Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock.

BACKGROUND: Sepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. OBJECTIVE: The aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). METHODS: A retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. RESULTS: One hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. CONCLUSIONS: Receipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Wogonin alleviates sepsis-induced acute lung injury by modulating macrophage polarization through the SIRT1-FOXO1 pathways.

Sepsis-induced acute lung injury is a common and severe complication of sepsis, for which effective treatments are currently lacking. Previous studies have demonstrated the influence of wogonin in treating acute lung injury (ALI). However, its precise mechanism of action remains unclear. To delve deeper into the mechanisms underlying wogonin's impacts in sepsis-induced acute lung injury, we established a mouse sepsis model through cecal ligation and puncture and conducted further cell experiments using lipopolysaccharide-treated MH-S and MLE-12 cells to explore wogonin's potential mechanisms of action in treating ALI. Our results revealed that wogonin significantly increased the survival rate of mice, alleviated pulmonary pathological damage and inflammatory cell infiltration, and activated the SIRT1-FOXO1 pathway. Additionally, wogonin suppressed the release of pro-inflammatory factors by M1 macrophages and induced the activation of M2 anti-inflammatory factors. Further in vitro studies confirmed that wogonin effectively inhibited M1 macrophage polarization through the activation of the SIRT1-FOXO1 pathway, thereby mitigating lung pathological changes caused by ALI. In summary, our study demonstrated that wogonin regulated macrophage M1/M2 polarization through the activation of the SIRT1-FOXO1 pathway, thereby attenuating the inflammatory response and improving pulmonary pathological changes induced by sepsis-induced ALI. This discovery provided a solid mechanistic foundation for the therapeutic use of wogonin in sepsis-induced ALI, shedding new light on potential strategies for the treatment of sepsis-induced ALI.

Biomarker Assessment of a High-Risk, Data-Driven Pediatric Sepsis Phenotype Characterized by Persistent Hypoxemia, Encephalopathy, and Shock.

OBJECTIVES: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata. DESIGN: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata. SETTING: Twenty-five PICUs across the United States. PATIENTS: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS. CONCLUSIONS: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.

Upregulation of PGC-1α expression by pioglitazone mediates prevention of sepsis-induced acute lung injury.

The imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages plays a critical role in the pathogenesis of sepsis-induced acute lung injury (ALI). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) may modulate macrophage polarization toward the M2 phenotype by altering mitochondrial activity. This study aimed to investigate the role of the PGC-1α agonist pioglitazone (PGZ) in modulating sepsis-induced ALI. A mouse model of sepsis-induced ALI was established using cecal ligation and puncture (CLP). An in vitro model was created by stimulating MH-S cells with lipopolysaccharide (LPS). qRT-PCR was used to measure mRNA levels of M1 markers iNOS and MHC-II and M2 markers Arg1 and CD206 to evaluate macrophage polarization. Western blotting detected expression of peroxisome proliferator-activated receptor gamma (PPARγ) PGC-1α, and mitochondrial biogenesis proteins NRF1, NRF2, and mtTFA. To assess mitochondrial content and function, reactive oxygen species levels were detected by dihydroethidium staining, and mitochondrial DNA copy number was measured by qRT-PCR. In the CLP-induced ALI mouse model, lung tissues exhibited reduced PGC-1α expression. PGZ treatment rescued PGC-1α expression and alleviated lung injury, as evidenced by decreased lung wet-to-dry weight ratio, pro-inflammatory cytokine secretion (tumor necrosis factor-α, interleukin-1ß, interleukin-6), and enhanced M2 macrophage polarization. Mechanistic investigations revealed that PGZ activated the PPARγ/PGC-1α/mitochondrial protection pathway to prevent sepsis-induced ALI by inhibiting M1 macrophage polarization. These results may provide new insights and evidence for developing PGZ as a potential ALI therapy.

Persistent high sepsis-induced coagulopathy and sequential organ failure assessment scores can predict the 28-day mortality of patients with sepsis: A prospective study.

