To investigate the association between renal mean perfusion pressure (MPP) and prognosis in sepsis-associated acute kidney injury (SA-AKI).

Data were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Group-based trajectory modeling (GBTM) was applied to identify dynamic MPP patterns, while restricted cubic spline (RCS) curves were utilized to confirm the non-linear relationship between MPP and mortality. Cox regression analysis assessed the risk of mortality across different MPP levels, adjusting for potential confounders. Subgroup analyses and sensitivity analyses were conducted to ensure the robustness of the findings.

A total of 2318 patients with SA-AKI were stratified into five MPP trajectories by GBTM. Patients in Traj-1 and Traj-2, characterized by consistently low MPP (<60 mmHg), demonstrated markedly higher 90-d mortality (62.86% and 26.98%). RCS curves revealed a non-linear inverse relationship between MPP and 90-d mortality, identifying 60 mmHg as the optimal threshold. Patients with MPP ≤ 60 mmHg exhibited significantly elevated 90-d mortality compared to those with MPP > 60 mmHg (29.81% vs. 20.88%). Cox regression analysis established Traj-1 and Traj-2 as independent risk factors for increased mortality relative to Traj-3 (60-70 mmHg), with hazard ratios (HRs) of 4.67 (95%-CI 3.28-6.67) and 1.45 (95%-CI 1.20-1.76). MPP > 60 mmHg was significantly associated with reduced 90-d mortality (HR 0.65, 95%-CI 0.55-0.77). Subgroup and PSM analyses supported these findings.

Dynamic MPP trajectory serves as a valuable prognostic biomarker for SA-AKI. Early monitoring of MPP trends offers critical insights into renal perfusion management, potentially improving outcomes in SA-AKI.

Sepsis is an uncontrolled systemic response to infection that leads to life-threatening organ dysfunction. The in-hospital mortality rate remains significantly high in septic shock patients with malignancies. This study investigates whether early and high-volume administration of sodium bicarbonate during continuous renal replacement therapy (CRRT) can reduce 28-day mortality, increase shock reversal rates, and shorten the duration of CRRT, mechanical ventilation, and intensive care unit (ICU) stays. The goal is to provide valuable clinical data for the management of cancer patients with sepsis-associated acute kidney injury (SAKI).

A retrospective study was performed on 88 patients who were admitted to the ICU and received continuous renal replacement therapy (CRRT) for acute renal failure secondary to sepsis at the Cancer Center of Sun Yat-sen University from March 2010 to October 2021. Based on the initiation time of CRRT and the volume of sodium bicarbonate infusion, patients were divided into four groups: the early high-volume group, early low-volume group, late high-volume group, and late low-volume group.

The results of this study showed that in the 28-day mortality model, established using the Cox proportional hazards method, early CRRT (HR 0.473; 95% CI 0.245-0.915, p = 0.026) and high-volume sodium bicarbonate infusion (HR 0.173; 95% CI 0.078-0.383, p < 0.001) were identified as two independent protective factors. The 28-day mortality rate in the early high-volume group (15.0%) was significantly lower than that of the other three groups (60.0%, 30.0%, and 75.0%, respectively; χ2 = 23.822, p < 0.001). Additionally, the shock reversal rate in the early high-volume group (80.0%) was significantly higher compared to the other groups (35.0%, 45.0%, and 35.7%; χ2 =13.576, p = 0.004). The duration of CRRT was shorter in the early high-volume group (35.0 ± 4.45 h) than in the other groups (70.0 ± 30.19 h, 48.0 ± 5.22 h, and 72.0 ± 19.84 h; χ2 =11.278, p = 0.01). Furthermore, the duration of mechanical ventilation (7.0 ± 3.33 days) was lower in the early high-volume group compared to the other groups (8.0 ± 1.12 days,10.0 ± 1.11 days, and 8.0 ± 2.65 days; χ2 =8.064, p = 0.045), as was the length of ICU stay (7.0 ± 0.89 days) compared to the other groups (13.0 ± 3.35 days, 10.0 ± 1.49 days, and10.0 ± 3.70 days; χ2 = 9.184, p = 0.027).

Early and high-volume administration of sodium bicarbonate during CRRT may reduce 28-day mortality and improve shock reversal rates in patients with sepsis-associated acute kidney injury complicated by malignancy. Prospective randomized controlled large sample studies are needed to confirm this.

Sepsis is a non-discriminatory inflammatory reaction that can result in a diverse array of organ dysfunctions, which can be fatal. Pyroptosis is a programmed mechanism of cell death that is distinguishable from apoptosis and other forms of cellular demise. However, the role of pyroptosis in sepsis remains to be further explored. In this study, by employing a combination of the difference analysis, WGCNA, Friends' analysis, and machine learning, the central gene S100A12 was successfully identified. S100A12 demonstrated superb diagnostic capabilities in both the integrated and external validation datasets. Furthermore, significant disparities were observed in the levels of monocytes, eosinophils, and neutrophils between sepsis patients and the control group, as per the findings of immune infiltration analysis. The aforementioned immune infiltrating cells exhibited an increase in expression levels among patients diagnosed with sepsis and were found to be significantly and positively associated with S100A12 expression. The results of the single-cell analysis indicated a significant expression of S100A12 in both neutrophils and monocytes, which was in complete alignment with the outcomes of immune infiltration. In summary, the pyroptosis-related gene S100A12 represents a potential biomarker for the diagnosis and treatment of sepsis.

Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines.

An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data.

A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87 h [95%CI - 1.23 h to - 0.51 h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11 ml [95%CI - 5.93 ml to 1.72 ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03 days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome.

POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU.

Sepsis is a life-threatening condition characterized by systemic inflammation and microcirculatory dysfunction. Methylene blue (MB), a compound with known antioxidant and anti-inflammatory properties, has been proposed as a potential therapeutic agent. This study aimed to investigate the effects of MB on survival rates and the preservation of mesenteric microcirculation in a rat model of endotoxemia. A total of 36 rats underwent cecal ligation and puncture (CLP) surgery to induce varying degrees of sepsis: mild (4 perforations), moderate (10 perforations), and severe (20 perforations). Animals received intravenous treatment with either MB (4 mg/kg) or saline. Survival was monitored for ten days. Additionally, intravital microscopy was used to assess leukocyte rolling and adhesion in mesenteric vessels following lipopolysaccharide (LPS)-induced sepsis. The experimental groups included saline, LPS + saline, MB + saline, LPS + MB, and MB + LPS. MB treatment significantly improved survival in the severe sepsis group, with a 30 % survival rate at ten days (p = 0.02, 95 % CI: 0.12-0.48), whereas all animals in the severe sepsis + saline group died within nine days. No significant survival benefit was observed in the mild and moderate sepsis groups (mild sepsis: p = 0.45, 95 % CI: 0.08-0.34; moderate sepsis: p = 0.32, 95 % CI: 0.15-0.51). In the LPS-induced model, treatment with both LPS and MB significantly reduced leukocyte rolling and adhesion (p < 0.001, 95 % CI: 0.45-0.75 for rolling; p < 0.03, 95 % CI: 0.30-0.60 for adhesion), with values comparable to those of the control group. In contrast, MB alone had no effect on leukocyte rolling or adhesion.In summary, MB significantly improved survival in severe sepsis and inhibited leukocyte migration in mesenteric vessels. These findings suggest that MB may protect the microcirculation and enhance survival under severe septic conditions, representing a promising therapeutic approach for sepsis management.

