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Background The potential adverse effects associated with invasive mechanical ventilation (MV) can lead to delayed decisions on starting MV. We aimed to explore the association between the timing of MV and the clinical outcomes in patients with sepsis ventilated in intensive care unit (ICU). Methods We analyzed data of adult patients with sepsis between September 2019 and December 2021. Data was collected through the Korean Sepsis Alliance from 20 hospitals in Korea. Patients who were admitted to ICU and received MV were included in the study. Patients were divided into ‘early MV’ and ‘delayed MV’ groups based on whether they were on MV on the first day of ICU admission or later. Propensity score matching was applied, and patients in the two groups were compared on a 1:1 ratio to overcome bias between the groups. Outcomes including ICU mortality, hospital mortality, length of hospital and ICU stay, and organ failure at ICU discharge were compared. Results Out of 2440 patients on MV during ICU stay, 2119 ‘early MV’ and 321 ‘delayed MV’ cases were analyzed. The propensity score matching identified 295 patients in each group with similar baseline characteristics. ICU mortality was lower in ‘early MV’ group than ‘delayed MV’ group (36.3% vs. 46.4%; odds ratio, 0.66; 95% confidence interval, 0.47–0.93; p  = 0.015). ‘Early MV’ group had lower in-hospital mortality, shorter ICU stay, and required tracheostomy less frequently than ‘delayed MV’ group. Multivariable logistic regression model identified ‘early MV’ as associated with lower ICU mortality (odds ratio, 0.38; 95% confidence interval, 0.29–0.50; p  < 0.001). Conclusion In patients with sepsis ventilated in ICU, earlier start (first day of ICU admission) of MV may be associated with lower mortality.

Background Timely administration of antibiotics is one of the most important interventions in reducing mortality in sepsis. However, administering antibiotics within a strict time threshold in all patients suspected with sepsis will require huge amount of effort and resources and may increase the risk of unintentional exposure to broad-spectrum antibiotics in patients without infection with its consequences. Thus, controversy still exists on whether clinicians should target different time-to-antibiotics thresholds for patients with sepsis versus septic shock. Methods This study analyzed prospectively collected data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Adjusted odds ratios (ORs) were compared for in-hospital mortality of patients who had received antibiotics within 1 h to that of those who did not. Spline regression models were used to assess the association of time-to-antibiotics as continuous variables and increasing risk of in-hospital mortality. The differences in the association between time-to-antibiotics and in-hospital mortality were assessed according to the presence of septic shock. Results Overall, 3035 patients were included in the analysis. Among them, 601 (19.8%) presented with septic shock, and 774 (25.5%) died. The adjusted OR for in-hospital mortality of patients whose time-to-antibiotics was within 1 h was 0.78 (95% confidence interval [CI] 0.61–0.99; p  = 0.046). The adjusted OR for in-hospital mortality was 0.66 (95% CI 0.44–0.99; p  = 0.049) and statistically significant in patients with septic shock, whereas it was 0.85 (95% CI 0.64–1.15; p  = 0.300) in patients with sepsis but without shock. Among patients who received antibiotics within 3 h, those with septic shock showed 35% ( p  = 0.042) increased risk of mortality for every 1-h delay in antibiotics, but no such trend was observed in patients without shock. Conclusion Timely administration of antibiotics improved outcomes in patients with septic shock; however, the association between early antibiotic administration and outcome was not as clear in patients with sepsis without shock.

Background Acute respiratory distress syndrome (ARDS) is etiologically and clinically a heterogeneous disease. Its diagnostic characteristics and subtype classification, and the application of these features to treatment, have been of considerable interest. Metabolomics is becoming important for identifying ARDS biology and distinguishing its subtypes. This study aimed to identify metabolites that could distinguish sepsis-induced ARDS patients from non-ARDS controls, using a targeted metabolomics approach, and to identify whether sepsis-induced direct and sepsis-induced indirect ARDS are metabolically distinct groups, and if so, confirm their metabolites and associated pathways. Methods This study retrospectively analyzed 54 samples of ARDS patients from a sepsis registry that was prospectively collected from March 2011 to February 2018, along with 30 non-ARDS controls. The cohort was divided into direct and indirect ARDS. Metabolite concentrations of five analyte classes (energy metabolism, free fatty acids, amino acids, phospholipids, sphingolipids) were measured using liquid chromatography–tandem mass spectrometry and gas chromatography–mass spectrometry by targeted metabolomics. Results In total, 186 metabolites were detected. Among them, 102 metabolites could differentiate sepsis-induced ARDS patients from the non-ARDS controls, while 14 metabolites could discriminate sepsis-induced ARDS subphenotypes. Using partial least-squares discriminant analysis, we showed that sepsis-induced ARDS patients were metabolically distinct from the non-ARDS controls. The main distinguishing metabolites were lysophosphatidylethanolamine (lysoPE) plasmalogen, PE plasmalogens, and phosphatidylcholines (PCs). Sepsis-induced direct and indirect ARDS were also metabolically distinct subgroups, with differences in lysoPCs. Glycerophospholipid and sphingolipid metabolism were the most significant metabolic pathways involved in sepsis-induced ARDS biology and in sepsis-induced direct/indirect ARDS, respectively. Conclusion Our study demonstrated a marked difference in metabolic patterns between sepsis-induced ARDS patients and non-ARDS controls, and between sepsis-induced direct and indirect ARDS subpheonotypes. The identified metabolites and pathways can provide clues relevant to the diagnosis and treatment of individuals with ARDS.

