{"title":"Comment: ineffectiveness of hemoadsorption in large animals with abdominal sepsis-a randomized controlled porcine study.","authors":"Gerd Klinkmann, Matteo Marcello, Faeq Husain-Syed, Gonzalo Ramírez-Guerrero, Thiago Reis, Claudio Ronco","doi":"10.1186/s40635-025-00764-6","DOIUrl":"https://doi.org/10.1186/s40635-025-00764-6","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"76"},"PeriodicalIF":2.8,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alfio Bronco, Francesco Fazzi, Liliana Amendolagine, Roberta Garberi, Stefano Cattaneo, Floriana Ferrari, Ezio Bonanomi, Giuseppe Foti, Emanuele Rezoagli
{"title":"Electrical impedance tomography in congenital heart disease: advancing non-invasive pulmonary perfusion assessment at bedside.","authors":"Alfio Bronco, Francesco Fazzi, Liliana Amendolagine, Roberta Garberi, Stefano Cattaneo, Floriana Ferrari, Ezio Bonanomi, Giuseppe Foti, Emanuele Rezoagli","doi":"10.1186/s40635-025-00783-3","DOIUrl":"10.1186/s40635-025-00783-3","url":null,"abstract":"<p><strong>Background: </strong>In congenital heart disease (CHD), the evaluation of pulmonary perfusion remains challenging, particularly in pediatric critically ill patients, where anatomical anomalies significantly impact pulmonary blood flow. We aim at demonstrating the reliability and the accuracy to investigate pulmonary perfusion in the presence of CHD by using electrical impedance tomography (EIT), a non-invasive, bedside, real-time, radiation-free imaging technique that assesses lung ventilation and perfusion.</p><p><strong>Results: </strong>This methodologies series explores the application of EIT in three pediatric critically ill patients with CHD admitted to the Pediatric Intensive Care Unit at Papa Giovanni XXIII Hospital, Bergamo, Italy: (1) a newborn post-corrective surgery for transposition of the great arteries; (2) an infant post-repair of tetralogy of Fallot with bilateral pulmonary branch stenosis; and (3) an infant with severe hypoxemia following Stage I Norwood-Sano repair. EIT perfusion was performed by injecting a bolus of 0.5 ml/kg of 5% saline through a central venous catheter during an inspiratory hold and was compared to standard imaging techniques that assess pulmonary perfusion. EIT findings were consistent with conventional imaging modalities that are not available at bedside (i.e., computed tomography, magnetic resonance imaging, angiography) or that do not allow regional assessment of lung perfusion and are operator dependent (i.e., ultrasound), demonstrating the reliability and the accuracy of EIT assessment. EIT provided critical insights into ventilation-perfusion dynamics, allowing to identify perfusion defects and guiding clinical decisions.</p><p><strong>Conclusions: </strong>This clinical investigation highlights the potential of EIT to improve pulmonary perfusion monitoring and clinical management of complex CHD cases in pediatric critically ill patients. Further research is needed to establish standardized protocols and validate the EIT clinical utility in larger cohorts.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"75"},"PeriodicalIF":2.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690113","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}
Muhtadi Alnababteh, Xizhong Cui, Mark Jeakle, Yan Li, Nancy Terry, Tom Gamble, Junfeng Sun, Shreya Kanth, Peter Q Eichacker, Parizad Torabi-Parizi
{"title":"A systematic review of adult animal models investigating ECMO use for ARDS: where to from here.","authors":"Muhtadi Alnababteh, Xizhong Cui, Mark Jeakle, Yan Li, Nancy Terry, Tom Gamble, Junfeng Sun, Shreya Kanth, Peter Q Eichacker, Parizad Torabi-Parizi","doi":"10.1186/s40635-025-00781-5","DOIUrl":"10.1186/s40635-025-00781-5","url":null,"abstract":"<p><strong>Background: </strong>Controlled clinical trials investigating ongoing questions about extracorporeal membrane oxygenation (ECMO) for patients with the acute respiratory distress syndrome (ARDS), including what the optimal mechanical ventilation (MV) tidal volume (TV) strategies are and whether ECMO potentiates injurious host responses, are difficult. We therefore conducted a systematic literature search and review to characterize studies investigating ECMO in adult animal lung injury models and to determine whether they inform these questions.</p><p><strong>Methods: </strong>A systematic literature search with relevant search terms was conducted of four data bases through 2/2/24.</p><p><strong>Results: </strong>Forty-five studies met inclusion criteria, and most parameters examined were represented similarly in studies with (n = 24) or without (n = 21) severe ARDS PaO<sub>2</sub>/FiO<sub>2</sub>s levels (≤ 100 mmHg or > 100 mmHg). Overall, while only 11 studies were published from 1971 to 2005, 5, 8, and 11 were published in subsequent 5-year periods up to 2020 and then 10 through 2/2/24 (Figure 1). Most studies investigated pig or sheep models (n = 32), but since 2016, six studies employed rat models. Eighteen studies administered lung lavage alone or with another lung injury challenge (17 with PaO<sub>2</sub>/FiO<sub>2</sub>s ≤ 100) and 9 used oleic acid. Although seven studies administered lipopolysaccharide, very different from clinical ARDS only one used a bacterial and none a viral challenge. Thirty-two studies employed V-V ECMO. The most frequent duration of ECMO investigated was 24 h in 16 studies but only 2 studies investigated longer periods (48 and 96 h). Differences in study questions, methodologies and outcome measures precluded formal meta-analysis. However, overall in studies that compared mechanical ventilation alone (MV) to ECMO groups or that compared differing ECMO groups: in 5 studies ECMO supported tidal volume reductions that approached apneic levels in 2; all but 1 of 10 studies indicated that ECMO with or without TV reductions either did not increase or reduced lung injury measures; 2 studies did while 4 did not find that ECMO aggravated molecular or cellular markers of inflammation; and only 2 studies examined host thrombotic responses with ECMO. Fig. 1 Flow diagram for the literature search CONCLUSION: Animal models to date have addressed important questions facing ECMO use for ARDS, but ones more closely simulating ARDS in patients appear warranted.