Acute kidney injury refers to sudden, potentially reversible, reduction in kidney function. Hypovolaemia is commonly the major risk factor. When acute kidney injury is established, fluid can accumulate leading to fluid overload. Undertaking a rigorous fluid assessment is vital in the management of a patient in hospital with acute kidney injury, as insufficient or excessive fluid can lead to increased morbidity and mortality.

The aim of this scoping review is to identify which clinical assessments are useful when undertaking fluid assessment in a patient with acute kidney injury, and to identify signs and symptoms of fluid overload or dehydration in patients in hospital with acute kidney injury.

The JBI methodology for scoping reviews was followed and reported using the PRISMA-ScR checklist. PubMed, CINAHL Plus and SCOPUS were searched for research papers relating to the signs and symptoms or fluid assessments in patients with acute kidney injury.

Fifteen research papers were identified with four key areas being: Fluid balance/urine output and weight; early warning scores; clinical signs and symptoms; holistic assessment. The primary studies included in this scoping review have shown that hypovolaemia may be indicated by low blood pressure, orthostatic hypotension, low Mean Arterial Pressure, elevated heart rate, prolonged capillary refill time on the sternum (> 4.5 s) and subjectively reported cold peripheries. With clinical symptoms including dry mouth, increased thirst and dry skin. Accurate documentation of urine output and fluid balance is crucial in determining fluid status.

The assessment of fluid should be holistic and include history taking, diagnosis, blood tests and associated clinical signs and symptoms.

Prompt recognition and treatment of patients with sepsis improve survival. Patients transported to hospital with sepsis often do not receive treatment until they are assessed in emergency departments. Initiation of treatments by paramedics at the point of first contact may improve outcomes for these patients.

The study design involves two randomised controlled trials (RCTs) conducted using a 2×2 factorial design comparing use of (1) early intramuscular ceftriaxone versus placebo and (2) an early liberal intravenous fluid strategy (up to 2 L normal saline) versus usual care resuscitation guided by paramedic medical directives. Patients who are ≥18 years of age will be eligible for inclusion if they have sepsis, defined as (1) paramedic suspicion of infection, (2) fever (temperature ≥38.0°C measured by paramedic or history of fever during the previous 24 hours), and (3) hypotension: SBP <100 mm Hg. The primary outcome is mortality prior to hospital discharge or within 90 days of admission. Secondary outcomes are all-cause mortality at 90 days after enrolment; organ dysfunction during first 24 hours (mechanical ventilation, vasopressor therapy, dialysis) and hospitalisation (mechanical ventilation; dialysis); rates and duration of hospital admission; rates of ICU admission during index hospitalisation; discharge destination; proportion of patients with positive blood cultures obtained in hospital (first 24 hours); microbiological profile including distribution of microorganism species and resistant organisms; proportion of patients receiving additional antibiotics within 6 hours and within 24 hours of hospital admission; frequency distribution of first antibiotics (if any) delivered within 24 hours of hospital arrival; mean time to antibiotics delivered within 24 hours of hospital arrival (if any); proportion of patients receiving fluid bolus (>250 mL) within 24 hours of hospital arrival; total amount of crystalloid infused during transport and first 24 hours of hospitalisation; and proportion of enrolled patients not suspected to have sepsis or infection by emergency department physicians. Safety outcomes include the proportion of patients with pulmonary oedema during transport to hospital and on initial chest X-ray and the proportion of patients with anaphylaxis or suspected allergic reactions to study medication.

This study has been approved through Clinical Trials Ontario's streamlined ethics review process (board of record, Sunnybrook Health Sciences Centre). It will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice guidelines and regulatory requirements. The final results will be disseminated to participating paramedic services through educational materials, presentations and interactive training. We anticipate our trial will achieve wide dissemination through publication in a peer-reviewed medical journal and presentation at international conferences targeting the fields of prehospital and emergency medicine, resuscitation and critical care.

NCT03068741.

Sepsis is a life-threatening organ dysfunction due to a dysfunctional response to infection. Delays in diagnosis have substantial impact on survival. Herein, blood samples from 586 in-house patients with suspected sepsis are used in conjunction with machine learning and cross-validation to define a six-gene expression signature of immune cell reprogramming, termed Sepset, to predict clinical deterioration within the first 24 h (h) of clinical presentation. Prediction accuracy (~90% in early intensive care unit (ICU) and 70% in emergency room patients) is validated in 3178 patients from existing independent cohorts. A RT-PCR-based Sepset detection test shows a 94% sensitivity in 248 patients to predict worsening of the sequential organ failure assessment scores within the first 24 h. A stand-alone centrifugal microfluidic instrument that automates whole-blood Sepset classifier detection is tested, showing a sensitivity of 92%, and specificity of 89% in identifying the risk of clinical deterioration in patients with suspected sepsis.

Lipopolysaccharide (LPS), a bacterial endotoxin prevalent in Gram-negative pathogens (e.g., Escherichia coli), induces severe immune responses linked to endotoxemia and hepatitis. Despite its clinical significance, conventional LPS detection methods (e.g., limulus amebocyte lysate assays) face challenges including operational complexity, high cost, and limited sensitivity. Addressing these limitations necessitates the development of innovative strategies for ultrasensitive LPS quantification.

We present an electrochemical biosensor integrating dual-signal amplification: (1) affinity amplification via phenylboronic acid-cis-diol covalent binding on LPS polysaccharide chains, and (2) photocatalytic amplification using perylene diimide (PDI)-mediated atom transfer radical polymerization (Photo-ATRP) under red light (615-650 nm). Thiol-functionalized DNA aptamers enable specific LPS capture, while PDI catalyzes rapid ferrocene monomer polymerization, achieving exponential signal enhancement. The sensor demonstrates exceptional performance: (1) Ultrahigh sensitivity: Detection limit of 0.25 fg/mL. (2) Wide dynamic range: Linear response from 1.0 fg/mL to 0.1 pg/mL. (3) Robust specificity: Minimal interference in human serum matrices.

