Journal of Intensive Care最新文献

Background: Erythropoietin (EPO), a glycoprotein hormone primarily produced in the kidneys, plays pleiotropic roles in hematopoietic and non-hematopoietic system. However, the clinical relevance of circulating EPO in sepsis progression and outcomes remains contentious and requires further elucidation.

Methods: Participants were categorized into three groups on the basis of EPO tertiles. The primary outcome was 28-day mortality. Multivariate Cox proportional regression analysis and restricted cubic spline regression were employed to evaluate the association between EPO levels and 28-day mortality in sepsis patients. Subgroup analyses were also conducted. Causal mediation analysis was conducted to explore the potential mediating role of EPO in the relationship between lactate and 28-day mortality.

Results: A total of 267 patients (65.17% male) were included in the study. The 28-day and hospital mortality rates were 23.22 and 31.20%, respectively. Multivariate Cox regression revealed significantly higher 28-day and hospital mortality in the highest EPO tertile compared to the lowest (HR 2.93, 95% CI 1.20-7.22; HR 2.47, 95% CI 1.05-5.81, respectively). Restricted cubic spline analysis demonstrated a progressively increasing mortality risk with elevated EPO levels. Subgroup analyses confirmed the consistency and stability of the effect size and direction across different subgroups. Moreover, causal intermediary analysis revealed that the association between lactate and 28-day mortality was partially mediated by EPO, with a mediation ratio of 12.59%.

Conclusions: Elevated EPO levels in patients with sepsis are correlated with unfavorable prognoses and may function as a prognostic biomarker for adverse outcomes.

Background: The gut has long been hypothesized to be the "motor" of critical illness, propagating inflammation and playing a key role in multiple organ dysfunction. However, the exact mechanisms through which impaired gut integrity potentially contribute to worsened clinical outcome remain to be elucidated. Critical elements of gut dysregulation including intestinal hyperpermeability and a perturbed microbiome are now recognized as potential therapeutic targets in critical care.

Main body: The gut is a finely tuned ecosystem comprising ~ 40 trillion microorganisms, a single cell layer intestinal epithelia that separates the host from the microbiome and its products, and the mucosal immune system that actively communicates in a bidirectional manner. Under basal conditions, these elements cooperate to maintain a finely balanced homeostasis benefitting both the host and its internal microbial community. Tight junctions between adjacent epithelial cells selectively transport essential molecules while preventing translocation of pathogens. However, critical illness disrupts gut barrier function leading to increased gut permeability, epithelial apoptosis, and immune activation. This disruption is further exacerbated by a shift in the microbiome toward a "pathobiome" dominated by pathogenic microbes with increased expression of virulence factors, which intensifies systemic inflammation and accelerates organ dysfunction. Research has highlighted several potential therapeutic targets to restore gut integrity in the host, including the regulation of epithelial cell function, modulation of tight junction proteins, and inhibition of epithelial apoptosis. Additionally, microbiome-targeted therapies, such as prebiotics, probiotics, fecal microbiota transplantation, and selective decontamination of the digestive tract have also been extensively investigated to promote restoration of gut homeostasis in critically ill patients. Future research is needed to validate the potential efficacy of these interventions in clinical settings and to determine if the gut can be targeted in an individualized fashion.

Conclusion: Increased gut permeability and a disrupted microbiome are common in critical illness, potentially driving dysregulated systemic inflammation and organ dysfunction. Therapeutic strategies to modulate gut permeability and restore the composition of microbiome hold promise as novel treatments for critically ill patients.

The 2024 revised edition of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock (J-SSCG 2024) is published by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine. This is the fourth revision since the first edition was published in 2012. The purpose of the guidelines is to assist healthcare providers in making appropriate decisions in the treatment of sepsis and septic shock, leading to improved patient outcomes. We aimed to create guidelines that are easy to understand and use for physicians who recognize sepsis and provide initial management, specialized physicians who take over the treatment, and multidisciplinary healthcare providers, including nurses, physical therapists, clinical engineers, and pharmacists. The J-SSCG 2024 covers the following nine areas: diagnosis of sepsis and source control, antimicrobial therapy, initial resuscitation, blood purification, disseminated intravascular coagulation, adjunctive therapy, post-intensive care syndrome, patient and family care, and pediatrics. In these areas, we extracted 78 important clinical issues. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members. As a result, 42 GRADE-based recommendations, 7 good practice statements, and 22 information-to-background questions were created as responses to clinical questions. We also described 12 future research questions.