BACKGROUND: The performance of the sepsis-induced coagulopathy (SIC) and sequential organ failure assessment (SOFA) scores in predicting the prognoses of patients with sepsis has been validated. This study aimed to investigate the time course of SIC and SOFA scores and their association with outcomes in patients with sepsis. METHODS: This prospective study enrolled 209 patients with sepsis admitted to the emergency department. The SIC and SOFA scores of the patients were assessed on days 1, 2, and 4. Patients were categorized into survivor or non-survivor groups based on their 28-day survival. We conducted a generalized estimating equation analysis to evaluate the time course of SIC and SOFA scores and the corresponding differences between the two groups. The predictive value of SIC and SOFA scores at different time points for sepsis prognosis was evaluated. RESULTS: In the non-survivor group, SIC and SOFA scores gradually increased during the first 4 days (P < 0.05). In the survivor group, the SIC and SOFA scores on day 2 were significantly higher than those on day 1 (P < 0.05); however, they decreased on day 4, dropping below the levels observed on day 1 (P < 0.05). The non-survivors showed higher SIC scores on days 2 (P < 0.05) and 4 (P < 0.001) than the survivors, whereas no significant differences were found between the two groups on day 1 (P > 0.05). The performance of SIC scores on day 4 for predicting mortality was more accurate than that on day 2, with areas under the curve of 0.749 (95% confidence interval [CI]: 0.674-0.823), and 0.601 (95% CI: 0.524-0.679), respectively. The SIC scores demonstrated comparable predictive accuracy for 28-day mortality to the SOFA scores on days 2 and 4. Cox proportional hazards models indicated that SIC on day 4 (hazard ratio [HR] = 3.736; 95% CI: 2.025-6.891) was an independent risk factor for 28-day mortality. CONCLUSIONS: The time course of SIC and SOFA scores differed between surviving and non-surviving patients with sepsis, and persistent high SIC and SOFA scores can predict 28-day mortality.

Assessment of urine CCL2 as a potential diagnostic biomarker for acute kidney injury and septic acute kidney injury in intensive care unit patients.

Acute kidney injury (AKI) is a prevalent and serious condition in the intensive care unit (ICU), associated with significant morbidity and mortality. Septic acute kidney injury (SAKI) contributes substantially to AKI cases in the ICU. However, current diagnostic methods have limitations, necessitating the exploration of novel biomarkers. In this study, we investigated the potential of plasma and urine CCL2 levels as diagnostic markers for AKI and SAKI in 216 ICU patients. Our findings revealed significant differences in plasma (p < 0.01) and urine CCL2 (p < 0.0001) levels between AKI and non-AKI patients in the ICU. Notably, urine CCL2 demonstrated promising predictive value for AKI, exhibiting high specificity and sensitivity (AUC = 0.8976; p < 0.0001). Furthermore, we observed higher urine CCL2 levels in SAKI compared to non-septic AKI (p < 0.001) and urine CCL2 could also differentiate SAKI from non-septic AKI (AUC = 0.7597; p < 0.0001). These results suggest that urine CCL2 levels hold promise as early biomarkers for AKI and SAKI, offering valuable insights for timely intervention and improved management of ICU patients.

Diastology in the intensive care unit: Challenges for the assessment and future directions.

Myocardial dysfunction is common in patients admitted to the intensive care unit (ICU). Septic disease frequently results in cardiac dysfunction, and sepsis represents the most common cause of admission and death in the ICU. The association between left ventricular (LV) systolic dysfunction and mortality is not clear for critically ill patients. Conversely, LV diastolic dysfunction (DD) seems increasingly recognized as a factor associated with poor outcomes, not only in sepsis but also more generally in critically ill patients. Despite recent attempts to simplify the diagnosis and grading of DD, this remains relatively complex, with the need to use several echocardiographic parameters. Furthermore, the current guidelines have several intrinsic limitations when applied to the ICU setting. In this manuscript, we discuss the challenges in DD classification when applied to critically ill patients, the importance of left atrial pressure estimates for the management of patients in ICU, and whether the study of cardiac dysfunction spectrum during critical illness may benefit from the integration of left ventricular and left atrial strain data to improve diagnostic accuracy and implications for the treatment and prognosis.

Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

Nicotinamide mononucleotide alleviates endotoxin-induced acute lung injury by modulating macrophage polarization via the SIRT1/NF-κB pathway.