This work establishes a paradigm for LPS detection through three key advances: (1) Operational simplicity: Eliminates enzymatic/nanomaterial dependencies via metal-free PDI photocatalysis. (2) Translational utility: Serum compatibility supports clinical diagnostics and point-of-care applications. (3) Catalytic innovation: Validates PDI as a high-efficiency photocatalyst for controlled polymer synthesis. The sensor's low-cost fabrication, rapid response (<4.5 h), and femtomolar sensitivity position it as a transformative tool for sepsis monitoring and biomedical research.

HOX transcript antisense intergenic RNA (HOTAIR) has been implicated in inflammation and vascular pathology, but its role in regulation of ADAM17 and sepsis-induced endothelial injury remains unclear.

LPS-treated human umbilical vein endothelial cells (HUVECs) modeled sepsis-induced endothelial injury, which were assessed via qRT-PCR, western blot and immunofluorescence. HOTAIR-knockout mice were treated with cecal ligation and perforation to establish sepsis model.

LPS-stimulation increased expression of HOTAIR and ADAM17 and decreased miR-326 levels in HUVECs. HOTAIR-knockdown by antisense oligonucleotides (ASOs) decreased ADAM17, TNF-α production and NF-κB activities; it also alleviated endothelial inflammation, VE-cadherin integrity damage, apoptosis and barrier dysfunction, while miR-326 inhibition reversed these effects. MiR-326 inhibited TNF-α/NF-κB via targeting ADAM17. Further experiments demonstrated recombinant TNF-α reversed the inhibitory effect of HOTAIR-ASOs on LPS-triggered TNF-α/NF-κB activation and downstream endothelial injury, which were further mitigated by NF-κB or p38 MAPK inhibitors. In-vivo experiments in HOTAIR-knockout mice confirmed the role of HOTAIR/miR-326/ADAM17 in regulating NF-κB and p38 MAPK inflammation, with improved lung injury and survival following sepsis.

The HOTAIR/miR-326/ADAM17 axis is a key regulator of inflammation, endothelial injury and barrier dysfunction during sepsis via modulation of TNF-α/NF-κB signaling, providing new insights into the mechanisms underlying endothelial injury in sepsis.

Objective : Recent studies have proposed that Krebs cycle metabolites may serve as potential biomarkers for prognosis in sepsis. However, whether these metabolites are associated with disease severity and can be applied to improve the effectiveness of current prognosis assessment in sepsis remains unclear and is explored in this study. Methods : This prospective multicenter cohort study was conducted in medical intensive care units (ICUs). From December 2019 to September 2022, consecutive patients admitted to medical ICUs for sepsis were screened and recruited. Plasma samples were obtained for measurements of cytokines and Krebs cycle metabolites, including citrate/isocitrate, cis-aconitate, alpha-ketoglutarate, succinate, fumarate, and malate. Results : In total, 97 patients admitted for sepsis were enrolled in the study. The 28-day mortality rate was 17.5%, and nonsurvivors exhibited significantly increased plasma lactate levels and Sequential Organ Failure Assessment (SOFA) scores. Plasma levels of Krebs cycle metabolites were significantly correlated with both plasma lactate and interleukin-6 levels. Except for citrate/isocitrate, all Krebs cycle metabolites were significantly elevated in patients with acute kidney injury. Multivariate Cox proportional hazard models, adjusted for plasma lactate levels and SOFA scores, revealed that plasma levels of alpha-ketoglutarate (adjusted hazard ratio [HR]: 2.404, P = 0.002), fumarate (adjusted HR: 1.904, P = 0.001) and malate (adjusted HR: 1.327, P = 0.019) were associated with increased risk of 28-day mortality. Conclusions : Study findings indicate that Krebs cycle metabolites, particularly alpha-ketoglutarate, fumarate, and malate, when applied with SOFA score, might enhance prognostic assessment in patients with sepsis.

Background: Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock. Methods: We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analog to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation. Results: Of 6,763 records, 17 trials (3,813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85-1.00], low certainty, 17 trials [3618 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84-1.01], moderate certainty, eight trials [2,408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17-5.10], low certainty, nine trials [2,981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96-283.17], low certainty, one trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87-1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69-0.97]). The findings were robust to multiple sensitivity and subgroup analyses. Conclusions: In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.

Partially hydrolyzed guar gum (PHGG) protects against intestinal barrier dysfunction and can ameliorate some intestinal diseases. However, whether PHGG has a role in protecting intestinal barrier function (IBF) during sepsis remains unclear. This study aimed to investigate the role and probable mechanism of PHGG in the intestinal mucosa in sepsis. A rat sepsis model was constructed using cecal ligation and puncture (CLP). FITC-dextran 4 (FD-4) flux, serum inflammatory mediator levels, tight junction (TJ) levels, jejunum mucosa pathology, and epithelial intercellular junction ultrastructure were monitored to evaluate the effect of PHGG on IBF. Caco-2 monolayers were used to study the impact and mechanism of PHGG on lipopolysaccharide (LPS)-induced barrier dysfunction in vitro. The expression of zonula occludens protein-1 and occludin and the location of P65 were studied by immunofluorescence. Nuclear factor kappa B (NF-κB) and myosin light chain kinase 3 (MLCK) pathway-related protein expression was verified by quantitative reverse transcriptase polymerase chain reaction or western blotting. The results indicated that the jejunal mucosa structure was destroyed, the villi were disrupted and shortened, and neutrophil infiltration was evident in the septic rats. Compared to Sham group, spetic rats had increased Chiu's score, serum inflammatory mediator levels, and FD-4 flux but decreased TJ and gap junction density. In addition, the expression of MLCK, p-MLC, and TJ proteins and the expression of P65 in the nucleus were increased in septic rats. Furthermore, compared to those in the Control group, LPS-treated Caco-2 cells showed lower cell viability and transepithelial electrical resistance, while had higher FD-4 flux and the expression of MLCK, p-MLC, TJ proteins and P65 in the nucleus. PHGG pretreatment reversed the above effects induced by CLP or LPS treatment. Moreover, SN50, an NF-κB inhibitor, attenuated the above effects of LPS on Caco-2 cells. Overall, PHGG reduced inflammation, increased TJ protein expression and localization, and relieved damage to the TJ structure and intestinal permeability through suppression of the NF-κB/MLCK pathway. This study provides new insights into the role of PHGG in sepsis therapy.

Early recognition of sepsis, a common life-threatening condition in intensive care units (ICUs), is beneficial for improving patient outcomes. However, most sepsis prediction models were trained and assessed in the ICU, which might not apply to emergency department (ED) settings.

