[Prediction of Ozone Pollution in Sichuan Basin Based on Random Forest Model].

To study the long-term variation in ozone (O3) pollution in Sichuan Basin,the spatiaotemporal distribution of O3 concentrations during 2017 to 2020 was analyzed using ground-level O3 concentration data and meteorological observation data from 18 cities in the basin. The dominant meteorological factors affecting the variation in O3 concentration were screened out,and a prediction model between meteorological factors and O3 concentration was constructed based on a random forest model. Finally,a prediction analysis of O3 pollution in the Sichuan Basin urban agglomeration during 2020 was carried out. The results showed that:① O3 concentrations displayed a fluctuating trend during the period from 2017 to 2020,with a downward trend in 2019 and a rebound in 2020. ② The fluctuating trend of O3 concentration was significantly influenced by relative humidity,daily maximum temperature,and sunshine hours,whereas wind speed,air pressure,and precipitation had less impact. The linear relationships between meteorological factors were different. Air pressure was negatively correlated with other meteorological factors,whereas the remaining meteorological factors had a positive correlation. ③ The goodness of fit statistics (R2) between the predicted and actual values of the O3 prediction model constructed based on random forest demonstrated a strong predictive performance and ability to accurately forecast the long-term daily variations in O3 concentration. The random forest O3 prediction model exhibited excellent stability and generalization capability. ④ The prediction analysis of O3 concentrations in 18 cities in the basin showed that the explanation rate of variables in the prediction model reached over 80% in all cities (except Ya'an),indicating that the random forest model predicted the trend of O3 concentration accurately.

Associations between cardiometabolic multimorbidity and cerebrospinal fluid biomarkers of Alzheimer's disease pathology in cognitively intact adults: the CABLE study.

BACKGROUND: Cardiometabolic multimorbidity is associated with an increased risk of dementia, but the pathogenic mechanisms linking them remain largely undefined. We aimed to assess the associations of cardiometabolic multimorbidity with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathology to enhance our understanding of the underlying mechanisms linking cardiometabolic multimorbidity and AD. METHODS: This study included 1464 cognitively intact participants from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) database. Cardiometabolic diseases (CMD) are a group of interrelated disorders such as hypertension, diabetes, heart diseases (HD), and stroke. Based on the CMD status, participants were categorized as CMD-free, single CMD, or CMD multimorbidity. CMD multimorbidity is defined as the coexistence of two or more CMDs. The associations of cardiometabolic multimorbidity and CSF biomarkers were examined using multivariable linear regression models with demographic characteristics, the APOE ε4 allele, and lifestyle factors as covariates. Subgroup analyses stratified by age, sex, and APOE ε4 status were also performed. RESULTS: A total of 1464 individuals (mean age, 61.80 years; age range, 40-89 years) were included. The markers of phosphorylated tau-related processes (CSF P-tau181: ß = 0.165, P = 0.037) and neuronal injury (CSF T-tau: ß = 0.065, P = 0.033) were significantly increased in subjects with CMD multimorbidity (versus CMD-free), but not in those with single CMD. The association between CMD multimorbidity with CSF T-tau levels remained significant after controlling for Aß42 levels. Additionally, significantly elevated tau-related biomarkers were observed in patients with specific CMD combinations (i.e., hypertension and diabetes, hypertension and HD), especially in long disease courses. CONCLUSIONS: The presence of cardiometabolic multimorbidity was associated with tau phosphorylation and neuronal injury in cognitively normal populations. CMD multimorbidity might be a potential independent target to alleviate tau-related pathologies that can cause cognitive impairment.

Association between antihyperlipidemic agents and the risk of chronic periodontitis in patients with hyperlipidemia: A population-based retrospective cohort study in Taiwan.

