Intensive Care Medicine Experimental最新文献

{"title":"29-mRNA host response signatures for classification of bacterial infection, viral infection and disease progression in COVID-19 pneumonia: a post hoc analysis of the SAVE-MORE randomized clinical trial.","authors":"Evdoxia Kyriazopoulou, Antigone Kotsaki, Asimina Safarika, Garyfallia Poulakou, Haralampos Milionis, Simeon Metallidis, Georgios Adamis, Archontoula Fragkou, Aggeliki Rapti, Pierluigi Del Vecchio, Ioannis Kalomenidis, Danae Kitzoglou, Andrea Angheben, Ilias Kainis, Konstantina Iliopoulou, Francesco Saverio Serino, Petros Bakakos, Vassiliki Tzavara, Sofia Ioannou, Lorenzo Dagna, Katerina Dimakou, Glykeria Tzatzagou, Maria Chini, Matteo Bassetti, Vasileios Kotsis, George Tsoukalas, Carlo Selmi, Sofia Nikolakopoulou, Michael Samarkos, Michael Doumas, Aikaterini Masgala, Ilias Papanikolaou, Aikaterini Argyraki, Karolina Akinosoglou, Styliani Symbardi, Periklis Panagopoulos, George N Dalekos, Oliver Liesenfeld, Timothy E Sweeney, Purvesh Khatri, Evangelos J Giamarellos-Bourboulis","doi":"10.1186/s40635-025-00777-1","DOIUrl":"10.1186/s40635-025-00777-1","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers based on host response signatures are currently under development for the critically ill. We applied a 29-mRNA classifier for the diagnosis and prognosis of suspected acute infection and sepsis (TriVerity^™, Inflammatix Inc.) in patients hospitalized with COVID-19.</p><p><strong>Methods: </strong>We applied three scores from locked classifiers (IMX-BVN-4 and IMX-SEV-4) from the 29-mRNA TriVerity^™ blood test in participants of the SAVE-MORE randomized clinical trial (ClinicalTrials.gov NCT04680949) at baseline and days 4 and 7 of treatment, to classify bacterial infection, viral infection and decompensation. Participants were adults hospitalized with confirmed COVID-19 pneumonia and plasma soluble urokinase plasminogen activator receptor (suPAR) levels of ≥ 6 ng/ml, randomized to placebo or anakinra treatment.</p><p><strong>Results: </strong>A total of 471 patients were studied. At baseline nearly 90% had a Very Low or Low IMX-BVN-4 Bacterial Score and Moderate, High or Very High IMX-BVN-4 Viral Score. Anakinra treatment had an effect on the expression of genes indicating IMX-SEV-4 High or Very High scores after a 7 day treatment compared to baseline (12.9% of anakinra-treated patients continued being classified as high severity vs 20.4% of placebo-treated patients, p 0.046).</p><p><strong>Conclusions: </strong>The classifiers were well tested in COVID-19 pneumonia and may become a useful tool for hospitalized patients.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"67"},"PeriodicalIF":2.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527827","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":"Digital twins suggest a mechanistic basis for differing responses to increased flow rates during high-flow nasal cannula therapy.","authors":"Hossein Shamohammadi, Sina Saffaran, Roberto Tonelli, Valentina Chiavieri, Giacomo Grasselli, Enrico Clini, Tommaso Mauri, Declan G Bates","doi":"10.1186/s40635-025-00773-5","DOIUrl":"10.1186/s40635-025-00773-5","url":null,"abstract":"<p><strong>Background: </strong>Inconsistent responses to increased flow rates have been observed in patients with acute hypoxemic respiratory failure (AHRF) treated with high-flow nasal cannula (HFNC) therapy, with a significant minority in two recent studies exhibiting increased respiratory effort at higher flow rates. Digital twins of patients receiving HFNC could help understand the physiological basis for differing responses.