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Background: The decision to discontinue intensive care unit (ICU) treatment during the end-oflife stage has recently become a significant concern in Korea, with an observed increase in life-sustaining treatment (LST) withdrawal. There is a growing demand for evidence-based support for patients, families, and clinicians in making LST decisions. This study aimed to identify factors influencing LST decisions in ICU inpatients and to analyze their impact on healthcare utilization. Methods: We retrospectively reviewed medical records of ICU patients with neurological disorders, infectious disorders, or cancer who were treated at a single university hospital between January 1, 2019 and July 7, 2021. Factors influencing the decision to withdraw LST were compared between those who withdrew LST and those who did not. Results: Among 54,699 hospital admissions, LST was withdrawn in 550 cases (1%). Cancer was the most common diagnosis, followed by pneumonia and cerebral infarction. Among ICU inpatients, LST was withdrawn from 215 (withdrawal group). The withdrawal group was older (78 vs. 75 years, P=0.002), had longer total hospital stays (16 vs. 11 days, P<0.001), and higher ICU readmission rates than the control group. There were no significant differences in the healthcare costs of ICU stay between the two groups. Most LST decisions (86%) were made by family. Conclusions: The decisions to withdraw LST of ICU inpatients were influenced by age, readmission, and disease category. ICU costs were similar between the withdrawal and control groups. Further research is needed to tailor LST decisions in the ICU. [ABSTRACT FROM AUTHOR]

Background: Sepsis and septic shock remain the leading causes of death in critically ill patients worldwide. Various biomarkers are available to determine the prognosis and therapeutic effects of sepsis. In this study, we investigated the effectiveness of presepsin as a sepsis biomarker. Methods: Patients admitted to the intensive care unit with major or minor diagnosis of sepsis were categorized into survival and non-survival groups. The white blood cell count and serum C-reactive protein, procalcitonin, and presepsin levels were measured in all patients. Results: The study included 40 patients (survival group, 32; non-survival group, 8; mortality rate, 20%). The maximum serum presepsin levels measured during intensive care unit admission were significantly higher in the non-survival group (median [interquartile range]: 4,205.5 pg/ml [1,155.8-10,094.0] vs. 741.5 pg/ml [520.0-1,317.5], P<0.05). No statistically significant intergroup differences were observed in the maximum, minimum, and mean values of the white blood cell count, as well as serum C-reactive protein, and procalcitonin levels. Based on the receiver operating characteristic curve, the area under the curve for presepsin as a predictor of sepsis mortality was 0.764. At a cut-off value of 1,898.5 pg/ml, the sensitivity and specificity of presepsin for prediction of sepsis-induced mortality were 75.0% and 87.5%, respectively. Conclusions: Early diagnosis of sepsis and prediction of sepsis-induced mortality are important for prompt initiation of treatment. Presepsin may serve as an effective biomarker for prediction of sepsis-induced mortality and for evaluation of treatment effectiveness. [ABSTRACT FROM AUTHOR]

Influenza infection induces lung epithelial cell injury via programmed cell death. Glutathione, a potent antioxidant, has been reported to be associated with influenza infection. We hypothesized that lung epithelial cell death during influenza infection is regulated by glutathione metabolism. Eight-weekold male and female BALB/c mice were infected with influenza (PR8: A/PR/8/34 [H1N1]) via intranasal instillation. Metabolomic analyses were performed on whole lung lysate after influenza infection. For in vitro analysis, Beas-2B cells were infected with influenza. RNA was extracted, and QuantiTect Primer Assay was used to assess gene expression. Glutathione concentrations were assessed by colorimetric assay. Influenza infection resulted in increased inflammation and epithelial cell injury in our murine model, leading to increased morbidity and mortality. In both our in vivo and in vitro models, influenza infection was found to induce apoptosis and necroptosis. Influenza infection led to decreased glutathione metabolism and reduced glutathione reductase activity in lung epithelial cells. Genetic inhibition of glutathione reductase suppressed apoptosis and necroptosis of lung epithelial cells. Pharmacologic inhibition of glutathione reductase reduced airway inflammation, lung injury, and cell death in our murine influenza model. Our results demonstrate that glutathione reductase activity is suppressed during influenza. Glutathione reductase inhibition prevents epithelial cell death and morbidity in our murine influenza model. Our results suggest that glutathione reductase-dependent glutathione metabolism may play an important role in the host response to viral infection by regulating lung epithelial cell death. [ABSTRACT FROM AUTHOR]