BACKGROUND: The lipid-lowering and anti-inflammatory effects of statins and fibrates may ameliorate periodontitis. Patients with hyperlipidemia tend to have a worse periodontal status. This study assessed the association between the use of statins/fibrates and the incidence of chronic periodontitis in patients with hyperlipidemia in Taiwan. METHODS: This retrospective cohort study enrolled patients newly diagnosed with hyperlipidemia between 2001 and 2012 from the 2000 Longitudinal Generation Tracking Database and followed them for 5 years. The study population was divided into four groups: statin monotherapy, fibrate monotherapy, combination therapy (both statins and fibrates), and control (neither statins nor fibrates). Each patient in the treatment group was matched at a ratio of 1:1 with a control. Chronic periodontitis risk was compared in the three study arms by using a Cox proportional hazard model. RESULTS: Chronic periodontitis risk was reduced by 25.7% in the combination therapy group compared with the control group (adjusted hazard ratio [aHR], 0.743; 95% confidence interval (CI), 0.678-0.815). Low dose (<360 cumulative defined daily dose [cDDD]) and shorter duration (<2 years) of statin monotherapy seem to be associated with an increased risk of chronic periodontitis; high dose (≥720 cDDD/≥1080 cDDD) and longer duration (≥3 years) of statin/fibrate monotherapy may be correlated with a lower risk of periodontitis. Hydrophobic statin users had a lower chronic periodontitis risk than hydrophilic statin users. CONCLUSION: Chronic periodontitis risk was lower in patients with hyperlipidemia on combination treatment with statins and fibrates, and the risk decreased when patients used statins or fibrates for >3 years.

Thromboembolic Presentations among Patients Hospitalized to the Intensive Care Unit for Coronavirus Disease 2019 (COVID-19) - A Northern Taiwan Single Center Experience.

Coronavirus Disease 2019 (COVID-19) has been associated with a high thromboembolic risk among patients in intensive care units. Asian populations may share a similar thromboembolic risk, but with a higher prevalence of arterial thromboembolism than venous thromboembolism. To clarify this risk in Taiwan, this single-center retrospective study collected 27 consecutive intensive care unit patients with COVID-19 confirmed by polymerase chain reaction, with a median age of 67.6 years (male 81.5%). Twenty-three patients received prophylactic anticoagulation (85.2%), and there were four bleeding events (14.8%). Nine patients had thromboembolism (33.3%), including three with deep vein thrombosis, two with peripheral artery thromboembolism, and four with ischemic stroke. There were no significant clinical differences between the patients with or without thromboembolism. Initial serum ferritin [adjusted odds ratio (OR): 13.19, 95% confidence interval (CI): 1.01-172.07] and peak serum procalcitonin (adjusted OR: 18.93, 95% CI: 1.08-330.91) were associated with a higher risk of thromboembolism. Furthermore, prophylactic anticoagulation (adjusted OR: 0.01, 95% CI: < 0.001-0.55) was associated with a lower risk of thromboembolism. All cases of deep vein thrombosis and one peripheral artery thromboembolism occurred at intravascular catheter locations. No association between thromboembolism and survival was found (age-adjusted hazard ratio: 0.55, 95% CI: 0.10-2.95). In conclusion, the prevalence of COVID-19 thromboembolism among Taiwanese patients in intensive care units was high, even with prophylactic anticoagulation. Serum ferritin and procalcitonin may identify high-risk populations. Prophylactic anticoagulation may reduce the risk of thromboembolism with a manageable bleeding risk. Larger prospective studies are needed to clarify the risk of COVID-19 thromboembolism and its risk factors in the post-Omicron era.

Effects of an interactive handgrip game on surgical patients requiring intensive care: An assessor-blinded randomized controlled trial.

OBJECTIVE: To explore the effect of an interactive handgrip game on psychological distress and handgrip strength among critically ill surgical patients. DESIGN: A randomised controlled trial. SETTING: A surgical intensive care unit. INTERVENTION: Participants were enrolled in the program within 48 hours of admission to the intensive care unit. Patients in the intervention group played a 20-minute interactive handgrip game twice daily for a maximum of three days in the intensive care unit in addition to routinely passive physical rehabilitation. Patients in the routine care group had a daily target of 20 min of passive physical rehabilitation as needed. MEASUREMENT: The primary outcomes included depression, anxiety, and stress measured using the shortened version of the Depression Anxiety Stress Score scale. The secondary outcomes were perceived sleep evaluated using the Richards-Campbell Sleep Questionnaire, delirium assessed using the Intensive Care Delirium Screening Checklist, and handgrip strength measured using handgrip dynamometry within a handgrip device. RESULTS: Two hundred and twenty-seven patients were eligible and 70 patients were recruited in the intervention (n = 35) and routine care groups (n = 35). The patients in the intervention group had lower scores (median = 6.0, 4.0, and 12.0) for depression, anxiety, and stress compared with those in the routine care group (12.0, 12.0, and 20.0; all p < 0.05). The interactive handgrip game did not significantly improve sleep quality and prevent the occurrence of delirium (both p > 0.05). The patients who received the interactive handgrip game intervention exhibited significantly enhanced handgrip strength in both hands over time (both p < 0.001). CONCLUSION: An interactive handgrip game may benefit the psychological well-being and handgrip strength of critically ill patients. IMPLICATIONS FOR CLINICAL PRACTICE: Interactive handgrip games is effective active exercise which should be integrated into routine nursing practice.

