Intensive Care Medicine Experimental最新文献

{"title":"Early sepsis recognition: a pilot study using a rapid high-multiplex host-response mRNA diagnostic test.","authors":"Jingyi Lu, Michèle A Ter Voert, Mehtap Ünal, Natalie N Whitfield, Oliver Liesenfeld, Jan C Ter Maaten, Timothy E Sweeney, Hjalmar R Bouma","doi":"10.1186/s40635-025-00735-x","DOIUrl":"10.1186/s40635-025-00735-x","url":null,"abstract":"<p><strong>Background: </strong>Early sepsis diagnosis is essential to allow timely initiation of adequate care. The TriVerity™ Test, performed on the Myrna™ Instrument, is the first rapid high-multiplex host-response mRNA diagnostic test that supports clinical decision-making by evaluating the likelihood of bacterial and/or viral infections and severity of illness. We present findings of the first, proof of concept, real-world evaluation in an emergency department (ED).</p><p><strong>Methods: </strong>Blood was collected in PAXgene^® Blood RNA tubes from adult patients visiting the ED with suspicion of infection between 4th December 2023 and 22nd January 2024. TriVerity was performed within 1 h (RNA extraction and amplification of 29 host mRNAs using LAMP technology on the Myrna Instrument within approximately 30 min). TriVerity generates three diagnostic scores (likelihood of bacterial infection, viral infection, and illness severity), each classified into five discrete interpretation bands (very low, low, moderate, high, and very high). Post hoc chart reviews were performed after hospital discharge to clinically adjudicate the infection status (consensus and forced adjudication).</p><p><strong>Results: </strong>Among 60 patients, there were 20 (33%) bacterial infections, 15 (25%) viral infections, 11 (18%) bacterial-viral coinfections and 14 (23%) did not have an infection under forced adjudication. Under consensus adjudication, bacterial results demonstrated 95% rule-in specificity and 95% rule-out sensitivity. Viral results demonstrated rule-in specificity 100% and 92% rule-out sensitivity. Since only three patients were admitted to the ICU or died in this cohort, we cannot draw firm conclusions about the predictive value of the test for severe endpoints.</p><p><strong>Conclusions: </strong>TriVerity is a rapid whole-blood host-response test to reliably detect the presence or absence of bacterial and/or viral infections, as well as to assess illness severity in patients presenting to the ED. Its quick turnaround time aligns with the ED workflow, offering timely insights for clinical decision-making. Results from upcoming large-scale validation studies will provide more detailed results on the diagnostic and prognostic accuracy of the test.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"21"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of artificial intelligence and logistic regression models for mortality prediction in acute respiratory distress syndrome: a systematic review and meta-analysis.","authors":"Yang He, Ning Liu, Jie Yang, Yucai Hong, Hongying Ni, Zhongheng Zhang","doi":"10.1186/s40635-024-00706-8","DOIUrl":"10.1186/s40635-024-00706-8","url":null,"abstract":"<p><strong>Background: </strong>The application of artificial intelligence (AI) in predicting the mortality of acute respiratory distress syndrome (ARDS) has garnered significant attention. However, there is still a lack of evidence-based support for its specific diagnostic performance. Thus, this systematic review and meta-analysis was conducted to evaluate the effectiveness of AI algorithms in predicting ARDS mortality.</p><p><strong>Method: </strong>We conducted a comprehensive electronic search across Web of Science, Embase, PubMed, Scopus, and EBSCO databases up to April 28, 2024. The QUADAS-2 tool was used to assess the risk of bias in the included articles. A bivariate mixed-effects model was applied for the meta-analysis. Sensitivity analysis, meta-regression analysis, and tests for heterogeneity were also performed.