To establish an early predictive model based on basic but essential information collected upon ED presentation for the follow-up diagnosis of sepsis observed in the ICU.

This study developed and validated a reliable model of sepsis prediction among ED patients by comparing 10 different methods based on retrospective electronic health record data from the MIMIC-IV database. In-ICU sepsis was identified as the primary outcome. The potential predictors encompassed baseline demographics, vital signs, pain scale, chief complaints and Emergency Severity Index (ESI). 80% and 20% of the total of 425 737 ED visit records were randomly selected for the train set and the test set for model development and validation, respectively.

Among the methods evaluated, XGBoost demonstrated an optimal predictive performance with an area under the curve (AUC) of 0.90 (95% CI: 0.90-0.91). Logistic regression exhibited a comparable predictive ability to XGBoost, with an AUC of 0.89 (95% CI: 0.89-0.90), along with a sensitivity and specificity of 85% (95% CI: 0.83-0.86) and 78% (95% CI: 0.77-0.80), respectively. Neither of the five commonly used severity scoring systems demonstrated satisfactory performance for sepsis prediction. The predictive ability of using ESI as the sole predictor (AUC: 0.79, 95% CI: 0.78-0.80) was also inferior to the model integrating ESI and other basic information.

The use of ESI combined with basic clinical information upon ED presentation accurately predicted sepsis among ED patients, strengthening its application in ED.

The proposed model may assist nurses in risk stratification management and prioritize interventions for potential sepsis patients, even in low-resource settings.

Bloodstream infection (BSI) is associated with high morbidity and mortality worldwide. Currently, BSI diagnosis relies on a time-consuming blood culture method, which usually takes 2 or more days to identify the causative pathogens. Cell-free DNA (cfDNA) refers to those small nucleic acid fragments residing in plasma and other body fluids, which have been used to detect cancer, organ transplantation injury, and pathogenic infections. A new multiplexed fluorescent quantitative PCR kit aiming at plasma microbial cfDNA was developed in this study. The kit contains multiple panels, and each panel covers multiple pathogens, including E. coli, K. pneumoniae, A. baumannii, H. influenzae, P. aeruginosa, E. faecalis, E. faecium, S. aureus, and S. epidermidis.

PCR primers and probes were designed based on effective bacterial sequence segments, which were obtained from the analysis of next-generation sequencing results of plasma samples of patients with bloodstream infections. Bioinformatics analyses and experimental evidence were used to test the conservativeness and specificity of the primers and probes. The lower detection limit of the kit was determined under optimal reaction conditions. Clinical samples were used to test the accuracy of the kit's detection.

The lower detection limit of the kit has reached ≤ 12 copies per reaction. Clinical samples testing results showed a 90.48% consistency between the kit and blood culture.

The kit provides a rapid, accurate, and reliable method for diagnosing bloodstream infections. This can quickly provide an etiological basis for clinical diagnosis and further treatment, potentially improving patient outcomes.

Background: Sepsis is a life-threatening condition characterized by multiple organ dysfunction. Blood cells abnormalities play a significant role in the onset and progression of sepsis; however, the potential causal relationship between platelets and sepsis remains unclear, as does whether immune cells mediate the interaction between platelets and sepsis. This study aims to explore the potential causal relationship between platelets and sepsis and analyze the mediating effect of immune cells. In addition, cell-to-cell communication was analyzed to explore the interaction between blood cells and immune cells. Material and methods: In this study, genome-wide association study data were utilized to examine the association between blood cells and sepsis. Two-sample Mendelian randomization (MR) and reverse MR were performed to investigate the potential causal relationship between blood cells and sepsis, with a specific focus on the relationship between platelets and sepsis. Subsequently, two-step MR was employed to identify the immune cells that mediate the interaction between platelets and sepsis and to assess their potential mediating effects. Cellchat software was used to analyze cell-to-cell communication. Results: The results of two-sample MR indicated that platelets were negatively correlated with sepsis (OR = 0.976, 95% CI 0.959-0.993, P = 0.005), suggesting that platelets have a protective effect against sepsis. Additionally, reverse MR demonstrated that sepsis had no significant effect on platelets (OR = 0.909, 95% CI 0.156-5.296, P = 0.916). The mediating effect analysis revealed that monocytes and B cells were important mediators in the relationship between platelets and sepsis. Notably, the correlation between platelets and sepsis shifted from negative to positive with the involvement of monocytes and B cells. The number and strength of cell-cell interactions were decreased in sepsis. Monocytes and B cells primarily regulate platelets through the CLEC signaling pathway, contributing to the pathogenesis of sepsis. Conclusion: This study confirmed the protective role of platelets in sepsis. Monocytes and B cells mediate changes in the genetic association between platelets and sepsis. Monocytes and B cells primarily interact with platelets via the CLEC pathway, thereby modulating the genetic association between platelets and sepsis. These findings indicate that thrombocytopenia, especially when accompanied by elevated monocytes and B cells, may serve as a potential marker for sepsis.

Sepsis is a potentially life-threatening condition triggered by infection that is responsible for an estimated 48,000 deaths in the UK each year. Its pathophysiology is complex, its symptomology non-specific and its clinical presentations extremely varied. Despite numerous campaigns to raise awareness of sepsis, it still goes undetected. In 2024, the National Institute for Health and Clinical Excellence revised its guideline on sepsis and the UK Sepsis Trust published the seventh edition of its Sepsis Manual. This article discusses the pathophysiology of sepsis and how emergency nurses should assess and manage patients with suspected sepsis. It describes the tools available to them, including the National Early Warning Score 2 and the Sepsis 6, and emphasises the importance of early antibiotic administration, serial lactate measurements, source control and antimicrobial stewardship.

Sepsis is a life-threatening condition characterized by widespread inflammatory response syndrome in the body resulting from infection. Previous studies have demonstrated that some inflammatory factors or nutritional elements contributed to deaths in patients diagnosed with sepsis. Nevertheless, the correlation between the (neutrophil + monocyte)/albumin (NMa) ratio and all-cause mortality of patients diagnosed with sepsis remains unclear. This study aims to investigate the association between the NMa ratio and all-cause mortality in sepsis patients and to develop a predictive model using machine learning techniques.

The clinical data were harvested from 13,851 patients with sepsis from the MIMIC-IV (3.1) database. We divided the subjects into four groups based on quartiles of the NMa ratio. The main endpoint was 30-day all-cause mortality, and the secondary endpoint was 90-day all-cause mortality. The relationship between the NMa ratio and adverse prognosis was investigated employing Cox proportional hazard regression, restricted cubic splines, and Kaplan‒Meier curves. Moreover, we employed Boruta algorithm to evaluate the predictive potential of the NMa ratio and established the prediction models utilizing machine learning algorithms.