CONTEXT: Sepsis-induced acute lung injury (ALI) is a severe condition with limited effective therapeutics; nicotinamide mononucleotide (NMN) has been reported to exert anti-inflammatory activities. OBJECTIVE: This study explores the potential mechanisms by which NMN ameliorates sepsis-induced ALI in vivo and in vitro. MATERIALS AND METHODS: Cultured MH-S cells and a murine model were used to evaluate the effect of NMN on sepsis-induced ALI. MH-S cells were stimulated with LPS (1 µg/mL) and NMN (500 µM) for 12 h grouping as control, LPS, and LPS + NMN. Cell viability, apoptotic status, and M1/2 macrophage-related markers were detected. The mice were pretreated intraperitoneally with NMN (500 mg/kg) and/or EX-527 (5 mg/kg) 1 h before LPS injection and randomized into 7 groups (n = 8): control, LPS, LPS + NMN, NMN, LPS + NMN + EX-527 (a SIRT1 inhibitor), LPS + EX-527, and EX-527. After 12 h, lung histopathology, W/D ratio, MPO activity, NAD+ and ATP levels, M1/2 macrophage-related markers, and expression of the SIRT1/NF-κB pathway were detected. RESULTS: In MH-S cells, NMN significantly decreased the apoptotic rate from 12.25% to 5.74%. In septic mice, NMN improved the typical pathologic findings in lungs and reduced W/D ratio and MPO activity, but increased NAD+ and ATP levels. Additionally, NMN suppressed M1 but promoted M2 polarization, and upregulated the expression of SIRT1, with inhibition of NF-κB-p65 acetylation and phosphorylation. Furthermore, inhibition of SIRT1 reversed the effects of NMN-induced M2 macrophage polarization. CONCLUSIONS: NMN protects against sepsis-induced ALI by promoting M2 macrophage polarization via the SIRT1/NF-κB pathway, it might be an effective strategy for preventing or treating sepsis-induced ALI.

Usefulness of the Quick-Sepsis Organ Failure Assessment Score in Cardiovascular Intensive Care Unit to Predict Prognosis in Acute Coronary Syndrome.

Triage of patients with acute coronary syndrome (ACS) at high risk of in-hospital complications is essential. In this study, we evaluated the quick sepsis organ failure assessment (qSOFA) score as a tool for predicting the prognosis of 964 patients admitted to the cardiovascular intensive care unit (CICU) with ACS over a 4-year period. In total, out of 964 patients included, with a percentage of 4.6% for 30-day mortality. The risk of 30-day mortality was independently associated with qSOFA ≥ 2 at admission (hazard ratio = 2.76, 95% CI 1.32-5.74, p = 0.007). For MACEs, qSOFA ≥ 2 at admission was a predictive factor with (odds ratio = 2.42, 95% CI 1.37-4.36, p = .002). A qSOFA ≥ 2 on admission had an AUC of 0.729 (95% CI [0.694, 0.762]), with a good specificity of 91.6%. For 30-day mortality, an AUC of 0.759 (95%CI [0.726, 0.792]) for cardiogenic shock with specificity of 92.5%. For MACEs, an AUC of 0.702 (95% CI [0.64, 0.700] with a specificity of 95%. Concerning the different scores tested, we found no significant difference between the Zwolle score and the qSOFA score for predicting prognosis, whereas the CADILLAC score was better than qSOFA for predicting 30-day mortality (AUC = 0.829 and De long test = 0.03). However, there was no difference between qSOFA and CADILLAC scores for predicting cardiogenic shock (De Long test at 0.08). This is the first study to evaluate qSOFA as a predictive score for 30-day mortality and MACEs, and the results are very encouraging, particularly for cardiogenic shock.

Missing Narrative: Examining the Impact of Disability on Post-Operative Infectious Complications.

Background: More than 20% of the population in the United States suffers from a disability, yet the impact of disability on post-operative outcomes remains understudied. This analysis aims to characterize post-operative infectious complications in patients with disability. Patients and Methods: This was a retrospective review of the National Readmission Database (2019) among patients undergoing common general surgery procedures. As per the U.S. Centers for Disease Control and Prevention (CDC), disability was defined as severe hearing, visual, intellectual, or motor impairment/caregiver dependency. A propensity-matched analysis comparing patients with and without a disability was performed to compare outcomes, including post-operative septic shock, sepsis, bacteremia, pneumonia, catheter-associated urinary tract infection (CAUTI), urinary tract infection (UTI), catheter-associated blood stream infection, Clostridioides Difficile infection, and superficial, deep, and organ/space surgical site infections during index hospitalization. Patients were matched using age, gender, comorbidities, illness severity, income, neighborhood, insurance, elective procedure, and the hospital's bed size and type. Results: A total of 710,548 patients were analysed, of whom 9,451(1.3%) had at least one disability. Motor disability was the most common (3,762; 40.5%), followed by visual, intellectual, and hearing impairment. Patients with disability were older (64 vs. 57 years; p < 0.001), more often insured under Medicare (65.2% vs. 37.3% p < 0.001) and had more medical comorbidities (Elixhauser comorbidity score ≥3; 69.2% vs. 41.9%; p < 0.001). After matching, 9,292 pairs were formed. Patients with a disability had a higher incidence of pneumonia (10.1% vs. 6.5%; p < 0.001), aspiration pneumonia (5.2% vs. 1.4%; p < 0.001), CAUTI (1.0% vs. 0.4%; p < 0.001), UTI (10.4% vs. 6.2%; p < 0.001), and overall infectious complications (21.8% vs. 14.5%; p < 0.001). Conclusions: Severe intellectual, hearing, visual, or motor impairments were associated with a higher incidence of infectious complications. Further investigation is needed to develop interventions to reduce disparities among this high-risk population.