</p><p><strong>Results: </strong>Eight studies were included in the analysis. The sensitivity, specificity, and summarized receiver operating characteristic (SROC) of the AI-based model in the validation set were 0.89 (95% CI 0.79-0.95), 0.72 (95% CI 0.65-0.78), and 0.84 (95% CI 0.80-0.87), respectively. For the logistic regression (LR) model, the sensitivity, specificity, and SROC were 0.78 (95% CI 0.74-0.82), 0.68 (95% CI 0.60-0.76), and 0.81 (95% CI 0.77-0.84). The AI model demonstrated superior predictive accuracy compared to the LR model. Notably, the predictive model performed better in patients with moderate to severe ARDS (SAUC: 0.84 [95% CI 0.80-0.87] vs. 0.81 [95% CI 0.77-0.84]).</p><p><strong>Conclusion: </strong>The AI algorithms showed superior performance in predicting the mortality of ARDS patients and demonstrated strong potential for clinical application. Additionally, we found that for ARDS, a highly heterogeneous condition, the accuracy of the model is influenced by the severity of the disease.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"23"},"PeriodicalIF":2.8,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11845658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sepsis-induced cardiac dysfunction: mitochondria and energy metabolism.","authors":"Xueting Yu, Jie Gao, Chunxiang Zhang","doi":"10.1186/s40635-025-00728-w","DOIUrl":"10.1186/s40635-025-00728-w","url":null,"abstract":"<p><p>Sepsis is a life-threatening multi-organ dysfunction syndrome caused by dysregulated host response to infection, posing a significant global healthcare challenge. Sepsis-induced myocardial dysfunction (SIMD) is a common complication of sepsis, significantly increasing mortality due to its high energy demands and low compensatory reserves. The substantial mitochondrial damage rather than cell apoptosis in SIMD suggests disrupted cardiac energy metabolism as a crucial pathophysiological mechanism. Therefore, we systematically reviewed the mechanisms underlying energy metabolism dysfunction in SIMD, including alterations in myocardial cell energy metabolism substrates, excitation-contraction coupling processes, mitochondrial dysfunction, and mitochondrial autophagy and biogenesis, summarizing potential therapeutic targets within them.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"20"},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11836259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between clock genes, melatonin and cardiovascular outcomes from ICU patients.","authors":"Jose M Jiménez-Pastor, Ignacio Morales-Cané, Francisco J Rodríguez-Cortés, Luna López-Coleto, Rocío Valverde-León, Pedro Arévalo-Buitrago, María J Medina-Valverde, Carmen De la Fuente-Martos, Darío Acuña-Castroviejo, Miguel Meira E Cruz, Raúl M Luque, André Sarmento-Cabral, Pablo J López-Soto","doi":"10.1186/s40635-025-00730-2","DOIUrl":"10.1186/s40635-025-00730-2","url":null,"abstract":"<p><strong>Background: </strong>Circadian rhythms, driven by biological clocks, help organisms align their physiological functions with environmental changes, promoting homeostasis. The central clock in the suprachiasmatic nucleus coordinates peripheral clocks via neurohumoral feedback involving proteins like CLOCK, BMAL1, CRY 1/2, and PER 1-3. In the ICU, these circadian processes often face disruptions from constant lighting, noise, and irregular sleep-wake cycles, impairing sleep quality and worsening stress responses. These disruptions can lead to adverse clinical effects, including higher cardiovascular complication rates. This study examines how ICU stays affect circadian rhythm regulators and their association with cardiovascular outcomes.</p><p><strong>Results: </strong>Significant differences were identified in melatonin levels and the expression of BMAL1, PER1, RORA, and NR1D1 between ICU stays of ≤7 days and >7 days. The APACHE-II severity scale influenced melatonin and the expression of CLOCK, PER2, CRY2, and RORA. Nonlinear relationships were observed between melatonin, clock genes, heart rate, and blood pressure (systolic and diastolic). In certain groups, molecular and physiological data showed correlations exceeding 90%.</p><p><strong>Conclusions: </strong>These findings highlight a robust association between circadian disruption, as measured by melatonin and clock genes, and cardiovascular physiological rhythms in ICU patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"19"},"PeriodicalIF":2.