Background: Shift work is common in healthcare, especially in emergency and intensive care, to maintain the quality of patient care. Night shifts are linked to health risks such as cardiovascular disease, metabolic disorders, and poor mental health. It has been suggested that inflammatory responses due to the disruption of circadian rhythm may contribute to health risks, but the detailed mechanisms remain unclear. This study aimed to analyze changes in gene expression in whole blood of healthcare workers before and after a night shift and investigate the molecular pathogenesis of these changes and their impact on health.

Methods: This was a single-center, prospective, observational study of four medical doctors working night shifts in the emergency department. Blood samples from the subjects were collected before and after the night shift, and RNA sequencing was performed to analyze changes in gene expression in whole blood. The data obtained were analyzed via Ingenuity Pathway Analysis (IPA) core analysis that included canonical pathway analysis, upstream regulator analysis, and functional network analysis. RNA bulk deconvolution was performed to estimate the relative abundance of immune cells. The IPA analysis match feature was also used to assess similarities of gene expression patterns with other diseases.

Results: We identified 302 upregulated and 78 downregulated genes (p < 0.05, |log2-fold change|> 0.5) as genes whose expression changed after the night shift. Canonical pathway analysis revealed that Toll-like receptors and other innate immune response pathways were activated. Upstream regulator analysis and functional network analysis also consistently indicated a predicted activation of innate immune and inflammatory responses. RNA bulk deconvolution showed changes in the proportions of several immune cells. IPA analysis match indicated that gene expression patterns after night shifts were highly correlated with several diseases, including major depressive disorder, in terms of immune and inflammatory responses.

Conclusion: The results revealed that innate immune and inflammatory responses are elicited after night shifts in healthcare workers and that gene expression patterns correlate with several diseases in terms of immune and inflammatory responses. These findings suggest that shift work may affect health risks through innate immune and inflammatory responses.

We commend the authors for their insightful study on inspiratory muscle training (IMT) in mechanically ventilated patients with difficult weaning, highlighting the robust use of maximum inspiratory pressure (MIP) as a key outcome. We suggest that a lower baseline maximum inspiratory pressure cutoff could better target patients with significant inspiratory dysfunction, improving the study's precision. Additionally, alternative imputation techniques, such as multiple imputation, could strengthen the handling of missing data. While the sample size calculation was appropriate, the unbalanced group sizes raise concerns about generalisability. Future research could benefit from subgroup analyses, individual response curves, and further investigation into the unexpected adverse effects observed in the low-intensity group to refine the inspiratory muscle training protocols.

Background: Sepsis is a critical condition associated with high morbidity and mortality, emphasizing the need for reliable biomarkers for its diagnosis and prognosis. This study uses advanced immunological techniques to evaluate monocytic CD39 (mCD39) expression as a potential marker in sepsis.

Methods: This prospective observational cohort study included 206 participants from the First Affiliated Hospital, Zhejiang University School of Medicine between April 2022 and September 2023. Participants were categorized into four groups: healthy donors, patients with mild infections, post-cardiac surgery patients (non-infectious inflammation), and sepsis patients. Peripheral Blood Mononuclear Cells were analyzed using mass cytometry time-of-flight (CyTOF) with a 42-marker immune panel and flow cytometry targeting monocytes. Statistical analyses included ROC curves for diagnostic and prognostic performance and Kaplan-Meier survival analysis for prognostic evaluation.

