In HIBECs, at least TLR2 and 4 are capable of mediating innate immune system function in vitro. This result, in conjunction with our recent finding that TLR4 expression is increased in biliary epithelial cells in primary biliary cirrhosis, suggests the involvement of TLRs in the development of chronic inflammatory cholangiopathies.

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Purpose: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation. Methods: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure. Results: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64). Conclusion: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely.

Aim: Although the concept of a rapid response system (RRS) has been gradually accepted in Japan, detailed information on the Japanese RRS is not well known. We provide the first report of the RRS epidemiological situation based on 4 years of RRS online registry data. Methods: This is a prospective observational study. All patients registered between January 2014 and March 2018 were eligible for this study. Data related to RRS including physiological measurements were recorded. The mortality rates after rapid response team/ medical emergency team (RRT/MET) intervention and after 30 days were recorded as outcomes. Results: In total, 6,784 cases were registered at 35 facilities. Cancer (23.1%) was the most common existing comorbidity. Limitation of medical treatment was identified in 12.7% of the cases. The respiratory category was most frequently activated in 41.3% of the cases. Only two institutions had received more than 15 calls per 1,000 admissions. During RRT/MET intervention, death occurred in 3.6% and transfers to intensive care units occurred in 28.2% of the cases. After 30 days, the mortality rate was significantly higher in the night than in the day shift (30.7% versus 20.4%, respectively, P < 0.01). Conclusions: We report the first epidemiological study of RRS in Japan. Japanese facilities had a very low rate of RRT/MET calls and a higher mortality rate in the night than in the day shift. Further promotion to increase the number of calls and implementation of a 24-h RRT/MET is required.

Purpose Improving the safety of general wards is a key to reducing serious adverse events in the postoperative period. We investigated the characteristics, treatment, and outcomes of postoperative patients managed by a rapid response system (RRS) in Japan to improve postoperative management. Methods This retrospective study analyzed cases requiring RRS intervention that were included in the In-Hospital Emergency Registry in Japan. We analyzed data reported by 34 Japanese hospitals between January 2014 and March 2018, mainly focusing on postoperative patients for whom the RRS was activated within 7 days of surgery. Non-postoperative patients, for whom the RRS was activated in all other settings, were used for comparison as necessary. Results There were 609 (12.7%) postoperative patients among the total patients in the registry. The major criteria were staff concerns (30.2%) and low oxygen saturation (29.7%). Hypotension, tachycardia, and inability to contact physicians were observed as triggers significantly more frequently in postoperative patients when compared with non-postoperative patients. Among RRS activations within 7 days of surgery, 68.9% of activations occurred within postoperative day 3. The ordering of tests (46.8%) and fluid bolus (34.6%) were major interventions that were performed significantly more frequently in postoperative patients when compared with non-postoperative patients. The rate of RRS activations resulting in ICU care was 32.8%. The mortality rate at 1 month was 16.2%. Conclusion Approximately, 70% of the RRS activations occurred within postoperative day 3. Circulatory problems were a more frequent cause of RRS activation in the postoperative group than in the non-postoperative group.