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of therapeutic plasma exchange on the inflammatory response in septic shock: a secondary analysis of the EXCHANGE-1 trial.","authors":"Andrea Sauer, Klaus Stahl, Benjamin Seeliger, Pedro David Wendel-Garcia, Felix Lehmann, Julius J Schmidt, Bernhard M W Schmidt, Tobias Welte, Konrad Peukert, Lennart Wild, Christian Putensen, Sascha David, Christian Bode","doi":"10.1186/s40635-025-00725-z","DOIUrl":"10.1186/s40635-025-00725-z","url":null,"abstract":"<p><strong>Background: </strong>Sepsis and septic shock, defined by a profound immune dysregulation, are among the leading causes of death in the intensive care unit (ICU). Despite advances in understanding the underlying pathophysiology, evidence for specific immunomodulatory treatment does not exist to date. Therapeutic plasma exchange (TPE) represents an adjunctive treatment approach to rebalance immune homeostasis. In the EXCHANGE-1 trial, we recently demonstrated a rapid hemodynamic improvement, possibly caused by the removal of harmful mediators and the replacement of protective plasma proteins. The aim of this secondary analysis is to further characterize the underlying immunomodulatory effects and to identify biomarkers that may predict treatment response.</p><p><strong>Methods: </strong>This secondary analysis included patients in early septic shock (< 24 h duration) and a norepinephrine (NE) dose of ≥ 0.4 μg/kg/min. Patients were randomized 1:1 to receive standard of care (SOC) or SOC + one single TPE and plasma samples were collected before and after TPE. Within-group and between group effects of circulating levels of acute-phase proteins [CRP and Pentraxin3 (PTX3)], inflammatory mediators (IL-4, IL-6, IL-8, IL-10, TNF-α, IL-2Rα/CD25) and damage-associated molecular pattern (DAMP) [cell-free DNA (cfDNA)] were analyzed via paired t test or Wilcoxon signed-rank test and a mixed-effects model. Multivariate mixed-effects modeling of NE and lactate reduction was performed to investigate if cfDNA could be associated with treatment response to TPE.</p><p><strong>Results: </strong>TPE led to a significant reduction in circulating acute-phase protein levels (CRP p = 0.00976, PTX3 p = 0.0001). Pro-inflammatory cytokines, such as circulating TNF-α-, IL-6- und IL-8-levels, were significantly reduced in both groups with no significant difference between treatment groups except for IL-2Rα/CD25 (p ≤ 0.0001). In a multivariate mixed-effects model, rising cfDNA levels over the first 6 h indicated refractoriness to SOC treatment regarding NE (p = 0.004) and lactate (p = 0.001), whereas those receiving TPE demonstrated sustained reductions in both parameters.</p><p><strong>Conclusions: </strong>In this secondary analysis of the EXCHANGE-1 trial adjunctive TPE is associated with the reduction of acute-phase proteins and IL-2Rα/CD25, however not with the reduction of pro-inflammatory cytokines. This phenomenon could contribute to the observed enhancement in hemodynamics among patients with septic shock. Furthermore, TPE may be particularly beneficial for patients with septic shock who exhibit rising levels of cfDNA.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"18"},"PeriodicalIF":2.8,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantification of facial cues for acute illness: a systematic scoping review.","authors":"Iris C Cramer, Eline G M Cox, Jip W T M de Kok, Jacqueline Koeze, Martje Visser, Hjalmar R Bouma, Ashley De Bie Dekker, Iwan C C van der Horst, R Arthur Bouwman, Bas C T van Bussel","doi":"10.1186/s40635-025-00719-x","DOIUrl":"10.1186/s40635-025-00719-x","url":null,"abstract":"<p><strong>Importance: </strong>The patient's face provides healthcare professionals with important information about the patient's general appearance and clinical condition.</p><p><strong>Objective: </strong>The primary aim of this review is to identify patients' facial cues that healthcare providers can use at the bedside to monitor the clinical condition of acutely ill patients.