Results: Sepsis patients exhibited significantly lower monocytic CD39 expression than mild infection and post-surgery groups (p < 0.05). The diagnostic performance analysis revealed that mCD39 effectively distinguished sepsis from mild infection (AUC = 0.877) and non-infectious inflammation (AUC = 0.935). Prognostic analysis identified low mCD39 expression as a strong predictor of short-term survival, with a 7-day survival AUC of 0.85 (p = 0.037). Kaplan-Meier analysis showed that sepsis patients with low mCD39 expression had significantly lower 28-day survival rates (56.7% vs. 80.6%, p = 0.016).

Conclusions: Low CD39 expression on monocytes might serve as a potential diagnostic biomarker and a strong predictor of poor prognosis in sepsis patients.

Background: Sepsis is characterized by organ dysfunction as a response to infection and is one of the leading causes of mortality and loss of health. The heterogeneous nature of sepsis, along with ethnic differences in susceptibility, challenges a thorough understanding of its etiology. This study aimed to propose prediction models by leveraging genetic-risk scores and clinical variables that can assist in risk stratification of patients.

Methods: A total of 1,403 patients from Taiwan, diagnosed with sepsis, were utilized. Genome-wide survival analysis was conducted, with death within 28 days from sepsis onset, as the primary event to report significantly associated SNPs. A polygenic risk score (PRS-sepsis) was constructed via clumping and thresholding method which was added to clinical-only models to generate better performing prognostic models for identifying high-risk patients. Kaplan-Meier analysis was conducted using PRS-sepsis.

Results: A total of five single-nucleotide-polymorphisms (SNPs) reached genome-wide significance (p < 5e-8), and 86 SNPs reached suggestive significance (p < 1e-5). The prognostic model using PRS-sepsis showed significantly improved performance with c-index [confidence interval (CI)] of 0.79 [0.62-0.96] and area under receiver operating characteristic curve (AUROC) [CI] of 0.78 [0.75-0.80], in comparison to clinical-only prognostic models (c-index [CI] = 0.63 [0.45- 0.81], AUROC [CI] = 0.61 [0.58-0.64]). The ethnic specificity was established for our proposed models by comparing it with models generated using significant SNPs from prior European studies (c-index [CI] = 0.63 [0.42-0.85], AUROC [CI] = 0.60 [0.58-0.63]). Kaplan-Meier plots showed that patient groups with higher PRSs have inferior survival probability compared to those with lower PRSs.

Conclusions: This study proposed genetic-risk models specific for Taiwanese populations that outperformed clinical-only models. Also it established a strong racial-effect on the underlying genetics of sepsis-related mortality. The model can potentially be used in real clinical setting for deciding precise treatment courses for patients at high-risk thereby reducing the possibility of worse outcomes.

Background: Lipoproteins and their component apolipoproteins play an important role in sepsis. However, little is known with regard to the association and causal contribution of these proteins to mortality in patients of different ancestries following septic shock. The objective of this study was to determine whether lipoprotein and apolipoprotein levels, and related genetic variants, are associated with clinical outcomes in septic shock.

Methods: We investigated the association between lipoprotein and apolipoprotein levels at the point of admission to the intensive care unit and in-hospital mortality in 687 Japan patients diagnosed with septic shock. For each clinically significant candidate protein, we extracted haplotype tag single nucleotide polymorphisms (SNPs) of the corresponding gene and examined the association of the candidate gene variants with 28-day mortality and organ dysfunction. We tested for replication in a Caucasian septic shock cohort (Vasopressin and Septic Shock Trial, VASST, n = 474). To determine whether the candidate lipoprotein causally contributed to septic shock outcome, we used a Mendelian randomization analysis based on polygenic scores generated from a genome-wide association study (GWAS) in the Japan cohort.