</p><p><strong>Methods: </strong>Patient data were collated from previous studies in AHRF patients who were continuously monitored with electrical impedance tomography and oesophageal manometry and received HFNC at flow rates of 30, 40 or 45 L/min. Patients, based on their responses to an increase in flow rate to 60 L/min, were categorised into two groups: five responders with reduced oesophageal pressure swings ΔP_es (- 3.1 cmH₂O on average), and five non-responders with increased ΔP_es (+ 2.0 cmH₂O on average). Two cohorts of digital twins were created based on these data using a multi-compartmental mechanistic cardiopulmonary simulator. Digital twins' responses to increased HFNC flow rates (60 L/min) were simulated with constant respiratory effort to assess changes in gas exchange and lung mechanics, and with varying respiratory effort to quantify their combined effects on lung mechanics and P-SILI indicators.</p><p><strong>Results: </strong>The digital twins accurately replicated patient-specific responses at all flow rates. Responder digital twins showed a mean 20 mL/cmH₂O increase in lung compliance at higher flow rates, versus a 6 mL/cmH₂O decrease in compliance with non-responders. In digital twins of responders versus non-responders, increased flow rates produced a mean change in lung stress of - 1.5 versus + 1.2 cmH₂O, in dynamic lung strain of - 8.8 versus + 16.4%, in driving pressure of - 1.3 versus + 1.1 cmH₂O, and in mechanical power of - 0.8 versus + 1.2 J/min. Higher flow rate dependent positive end-expiratory pressure in digital twins of non-responders did not cause recruitment, and reduced tidal volumes due to higher functional residual capacities-to compensate for the resulting worsened gas-exchange, non-responders increased their respiratory effort, in turn increasing patient self-inflicted lung injury (P-SILI) indicators. In digital twins of responders, reductions in tidal volumes due to higher FRCs resulting from increased PEEP were outweighed by alveolar recruitment. This increased compliance and improved gas exchange, permitting reduced respiratory effort and decreases in P-SILI indicators.</p><p><strong>Conclusions: </strong>Failure to reduce spontaneous respiratory efforts in response to increased HFNC flow rates could be due to a deterioration in lung mechanics, with an attendant risk of P-SILI.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"66"},"PeriodicalIF":2.8,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505641","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":"Animal models of critical care illnesses: current reality, future directions.","authors":"John F Fraser, Shigeaki Inoue, Yongming Yao, Marcin F Osuchowski","doi":"10.1186/s40635-025-00776-2","DOIUrl":"10.1186/s40635-025-00776-2","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"65"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484291","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":"Citrate regional anticoagulation of 500 ml/min of extracorporeal blood flow: an experimental study.","authors":"Sebastiano Maria Colombo, Luigi Vivona, Michele Battistin, Vittorio Scaravilli, Alessandro Galli, Chiara Anzanello, Elisa Cipriani, Francesca Gori, Serena Todaro, Carlo Valsecchi, Daniele Dondossola, Anna Paola Marcello, Andrea Carlin, Antonio Pesenti, Giacomo Grasselli, Alberto Zanella","doi":"10.1186/s40635-025-00771-7","DOIUrl":"10.1186/s40635-025-00771-7","url":null,"abstract":"<p><strong>Background: </strong>Regional citrate anticoagulation (RCA) is the most widespread technique which allows to perform extracorporeal treatments, avoiding the complications of systemic anticoagulation. Due to limited citrate clearance, RCA may be applied only to low extracorporeal blood flows (i.e., BF < 200 ml/min). In this proof of concept study, we developed an innovative RCA technique based on Ion Exchange Resin (i-ER) technology capable of regionally anticoagulating BF up to 500 mL/min.</p><p><strong>Methods: </strong>Six healthy swine (41.0 ± 3.1 kg) were sedated, mechanically ventilated, and connected to a prototype extracorporeal circuit for continuous renal replacement therapy featuring a citrate-removal stage based on absorbent materials and replacement fluids. Blood flow was 500 ml/min. Sodium citrate was continuously infused at the circuit inlet (5 mmol/L). Heparin was continuously infused. Citrate concentration and Kaolin Heparinase thromboelastography (KH-TEG) were measured on arterial blood, extracorporeal blood downstream the citrate infusion port, and downstream the citrate-removal stage. Samples were collected at baseline, 2, 8, 15, 30, 45, 60, 90, and 120 min for citrate and at baseline, 2, 30, 60, and 120 min for KH-TEG. Calcium chloride was infused to maintain systemic ionized calcium within the physiological range. The experiment lasted 2 h.