After adjusting for confounders, each unit increase in the NMa ratio was associated with a 1.8% and 1.6% higher risk of 30-day and 90-day all-cause mortality, respectively (P < 0.001), indicating a linear relationship, and when treated as a categorical variable, the Quartile 4 group demonstrated a significantly higher mortality risk. Boruta feature selection also displayed that the NMa ratio possessed a higher Z score, and the models established utilizing the Cox and Random Forest algorithm identified excellent predictive performance (area under the curve (AUC) = 0.72, AUC = 0.74, respectively).

The NMa ratio is strongly and linearly associated with 30-day and 90-day all-cause mortality, with higher levels significantly increasing mortality risk, even after adjusting for potential confounders. Predictive models using Cox regression and Random Forest algorithms showed strong performance, indicating that the NMa ratio could function as a predictor of negative prognosis in patients with sepsis.

Macrophage pyroptosis represents a pivotal mechanism underlying acute liver injury during sepsis. Chloride intracellular channel proteins (CLICs) have been linked to inflammatory reflexes, with IAA94 serving as an inhibitor of channel formation characteristic of CLICs. In a mouse model, IAA94 demonstrated efficacy in reducing pro-inflammatory cytokines in liver tissues, decreasing macrophage in the liver, inhibiting the development of the pro-fibrosis phenotype, and alleviating tissue injury. Additionally, IAA94 exhibited inhibitory effects on the activation of NLRP3 inflammasome, leading to the suppression of pyroptosis in J774A.1 cells and the liver. Additionally, IAA94 was observed to impede the interaction between NEK7 and NLRP3. Furthermore, it was observed that the conditioned medium of pyroptotic macrophages treated with IAA94 induced an attenuated inflammatory response in hepatocytes in comparison to that induced by the conditioned medium of pyroptotic macrophages. However, NLRP3 overexpression impeded the beneficial effects of IAA94. In conclusion, IAA94 has the capacity to impede NLRP3 inflammasome formation-mediated pyroptosis by blocking CLICs-mediated chloride efflux and the inhibition of NEK7-NLRP3 interactions, thereby establishing CLICs as a promising therapeutic target against liver inflammation.

Sepsis is a medical emergency requiring timely management and available global evidence suggests that healthcare workers and students are poorly prepared to effectively diagnose and treat such patients. This study evaluates the inter-relationship of healthcare students' attitudes towards, knowledge of and practice of sepsis management as they progress through training in Jamaica.

A prospective cross-sectional survey using an anonymous self-administered questionnaire with convenience sampling was performed among healthcare students at all levels of training. All available medical and nursing students from the major public medical and nursing schools in the Kingston Metropolitan Area were included in the study. The questionnaire was composed of 25 items covering aspects of the knowledge, attitudes, and practice of sepsis management.

The study population consisted of 292 respondents; 210 medical and 82 nursing students. The need for fluid resuscitation before ICU admission (72.6%) was the practice question that was correctly identified by the majority of students. Most of the remaining items were correctly identified by approximately half of the students including signs of sepsis such as altered mental state (56.1%), low systolic blood pressure (53.7%) and tachypnea (50.6%). In contrast, very few students could identify the signs that indicated the presence of septic shock such as high serum lactate and the need for vasopressors and only 7% of students knew the correct annual sepsis mortality rate. Nursing students had higher overall mean correct knowledge and correct practice scores compared to medical students and lower incorrect practice scores, although there was no difference in incorrect knowledge scores between the 2 respondent groups. A subgroup analysis of students in their final stage of training revealed a more comparable performance of the 2 student groups, highlighting the improved performance by both nursing and medical students who received either formal sepsis training or were in the late stage of training. Jamaican healthcare students agree that more training on sepsis is needed (98.3%) and that sepsis care bundles should be implemented during their training courses (94.2%).

This study revealed differences in the healthcare students' attitudes, knowledge of and practice of sepsis in Jamaica. There is the need for training on sepsis and implementation of sepsis care bundles.

Minimally invasive surgery has become the gold standard for colorectal cancer treatment. Approximately 40% of patients undergoing elective colorectal resection develop postoperative complications. The median time to clinical diagnosis of a postoperative complication ranges between 5 and 8 days. Early detection of complications can reduce their morbidity and negative impact. This study aims to evaluate the effectiveness of routine postoperative inflammatory markers in predicting early postoperative complications in patients undergoing elective minimally invasive surgery for colorectal cancer.

This study was conducted at a single center and is a retrospective analysis of a prospectively mantained database. We included 397 consecutive patients who underwent elective minimally invasive surgery for colorectal cancer between May 2012 and September 2023. Routine inflammatory parameters, including C-reactive protein, Glasgow Prognostic Score, and neutrophil-lymphocyte ratio, were analyzed to identify those associated with postoperative complications. The cutoff values for these markers were determined using receiver-operating characteristic (ROC) curve analysis with the Youden index method.

Of the patients, 29.2% experienced postoperative complications, with major complications (Clavien-Dindo ≥ III) occurring in 11.3%. On postoperative day 3, C-reactive protein level < 125 mg/L, Glasgow Prognostic Score < 2.12, and neutrophil-lymphocyte ratio < 5.26 were significantly associated with lower risk of postoperative complications (p < 0.0001). NLR was the best parameter to identify patients unlikely to experience a postoperative complication on day 3, with a cutoff value of 5.26 and a negative predictive value (NPV) of 83%.

Neutrophil-lymphocyte ratio, C-reactive protein, and Glasgow Prognostic Score on POD3 can predict postoperative complications in patients who undergoing minimally invasive surgery for colorectal cancer. These inflammatory markers demonstrated high negative predictive value, effectively identifying patients who are unlikely to develop complications and providing valuable information for safe early discharge.

Rationale: Early detection, standardized therapy, adequate infrastructure, and strategies for quality improvement should constitute essential components of every hospital's sepsis plan. Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute-care hospitals. Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals. This included the use of sepsis definitions, the implementation of sepsis guideline recommendations, diagnostic and therapeutic infrastructure, antibiotic stewardship, and quality improvement initiatives (QIIs) in hospitals. Measurements and Main Results: A total of 1,023 hospitals in 69 countries were included. Most of them, 835 (81.6%), were in Europe. Sepsis screening was used in 54.2% of emergency departments (EDs), 47.9% of wards, and 61.7% of ICUs. Sepsis management was standardized in 57.3% of EDs, 45.2% of wards, and 70.7% of ICUs. The implementation of comprehensive QIIs was associated with increased screening (EDs, +33.3%; wards, +44.4%; ICUs, +23.8% absolute difference) and increased standardized sepsis management (EDs, +33.6%; wards, +40.0%; ICUs, +17.7% absolute difference) compared with hospitals without QIIs. A total of 9.8% of hospitals had implemented ongoing QIIs, and 4.6% had invested in sepsis programs. Conclusions: The findings indicate that there is considerable room for improvement in a large number of mainly European hospitals, particularly with regard to early identification and standardized management of sepsis, the availability of guidelines, diagnostic and therapeutic infrastructure, and the implementation of QIIs. Further efforts are required to implement a more comprehensive and appropriate quality of care.

