospitalizations and ED visits, previous studies have not considered the differences between urban and rural areas. In addressing this gap, this study examines the association between PX and hospitalizations/ED visits on isolated islands. METHODS: This prospective cohort study was conducted on 5 isolated islands in Okinawa, Japan. We assessed the PX of primary care using the Japanese version of the Primary Care Assessment Tool (JPCAT), which comprises 6 domains: first contact, longitudinality, coordination, comprehensiveness (services available), comprehensiveness (services provided), and community orientation. The primary outcome was hospitalizations and ED visits in a year. We used a mixed effect model to adjust clustering within islands and individual covariates. FINDINGS: Of 1,258 residents, 740 responded to a questionnaire for PX measurement. There were 73 hospitalizations and 62 ED visits. Adjusting for confounding and geographical clustering, hospitalizations had significant positive association with the PX score of each patient. ED visits were not associated with the total score of the JPCAT. CONCLUSION: On the isolated islands, PX in primary care had positive correlation with hospitalizations. The contrast of our findings to those of previous studies may be due to the close patient-doctor relationship on isolated islands.