Sedation Therapy in Intensive Care Units: Harnessing the Power of Antioxidants to Combat Oxidative Stress.

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.

The predictive value of modified soluble urokinase plasminogen activator receptor (suPAR) with National Early Warning Score (NEWS) for mortality in emergency elderly patients in Japan: a prospective pilot study.

Aim: The aim of this study is to evaluate the ability of soluble urokinase plasminogen activator receptor (suPAR) and modified suPAR with National Early Warning Score (NEWS) for detecting mortality in elderly emergency patients who are older than 70 years. Methods: This is a secondary analysis of our previous study, which was a single-center prospective pilot study, carried out for 21 months in the emergency department of a secondary emergency institution in Japan. This study was carried out between September 16, 2020, and June 21, 2022. The study included all patients without trauma aged 70 years or older who presented to the emergency department. Discrimination was assessed by plotting the receiver-operating characteristic curve and calculating the area under the receiver-operating characteristic curve (AUC). Results: During the study period, 47 eligible older patients were included, among which 8 (17.0%) patients died. The median suPAR was significantly lower in the survivor's group than in the nonsurvivor's group (P < 0.01). For suPAR, the AUC for the prediction of mortality was 0.805 (95% confidence interval 0.633-0.949, P < 0.001). The AUC of modified suPAR with NEWS for mortality was higher than that of suPAR [0.865 (95% confidence interval 0.747-0.958, P < 0.001)]. Conclusion: Our single-center study has demonstrated the high utility of modified suPAR with NEWS as a predictive tool of mortality in elderly emergency patients. Evidence from multicenter studies is needed for introducing modified suPAR with NEWS in the emergency department setting.

Ability of combined soluble urokinase plasminogen activator receptor to predict preventable emergency attendance in older patients in Japan: a prospective pilot study.

Soluble urokinase plasminogen activator receptor (suPAR) is a strong and nonspecific inflammatory biomarker that reflects various immunologic reactions, organ damage, and risk of mortality in the general population. Although prior research in acute medical patients showed that an elevation in suPAR is related to intensive care unit admission and risk of readmission and mortality, no studies have focused on the predictive value of suPAR for preventable emergency attendance (PEA). This study aims to evaluate the predictive value of suPAR, which consists of a combination of white blood cell count (WBC), C-reactive protein (CRP), and the National Early Warning Score (NEWS), for PEA in older patients (>65 years) without trauma who presented to the emergency department (ED). This single-center prospective pilot study was conducted in the ED of the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Hachiouji City, Tokyo, Japan, from September 16, 2020, to June 21, 2022. The study included all patients without trauma aged 65 years or older who were living in their home or a facility and presented to the ED when medical professionals decided an emergency consultation was required. Discrimination was assessed by plotting the receiver-operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC). During the study period, 49 eligible older patients were included, and thirteen (26.5%) PEA cases were detected. The median suPAR was significantly lower in the PEA group than in the non-PEA group (p < 0.05). For suPAR, the AUC for the prediction of PEA was 0.678 (95% CI 0.499-0.842, p < 0.05), and there was no significant difference from other variables as follows: 0.801 (95% CI 0.673-0.906, p < 0.001) for WBC, 0.833 (95% CI 0.717-0.934, p < 0.001) for CRP, and 0.693 (95% CI 0.495-0.862, p < 0.05) for NEWS. Furthermore, the AUC for predicting PEA was 0.867 (95% CI 0.741-0.959, p < 0.001) for suPAR + WBC + CRP + NEWS, which was significantly higher than that of the original suPAR (p < 0.01). The cutoff values, sensitivity, specificity, and odds ratio of suPAR and suPAR + WBC + CRP + NEWS were 7.5 and 22.88, 80.6% and 83.3%, 53.8% and 76.9%, and 4.83 and 16.67, respectively. This study has several limitations. First, this was pilot study, and we included a small number of older patients. Second, the COVID-19 pandemic occurred during the study period, so that there may be selection bias in the study population. Third, our hospital is a secondary emergency medical institution, and as such, we did not treat very fatal cases, which could be another cause of selection bias. Our single-center study has demonstrated the moderate utility of the combined suPAR as a triage tool for predicting PEA in older patients without trauma receiving home medical care. Before introducing suPAR to the prehospital setting, evidence from multicenter studies is needed.

The evaluation of factors affecting antibody response after administration of the BNT162b2 vaccine: a prospective study in Japan.