Purpose Intubation in patients with respiratory failure can be avoided by high-flow nasal cannula (HFNC) use. However, it is unclear whether waiting until HFNC fails, which would delay intubation, has adverse effects. The present retrospective observational study assessed overall ICU mortality and other hospital outcomes of patients who received HFNC therapy that failed. Methods All consecutive patients in one tertiary hospital who received HFNC therapy that failed and who then required intubation between January 2013 and March 2014 were enrolled and classified according to whether intubation started early (within 48 h) or late (at least 48 h) after commencing HFNC. Results Of the 175 enrolled patients, 130 (74.3 %) and 45 (25.7 %) were intubated before and after 48 h of HFNC, respectively. The groups were similar in terms of most baseline characteristics. The early intubated patients had better overall ICU mortality (39.2 vs. 66.7 %; P  = 0.001) than late intubated patients. A similar pattern was seen with extubation success (37.7 vs. 15.6 %; P  = 0.006), ventilator weaning (55.4 vs. 28.9 %; P  = 0.002), and ventilator-free days (8.6 ± 10.1 vs. 3.6 ± 7.5; P  = 0.011). In propensity-adjusted and -matched analysis, early intubation was also associated with better overall ICU mortality [adjusted odds ratio (OR) = 0.317, P  = 0.005; matched OR = 0.369, P  = 0.046]. Conclusions Failure of HFNC might cause delayed intubation and worse clinical outcomes in patients with respiratory failure. Large prospective and randomized controlled studies on HFNC failure are needed to draw a definitive conclusion.

We investigated the proportion and characteristics of severe Corynebacterium striatum pneumonia in South Korea during 2014-2019. As part of an ongoing observational study of severe pneumonia among adult patients, we identified 27 severe C. striatum pneumonia cases. Most (70.4%) cases were hospital-acquired, and 51.9% of patients were immunocompromised. C. striatum cases among patients with severe hospital-acquired pneumonia (HAP) increased from 1.0% (2/200) during 2014-2015 to 5.4% (10/185) during 2018-2019, but methicillin-resistant Staphylococcus aureus (MRSA) infections among severe HAP cases decreased from 12.0% to 2.7% during the same timeframe. During 2018-2019, C. striatum was responsible for 13.3% of severe HAP cases from which bacterial pathogens were identified. The 90-day mortality rates were similarly high in the C. striatum and MRSA groups. C. striatum was a major cause of severe HAP and had high mortality rates. This pathogen is emerging as a possible cause for severe pneumonia, especially among immunocompromised patients.

Background Numerous epidemiological studies investigating gender-dependent clinical outcomes in sepsis have shown conflicting evidence. This study aimed to investigate the effect of gender on in-hospital mortality due to sepsis according to age group. Methods This study used data from the Korean Sepsis Alliance, an ongoing nationwide prospective multicenter cohort from 19 participating hospitals in South Korea. All adult patients diagnosed with sepsis in the emergency departments of the participating hospitals between September 2019 and December 2021 were included in the analysis. Clinical characteristics and outcomes were compared between male and female. Eligible patients were stratified by age into 19–50 years, 50–80 years, and ≥ 80 years old individuals. Results During the study period, 6442 patients were included in the analysis, and 3650 (56.7%) were male. The adjusted odds ratio (OR) [95% confidence interval (CI)] for in-hospital mortality for male compared with female was 1.15 (95% CI = 1.02–1.29). Interestingly, in the age 19–50 group, the risk of in-hospital mortality for males was significantly lower than that of females [0.57 (95% CI = 0.35–0.93)]. For female, the risk of death remained relatively stable until around age 80 ( P for linearity = 0.77), while in males, there was a linear increase in the risk of in-hospital death until around age 80 ( P for linearity < 0.01). Respiratory infection (53.8% vs. 37.4%, p  < 0.01) was more common in male, whereas urinary tract infection (14.7% vs. 29.8%, p  < 0.01) was more common in female. For respiratory infection, male had significantly lower in-hospital mortality than female in the age 19–50 groups (adjusted OR = 0.29, 95% CI = 0.12–0.69). Conclusions Gender may influence age-associated sepsis outcomes. Further studies are needed to replicate our findings and fully understand the interaction of gender and age on the outcomes of patients with sepsis.