</p><p><strong>Results: </strong>During the whole experiment, KH-TEG in the artery showed normal coagulation: reaction time (R) was 8.30[6.80-10.10] min, with Maximum Amplitude (MA) of 71.70[67.90-77.00] mm, while in the extracorporeal circuit, KH-TEG showed no sign of clot formation R > 60 min, MA = 0 mm. Citrate concentrations in blood samples were stable within 30 min, then slowly increased. The efficacy of the citrate-removal dropped from 93.8 ± 3.4% to 48.3 ± 1.5% at the beginning (2 min) and at the end (2 h), respectively (p < 0.001), due to loss of efficiency of the iERs.</p><p><strong>Conclusions: </strong>This study demonstrates that iER-based RCA is a feasible and effective technique for regional anticoagulation of extracorporeal blood flow up to 500 mL/min for 60 min without significant complications.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"64"},"PeriodicalIF":2.8,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475110","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":"Physiology, imaging and proteomics of non-ventilated vs. non-perfused lung injury: an experimental study.","authors":"Anna Damia, Ines Marongiu, Elena Spinelli, Francesco Damarco, Clarissa Uslenghi, Giovanni Lorenzo Rumi, Michele Battistin, Caterina Lonati, Alessandra Maria Storaci, Gianluca Lopez, Maria Rosaria De Filippo, Fabiana Madotto, Cristina Banfi, Alice Mallia, Lorenzo Rosso, Valentina Vaira, Tommaso Mauri","doi":"10.1186/s40635-025-00772-6","DOIUrl":"10.1186/s40635-025-00772-6","url":null,"abstract":"<p><strong>Background: </strong>The exclusion of one lung from ventilation or pulmonary artery perfusion triggers pathological mechanisms that can lead to lung injury. Although the final effect is similar for both insults, the underlying mechanisms may differ. Primary aim of this study was to compare severity of lung injury between non-ventilated (NVLI) and non-perfused (NPLI) lung injury. Secondary aims were to compare physiologic, imaging and proteomic signatures of NVLI vs NPLI.</p><p><strong>Methods: </strong>Sedated and paralyzed healthy female piglets (weight = 36 ± 5 kg) were mechanically ventilated for 24 h after left pulmonary artery ligation (NPLI group, n = 11) or exclusion from ventilation of the left lung (NVLI group, n = 10). Physiological data including electrical impedance tomography imaging of regional ventilation and perfusion were collected. Histological scoring was performed blindly as well as proteomic analysis of broncho-alveolar lavage (BAL) fluids and lung tissue samples at the end of the experiment.</p><p><strong>Results: </strong>The left lung of both groups received similarly low fraction (< 20%) of blood flow. The left side of the NPLI group was characterized by ventilation distributed only to the dead space and high ventilation/perfusion compartments, while the left lung of the NVLI group was characterized by perfusion only to the shunt compartment. The left lung of the NVLI group showed severe pulmonary vascular dysfunction (pulmonary vascular resistance > 2000 dyne/s/cm^-5), while the left lung of the NPLI group was ventilated with raising inspiratory stress (driving pressure > 20 cmH₂O at the end of the experiment and progressive decline in left lung compliance). The histologic lung injury score was higher for the left lung of the NVLI group compared to the left lung of the NPLI (left histological score: 10.3 ± 2.0 vs 6.4 ± 1.6, p < 0.0001), and pro-inflammatory alveolar cytokines were similarly more expressed in the left lung of the NVLI versus NPLI group (IL-1β: 418 ± 416 vs 53 ± 71, p < 0.001; IL-6: 406 ± 455 vs 99 ± 93, p = 0.036). Proteomic analysis showed signature specific for the two injuries, with two proteins, namely PRDX5 and DCTN1, being upregulated in NVLI left lung compared with the left NPLI lung. The right lung developed injury only in the NVLI group (right histological score: 5.5 ± 1.9 vs 3.0 ± 0.7, p < 0.001).