To identify clinical characteristics and serological biomarkers that predicted subsequent nosocomial infection in ATTIRE trial patients.

We identified 360 patients at hospitalization without infection and not prescribed antibiotics and compared clinical characteristics between those who subsequently developed a nosocomial infection and not. In a 68-patient subcohort, we compared plasma biomarkers of bacterial translocation, infection, and inflammation at hospitalization between those who developed a nosocomial infection and not. In a 56-patient subcohort, we investigated plasma lipidomic profiles in those who did and did not develop nosocomial infection using Lipotype Shotgun platform analysis and multivariate statistical techniques. To further investigate lipid pathways, we compared outcomes in patients taking statins or not at hospitalization.

Serum bilirubin >188 µmol/L at hospitalization predicted subsequent nosocomial infection in univariate and multivariate analyses, with 80% specificity. The most common nosocomial infections were respiratory tract (29%) and those developing infection had significantly greater 28 and 90-day mortality than those not (p=9.34E-05 and 0.014). Serological biomarkers of bacterial translocation, infection, and inflammation did not predict subsequent infection. Partial least squares discriminatory analyses identified cholesterol esters (CEs) (CE.18.1.2, CE.18.1.0, and CE.16.0.0) as important predictors of infection but provided only a small improvement in predictive ability over bilirubin alone. RNA-sequencing analyses suggest this is mediated by a downregulation of the cellular cholesterol esterification enzyme sterol O-acyltransferase 1. Statin use was not associated with nosocomial infection prevention.

In ATTIRE, elevated serum bilirubin at hospitalization was the only clinical characteristic that predicted subsequent development of nosocomial infection. Considering the rising incidence of antimicrobial resistance, these data could be used to limit antibiotic prophylaxis or aid trial design for investigating use in high-risk patients.

Background: The global population is aging, and the proportion of elderly patients admitted to ICUs is increasing. In this scenario, achieving a balance between judicious utilization of a limited and high-cost resource and providing optimal intensity of care presents a challenge given that in very elderly patients the value of ICU care is uncertain. The aim of our study was to evaluate the survival of older subjects admitted to ICU who require mechanical ventilation at different levels of treatment intensity. Methods: A comprehensive longitudinal ICU database was retrospectively analyzed at a single tertiary center, from January 2008-December 2014, of ICU subjects 80 y old or older who required mechanical ventilation. Results: From January 2009-December 2014, 482 subjects were admitted to the ICU and required mechanical ventilation. Among them, 376 (78%) were age 80-89 y; and 106 (22%) were age ≥ 90 y, with a mean age of 85.84 (4.56). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 21.53 (7.42), and the mean Sequential Organ Failure Assessment score was 5.75 (3.38). The total mortality during ICU admission was 46%, and the hospital mortality was 58%. Only age higher than 90 y (1.41 [1.05-1.91], P = .02) and APACHE score (1.03 [1.01-1.05], P < .001) were associated with mortality after adjustments. The Therapeutic Intervention Scoring System score was analyzed in tertiles and was not related to mortality in univariate analysis or after adjustments. Conclusions: Our data indicate that in older subjects who received mechanical ventilation higher intensity of treatment does not seem to translate into a survival benefit. This finding highlights the importance of considering individualized treatment plans for elderly patients in the ICU.

Severe community-acquired pneumonia (sCAP) is associated with higher morbidity and mortality. The use of glucocorticoids to improve the prognosis of severe community-acquired pneumonia remains a topic of controversy.

Following the guidelines given in the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), we conducted a systematic review and meta-analysis to evaluate the effects of glucocorticoids on mortality and duration of mechanical ventilation in patients with sCAP. Randomized controlled studies investigating the use of glucocorticoids in the treatment of sCAP were extracted from PubMed, Embase, Cochrane Library, and Web of Science. Statistical analysis was performed to compare the differences in in-hospital mortality, mechanical ventilation duration, gastrointestinal bleeding, secondary infection, and other outcome measures between the glucocorticoid group and the control group.

A total of 8 studies involving 1769 patients were included in the analysis. The hospital mortality in the glucocorticoid group was significantly lower than that in the control group [8 studies, relative risk (RR) 0.59; 95% CI 0.47-0.76, p < 0.01. I2 = 25%, low certainty]. The duration of mechanical ventilation in the glucocorticoid group was significantly shorter than that in the control group [Mean Difference (MD) -3.08; 95% CI -4.96 to -1.19, p < 0.01; I2 = 0%, low certainty]. There was no significant difference in the incidence of gastrointestinal bleeding (RR 0.94; 95% CI 0.55-1.63, p = 0.84, I2 = 0%, low certainty) or secondary infection (RR 0.85; 95% CI 0.58-1.25, p = 0.85, I2 = 2%, moderate certainty) between the glucocorticoid group and the control group. In subgroup analysis, mortality was significantly lower in the hydrocortisone group compared to the control group (6.3% vs. 14.6%, RR 0.43; 95% CI 0.29-0.62, p < 0.01, I2 = 0%, very low certainty). However, there was no significant difference in mortality between the methylprednisolone group and the control group (15.6% vs. 19.9%, RR 0.78; 95% CI 0.57-1.08, p = 0.14, I2 = 0%, moderate certainty).

Glucocorticoids can reduce mortality in patients with sCAP, and the effect may vary depending on the type and the dose of glucocorticoids used. Additionally, glucocorticoid treatment can lead to a shorter duration of mechanical ventilation, as well as the length of ICU stay, without increasing the risk of gastrointestinal bleeding or secondary infection in patients with sCAP. PROSPERO registration: CRD42023416525.