Associations of Lung Function Decline with Risks of Cognitive Impairment and Dementia: A Meta-Analysis and Systematic Review.

BACKGROUND: There are controversies surrounding the effects of lung function decline on cognitive impairment and dementia. OBJECTIVE: We conducted a meta-analysis and systematic review to explore the associations of lung function decline with the risks of cognitive impairment and dementia. METHODS: The PubMed, EMBASE, and the Cochrane Library were searched to identify prospective studies published from database inception through January 10, 2023. We pooled relative risk (RR) and 95% confidence intervals (CI) using random-effects models. The Egger test, funnel plots, meta-regression, sensitivity, and subgroup analyses were conducted to detect publication bias and investigate the source of heterogeneity. RESULTS: Thirty-three articles with a total of 8,816,992 participants were subjected to meta-analysis. Poorer pulmonary function was associated with an increased risk of dementia (FEV: RR = 1.25 [95% CI, 1.17-1.33]; FVC: RR = 1.40 [95% CI, 1.16-1.69]; PEF: RR = 1.84 [95% CI, 1.37-2.46]). The results of the subgroup analyses were similar to the primary results. Individuals with lung diseases had a higher combined risk of dementia and cognitive impairment (RR = 1.39 [95% CI, 1.20-1.61]). Lung disease conferred an elevated risk of cognitive impairment (RR = 1.37 [95% CI, 1.14-1.65]). The relationship between lung disease and an increased risk of dementia was only shown in total study participants (RR = 1.32 [95% CI, 1.11-1.57]), but not in the participants with Alzheimer's disease (RR = 1.39 [95% CI, 1.00-1.93]) or vascular dementia (RR = 2.11 [95% CI, 0.57-7.83]). CONCLUSION: Lung function decline was significantly associated with higher risks of cognitive impairment and dementia. These findings might provide implications for the prevention of cognitive disorders and the promotion of brain health.

Dynamic prevalence of sleep disturbance among critically ill patients in intensive care units and after hospitalisation: A systematic review and meta-analysis.

BACKGROUND: Sleep disturbance is a common complaint among critically ill patients in intensive care units and after hospitalisation. However, the prevalence of sleep disturbance among critically ill patients varies widely. OBJECTIVE: To estimate the prevalence of sleep disturbance among critically ill patients in the intensive care unit and after hospitalisation. METHODS: Electronic databases were searched from their inception until 15 August 2022. Only observational studies with cross-sectional, prospective, and retrospective designs investigating sleep disturbance prevalence among critically ill adults (aged ≥ 18 years) during intensive care unit stay and after hospitalisation were included. RESULTS: We found 13 studies investigating sleep disturbance prevalence in intensive care units and 14 investigating sleep disturbance prevalence after hospitalisation, with 1,228 and 3,065 participants, respectively. The prevalence of sleep disturbance during an ICU stay was 66 %, and at two, three, six and ≥ 12 months after hospitalisation was 64 %, 49 %, 40 %, and 28 %, respectively. Studies using the Richards-Campbell Sleep Questionnaire detected a higher prevalence of sleep disturbance among patients in intensive care units than non-intensive care unit specific questionnaires; studies reported comparable sleep disturbance prevalence during intensive care stays for patients with and without mechanical ventilation. CONCLUSION: Sleep disturbance is prevalent in critically ill patients admitted to an intensive care unit and persists for up to one year after hospitalisation, with prevalence ranging from 28 % to 66 %. The study results highlight the importance of implementing effective interventions as early as possible to improve intensive care unit sleep quality.

Comparative effectiveness of non-pharmacological interventions for preventing delirium in critically ill adults: A systematic review and network meta-analysis.