</p><p><strong>Conclusions: </strong>Lung injury is more severe in terms of lung histological score in the collapsed lung of the NVLI group and involves also contralateral areas. At the mechanistic level, NVLI has specific physiologic mechanisms like vascular dysfunction and inflammation and presents unique proteomic profile in comparison to NPLI.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"63"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475111","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":"Left ventricular systolic longitudinal strain in mechanically ventilated patients in the intensive care unit: assessment of global and chamber reproducibility.","authors":"Matías Pécora, Piero Pastorini, Roberto Farolini, Gastón Burghi, F Javier Hurtado","doi":"10.1186/s40635-025-00770-8","DOIUrl":"10.1186/s40635-025-00770-8","url":null,"abstract":"<p><strong>Introduction: </strong>In the intensive care unit (ICU), left ventricular systolic function is traditionally assessed by measuring the left ventricular ejection fraction (LVEF). Recently, left ventricular global systolic longitudinal strain (SL-S) has emerged as a more sensitive marker of myocardial function in this setting. However, obtaining high-quality echocardiographic images remains a significant challenge, particularly in patients undergoing invasive mechanical ventilation (IMV), and data on the feasibility and reproducibility of these measurements in critically ill patients are limited.</p><p><strong>Objective: </strong>To assess the feasibility and reproducibility (both global and per chamber) of SL-S and LVEF (both manual and automatic) in ICU patients under IMV.</p><p><strong>Materials and methods: </strong>Thirty ICU patients receiving IMV were randomly selected. The feasibility and reproducibility of SL-S (global and per chamber) and LVEF were assessed using both manual and automatic methods. The analysis was performed using the intraclass correlation coefficient (ICC) with its 95% confidence interval (CI), and Bland-Altman analysis (BA), which reported the mean difference and limits of agreement (lower-upper limits of agreement).</p><p><strong>Results: </strong>SL-S was feasible in 70% of patients and demonstrated excellent intra- and interobserver reproducibility for both manual and automatic methods. Intraobserver reproducibility for automatic SL-S: ICC 0.97 (CI: 0.94-0.99), BA 0.26 (-1.89 to 2.40) and interobserver reproducibility: ICC 0.96 (CI: 0.92-0.98), and BA 0.53 (-2.41 to 3.47). The reproducibility of manual SL-S was comparable to automatic measurements. Additionally, the reproducibility per chamber was excellent. LVEF was feasible in 80% of patients. Manual LVEF (Simpson's biplane) reproducibility demonstrated good reproducibility: intraobserver ICC: 0.82 (CI: 0.48-0.93), BA -5.00 (-19.70 to 9.70); interobserver ICC 0.78 (CI: 0.55-0.91), BA 7.50 (-5.40 to 20.40). Automatic LVEF (auto-LVEF) demonstrated excellent reproducibility: intraobserver ICC: 0.94 (CI: 0.86-0.98), BA -0.95 (-10.02 to 8.13); and interobserver ICC: 0.94 (CI: 0.87-0.97), BA 1.75 (-6.38 to 10.33).</p><p><strong>Conclusion: </strong>SL-S (global and per chamber) and auto-LVEF were feasible and showed excellent reproducibility. LVEF demonstrated the highest feasibility, while SL-S exhibited the greatest reproducibility. These parameters may represent a useful tool in the evaluation of LV function in ICU patients under IMV.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"62"},"PeriodicalIF":2.