Background Despite the clinical importance of sepsis-associated acute kidney injury (SA-AKI), little is known about its epidemiology. We aimed to investigate the incidence and outcomes of SA-AKI, as well as the risk factors for mortality among patients with severe SA-AKI in critically ill patients. Methods This secondary multicenter, observational, prospective cohort analysis of sepsis in South Korea evaluated patients aged ≥ 19 years admitted to intensive care units with a diagnosis of sepsis. The primary outcome was the incidence of SA-AKI, defined using the new consensus definition of the Acute Disease Quality Initiative 28 Workgroup. Secondary outcomes were in-hospital mortality and risk factors for in-hospital mortality. Results Between September 2019 and December 2022, 5100 patients were admitted to intensive care units with a diagnosis of sepsis, and 3177 (62.3%) developed SA-AKI. A total of 613 (19.3%), 721 (22.7%), and 1843 (58.0%) patients had stage 1, 2, and 3 SA-AKI, respectively. Severe SA-AKI (stages 2 and 3 combined) was associated with an increased risk of in-hospital mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle was associated with a decreased risk of in-hospital mortality in severe SA-AKI (adjusted odds ratio, 0.62; 95% confidence interval, 0.48–0.79; P  < 0.001). Conclusions Of the patients admitted to the intensive care unit for sepsis, 62.3% developed SA-AKI. Severe SA-AKI was associated with an increased risk of mortality. Adherence to the fluid resuscitation component of the one-hour sepsis bundle can potentially improve outcomes in these patients.

The characteristics of severe human parainfluenza virus (HPIV)-associated pneumonia in adults have not been well evaluated. We investigated epidemiologic and clinical characteristics of 143 patients with severe HPIV-associated pneumonia during 2010-2019. HPIV was the most common cause (25.2%) of severe virus-associated hospital-acquired pneumonia and the third most common cause (15.7%) of severe virus-associated community-acquired pneumonia. Hematologic malignancy (35.0%), diabetes mellitus (23.8%), and structural lung disease (21.0%) were common underlying conditions. Co-infections occurred in 54.5% of patients admitted to an intensive care unit. The 90-day mortality rate for HPIV-associated pneumonia was comparable to that for severe influenza virus-associated pneumonia (55.2% vs. 48.4%; p = 0.22). Ribavirin treatment was not associated with lower mortality rates. Fungal co-infections were associated with 82.4% of deaths. Clinicians should consider the possibility of pathogenic co-infections in patients with HPIV-associated pneumonia. Contact precautions and environmental cleaning are crucial to prevent HPIV transmission in hospital settings.

The current early warning scores may be insufficient for medical emergency teams (METs) to use in assessing the severity and the prognosis of activated patients. We evaluated the predictive powers of the Modified Early Warning Score (MEWS) and the National Early Warning Score (NEWS) for 28-day mortality and to analyze predictors of 28-day mortality in general ward patients who activate the MET. Adult general ward inpatients who activated the MET in a tertiary referral teaching hospital between March 2009 and December 2016 were included. The demographic and clinical characteristics and physiologic parameters at the time of MET activation were collected, and MEWS and NEWS were calculated. A total of 6,729 MET activation events were analyzed. Patients who died within 28 days were younger (mean age 60 vs 62 years), were more likely to have malignancy (72% vs 53%), were more likely to be admitted to the medical department rather than the surgical department (93% vs 80%), had longer intervals from admission to MET activation (median, 7 vs 5 days), and were less likely to activate the MET during nighttime hours (5 PM to 8 AM) (61% vs 66%) compared with those who did not die within 28 days (P < 0.001 for all comparisons). The areas under the receiver operating characteristic curves of MEWS and NEWS for 28-day mortality were 0.58 (95% CI, 0.56-0.59) and 0.60 (95% CI, 0.59-0.62), which were inferior to that of the logistics regression model (0.73; 95% CI, 0.72-0.74; P < 0.001 for both comparisons). Both the MEWS and NEWS had poor predictive powers for 28-day mortality in patients who activated the MET. A new scoring system is needed to stratify the severity and prognosis of patients who activated the MET.

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.