Background: Surgical quality datasets are critical to decision-making tools including surgical infection (SI). Machine learning models (MLMs), a branch of artificial intelligence (AI), are increasingly being ingrained within surgical decision-making algorithms. However, given the unique and distinct functioning of individual models, not all models may be suitable for acutely ill surgical patients. Patients and Methods: This is a 5-year retrospective review of National Surgical Quality Improvement Program (NSQIP) patients who underwent an operation. The data were reviewed for demographics, medical comorbidities, rates, and sites of infection. To generate the MLMs, data were imported into Python, and four common MLMs, extreme gradient boosting, K-nearest neighbor (KNN), random forest, and logistic regression, as well as two novel models (flexible discriminant analysis and generalized additive model) and ensemble modeling, were generated to predict post-operative SIs. Outputs included area under the receiver-operating characteristic curve (AUC ROC) including recall curves. Results: Overall, 624,625 urgent and emergent NSQIP patients were included. The overall infection rate was 8.6%. Patients who sustained a post-operative infection were older, more likely geriatric, male, diabetic, had chronic obstructive pulmonary disease, were smokers, and were less likely White race. With respect to MLMs, all four MLMs had reasonable accuracy. However, a hierarchy of MLMs was noted with predictive abilities (XGB AUC = 0.85 and logistic regression = 0.82), wherein KNN has the lowest performance (AUC = 0.62). With respect to the ability to detect an infection, precision recall of XGB performed well (AUC = 0.73), whereas KNN performed poorly (AUC = 0.16). Conclusions: MLMs are not created nor function similarly. We identified differences with MLMs to predict post-operative infections in surgical patients. Before MLMs are incorporated into surgical decision making, it is critical that surgeons are at the fore of understanding the role and functioning of MLMs.

Salmonella Typhi (S. Typhi) is a Gram-negative bacterium that exclusively infects humans and causes typhoid fever- a major global public health concern responsible for approximately 9 million infections and 110,000 deaths annually. Macrophages, a key component of the innate immune system, play essential roles in pathogen clearance, antigen presentation, immune regulation, and tissue repair. As one of the primary targets of S. Typhi infection, macrophages significantly influence disease onset and progression. S. Typhi expresses a range of virulence factors, including the virulence-associated (Vi) capsule, outer membrane proteins (OMPs), flagella, fimbriae, type III secretion systems (T3SSs) and other genes encoded on Salmonella pathogenicity islands (SPIs), as well as toxins, regulatory factors, and virulence plasmids. These virulence factors facilitate S. Typhi's intracellular survival within macrophages by mediating processes such as adhesion, invasion, nutrient acquisition and immune evasion, ultimately enabling systemic infection. This review explores the role and molecular mechanisms of S. Typhi virulence factors in counteracting macrophage antimicrobial functions, providing insights for future research on typhoid pathogenesis and the development of potential therapeutic interventions.

Sepsis, a critical medical condition resulting from an irregular immune response to infection, leads to life-threatening organ dysfunction. Despite medical advancements, the critical need for research into dependable diagnostic markers and precise therapeutic targets.

We screened out five gene expression datasets (GSE69063, GSE236713, GSE28750, GSE65682 and GSE137340) from the Gene Expression Omnibus. First, we merged the first two datasets. We then identified differentially expressed genes (DEGs), which were subjected to KEGG and GO enrichment analyses. Following this, we integrated the DEGs with the genes from key modules as determined by Weighted Gene Co-expression Network Analysis (WGCNA), identifying 262 overlapping genes. 12 core genes were subsequently selected using three machine-learning algorithms: random forest (RF), Least Absolute Shrinkage and Selection Operator (LASSO), and Support Vector Machine-Recursive Feature Elimination (SVW-RFE). The utilization of the receiver operating characteristic curve in conjunction with the nomogram model served to authenticate the discriminatory strength and efficacy of the key genes. CIBERSORT was utilized to evaluate the inflammatory and immunological condition of sepsis. Astragalus, Salvia, and Safflower are the primary elements of Xuebijing, commonly used in the clinical treatment of sepsis. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), we identified the chemical constituents of these three herbs and their target genes.

We found that CD40LG is not only one of the 12 core genes we identified, but also a common target of the active components quercetin, luteolin, and apigenin in these herbs. We extracted the common chemical structure of these active ingredients -flavonoids. Through docking analysis, we further validated the interaction between flavonoids and CD40LG. Lastly, blood samples were collected from healthy individuals and sepsis patients, with and without the administration of Xuebijing, for the extraction of peripheral blood mononuclear cells (PBMCs). By qPCR and WB analysis. We observed significant differences in the expression of CD40LG across the three groups. In this study, we pinpointed candidate hub genes for sepsis and constructed a nomogram for its diagnosis.

This research not only provides potential diagnostic evidence for peripheral blood diagnosis of sepsis but also offers insights into the pathogenesis and disease progression of sepsis.

Fluid is an essential component of initial resuscitation in sepsis or burns. Meanwhile, the optimal strategy of titrating fluids for both of the two conditions remains uncertain. In this bibliometric analysis, we compared the similarities and differences in fluid resuscitation between sepsis and burns in recent publications.

Literatures related to fluid resuscitation in either sepsis or burns were searched in the Web of Science database Core Collection from January 1, 1992, to December 31, 2022. CiteSpace and VOSviewer was used for bibliometric analysis.

A total of 1,549 and 468 publications on fluid resuscitation in sepsis and burns were retrieved from 1992 to 2022. Based on the occurrences, 341 and 86 high-frequency keywords were screened out from sepsis and burns publications, respectively, which were similarly categorized into 5 clusters [i.e. "mechanisms of hypovolemia" (cluster 1), "titration of fluid" (cluster 2), "outcomes or complications" (cluster 3), "pathophysiological alternations" (cluster 4), and "fluid types and others" (cluster 5)]. The high-frequency keywords of the top 20 were more concentrated in cluster 3 and cluster 2, with "mortality" ranked the top in both sepsis and burns literature. Significantly, 3 keywords in cluster 2 ranked in the top 5, including "goal directed resuscitation" (the 3rd), fluid responsiveness (the 4th) and fluid balance (the 5th) in sepsis literature, while the keywords of "microvascular exchange" (cluster 1) and "abdominal compartment syndrome" (ACS, cluster 3) ranked at the second and the fifth place in burns publications. Keyword burst analysis demonstrated that the keyword with the highest burst strength (BS) was "formula" (BS = 5.88, 2008-2014), followed by management (BS = 4.79, 2012-2022), ACS (BS = 4.76, 2006-2010), and fluid creep (BS = 4.74, 2011-2016) in burn publications, but they were dobutamine (BS = 12.31, 1992-2008), cardiac output (BS = 9.79, 1993-2001), catecholamine (BS = 9.54, 1993-2006), and consumption (BS = 7.52, 1992-2006) in sepsis literature. Moreover, the most frequently cited article in either sepsis or burns was categorized into cluster 2, that investigated goal-directed fluid therapy for sepsis and formula improvement for burns resuscitation.

It was demonstrated that the research priorities in titrating fluid were mainly concentrated on targeting hemodynamics in sepsis vs. improving formula (which briefly calculates the increased microvascular permeability) in burns, while concerning of "outcomes and complications" in fluid resuscitation similarly after 1992. However, hemodynamics and microvascular permeability have been simultaneously well considered in few previous studies regarding fluid resuscitation in either sepsis or burns.