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12173981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316853","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":"Advancing omics technologies in acute respiratory distress syndrome: paving the way for personalized medicine.","authors":"Lou'i Al-Husinat, Mohammad Araydah, Sarah Al Sharie, Saif Azzam, Denise Battaglini, Arqam Alrababah, Rana Haddad, Khaled Al-Asad, Claudia C Dos Santos, Marcus J Schultz, Fernanda F Cruz, Pedro L Silva, Patricia R M Rocco","doi":"10.1186/s40635-025-00766-4","DOIUrl":"10.1186/s40635-025-00766-4","url":null,"abstract":"<p><p>Despite advances in critical care, acute respiratory distress syndrome (ARDS) remains a potentially life-threatening condition with high mortality. The heterogeneous nature of ARDS, caused by diverse etiologies, poses considerable challenges to accurate diagnosis, treatment, and prognosis. Conventional methods often fail to elucidate the pathophysiology of ARDS, thus limiting therapeutic efficacy. However, recent advances in omics technologies, including genomics, transcriptomics, proteomics, metabolomics, lipidomics, and epigenomics, have provided deeper insights into ARDS mechanisms. Genomic studies have identified genetic variants associated with ARDS susceptibility, such as polymorphisms in genes encoding angiotensin-converting enzyme, surfactant proteins, toll-like receptor 4, interleukin-6, Fas/FasL, and vascular endothelial growth factor, offering potential therapeutic targets. Transcriptomic and proteomic reveal distinct biomarker profiles associated with ARDS pathogenesis, including dysregulated inflammatory signaling, epithelial and endothelial barrier dysfunction, and compromised immune responses. Metabolomics has highlighted biomarkers, such as phenylalanine and choline, aiding in severity assessment, subphenotype stratification, and treatment response prediction. Lipidomics has uncovered disruptions in lipid metabolism, including altered phospholipids, sphingolipids, and eicosanoids, with key lipid species such as lysophosphatidylcholine and ceramide emerging as biomarkers for severity and outcomes. Epigenomics explores DNA methylation, histone modifications, and non-coding RNAs, revealing their role in regulating inflammation, immune responses, and tissue repair in ARDS. These epigenetic changes hold promise for biomarker discovery and personalized therapy. Integrating these omics technologies advances our understanding of ARDS pathophysiology, enabling precision medicine approaches. This review examines the latest advancements in omics research related to ARDS, emphasizing its role in developing personalized diagnostics and therapeutic strategies to improve disease monitoring, prognosis, and treatment outcomes.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"61"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144283796","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":"Prediction of lung overdistension during mechanical ventilation using micro-RNA and gene expression.","authors":"Cecilia López-Martínez, Paula Martín-Vicente, Laura Amado-Rodríguez, Inés López-Alonso, Margarita Fernández-Rodríguez, Adrián González-López, Pablo Martínez-Camblor, Juan Gómez, Andrew J Boyle, Cecilia M O'Kane, Daniel F McAuley, James N Tsoporis, Claudia Dos Santos, Guillermo M Albaiceta","doi":"10.1186/s40635-025-00768-2","DOIUrl":"10.1186/s40635-025-00768-2","url":null,"abstract":"<p><strong>Background: </strong>Overstretching of lung parenchyma may lead to injury, especially during mechanical ventilation. To date, there are no specific biomarkers of lung stretch, but transcriptomic signatures have not been explored. Our objective was to identify stretch-specific signatures using micro-RNA and gene expression.</p><p><strong>Methods: </strong>Data on micro-RNA and RNA expression in response to stretch in experimental models were systematically pooled. Signatures were identified as those micro-RNAs or genes with differential expression in samples from stretched cells or tissues, and optimized using a greedy algorithm. Expression data was used to calculate transcriptomic scores. The accuracy of these scores was validated in animal models of lung injury, ex vivo mechanically ventilated human lungs, and bronchoalveolar lavage fluid (BALF, n = 7) and in serum samples (n = 31) of mechanically ventilated patients.