Does Semaglutide Use Decrease Complications and Costs Following Total Knee Arthroplasty?

BACKGROUND: Diabetes mellitus (DM) and obesity are associated with total knee arthroplasty (TKA) complications. Semaglutide, a medication for DM and weight loss, can potentially affect TKA outcomes. This study investigated whether semaglutide use during TKA demonstrates fewer: (1) medical complications; (2) implant-related complications; (3) readmissions; and (4) costs. METHODS: A retrospective query was performed using a National database to 2021. Patients undergoing TKA for osteoarthritis with DM and semaglutide use were successfully propensity score-matched to controls semaglutide = 7,051; control = 34,524. Outcomes included 90-day postoperative medical complications, 2-year implant-related complications, 90-day readmissions, in-hospital lengths of stay, and costs. Multivariate logistical regressions calculated odds ratios (ORs), 95% confidence intervals, and P values (P < .003 as significance threshold after Bonferroni correction). RESULTS: Semaglutide cohorts had higher incidence and odds of myocardial infarction (1.0 versus 0.7%; OR 1.49; P = .003), acute kidney injury (4.9 versus 3.9%; OR 1.28; P < .001), pneumonia (2.8 versus 1.7%; OR 1.67; P < .001), and hypoglycemic events (1.9 versus 1.2%; OR 1.55; P < .001), but lower odds of sepsis (0 versus 0.4%; OR 0.23; P < .001). Semaglutide cohorts also had lower odds of prosthetic joint infections (2.1 versus 3.0%; OR 0.70; P < .001) and readmission (7.0 versus 9.4%; OR 0.71; P < .001), and trended toward lower odds of revisions (4.0 versus 4.5%; OR 0.86; P = .02) and 90-day costs ($15,291.66 versus $16,798.46; P = .012). CONCLUSION: Semaglutide use during TKA decreased risk for sepsis, prosthetic joint infections, and readmissions, but also increased risk for myocardial infarction, acute kidney injury, pneumonia, and hypoglycemic events.

Validation of National Early Warning Score and Quick Sequential (sepsis-related) Organ Failure Assessment in acute myeloid leukaemia patients treated with intensive chemotherapy.

OBJECTIVES: Chemotherapy-induced neutropenia in acute myeloid leukaemia (AML) is a risk factor for life-threatening infections. Early diagnosis and prompt interventions are associated with better outcomes, but the prediction of infection severity remains an open question. Recently, National Early Warning Score (NEWS) and quick sequential organ failure assessment (qSOFA) scores were proposed as warning clinical instruments predicting in-hospital mortality, but their role in the haematological context is still unknown. METHODS: We retrospectively assess the predictive role of NEWS and qSOFA in a large and homogeneous cohort of adult AML patients treated with intensive chemotherapy. In a total of 1048 neutropenic episodes recorded in 334 consecutive patients, the scores were applied to predict outcomes on the same day of fever onset, and after 24 and 48 h from score calculation. RESULTS: Both NEWS and qSOFA significantly predicted death, with more accuracy on the same day (NEWS AUROC 0.984 and qSOFA AUROC 0.969) and after 24 h (NEWS AUROC 0.928 and qSOFA AUROC 0.887), while remained moderately accurate after 48 h. Furthermore, also ICU admission was accurately predicted at fever onset and after 24 h. CONCLUSIONS: Both scores were useful tools in the management of post chemotherapy neutropenic febrile AML patients.

The role of cerebrospinal fluid levels of neutrophil gelatinase-associated lipocalin (NGAL) and electroencephalography in the assessment of impaired consciousness in the context of infection.