The aim of this study was to evaluate the antibody reaction after administration of the BNT162b2 vaccine, and to reveal the factors that affect antibody production. This prospective study was carried out in the Association of EISEIKAI Medical and Healthcare Corporation Minamitama Hospital, in Tokyo, Japan, from April 15, 2021 to June 09, 2021. All our hospital's workers who were administered the BNT162b2 vaccine as part of a routine program were included in this study. We calculated the anti-SARS-CoV-2 spike-specific antibody titter (1) before vaccination, (2) 7 to 20 days after the first vaccination, and (3) A total of 7 to 20 days after the second vaccination. The low-antibody titer group (LABG) was defined as the group having less than 25 percentiles of antibody titer. Univariate and Multivariate logistic regression analysis were performed to ascertain the effects of factors on the likelihood of LABG. A total of 374 participants were eventually included in our study, and they were divided into 94 LABG and 280 non-LABG. All samples showed significant antibody elevation in the second antibody test, with a mean value of 3,476 U/mL. When comparing the LABG and non-LABG groups, the median age, blood sugar, and HbA1c were significantly higher in the LABG group. The rates of participants with low BMI (<18.5) and high BMI (>30) were significantly higher in the LABG group. The proportion of chronic lung disease, hypertension, diabetes, dyslipidemia, autoimmune disease, and cancer were significantly higher in the LABG group. Although there was no significant difference confirmed with respect to the exercise hours per day, the proportion of participants that did not perform outdoor exercises was significantly higher in the LABG group. The time interval between the second vaccination and the second antibody test, and between the first and the second vaccination was significantly longer in the non-LABG group. In the multivariate logistic regression analysis, older than 60 years, the past history of hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Again, our single-center study demonstrates that older than 60 years, hypertension, HbA1c higher than 6.5%, and lack of outdoor exercises were significant suppressors of antibody responses, whereas the length of days from the first to the second vaccination longer than 25 days promoted a significant antibody response. Evidence from multi-center studies is needed to develop further vaccination strategies.

Comparison of the National Early Warning Score (NEWS) and the Modified Early Warning Score (MEWS) for predicting admission and in-hospital mortality in elderly patients in the pre-hospital setting and in the emergency department.

The aim of this study is to evaluate the usefulness of the pre-hospital National Early Warning Score (pNEWS) and the pre-hospital Modified Early Warning Score (pMEWS) for predicting admission and in-hospital mortality in elderly patients presenting to the emergency department (ED). We also compare the value of the pNEWS with that of the ED NEWS (eNEWS) and ED MEWS (eMEWS) for predicting admission and in-hospital mortality. This retrospective, single-centre observational study was carried out in the ED of Jikei University Kashiwa Hospital, in Chiba, Japan, from 1st April 2017 to 31st March 2018. All patients aged 65 years or older were included in this study. The pNEWS/eNEWS were derived from seven common physiological vital signs: respiratory rate, peripheral oxygen saturation, the presence of inhaled oxygen parameters, body temperature, systolic blood pressure, pulse rate and Alert, responds to Voice, responds to Pain, Unresponsive (AVPU) score, whereas the pMEWS/eMEWS were derived from six common physiological vital signs: respiratory rate, peripheral oxygen saturation, body temperature, systolic blood pressure, pulse rate and AVPU score. Discrimination was assessed by plotting the receiver operating characteristic (ROC) curve and calculating the area under the ROC curve (AUC). The median pNEWS, pMEWS, eNEWS and eMEWS were significantly higher at admission than at discharge (p < 0.001). The median pNEWS, pMEWS, eNEWS and eMEWS of non-survivors were significantly higher than those of the survivors (p < 0.001). The AUC for predicting admission was 0.559 for the pNEWS and 0.547 for the pMEWS. There was no significant difference between the AUCs of the pNEWS and the pMEWS for predicting admission (p = 0.102). The AUCs for predicting in-hospital mortality were 0.678 for the pNEWS and 0.652 for the pMEWS. There was no significant difference between the AUCs of the pNEWS and the pMEWS for predicting in-hospital mortality (p = 0.081). The AUC for predicting admission was 0.628 for the eNEWS and 0.591 for the eMEWS. The AUC of the eNEWS was significantly greater than that of the eMEWS for predicting admission (p < 0.001). The AUC for predicting in-hospital mortality was 0.789 for the eNEWS and 0.720 for the eMEWS. The AUC of the eNEWS was significantly greater than that of the eMEWS for predicting in-hospital mortality (p < 0.001). For admission and in-hospital mortality, the AUC of the eNEWS was significantly greater than that of the pNEWS (p < 0.001, p < 0.001), and the AUC of the eMEWS was significantly greater than that of the pMEWS (p < 0.01, p < 0.05). Our single-centre study has demonstrated the low utility of the pNEWS and the pMEWS as predictors of admission and in-hospital mortality in elderly patients, whereas the eNEWS and the eMEWS predicted admission and in-hospital mortality more accurately. Evidence from multicentre studies is needed before introducing pre-hospital versions of risk-scoring systems.