Results: In the Japan cohort, low apolipoprotein A-II levels were associated with increased septic shock mortality (adjusted odds ratio, 1.05; 95%CI, 1.02-1.09; P < 0.001). For a haplotype tag SNP of the corresponding ApoA2 gene, rs6413453 GG carriers had significantly higher 28-day mortality (adjusted hazard ratio [aHR], 1.79; 95% confidence interval [CI], 1.06-3.04; P = 0.029) and significantly fewer days free of cardiovascular, respiratory, renal and neurologic dysfunction than AG/AA carriers. This result was replicated in the Caucasian septic shock cohort (28-day mortality: aHR, 1.65; 95% CI, 1.02-2.68; P = 0.041). Mendelian randomization using 9 SNPs from an apolipoprotein A-II GWAS suggested that genetically decreased levels of apolipoprotein A-II were a causal factor for increased mortality in septic shock (odds ratio for mortality due to a 1 mg/dL decrease in apolipoprotein A-II is 1.05 [95% CI; 1.01-1.03, P = 0.0022]).

Conclusions: In septic shock, apolipoprotein A-II levels and ApoA2 genetic variations are important factors associated with outcome.

Purpose: Acute respiratory distress syndrome (ARDS) is a prevalent respiratory condition associated with significant mortality. Current literature on ARDS epidemiology reports a wide range of incidence (7.2-78.9/100,000 population/year), hospital mortality (32-51%), and associated costs ($8476-$547,974). We have analyzed epidemiological trends of mechanically ventilated ARDS (MV-ARDS) in Spain from 2000 to 2022 using the Minimum Basic Data Set (MBDS), focusing on MV-ARDS incidence, associated mortality, and economic impact.

Methods: We conducted a nationwide, population-based retrospective study of all hospitalizations for MV-ARDS in Spanish hospitals-from January 1, 2000 to December 31, 2022-using MBDS records, with an estimated coverage of 99.5%. The study reports MV-ARDS incidence per 100,000 population/year, hospital mortality rate, and mean cost per patient. We also considered the effect of COVID-19 on MV-ARDS epidemiology.

Results: We analyzed 93,192 records of patients with a new diagnosis of MV-ARDS during the study period. MV-ARDS incidence ranged from 2.96 to 20.14/100,000 population-years, peaking in 2021. Mortality ranged between 38.0 and 55.0%, showing a declining trend, while the cost per patient increased, stabilizing ~€30,000-€40,000 after reaching a peak of €42,812 in 2011. During the COVID-19 pandemic, hospital stay lengthened (p < 0.001), while hospital mortality decreased (p < 0.001). There was an increased proportion of patients with obesity and diabetes mellitus, with fungal or viral etiologies.

Conclusion: This is the largest epidemiological study on ARDS in Europe. MV-ARDS incidence has stabilized in recent years, with mortality showing a declining trend. ARDS-related costs have increased nearly fourfold. MBDS data could enhance ARDS understanding and guide future studies.

Background: Neurological outcomes after out-of-hospital cardiac arrest (OHCA) depend on multiple factors, including the patient's baseline condition and post-arrest management. The SLANT, developed specifically for OHCA survivors treated with targeted temperature management (TTM), requires further validation, particularly in Asian populations.

Methods: This multicenter retrospective cohort study analyzed data from 2016 to 2023, examining demographics, pre-arrest conditions, resuscitation events, and laboratory biomarkers following TTM. The primary outcome was defined as a poor neurological outcome at hospital discharge. Model performance was assessed using the area under the receiver operating characteristic curve. Multivariate logistic regression analysis was used to analyze the included variables.

Results: A total of 448 eligible adult patients were included, of whom 77.9% experienced poor neurological outcomes at discharge. The performance of the current cohort was comparable to that of the original SLANT cohort, achieving an area under the curve of 0.797 (95% confidence interval: 0.746-0.849). All five factors of the SLANT score remained statistically significant in predicting poor neurological outcomes. At a cutoff of ≥ 6.5, the SLANT score demonstrated a specificity of 53.5% and positive predictive value (PPV) of 86.9%. Increasing the cutoff value to 8.5 improved the specificity to 66.7% and the PPV to 89.6%.

Conclusion: The SLANT showed high PPV for predicting poor neurological outcomes at discharge in patients with OHCA undergoing TTM across a multicenter Asian cohort. Combining the score with other neurological assessments is recommended for improved neuroprognostication.