INTRODUCTION: The sepsis syndrome is potentially affecting several organs and systems irrespectively of the primary source of the infection. Alterations of the brain function in sepsis patients may result either from a primary central nervous system (CNS) infection or could be part of the sepsis-associated encephalopathy (SAE), a common complication of sepsis, characterized by a diffuse dysfunction of the brain due to an infection elsewhere in the body without overt CNS infection. Aim of the study was to evaluate the usefulness of electroencephalography and the biomarker neutrophil gelatinase-associated lipocalin (NGAL) when measured in the cerebrospinal fluid (CSF) in the management of these patients. METHODS: Patients presenting at the emergency department with altered mental status and signs of infection were included in this study. Among initial assessment and treatment of the patients based on the international guidelines for treating sepsis, NGAL was measured in the cerebrospinal fluid (CSF) using ELISA technique. Electroencephalography was performed when possible within 24 hours after admission and EEG abnormalities were recorded. RESULTS: 32 of 64 patients included in this study were diagnosed with central nervous system (CNS) infection. CSF NGAL was significantly higher in patients with CNS infection compared to patients without CNS infection (18.1 [5.1-71.1] vs 3.6 [1.2-11.6]; p<0.001). There was a trend for higher CSF NGAL in patients with EEG abnormalities, which did not reach statistical significance (p=0.106). CSF NGAL levels were similar between survivors and non-survivors (medians: 7.04 vs 11.79). CONCLUSION: In patients presenting at the emergency department with altered mental status and signs of infection, CSF NGAL was significantly higher in patients with CSF infection. Its role in this acute setting should be evaluated further. CSF NGAL could be suggestive of EEG abnormalities.

Sepsis, critical illness, communication, swallowing and Sustainable Development Goals 3, 4, 10.

PURPOSE: Sepsis is a major global health problem with an estimated 49 million cases globally each year causing as many as 11 million deaths. The primary objective of this commentary is to describe the impacts of sepsis and critical illness on communication and swallowing function, and to discuss management strategies considering the Sustainable Development Goals (SDGs). RESULT: Communication and swallowing disabilities can occur with sepsis and critical illness. A holistic framework to optimise function, recovery, and future research priorities across the lifespan can be developed through the SDGs. CONCLUSION: Communication and swallowing disabilities following critical illness associated with sepsis have global impacts. Early multidisciplinary engagement is key to optimising individuals' function. Collaborative research, education, and public awareness is urgently needed to increase equity in health outcomes across populations. This commentary paper supports progress towards good health and well-being (SDG 3), quality education (SDG 4) and reduced inequalities (SDG 10).

Prediction and risk assessment of sepsis-associated encephalopathy in ICU based on interpretable machine learning.

Sepsis-associated encephalopathy (SAE) is a major complication of sepsis and is associated with high mortality and poor long-term prognosis. The purpose of this study is to develop interpretable machine learning models to predict the occurrence of SAE after ICU admission and implement the individual prediction and analysis. Patients with sepsis admitted to ICU were included. SAE was diagnosed as glasgow coma score (GCS) less than 15. Statistical analysis at baseline was performed between SAE and non-SAE. Six machine learning classifiers were employed to predict the occurrence of SAE, and the adjustment of model super parameters was performed by using Bayesian optimization method. Finally, the optimal algorithm was selected according to the prediction efficiency. In addition, professional physicians were invited to evaluate our model prediction results for further quantitative assessment of the model interpretability. The preliminary analysis of variance showed significant differences in the incidence of SAE among patients with pathogen infection. There were significant differences in physical indicators like respiratory rate, temperature, SpO2 and mean arterial pressure (P < 0.001). In addition, the laboratory results were also significantly different. The optimal classification model (XGBoost) indicated that the best risk factors (cut-off points) were creatinine (1.1 mg/dl), mean respiratory rate (18), pH (7.38), age (72), chlorine (101 mmol/L), sodium (138.5 k/ul), SAPSII score (23), platelet count (160), and phosphorus (2.4 and 5.0 mg/dL). The ranked features derived from the best model (AUC is 0.8837) were mechanical ventilation, duration of mechanical ventilation, phosphorus, SOFA score, and vasopressin usage. The SAE risk prediction model based on XGBoost created here can make very accurate predictions using simple indicators and support the visual explanation. The interpretable model was effectively evaluated by professional physicians and can help them predict the occurrence of SAE more intuitively.

[Research Progress in Clinical Electrophysiological Assessment of Patients with Sepsis-Associated Encephalopathy].