BACKGROUND: Delirium presents a serious health problem in critically ill patients in intensive care units. However, knowledge regarding the selections of the optimal non-pharmacological interventions remains unclear. OBJECTIVES: To compare the effects of non-pharmacological interventions by combining direct and indirect evidence on the incidence and duration of delirium in intensive care units. DESIGN: A systematic review and network meta-analysis. DATA SOURCES: A comprehensive search of five electronic databases, including PubMed, EMBASE, CINAHL, Cochrane CENTRAL, and ProQuest Dissertations and Theses A&I were conducted. Only randomized control trials published from the inception to December 28, 2021 were included. REVIEW METHODS: Two reviewers independently screened the title and abstract for eligibility according to the inclusion and exclusion criteria. The random-effect network meta-analysis was used to estimate the comparative effects of non-pharmacological interventions in reducing delirium incidence and duration. RESULTS: A total of 29 studies with 7005 critically ill patients were enrolled. Twenty-six and eleven studies reported the delirium incidence and duration, respectively. Component-based intervention comparison revealed that multicomponent strategy was the most effective non-pharmacological intervention compared to usual care in reducing incidence of ICU delirium (Odd ratio [OR]=0.43, 95% CI= 0.22-0.84) but not ICU delirium duration. Treatment-based intervention comparisons indicated that specific multi-treatment interventions significantly reduced the ICU delirium incidence and duration, particularly the involvement of early mobilization and family participation (OR = 0.12 with 95% CI = 0.02 to 0.83; mean difference = -1.34 with 95% CI = -2.52 to -0.16, respectively). CONCLUSION: Our study suggests that the multicomponent strategy was the most effective non-pharmacological intervention in reducing the incidence of ICU delirium. Early mobilization and family participation involvement in non-pharmacological interventions seemed to be more effective in reducing the incidence of ICU delirium. These results of network-meta analysis could be an important evidence-based for clinical healthcare providers to optimize the critical care protocol. TWEETABLE ABSTRACT: Network meta-analysis of 29 randomised controlled trials with 7005 patients finds that multicomponent interventions, particularly those involving early mobilization, family participation, cognitive stimulation, reorientation, sensory stimulation, environment control and clinical adjustment, is the most effective non-pharmacological strategy to reduce the incidence of delirium in intensive care units.

Antrodia cinnamomea and its compound dehydroeburicoic acid attenuate nonalcoholic fatty liver disease by upregulating ALDH2 activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent liver disease, but currently has no specific medication in clinic. Antrodia cinnamomea (AC) is a medicinal fungus and it has been shown that AC can inhibit high fat diet (HFD)-induced lipid deposition in mouse livers, but the effective monomer in AC and mechanism against NAFLD remain unclear. It has been reported that aldehyde dehydrogenase 2 (ALDH2) activation shows protective effects on NAFLD. Our previous study demonstrates that AC and its monomer dehydroeburicoic acid (DEA) can upregulate the ALDH2 activity on alcoholic fatty liver disease mouse model, but it is not clear whether the anti-NAFLD effects of AC and DEA are mediated by ALDH2. AIM TO STUDY: To elucidate the active compound in AC against NAFLD, study whether ALDH2 mediates the anti-NAFLD effects of AC and its effective monomer. MATERIALS AND METHODS: WT mice, ALDH2-/- mice and ALDH2-/- mice re-expressed ALDH2 by lentivirus were fed with a methionine-choline deficient (MCD) diet or high fat diet (HFD) to induce NAFLD, and AC at the different doses (200 and/or 500 mg/kg body weight per day) was administrated by gavage at the same time. Primary hepatocytes derived from WT and ALDH2-/-mice were stimulated by oleic acid (OA) to induce lipid deposition, and the cells were treated with AC or DEA in the meantime. Lentivirus-mediated ALDH2-KD or ALDH2-OE were used to knock down or overexpress ALDH2 expression in HepG2 cells, respectively. Finally, the effects of DEA against NAFLD as well as its effects on upregulating liver ALDH2 and removing the harmful aldehyde 4-hydroxynonenal (4-HNE) were studied in the MCD diet-induced NAFLD mouse model. RESULTS: In WT mice fed with a MCD diet or HFD, AC administration reduced hepatic lipid accumulation, upregulated ALDH2 activity in mouse livers, decreased 4-HNE contents both in mouse livers and serum, inhibited lipogenesis, inflammation and oxidative stress and promoted fatty acid ß-oxidation. These effects were abolished in ALDH2 KO mice but could be restored by re-expression of ALDH2 by lentivirus. In primary hepatocytes of WT mice, AC and DEA inhibited OA-induced lipid accumulation and triglyceride (TG) synthesis, promoting the ß-oxidation of fatty acid in the meantime. However, these effects were lost in primary hepatocytes of ALDH2 KO mice. Moreover, the expression level of ALDH2 significantly affected the inhibitory effects of AC and DEA on OA-induced lipid deposition in HepG2 cells. The effects of AC and DEA on suppressing lipid deposition, inhibiting mitochondrial ROS levels, reducing TG synthesis, and promoting ß-oxidation of fatty acid were all enhanced with the overexpression of ALDH2 and reduced with the knockdown of ALDH2 expression. DEA showed dose-dependent effects on inhibiting liver lipid deposition, elevating ALDH2 activity and reducing 4-HNE levels in the livers of MCD diet-induced NAFLD mice. CONCLUSION: DEA is the effective compound in AC against NAFLD. The related anti-NAFLD mechanisms of AC and DEA were through upregulating ALDH2 expression and activity, thus enhancing the elimination of 4-HNE in the livers, and sequentially alleviating oxidative stress and inflammation, promoting fatty acid ß-oxidation and decreasing lipogenesis.