</p><p><strong>Evidence review: </strong>Studies about facial cues for acute illness were systematically searched in PubMed, Embase, Cochrane, and Cumulative Index to Nursing & Allied Health (CINAHL) databases. Studies on vital signs, pain, psychiatric illnesses, animal studies, qualitative studies, case reports, and systematic reviews were excluded. Acute illness was defined as any life-threatening condition or condition that required immediate intervention to prevent serious morbidity, permanent disability, or mortality. An overview of all identified facial cues was created.</p><p><strong>Findings: </strong>In total, 35 different facial cues were identified in 13 studies. A total of 21 were related to facial appearance, with the most frequently reported cues being closed eyes (2 studies), pale lips (2 studies), parted lips (3 studies), droopy mouth (3 studies), and paler skin tone (2 studies). In addition, 14 facial expression features were identified, characterized primarily by more sad, less happy, and less surprised. Most cues have only been described in a single study without external validation, limiting the generalizability of definitions of these cues and their clinical applicability.</p><p><strong>Conclusions and relevance: </strong>This systematic scoping review identified 35 facial cues associated with acute illness in patients in the hospital, highlighting the potential of facial observation to enhance clinical assessments. However, the lack of standardization limits applicability in healthcare. Future research should refine the setting of acute illness, develop diverse datasets, and validate the predictive value of facial cues across various populations.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"17"},"PeriodicalIF":2.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-ventilator synchrony under non-invasive ventilation is improved by an automated real time waveform analysis algorithm: a bench study.","authors":"Yann Renaud, Jocelyne Auroi, Davy Cabrio, Ermes Lupieri, Jean-Daniel Chiche, Lise Piquilloud","doi":"10.1186/s40635-025-00726-y","DOIUrl":"10.1186/s40635-025-00726-y","url":null,"abstract":"<p><strong>Background: </strong>Because of inherent leaks, obtaining good patient-ventilator synchrony during non-invasive ventilation (NIV) is challenging. The IntelliSync + ^® software (Hamilton medical, Bonaduz, CH), that can be used together with the NIV mode, performs real-time automated analysis of airway pressure- and flow-time curves to detect the transition between inspiration and expiration. It then controls the ventilator inspiratory and expiratory valves to improve patient-ventilator synchrony. The main goal of this NIV bench study was to evaluate the impact of IntelliSync + ^® on synchrony in the presence of leaks of 9 and 20 L/min in the tested ventilator circuit (no face mask used), with normal, obstructive and restrictive respiratory mechanics and two levels of NIV pressure support (PS 8 and 14 cmH₂O). For this, the time needed to trigger the ventilator (Td) and the difference between the end of the simulated breath and the termination of pressurization (Tiex) were measured. The number of classical asynchronies and the ventilator pressurization capacity were also assessed.</p><p><strong>Results: </strong>Compared to NIV delivered with the classical NIV mode (compensating leaks and limiting inspiratory time to 2 s), activating IntelliSync + ^® improved Tiex and, to a lesser extent, Td in clinically relevant setups. IntelliSync + ^® also showed a trend towards reducing classical asynchronies, particularly directly after leak flow increase. The impact of the system was most significant with high PS levels and pathological respiratory mechanics. Especially, in the obstructive model, in the presence of large leak (20 L/min) and PS 14 cmH₂O, Tiex decreased from 0.61 [0.56-0.64] to 0.16 [0.07-0.18] s and Td from 0.07 [0.06-0.08] to 0.06 [0.06-0.08] s. In less challenging situations, IntelliSync + ^® was less beneficial. Overall, ventilator pressurization was improved when IntelliSync + ^® was activated.