Early absolute lymphocyte count was associated with one-year mortality in critically ill surgical patients: A propensity score-matching and weighting study.

BACKGROUND: Absolute lymphocyte count (ALC) is a crucial indicator of immunity in critical illness, but studies focusing on long-term outcomes in critically ill patients, particularly surgical patients, are still lacking. We sought to explore the association between week-one ALC and long-term mortality in critically ill surgical patients. METHODS: We used the 2015-2020 critical care database of Taichung Veterans General Hospital (TCVGH), a referral hospital in central Taiwan, and the primary outcome was one-year all-cause mortality. We assessed the association between ALC and long-term mortality by measuring hazard ratios (HRs) with 95% confidence intervals (CIs). Furthermore, we used propensity score-matching and -weighting analyses, consisting of propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS), to validate the association. RESULTS: A total of 8052 patients were enrolled, with their one-year mortality being 24.2%. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.140, 95% CI 1.091-1.192). Moreover, this association tended to be stronger among younger patients, patients with fewer comorbidities and lower severity. The association between low ALC and mortality in original, PSM, IPTW, and CBPS populations were 1.497 (95% CI 1.320-1.697), 1.391 (95% CI 1.169-1.654), 1.512 (95% CI 1.310-1.744), and 1.511 (95% CI 1.310-1.744), respectively. Additionally, the association appears to be consistent, using distinct cutoff levels to define the low ALC. CONCLUSIONS: We identified that early low ALC was associated with increased one-year mortality in critically ill surgical patients, and prospective studies are warranted to confirm the finding.

The Association Between Absolute Lymphocyte Count and Long-Term Mortality in Critically Ill Medical Patients: Propensity Score-Based Analyses.

Objective: Absolute lymphocyte count (ALC) has been implicated with short-term outcomes in a number of diseases, and we aimed to investigate the association between week-one ALC and long-term mortality in patients who were admitted to the medical intensive care units (ICUs). Methods: We enrolled patients who were admitted to the medical ICUs at the Taichung Veterans General Hospital, a referral centre located in central Taiwan, between 2015 and 2020 to conduct this retrospective cohort study. The outcome of interest was long-term all-cause mortality, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the association. Furthermore, we employed propensity score-matching (PSM) and weighting techniques, consisting of inverse probability of treatment weighting (IPTW) and covariate balancing propensity score (CBPS), to confirm the association between ALC and mortality. Results: A total of 5722 critically ill patients were enrolled, and the one-year mortality was 44.8%. The non-survivor group had a lower ALC (1549, 1027-2388 vs 1948, 1373-2743 counts/µL, p<0.01) compared with those in the survivor group. Cox regression showed that low ALC was independently associated with mortality (adjHR 1.091, 95% CI 1.050-1.134). Propensity score-based analyses demonstrated the robust association, with adjHRs in the original, PSM, IPTW, and CBPS populations of 1.327 (95% CI 1.224-1.438), 1.301 (95% CI 1.188-1.424), 1.292 (95% CI 1.186-1.407), and 1.297 (95% CI 1.191-1.412), respectively. Sensitivity analyses further showed that the association between low ALC and mortality existed in a dose-response manner. Conclusion: We found that low ALC was associated with long-term mortality in critically ill patients; further studies are warranted to validate and translate these findings into clinical utility.

Association between early blood urea nitrogen-to-albumin ratio and one-year post-hospital mortality in critically ill surgical patients: a propensity score-matched study.

BACKGROUND: Blood urea nitrogen to albumin ratio (BAR) is increasingly recognized as an early predictor for short-term outcomes in critically ill patients, but the association of BAR with long-term outcomes in critically ill surgical patients remains underexplored. METHODS: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at Taichung Veterans General Hospital between 2015 and 2020, and the dates of death were retrieved from Taiwan's National Health Insurance Research Database. In addition to Cox regression, we also used propensity score matching to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year post-hospital mortality of the variables. RESULTS: A total of 8,073 eligible subjects were included for analyses. We found that age, male gender, high Charlson Comorbidity Index, high Acute Physiology and Chronic Health Evaluation II score, positive microbial culture, and leukocytosis were predictors for mortality, whereas high body mass index, scheduled surgery, and high platelet counts were protective factors against long-term mortality. The high BAR was independently associated with increased post-hospital mortality after adjustment for the aforementioned covariates (adjHR 1.258, 95% CI, 1.127-1.405). Notably, the association tended to be stronger in females and patients with fewer comorbidities and lower disease severity of critical illness. The propensity score matching, dividing subjects by BAR higher or lower than 6, showed a consistent association between week-one BAR and post-hospital mortality (adjHR 1.503, 95% CI 1.247-1.811). CONCLUSIONS: BAR is a newly identified predictor of short-term outcome, and we identified long-term outcome-relevant factors, including BAR, and the identified factors may be useful for risk stratification of long-term outcomes in patients discharged from surgical ICUs.