Prevalence of Vitamin D Deficiency and Associated Factors in Critically Ill Patients: A Multicenter Observational Study.

Background: Vitamin D deficiency is common in the general population worldwide, and the prevalence and severity of vitamin D deficiency increase in critically ill patients. The prevalence of vitamin D deficiency in a community-based cohort in Northern Taiwan was 22.4%. This multicenter cohort study investigated the prevalence of vitamin D deficiency and associated factors in critically ill patients in Northern Taiwan. Methods: Critically ill patients were enrolled and divided into five groups according to their length of stay at intensive care units (ICUs) during enrolment as follows: group 1, <2 days with expected short ICU stay; group 2, <2 days with expected long ICU stay; group 3, 3-7 days; group 4, 8-14 days; and group 5, 15-28 days. Vitamin D deficiency was defined as a serum 25-hydroxyvitamin D (25(OH)D) level < 20 ng/ml, and severe vitamin D deficiency was defined as a 25(OH)D level < 12 ng/ml. The primary analysis was the prevalence of vitamin D deficiency. The exploratory analyses were serial follow-up vitamin D levels in group 2, associated factors for vitamin D deficiency, and the effect of vitamin D deficiency on clinical outcomes in critically ill patients. Results: The prevalence of vitamin D deficiency was 59% [95% confidence interval (CI) 55-62%], and the prevalence of severe vitamin D deficiency was 18% (95% CI 15-21%). The median vitamin D level for all enrolled critically ill patients was 18.3 (13.7-23.9) ng/ml. In group 2, the median vitamin D levels were <20 ng/ml during the serial follow-up. According to the multivariable analysis, young age, female gender, low albumin level, high parathyroid hormone (PTH) level, and high sequential organ failure assessment (SOFA) score were significantly associated risk factors for vitamin D deficiency. Patients with vitamin D deficiency had longer ventilator use duration and length of ICU stay. However, the 28- and 90-day mortality rate were not associated with vitamin D deficiency. Conclusions: This study demonstrated that the prevalence of vitamin D deficiency is high in critically ill patients. Age, gender, albumin level, PTH level, and SOFA score were significantly associated with vitamin D deficiency in these patients.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Do-not-attempt resuscitation independently predict in-hospital mortality in septic patients.

INTRODUCTION: Sepsis patients require timely and appropriate treatment in an intensive care setting. However, "do-not-attempt resuscitation" (DNAR) status may affect physicians' priorities and treatment preferences. The aim of this study was to evaluate whether DNAR status affects the outcomes of septic patients. METHODS: This was a retrospective cohort study included septic patients admitted to the emergency department intensive care unit (ED-ICU) in a university-based teaching hospital during April-November 2015. Septic patients admitted to the ED-ICU were included. RESULTS: Of the 132 eligible patients, 49.2% (65/132) had DNAR status (median age 80 years old, IQR, 73-86). The overall in-hospital mortality rate was 28.8% (38/132). Non-survivors had a higher percentage of receiving inotropes/vasopressors (52.6% vs 34.0%, p = 0.048), higher median Charlson comorbidity index scores [8.5 (IQR, 7-11.75) vs 8 (IQR, 6-9), p = 0.012], higher APACHE II score [25 (IQR, 20-30.25) vs 20 (IQR, 17-25), p = 0.002], and higher SOFA score [7 (IQR, 6-11) vs 6 (IQR,4-8), p = 0.012]. There was no significant difference in intubation among the two groups. In a multivariate logistic regression analysis, DNAR status was an independent predictor of in-hospital mortality (odds ratio = 6.22, 95% confidence interval (CI) = (2.71-17.88), p < 0.001). The area under the ROC curve for the logistic regression model was 0.84 [95% CI = (0.77-0.92), p < 0.001]. In subgroup analysis, DNAR status remained an independent predictor of mortality among age ≥65 years and ≥80 years. CONCLUSION: After adjusting for comorbidities, treatments, and illness severity, DNAR status was associated with in-hospital mortality of septic patients. Further studies should evaluate physicians' attitudes toward septic patients with DNAR status.