Sepsis-associated encephalopathy(SAE) caused by infections outside the central nervous system always presents extensive brain damage.It is common in clinical practice and associated with a poor prognosis.There are problems in the assessing and diagnosing of SAE.Many factors,such as sedation and mechanical ventilation,make it difficult to assess SAE,while electrophysiological examination may play a role in the assessment.We reviewed the studies of electrophysiological techniques such as electroencephalography and somatosensory evoked potentials for monitoring SAE,hoping to provide certain evidence for the clinical evaluation and diagnosis of SAE.

The Quick Sepsis-Related Organ Failure Assessment Score Is Prognostic of Pancreatitis Severity in Patients With Alcohol-Induced Pancreatitis.

OBJECTIVES: The aim of this study was to determine if the quick Sepsis-Related Organ Failure Assessment (qSOFA) score assessed at and 48 hours after admission is prognostic for alcohol-induced acute pancreatitis (AAP) severity. METHODS: This is a retrospective cohort review study of 161 patients admitted to a single academic hospital in Houston, TX, with the diagnosis of AAP. Receiver operator characteristics analysis and logistic regression were used to assess the diagnostic accuracy and prognostic ability of the qSOFA score. RESULTS: A qSOFA score of 2 or higher at and 48 hours after admission had a specificity of 94% or greater and sensitivity of 33% or higher for pancreatitis severity and need for intensive care admission, intubation, or vasopressors. The qSOFA score at and 48 hours after admission was prognostic of intensive care unit admission by an adjusted odds ratio of 48.5 (95% confidence interval [CI], 6.4-1013.3; P < 0.001) and 18.8 (95% CI, 2.2-467.3; P < 0.05), respectively. The qSOFA score at admission was prognostic of severe pancreatitis by an adjusted odds ratio of 35.3 (95% CI, 7.2-224.3; P < 0.001). CONCLUSIONS: A qSOFA score of 2 or higher is highly specific and prognostic of multiple clinical outcomes both at and 48 hours after admission in patients with AAP.

Prognostic value of serial score measurements of the national early warning score, the quick sequential organ failure assessment and the systemic inflammatory response syndrome to predict clinical outcome in early sepsis.

BACKGROUND AND IMPORTANCE: Sepsis is a common and potentially lethal syndrome, and early recognition is critical to prevent deterioration. Yet, currently available scores to facilitate recognition of sepsis lack prognostic accuracy. OBJECTIVE: To identify the optimal time-point to determine NEWS, qSOFA and SIRS for the prediction of clinical deterioration in early sepsis and to determine whether the change in these scores over time improves their prognostic accuracy. DESIGN: Post hoc analysis of prospectively collected data. SETTINGS AND PARTICIPANTS: This study was performed in the emergency department (ED) of a tertiary-care teaching hospital. Adult medical patients with (potential) sepsis were included. OUTCOME MEASURES AND ANALYSIS: The primary outcome was clinical deterioration within 72 h after admission, defined as organ failure development, the composite outcome of ICU-admission and death. Secondary outcomes were the composite of ICU-admission/death and a rise in SOFA at least 2. Scores were calculated at the ED with 30-min intervals. ROC analyses were constructed to compare the prognostic accuracy of the scores. RESULTS: In total, 1750 patients were included, of which 360 (20.6%) deteriorated and 79 (4.5%) went to the ICU or died within 72 h. The NEWS at triage (AUC, 0.62; 95% CI, 0.59-0.65) had a higher accuracy than qSOFA (AUC, 0.60; 95% CI, 0.56-0.63) and SIRS (AUC, 0.59; 95% CI, 0.56-0.63) for predicting deterioration. The AUC of the NEWS at 1 h (0.65; 95% CI, 0.63-0.69) and 150 min after triage (0.64; 95% CI, 0.61-0.68) was higher than the AUC of the NEWS at triage. The qSOFA had the highest AUC at 90 min after triage (0.62; 95% CI, 0.58-0.65), whereas the SIRS had the highest AUC at 60 min after triage (0.60; 95% CI, 0.56-0.63); both are not significantly different from triage. The NEWS had a better accuracy to predict ICU-admission/death <72 h compared with qSOFA (AUC difference, 0.092) and SIRS (AUC difference, 0.137). No differences were found for the prediction of a rise in SOFA at least 2 within 72 h between the scores. Patients with the largest improvement in any of the scores were more prone to deteriorate. CONCLUSION: NEWS had a higher prognostic accuracy to predict deterioration compared with SIRS and qSOFA; the highest accuracy was reached at 1 h after triage.