Anaemia in the first week may be associated with long-term mortality among critically ill patients: propensity score-based analyses.

BACKGROUND: Anaemia is highly prevalent in critically ill patients; however, the long-term effect on mortality remains unclear. METHODS: We retrospectively included patients admitted to the medical intensive care units (ICUs) during 2015-2020 at the Taichung Veterans General Hospital. The primary outcome of interest was one-year mortality, and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined to assess the association. We used propensity score matching (PSM) and propensity score matching methods, including inverse probability of treatment weighting (IPTW) as well as covariate balancing propensity score (CBPS), in the present study. RESULTS: A total of 7,089 patients were eligible for analyses, and 45.0% (3,189/7,089) of them had anaemia, defined by mean levels of haemoglobin being less than 10 g/dL. The standardised difference of covariates in this study were lower than 0.20 after matching and weighting. The application of CBPS further reduced the imbalance among covariates. We demonstrated a similar association, and adjusted HRs in original, PSM, IPTW and CBPS populations were 1.345 (95% CI 1.227-1.474), 1.265 (95% CI 1.145-1.397), 1.276 (95% CI 1.142-1.427) and 1.260 (95% CI 1.125-1.411), respectively. CONCLUSIONS: We used propensity score-based analyses to identify that anaemia within the first week was associated with increased one-year mortality in critically ill patients.

Week-One Anaemia was Associated with Increased One-Year Mortality in Critically Ill Surgical Patients.

Background: Anaemia has a deleterious effect on surgical patients, but the long-term impact of anaemia in critically ill surgical patients remains unclear. Methods: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at a tertiary referral centre in central Taiwan between 2015 and 2020. We used both Cox proportional hazards analysis and propensity score-based analyses, including propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and covariate balancing propensity score (CBPS) to determine hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year mortality. Results: A total of 7,623 critically ill surgical patients were enrolled, and 29.9% (2,280/7,623) of them had week-one anaemia (haemoglobin <10 g/dL). We found that anaemia was independently associated with an increased risk of one-year mortality after adjustment for relevant covariates (aHR, 1.170; 95% CI, 1.045-1.310). We further identified a consistent strength of association between anaemia and one-year mortality in propensity score-based analyses, with the adjusted HRs in the PSM, IPTW, and CBPS were 1.164 (95% CI 1.025-1.322), 1.179 (95% CI 1.030-1.348), and 1.181 (1.034-1.349), respectively. Conclusions: We identified the impact on one-year mortality of anaemia in critically ill surgical patients, and more studies are needed to validate our findings.

A Positive Fluid Balance in the First Week Was Associated With Increased Long-Term Mortality in Critically Ill Patients: A Retrospective Cohort Study.

Introduction: Early fluid balance has been found to affect short-term mortality in critically ill patients; however, there is little knowledge regarding the association between early cumulative fluid balance (CFB) and long-term mortality. This study aims to determine the distinct association between CFB day 1-3 (CFB 1-3) and day 4-7 (CFB 4-7) and long-term mortality in critically ill patients. Patients and Methods: This study was conducted at Taichung Veterans General Hospital, a tertiary care referral center in central Taiwan, by linking the hospital critical care data warehouse 2015-2019 and death registry data of the Taiwanese National Health Research Database. The patients followed up until deceased or the end of the study on 31 December 2019. We use the log-rank test to examine the association between CFB 1-3 and CFB 4-7 with long-term mortality and multivariable Cox regression to identify independent predictors during index admission for long-term mortality in critically ill patients. Results: A total of 4,610 patients were evaluated. The mean age was 66.4 ± 16.4 years, where 63.8% were men. In patients without shock, a positive CFB 4-7, but not CFB 1-3, was associated with 1-year mortality, while a positive CFB 1-3 and CFB 4-7 had a consistent and excess hazard of 1-year mortality among critically ill patients with shock. The multivariate Cox proportional hazard regression model identified that CFB 1-3 and CFB 4-7 (with per 1-liter increment, HR: 1.047 and 1.094; 95% CI 1.037-1.058 and 1.080-1.108, respectively) were independently associated with high long-term mortality in critically ill patients after adjustment of relevant covariates, including disease severity and the presence of shock. Conclusions: We found that the fluid balance in the first week, especially on days 4-7, appears to be an early predictor for long-term mortality in critically ill patients. More studies are needed to validate our findings and elucidate underlying mechanisms.

Relationship between exposure to ozone and exacerbation requiring hospital admission among patients with asthma: a case-control study in central Taiwan.