Characteristics and outcomes of "Do Not Resuscitate" patients admitted to the emergency department-Intensive care unit.

BACKGROUND: Appropriate utilization of intensive care unit (ICU) beds are essential. Patients with critical illness who have do not resuscitate (DNR) have a reduced priority of intensive care. However, the possibility of recovery/survival is ambiguous and multifactorial. OBJECTIVE: To deliberate the characteristics and outcomes of critical illness in patients with prior DNR who were admitted to the emergency department (ED)-ICU. METHOD: This was a retrospective cohort study conducted between April 2015 and November 2015 in a university-based hospital. Non-traumatic patients with DNR admitted to ED-ICU from ED were included. RESULTS: Seventy-eight non-trauma patients with prior DNR status were included in the final analysis. 51.3% (40/78) patients were male with median age 83 (IQR: 75-89) years. The median APACHE II score was 24.5 (IQR: 20-30). 50% (39/78) of the DNR patients survived to discharge. Patients who survived to discharge had lower APACHE II score (23 (IQR: 20-28) vs. 28 (18-38), p = 0.028). There was no significant difference in age, gender, and Charlson index. ROC curves were constructed, generating a cut-off of the APACHE II score at 29.5 for determining survival to discharge (AUC = 0.644, p = 0.028). In multivariate Cox proportional model, APACHE II score above 29.5 was an independent predictor for mortality. (Hazard ratio = 2.46; 95% confidence interval: 1.04-5.83, p = 0.042). CONCLUSION: Our study found that 50% of patients with prior DNR on ICU admission survived to discharge, indicating that aggressive care is not definitely futile. Further prospective studies are required to evaluate the cost-effectiveness and patients' and/or families' satisfaction of the ICU admission of DNR patients.

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

BACKGROUND: Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. METHODS: We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. RESULTS: The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. CONCLUSIONS: These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

Red blood cell distribution width is associated with mortality in elderly patients with sepsis.

INTRODUCTION: RDW is a prognostic biomarker and associated with mortality in cardiovascular disease, stroke and metabolic syndrome. For elderly patients, malnutrition and multiple comorbidities exist, which could affect the discrimination ability of RDW in sepsis. The main purpose of our study was to evaluate the prognostic value of RDW in sepsis among elderly patients. METHODS: This was a retrospective cohort study conducted in emergency department intensive care units (ED-ICU) between April 2015 and November 2015. Elderly patients (≥65years old) who were admitted to the ED-ICU with a diagnosis of severe sepsis and/or septic shock were included. The demographic data, biochemistry data, qSOFA, and APACHE II score were compared between survivors and nonsurvivors. RESULTS: A total of 117 patients was included with mean age 81.5±8.3years old. The mean APACHE II score was 21.9±7.1. In the multivariate Cox proportional hazards model, RDW level was an independent variable for mortality (hazard ratio: 1.18 [1.03-1.35] for each 1% increase in RDW, p=0.019), after adjusting for CCI, any diagnosed malignancy, and eGFR. The AUC of RDW in predicting mortality was 0.63 (95% confidence interval [CI]: 0.52-0.74, p=0.025). In subgroup analysis, for qSOFA <2, nonsurvivors had higher RDW levels than survivors (17.0±3.3 vs. 15.3±1.4%, p=0.044). CONCLUSIONS: In our study, RDW was an independent predictor of in-hospital mortality in elderly patients with sepsis. For qSOFA scores <2, higher RDW levels were associated with poor prognosis. RDW could be a potential parameter used alongside the clinical prediction rules.