</p><p><strong>Results: </strong>Six micro-RNAs (mir-383, mir-877, mir-130b; mir-146b, mir-181b, and mir-26b) were differentially expressed in stretched cell cultures (n = 24). Amongst the genes regulated by these micro-RNAs, a 451-gene signature was identified in vitro (n = 106) and refined using data from animal models (n = 143) to obtain a 6-gene signature (Lims1, Atp6v1c1, Dedd, Bclb7, Ppp1r2 and F3). Transcriptomic scores were significantly higher in samples submitted to stretch or injurious mechanical ventilation. The microRNA and RNA signatures were validated in human tissue, BALF and serum, with areas under the ROC curve between 0.7 and 1 to identify lung overdistention.</p><p><strong>Conclusions: </strong>Lung cell stretch induces the expression of specific micro-RNA and genes. The potential of these signatures to identify lung stretch in a clinical setting must be explored.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"60"},"PeriodicalIF":2.8,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247752","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":"Intensive care infection score: ICIS discriminates between infected and uninfected critically ill patients in routine intensive care unit practice.","authors":"Emre Deniz, Stefanie Klatte, Nilgün Tekin-Bubenheim, Mathias Zimmermann","doi":"10.1186/s40635-025-00767-3","DOIUrl":"10.1186/s40635-025-00767-3","url":null,"abstract":"<p><strong>Background: </strong>Diagnosis of infectious inflammation is challenging as acute phase protein expression is nonspecific, limiting the utility of well-established biomarkers, such as procalcitonin (PCT) and C-reactive protein (CRP). The emergent blood cell-derived Intensive Care Infection Score (ICIS) is an innovative approach for the sensitive and specific diagnosis of infection in intensive care unit (ICU) patients. This study aimed to confirm the suitability of routine ICIS use in various ICU settings.</p><p><strong>Methods: </strong>This retrospective study included 115 patients from three ICUs. Seventy-five patients were diagnosed as infected and 40 as uninfected. ICIS, CRP, and PCT were compared to routine clinical assessment to evaluate their effectiveness in predicting infection in critically ill patients.</p><p><strong>Results: </strong>ICIS was superior to CRP and PCT in discriminating infection from no infection on day 1 in the ICU. In receiver operating characteristic curve analysis, ICIS exhibited an AUC = 0.984, sensitivity of 90.7%, specificity of 97.5%, positive predictive value (PPV) of 97.7% and negative predictive value (NPV) of 89.9%, by the best cutoff value of 3. CRP gave an AUC = 0.727, PPV of 70.0% and NPV of 67.8% by best cutoff value of 8.3 mg/L with a sensitivity of 74.7% and specificity of 62.5%. The best cutoff value of 0.9 ng/mL was calculated for PCT with an AUC = 0.812, PPV of 84.4%, NPV of 70.3%, sensitivity of 69.3% and specificity of 85.0%.</p><p><strong>Conclusions: </strong>ICIS outperformed CRP and PCT in identifying infection in critically ill patients across different ICU settings on the first day in the ICU. The high NPV emphasizes the potential of ICIS as an adjuvant tool to rule out infections thereby facilitating the reduction of antibiotic overuse and consequently limiting antimicrobial resistance (AMR) development. ICIS appears suitable for routine implementation in various ICU settings.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"58"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225387","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":"Sub-phenotyping in critical care: a valuable strategy or methodologically fragile path?","authors":"Jim M Smit, Annemijn H Jonkman, Jesse H Krijthe","doi":"10.1186/s40635-025-00769-1","DOIUrl":"10.1186/s40635-025-00769-1","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"59"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234012","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}