OBJECTIVE: The convergence of asthma and air pollutants in ageing populations is currently a growing health issue worldwide, and hence there is an essential need to investigate the association between exposure to air pollution, particularly ozone (O3), and exacerbation requiring admission in patients with asthma. SETTING: A case-control study at a tertiary referral hospital in central Taiwan. PARTICIPANTS: We used an asthma cohort, which included 11 400 patients with asthma, for the period 2006-2018 at Taichung Veterans General Hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: We identified patients who had admitted for exacerbation as cases and selected patients with asthma without exacerbation, matching (1:4) the cases for age, gender and season of exacerbation, as controls. Data on hourly level of air pollutants were obtained from the Taiwan Environmental Protection Administration. We used conditional logistic regression and calculated adjusted ORs (adjORs) with 95% CIs. RESULTS: We enrolled 11 400 participants with asthma, and 4.4% (501) of them had been admitted for exacerbation. Participants with asthma with exacerbation requiring hospitalisation were exposed to a higher level of O3 8-hour daily maximum (adjOR 1.009, 95% CI 1.001 to 1.016) and were more likely to have high Charlson Comorbidity Index (CCI ≥3; adjOR 2.198, 95% CI 1.729 to 2.794) and asthma-chronic obstructive pulmonary disease overlap (adjOR 4.542, 95% CI 3.376 to 6.611) compared with those without exacerbation. The aforementioned associations between exacerbation of asthma requiring hospitalisation and exposure to O3 were similar when defined by either O3 1-hour daily maximum or O3 24-hour average. Moreover, the O3 relevant exacerbation of asthma mainly existed in those aged older than 65 years and patients with medical comorbidities, including gastrointestinal diseases, cardiovascular diseases, neurological diseases, diabetes and renal disease. CONCLUSIONS: Our findings highlight the need for vigilance of exposure to O3 among elderly with asthma, particularly those with medical comorbidities. Further studies are warranted to investigate the underlying mechanisms.

Impact of Early Fluid Balance on Long-Term Mortality in Critically Ill Surgical Patients: A Retrospective Cohort Study in Central Taiwan.

Fluid balance is an essential issue in critical care; however, the impact of early fluid balance on the long-term mortality in critically ill surgical patients remains unknown. This study aimed to address the impact of day 1-3 and day 4-7 fluid balance on the long-term mortality in critically ill surgical patients. We enrolled patients who were admitted to surgical intensive care units (ICUs) during 2015-2019 at a tertiary hospital in central Taiwan and retrieved date-of-death from the Taiwanese nationwide death registration profile. We used a Log-rank test and a multivariable Cox proportional hazards regression model to determine the independent mortality impact of early fluid balance. A total of 6978 patients were included for analyses (mean age: 60.9 ± 15.9 years; 63.9% of them were men). In-hospital mortality, 90-day mortality, 1-year and overall mortality was 10.3%, 15.8%, 23.8% and 31.7%, respectively. In a multivariable Cox proportional hazard regression model adjusted for relevant covariates, we found that positive cumulative day 4-7 fluid balance was independently associated with long-term mortality (aHR 1.083, 95% CI 1.062-1.105), and a similar trend was found on day 1-3 fluid balance, although to a lesser extent (aHR 1.027, 95% CI 1.011-1.043). In conclusion, the fluid balance in the first week of ICU stay, particularly day 4-7 fluid balance, may affect the long-term outcome in critically ill surgical patients.

Culture positivity may correlate with long-term mortality in critically ill patients.

BACKGROUND: The long-term outcome is currently a crucial issue in critical care, and we aim to address the association between culture positivity and long-term mortality in critically ill patients. METHODS: We used the 2015-2019 critical care database at Taichung Veterans General Hospital and Taiwanese nationwide death registration files. Multivariable Cox proportional hazards regression model was conducted to determine hazard ratio (HR) and 95% confidence interval (CI). RESULTS: We enrolled 4488 critically ill patients, and the overall mortality was 55.2%. The follow-up duration among survivors was 2.2 ± 1.3 years. We found that 52.6% (2362/4488) of critically ill patients had at least one positive culture during the admission, and the number of patients with positive culture in the blood, respiratory tract and urinary tract were 593, 1831 and 831, respectively. We identified that a positive culture from blood (aHR 1.233; 95% CI 1.104-1.378), respiratory tract (aHR 1.217; 95% CI 1.109-1.364) and urinary tract (aHR 1.230; 95% CI 1.109-1.364) correlated with an increased risk of long-term mortality after adjusting relevant covariates. CONCLUSIONS: Through linking two databases, we found that positive culture in the blood, respiratory tract and urinary tract during admission correlated with increased long-term overall mortality in critically ill patients.

The association between culture positivity and long-term mortality in critically ill surgical patients.