Rationale: The Sequential Organ Failure Assessment (SOFA) tool is a commonly used measure of illness severity. Calculation of the respiratory subscore of SOFA is frequently limited by missing arterial oxygen pressure (PaO2) data. Although missing PaO2 data are commonly replaced with normal values, the performance of different methods of substituting PaO2 for SOFA calculation is unclear. Objectives: The study objective was to compare the performance of different substitution strategies for missing PaO2 data for SOFA score calculation. Methods: This retrospective cohort study was performed using the Weill Cornell Critical Care Database for Advanced Research from a tertiary care hospital in the United States. All adult patients admitted to an intensive care unit (ICU) from 2011 to 2019 with an available respiratory SOFA score were included. We analyzed the availability of the PaO2/fraction of inspired oxygen (FiO2) ratio on the first day of ICU admission. In those without a PaO2/FiO2 ratio available, the ratio of oxygen saturation as measured by pulse oximetry to FiO2 was used to calculate a respiratory SOFA subscore according to four methods (linear substitution [Rice], nonlinear substitution [Severinghaus], modified respiratory SOFA, and multiple imputation by chained equations [MICE]) as well as the missing-as-normal technique. We then compared how well the different total SOFA scores discriminated in-hospital mortality. We performed several subgroup and sensitivity analyses. Results: We identified 35,260 unique visits, of which 9,172 included predominant respiratory failure. PaO2 data were available for 14,939 (47%). The area under the receiver operating characteristic curve for each substitution technique for discriminating in-hospital mortality was higher than that for the missing-as-normal technique (0.78 [0.77-0.79]) in all analyses (modified, 0.80 [0.79-0.81]; Rice, 0.80 [0.79-0.81]; Severinghaus, 0.80 [0.79-0.81]; and MICE, 0.80 [0.79-0.81]) (P < 0.01). Each substitution method had a higher accuracy for discriminating in-hospital mortality (MICE, 0.67; Rice, 0.67; modified, 0.66; and Severinghaus, 0.66) than the missing-as-normal technique. Model calibration for in-hospital mortality was less precise for the missing-as-normal technique than for the other substitution techniques at the lower range of SOFA and among the subgroups. Conclusions: Using physiologic and statistical substitution methods improved the total SOFA score's ability to discriminate mortality compared with the missing-as-normal technique. Treating missing data as normal may result in underreporting the severity of illness compared with using substitution. The simplicity of a direct oxygen saturation as measured by pulse oximetry/FiO2 ratio-modified SOFA technique makes it an attractive choice for electronic health record-based research. This knowledge can inform comparisons of severity of illness across studies that used different techniques. [ABSTRACT FROM AUTHOR]

Background: This study examined the experience of withholding or withdrawing life-sustaining treatment in patients hospitalized in the intensive care units (ICUs) of a tertiary care center. It also considers the role that intensivists play in the decision-making process regarding the withdrawal of life-sustaining treatment. Methods: We retrospectively analyzed the medical records of 227 patients who decided to withhold or withdraw life-sustaining treatment while hospitalized at Ewha Womans University Medical Center Mokdong between April 9 and December 31, 2018. Results: The 227 hospitalized patients included in the analysis withheld or withdrew from life-sustaining treatment. The department in which life-sustaining treatment was withheld or withdrawn most frequently was hemato-oncology (26.4%). Among these patients, the most common diagnosis was gastrointestinal tract cancer (29.1%). A majority of patients (64.3%) chose not to receive any life-sustaining treatment. Of the 80 patients in the ICU, intensivists participated in the decision to withhold or withdraw life-sustaining treatment in 34 cases. There were higher proportions of treatment withdrawal and ICU-to-ward transfers among the cases in whom intensivists participated in decision making compared to those cases in whom intensivists did not participate (50.0% vs. 4.3% and 52.9% vs. 19.6%, respectively). Conclusions: Through their participation in end-of-life discussions, intensivists can help patients' families to make decisions about withholding or withdrawing life-sustaining treatment and possibly avoiding futile treatments for these patients. [ABSTRACT FROM AUTHOR]