</p><p><strong>Conclusions: </strong>In this NIV bench model, IntelliSync + ^®, used in addition to NIV-PS, improved both expiratory and inspiratory synchrony. It was particularly efficient in the presence of obstructive and restrictive respiratory mechanics and high-pressure support levels. These pre-clinical results tend to support the ability of IntelliSync + ^® to improve patient-ventilator synchrony in the presence of leaks and provide pre-clinical data supporting a clinical evaluation of the automated algorithm during NIV.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"16"},"PeriodicalIF":2.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11822138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can nebulised heparin reduce acute lung injury in patients with SARS‑CoV‑2 requiring advanced respiratory support in Ireland: the CHARTER‑Ireland phase Ib/IIa, randomised, parallel-group, open-label study.","authors":"David Cosgrave, Bairbre McNicholas, Ciara Hanley, John Robert Sheehan, Padraig Calpin, Maeve Kernan, Darragh Murphy, Alberto Alvarez-Iglesias, John Ferguson, Camilla Giacomini, Christine Greene, Catriona Cody, Shane McGeary, Marion Murphy, Marianne Fitzgerald, Gerard Curley, Barry Dixon, Roger J Smith, Claire Masterson, Daniel O'Toole, Frank van Haren, John G Laffey","doi":"10.1186/s40635-025-00727-x","DOIUrl":"10.1186/s40635-025-00727-x","url":null,"abstract":"<p><strong>Background: </strong>Nebulised unfractionated heparin may attenuate COVID-19 ARDS by reducing pulmonary microvascular thrombosis, blocking SARS-CoV-2 entry into cells, and decreasing lung inflammation. COVID-19 patients with a raised D-dimer have areas of pulmonary hypoperfusion on CT perfusion scans of the lung and have increased mortality risk.</p><p><strong>Methods: </strong>This was a phase Ib/IIa open-label multi-centre, randomised controlled trial. The study was designed to evaluate whether nebulised unfractionated heparin decreased D-dimer concentrations, with safety as a co-primary outcome.</p><p><strong>Results: </strong>Forty patients were recruited, with 20 patients into each group. Mean age was 56.6 (SD 11.5) in the heparin group and 51.3 (SD 14.7) in the standard care group, while 60% of participants were male. There was no change in D-dimers from baseline to day 10 (heparin group mean change - 316.5, [SD 1840.3] and control group mean change - 321.7 [SD 3589.4]; p = 0.996). Fourteen patients suffered at least one serious adverse event, 9 patients the Heparin group and 5 in the control group. Eight patients had one or more bleeding events, 5 in the heparin group and 3 in the control group, but were no cases of pulmonary bleeding, of severe haemorrhage or of heparin-induced thrombocytopenia. Patients receiving heparin therapy had lower PaO₂/FiO₂ ratios, increased oxygenation indices, and decreased ROX index profiles, up to day 10. The time to separation from respiratory support, and the time to ICU or hospital discharge was similar in both groups. There were 3 deaths in the Heparin group and 2 in the control group.</p><p><strong>Conclusions: </strong>Nebulised unfractionated heparin was safe and well tolerated, but did not reduce D-dimer concentrations, and worsened oxygenation indices in patients with COVID-19 ARDS.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"15"},"PeriodicalIF":2.8,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated positron emission tomography tracing neutrophil elastase in a porcine intensive-care sepsis model.","authors":"Frida Wilske, Olof Eriksson, Rose-Marie Amini, Sergio Estrada, Helena Janols, Amina Khalil, Anders Larsson, Miklós Lipcsey, Sara Mangsbo, Jonathan Sigfridsson, Jan Sjölin, Paul Skorup, Anders Wall, Viola Wilson, Markus Castegren, Gunnar Antoni","doi":"10.1186/s40635-025-00721-3","DOIUrl":"10.1186/s40635-025-00721-3","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil granulocytes are important parts of the defence against bacterial infections. Their action is a two-edged sword, the mediators killing the intruding bacteria are at the same time causing tissue damage. Neutrophil activation is part of the dysregulated immune response to infection defining sepsis and neutrophil elastase is one of the powerful proteases causing both effects and damage. Inhibition of neutrophil elastase has been tried in sepsis and ARDS, so far with inconclusive results.