BACKGROUND: The long-term outcome is an essential issue in critically ill patients, and the identification of early determinant is needed for risk stratification of the long-term outcome. In the present study, we investigate the association between culture positivity during admission and long-term outcome in critically ill surgical patients. METHODS: We linked the 2015-2019 critical care database at Taichung Veterans General Hospital with the nationwide death registration files in Taiwan. We described the long-term mortality and proportion of culture positivity among enrolled subjects. We used a log-rank test to estimate survival curves between patients with and without positive cultures and a multivariable Cox proportional hazards regression model to determine hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 6748 critically ill patients were enrolled, and 32.5% (2196/6749) of them died during the follow-up period, with the overall follow-up duration was 1.8 ± 1.4 years. We found that 31.4% (2122/6748) of critically ill patients had at least one positive culture during the index admission, and the number of patients with positive culture in the blood, respiratory tract, urinary tract, skin and soft tissue and abdomen were 417, 1702, 554, 194 and 139, respectively. We found that a positive culture from any sites was independently associated with high long-term mortality (aHR 1.579, 95% CI 1.422-1.754) after adjusting relevant covariates, including age, sex, body-mass index, comorbidities, severity score, shock, early fluid overload, receiving mechanical ventilation and the need of renal replacement therapy for critical illness. CONCLUSIONS: We linked two databases to identify that a positive culture during admission was independently correlated with increased long-term mortality in critically ill surgical patients. Our findings highlight the need for vigilance among patients with a positive culture during admission, and more studies are warranted to validate our findings and to clarify underlying mechanisms.

Conservation region finding for influenza A viruses by machine learning methods of N-linked glycosylation sites and B-cell epitopes.

Influenza type A, a serious infectious disease of the human respiratory tract, poses an enormous threat to human health worldwide. It leads to high mortality rates in poultry, pigs, and humans. The primary target identity regions for the human immune system are hemagglutinin (HA) and neuraminidase (NA), two surface proteins of the influenza A virus. Research and development of vaccines is highly complex because the influenza A virus evolves rapidly. This study focused on three genetic features of viral surface proteins: ribonucleic acid (RNA) sequence conservation, linear B-cell epitopes, and N-linked glycosylation. On the basis of these three properties, we analyzed 12,832 HA and 9487 NA protein sequences, which we retrieved from the influenza virus database. We classified the viral surface protein sequences into the 18 HA and 11 NA subtypes that have been identified thus far. Using available analytic tools, we searched for the representative strain of each virus subtype. Furthermore, using machine learning methods, we looked for conservation regions with sequences showing linear B-cell epitopes and N-linked glycosylation. Compared to the prediction of the Immune Epitope Database (IEDB) antibody neutralization response (i.e., screening of antibody sequence regions), in this study, the virus sequence coverage was large and accurate and contained N-linked glycosylation sites. The results of this study proved that we can use the machine learning-based prediction method to solve the problem of vaccine invalidation that occurred during the rapid evolution of the influenza A virus and also as a prevaccine assessment. In addition, the screening fragments can be used as a universal influenza vaccine design reference in the future.

Objective fidelity evaluation in multisensory virtual environments: auditory cue fidelity in flight simulation.

We argue that objective fidelity evaluation of virtual environments, such as flight simulation, should be human-performance-centred and task-specific rather than measure the match between simulation and physical reality. We show how principled experimental paradigms and behavioural models to quantify human performance in simulated environments that have emerged from research in multisensory perception provide a framework for the objective evaluation of the contribution of individual cues to human performance measures of fidelity. We present three examples in a flight simulation environment as a case study: Experiment 1: Detection and categorisation of auditory and kinematic motion cues; Experiment 2: Performance evaluation in a target-tracking task; Experiment 3: Transferrable learning of auditory motion cues. We show how the contribution of individual cues to human performance can be robustly evaluated for each task and that the contribution is highly task dependent. The same auditory cues that can be discriminated and are optimally integrated in experiment 1, do not contribute to target-tracking performance in an in-flight refuelling simulation without training, experiment 2. In experiment 3, however, we demonstrate that the auditory cue leads to significant, transferrable, performance improvements with training. We conclude that objective fidelity evaluation requires a task-specific analysis of the contribution of individual cues.

The rubber hand illusion in a mirror.

In the rubber hand illusion (RHI) one's hand is hidden, and a fake hand is visible. We explored the situation in which visual information was available indirectly in a mirror. In the mirror condition, compared to the standard condition (fake hand visible directly), we found no reduction of the RHI following synchronised stimulation, as measured by crossmanual pointing and by a questionnaire. We replicated the finding with a smaller mirror that prevented visibility of the face. The RHI was eliminated when a wooden block replaced the fake hand, or when the hand belonged to another person or mannequin. We conclude that awareness of the reflection is the critical variable, despite the distant visual localisation of the hand in a mirror and the third-person perspective. Stimuli seen in a mirror activate the same response as stimuli seen in peripersonal space, through knowledge that they are near one's body.