Background: Idiopathic pulmonary fibrosis (IPF) is a rapidly progressive, fatal lung disease that affects older adults. One of the detrimental natural histories of IPF is acute exacerbation of IPF (AE-IPF), of which bacterial infection is reported to play an important role. However, the mechanism by which bacterial infection modulates the fibrotic response remains unclear.Objectives: Altered glucose metabolism has been implicated in the pathogenesis of fibrotic lung diseases. We have previously demonstrated that glucose transporter 1 (GLUT1)-dependent glycolysis regulates fibrogenesis in a murine fibrosis model. To expand on these findings, we hypothesised that GLUT1-dependent glycolysis regulates acute exacerbation of lung fibrogenesis during bacterial infection via AIM2 inflammasome activation.Results: In our current study, using a murine model of Streptococcus pneumoniae (S. pneumoniae) infection, we investigated the potential role of GLUT1 on mediating fibrotic responses to an acute exacerbation during bleomycin-induced fibrosis. The results of our current study illustrate that GLUT1 deficiency ameliorates S. pneumoniae-mediated exacerbation of lung fibrosis (wild type (WT)/phosphate buffered saline (PBS), n=3; WT/S. pneumoniae, n=3; WT/Bleomycin, n=5 ; WT/Bleomycin+S. pneumoniae, n=7; LysM-Cre-Glut1fl/f /PBS, n=3; LysM-Cre-Glut1fl/fl /S. pneumoniae, n=3; LysM-Cre-Glut1fl/fl /Bleomycin, n=6; LysM-Cre-Glut1fl/fl /Bleomycin+S. pneumoniae, n=9, p=0.041). Further, the AIM2 inflammasome, a multiprotein complex essential for sensing cytosolic bacterial DNA as a danger signal, is an important regulator of this GLUT1-mediated fibrosis and genetic deficiency of AIM2 reduced bleomycin-induced fibrosis after S. pneumoniae infection (WT/PBS, n=6; WT/Bleomycin+S. pneumoniae, n=15; Aim2-/-/PBS, n=6, Aim2-/-/Bleomycin+S. pneumoniae, n=11, p=0.034). GLUT1 deficiency reduced expression and function of the AIM2 inflammasome, and AIM2-deficient mice showed substantial reduction of lung fibrosis after S. pneumoniae infection.Conclusion: Our results demonstrate that GLUT1-dependent glycolysis promotes exacerbation of lung fibrogenesis during S. pneumoniae infection via AIM2 inflammasome activation. [ABSTRACT FROM AUTHOR]

Epidemiological and experimental evidence has emerged that a dysregulated inflammation is associated with most of the tumors, and many studies have begun to unravel the molecular pathways linking inflammation and cancer. As a typical example linking these associations, Helicobacter pylori (H. pylori) infection-associated atrophic gastritis has been recognized as precursor lesion of gastric cancer. The identification of transcription factors such as NF-κB and STAT3, and their gene products such as IL-8, COX-2, iNOS, cytokines, chemokines and their receptors, etc have laid the molecular foundation for our understanding of the decisive role of inflammation in carcinogenesis. In addition to the role as the initiator of cancer, inflammation contributes to survival and proliferation of malignant cells, tumor angiogenesis, and even metastasis. In this review, the fundamental mechanisms of H. pylori-induced carcinogenesis as well as the possibility of cancer prevention through suppressing H. pylori-induced inflammation are introduced. We infer that targeting inflammatory pathways have a potential role to detour the unpleasant journey to H. pylori-associated gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

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