</p><p><strong>Methods: </strong>We used positron emission tomography (PET) combined with computed tomography (CT) and the selective and specific neutrophil elastase inhibitor PET-tracer [¹¹C]GW457427 ([¹¹C]NES), in an intensive care unit porcine Escherichia coli sepsis model with the primary aim to visualise the biodistribution of neutrophil elastase in the initial acute phase of the septic reaction. Repeated PET-CT investigations were performed before and after induction of sepsis.</p><p><strong>Results: </strong>At baseline [¹¹C]NES uptake was found in the bone marrow, spleen and liver. The uptake in the bone marrow was markedly increased two hours into the sepsis, whereas in spleen and liver the uptake was not as markedly changed compared to baseline. At 4 h after the sepsis induction [¹¹C]NES in the bone marrow decreased while the uptake increased in the spleen, liver and lungs.</p><p><strong>Conclusion: </strong>The neutrophil elastase PET-tracer [¹¹C]NES is a novel and unique instrument to study the acute innate neutrophil immune response in sepsis and associated vital organ failure. We here present images and quantitative data of the neutrophil elastase distribution the first hours of acute experimental sepsis. Surprisingly, a pronounced increase of neutrophil elastase was found in the bone marrow 2 h into the sepsis reaction followed at 4 h by increase in the liver, spleen and lungs and a concomitant reduction of the tracer uptake in bone marrow.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"14"},"PeriodicalIF":2.8,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regional cerebral oxygen saturation during initial mobilization of critically ill patients is associated with clinical outcomes: a prospective observational study.","authors":"Ryota Imai, Takafumi Abe, Kentaro Iwata, Seigo Yamaguchi, Takeshi Kitai, Atsuhiro Tsubaki","doi":"10.1186/s40635-025-00722-2","DOIUrl":"10.1186/s40635-025-00722-2","url":null,"abstract":"<p><strong>Background: </strong>Vital signs help determine the safety of early mobilization in critically ill patients in intensive care units. However, none of these variables directly assess cerebral circulation. Therefore, we aimed to investigate the relationship of regional cerebral oxygen saturation (rSO₂) and vital signs with in-hospital death in critically ill patients.</p><p><strong>Methods: </strong>This prospective study included critically ill patients admitted to the Uonuma Kikan Hospital Emergency Center who received physical therapy between June 2020 and December 2022. We continuously measured rSO₂ during the initial mobilization using a wearable brain near-infrared spectroscopy device. With in-hospital death as the primary endpoint, the association between rSO₂ and in-hospital death was assessed in Analysis 1 to determine the rSO₂ cut-off value that predicts in-hospital death. In Analysis 2, patients were categorised into survival and non-survival groups to examine the temporal changes in vital signs and rSO₂ associated with postural changes during mobilization.</p><p><strong>Results: </strong>Of the 132 eligible patients, 98 were included in Analysis 1, and 70 were included in Analysis 2. Analysis 1 demonstrated that lower premobilization rSO₂ was independently associated with in-hospital death (odds ratio 0.835, 95% confidence interval 0.724-0.961, p = 0.012). Receiver operating characteristic curve analysis identified an optimal rSO₂ cut-off value of 57% for predicting in-hospital death (area under the curve 0.818, sensitivity 73%, specificity 83%). Analysis 2 showed that rSO₂ changes during mobilization were unrelated to changes in vital signs, suggesting rSO₂ as an independent prognostic marker.</p><p><strong>Conclusions: </strong>The results suggest that rSO₂ measured during initial mobilization is associated with in-hospital death in critically ill patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"13"},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11790542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}