In the mammalian cardiovascular system, endothelial glycocalyx is a gel-like layer that covers the luminal surface of endothelial cells (ECs) and plays crucial roles in vascular homeostasis, permeability and leukocyte adhesion. Degradation of this structure occurs early in sepsis and becomes accordingly dysfunctional. In severe cases, it is not self-regulated by the organism. However, the relationship between the glycocalyx and the occurrence and development of sepsis remains poorly understood. One possibility is that thinned glycocalyx promotes leukocyte recognition and adhesion, thereby facilitating the elimination of pathogens from infected areas. This may represent a protective mechanism developed by the organism during through evolutionary processes. However, if the damage persists and disrupts the dynamic balance of the microcirculation, interstitial edema or organ failure can occur. Thus, we asked the questions, what is the precise composition and structure of the glycocalyx? How is it degraded? What animal models are available to study the relationship between the glycocalyx and sepsis? What glycocalyx biomarkers are found in the blood of patients with sepsis? To determine whether sepsis can be treated by interfering with the glycocalyx, this study provides a systematic summary and discussion of the latest progress in addressing these questions.

Pathophysiologic changes in the early and late phases of septic shock affect the pharmacokinetic (PK) parameters, varying dose adjustments may be necessary. This study aimed to create the PK models of vancomycin in the early and late phases of septic shock and to describe the association between the area under the curve from 0 to 24 h (AUC0-24) and acute kidney injury (AKI). The data from patients with septic shock receiving vancomycin was collected either prospectively or retrospectively. A nonlinear mixed-effects modeling approach was used to develop the PK models. A total of 208 septic shock patients were enrolled and classified into the early (n = 96) and the late phase (n = 112). A two-compartment PK model is the best base model for both phases of septic shock. The model that best predicted the clearance (CL) of both phases was the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, which was not indexed to body surface area (BSA). Albumin (ALB) was a covariate associated with vancomycin CL only in the late phase. The typical values of CL and volume of distribution (Vd) in the early phase were 1.71 L/h and 68.94 L. In the late phase, CL was 1.65 L/h, and Vd was 66.36 L. The AKI was observed in patients with a high simulated AUC0-24. The population PK model of vancomycin in the early and late phases of septic shock has been established. The CKD-EPI not indexed to BSA predicts vancomycin CL in both phases. ALB was associated with CL in the late phase.

Most current guideline statements support some level of unrestricted glycemic management in critically ill adult patients. Nevertheless, the effectiveness of liberal glucose control is currently not well-supported by evidence. Therefore, our objective is to investigate the influence of liberal glucose control (> 180 mg/dl) on critically ill patients in the intensive care unit (ICU).

Until November 23, 2023, English language literature was thoroughly and systematically searched through multiple databases, including PubMed, Embase, Cochrane Library, and Web of Science. Our primary endpoints of interest were the occurrence of hypoglycemia, mortality in the ICU, and mortality during hospitalization. In addition, our secondary outcomes comprised of 90-day mortality, bloodstream infections, the proportion of patients necessitating renal replacement therapy (RRT), the length of time under mechanical ventilation, duration of stay in the ICU, and length of the overall hospitalization. Weighted mean difference (WMD) and relative risk (RR) were respectively computed as overall effect size for continuous and dichotomous data and reported with their 95% confidence intervals (95% CI).

A total of 9 studies were incorporated, which included 14,878 patients in the ICU. Compared with other blood glucose target control groups, liberal glucose control significantly reduced the incidence of hypoglycemia (RR = 0.41; 95% CI:0.25 to 0.69; P = 0.001), but increased ICU mortality (RR = 1.23; 95% CI:1.03 to 1.48; P = 0.023), in-hospital mortality risk (RR = 1.18; 95% CI:1.03 to 1.35; P = 0.020), and the risk of requiring RRT (RR = 1.26; 95% CI:1.11 to1.42; P < 0.001).

Liberal glucose control can reduce the risk of hypoglycemia but increases the risks of ICU mortality, in-hospital mortality, and the requirement for RRT. To confirm the outcomes further, large-scale, high-quality clinical trials are necessary.

Mechanical ventilation can be a life-saving intervention, but its implementation requires a multidisciplinary approach, with an understanding of its indications and contraindications due to the potential for complications. The management of mechanical ventilation should be part of the curricula during clinical training; however, trainees and practicing professionals frequently report low confidence in managing mechanical ventilation, often seeking additional sources of knowledge. Review articles, consensus statements and clinical practice guidelines have become important sources of guidance in mechanical ventilation, and although clinical practice guidelines offer rigorously developed recommendations, they take a long time to develop and can address only a limited number of clinical questions. The Associação de Medicina Intensiva Brasileira and the Sociedade Brasileira de Pneumologia e Tisiologia sponsored the development of a joint statement addressing all aspects of mechanical ventilation, which was divided into 38 topics. Seventy-five experts from all regions of Brazil worked in pairs to perform scoping reviews, searching for publications on their specific topic of mechanical ventilation in the last 20 years in the highest impact factor journals in the areas of intensive care, pulmonology, and anesthesiology. Each pair produced suggestions and considerations on their topics, which were presented to the entire group in a plenary session for modification when necessary and approval. The result was a comprehensive document encompassing all aspects of mechanical ventilation to provide guidance at the bedside. In this article, we report the methodology used to produce the document and highlight the most important suggestions and considerations of the document, which has been made available to the public in Portuguese.

The insertion of a peripheral venous line is of paramount importance in the stabilisation of critically ill patients. It is a preferred method of venous access over more invasive techniques due to its immediacy and fewer complications. Difficulties of catheterisation can result in delays to treatment, increased complication risks and pain, and a waste of valuable time and healthcare resources. Our hypothesis is that infrared vein illumination could improve the success rate of peripheral venous catheterisation in critically ill patients at risk of difficult catheterisation.

This is a prospective, multicentre, randomised, open-label controlled trial. It will be conducted in France and will involve critically ill patients at risk of difficult peripheral catheterisation. Patients will be randomly assigned to usual care or infrared vein illumination. The primary outcome is the rate of successful peripheral venous catheterisation at first puncture. Secondary outcomes include time to placement, overall rate of successful peripheral venous catheterisation, number of punctures, quality (calibre of the catheter), replacement rate, need for central line and local complications (dysfunction, diffusion, haematoma and lymphangitis).

The study has been granted ethical approval (CPP Ile de France 1). Following the provision of informed consent, patients will be included in the study. The results will be submitted for publication in peer-reviewed journals.

NCT03932214.