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"74"},"PeriodicalIF":2.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12274183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659145","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}
Jim M Smit, Jasper Van Bommel, Diederik A M P J Gommers, Marcel J T Reinders, Michel E Van Genderen, Jesse H Krijthe, Annemijn H Jonkman
{"title":"Switching from controlled to assisted mechanical ventilation: a multi-center retrospective study (SWITCH).","authors":"Jim M Smit, Jasper Van Bommel, Diederik A M P J Gommers, Marcel J T Reinders, Michel E Van Genderen, Jesse H Krijthe, Annemijn H Jonkman","doi":"10.1186/s40635-025-00785-1","DOIUrl":"10.1186/s40635-025-00785-1","url":null,"abstract":"<p><strong>Background: </strong>Switching from controlled to assisted ventilation is crucial in the trajectory of intensive care unit (ICU) stay, but no guidelines exist. We described current practices, analyzed patient characteristics associated with switch success or failure, and explored the feasibility to predict switch failure.</p><p><strong>Methods: </strong>In this retrospective study, we obtained highly granular longitudinal ICU data sets from three medical centers, covering demographics, severity scores, vital signs, ventilation, and laboratory parameters. The primary endpoint was switch success, considering a switch attempt to be successful if a patient did not return to controlled ventilation for the next 72 h while alive, and to be failed otherwise. We compared the characteristics of patients with successful vs. failed first switch attempts at ICU admission, immediately before, and 3 h after the attempt. We trained LASSO logistic regression models to predict switch failure.</p><p><strong>Results: </strong>In 4524/6715 (67%) patients attempting a switch, the first attempt failed. The first switch attempt, regardless of success or failure, was generally made at normalized PaCO<sub>2</sub> and pH levels, with PEEP < 10 cmH<sub>2</sub>O and PaO<sub>2</sub>/FiO<sub>2</sub> indicating mild injury. Despite very similar baseline disease severity, switch failure was associated with significantly worse outcomes, including a 28-day mortality of 27% vs. 16% and median ventilator-free days of 16 vs. 22 (p < 0.001). Failed attempts were initiated significantly earlier than successful ones (median 1.8 vs. 1.3 days, p < 0.001). Before the switch, PaO<sub>2</sub>/FiO<sub>2</sub>, if measured at PEEP > 10 cmH<sub>2</sub>O, and respiratory system compliance was lower in patients with switch failure (median 185 vs. 205 mmHg, p < 0.001; 39 vs. 41 mL/cmH<sub>2</sub>O, P = 0.001), and post-switch, patients with switch failure experienced greater deterioration in gas exchange and minimal improvement in ventilatory parameters post-switch. Contrary to our hypotheses, patient characteristics for failed vs. successful switches were surprisingly similar, resulting in prediction models with limited discriminative performance.</p><p><strong>Conclusions: </strong>Approximately two-thirds of attempts to switch patients to assisted ventilation fail, which are associated with significantly worse clinical outcomes, despite similar baseline disease severity. Contrary to our hypotheses, patients with successful and failed attempts showed similar characteristics, making switch failure difficult to predict. These findings underscore the importance of preventing switch failures and, given the retrospective nature of this study, highlight the need for prospective studies to better understand the reasons for switch failure and when spontaneous breathing can be safely initiated.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"73"},"PeriodicalIF":2.8,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12267752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144642516","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}
Elissa M Milford, Dusan Marjanovic, Heidi Ho, Steven Wallis, Dominik F Draxler, Biswadev Mitra, Russell L Gruen, Robert Medcalf, Stephen Bernard, Colin McArthur, Marc Meagele, Brian Burns, Dashiell Gantner, Michael C Reade
{"title":"Tranexamic acid did not attenuate the acute rise in plasma syndecan-1 in a severely injured cohort: a laboratory analysis of the PATCH clinical trial.","authors":"Elissa M Milford, Dusan Marjanovic, Heidi Ho, Steven Wallis, Dominik F Draxler, Biswadev Mitra, Russell L Gruen, Robert Medcalf, Stephen Bernard, Colin McArthur, Marc Meagele, Brian Burns, Dashiell Gantner, Michael C Reade","doi":"10.1186/s40635-025-00784-2","DOIUrl":"10.1186/s40635-025-00784-2","url":null,"abstract":"<p><strong>Background: </strong>Injury to the vascular endothelium occurs in up to 34% of patients acutely following severe traumatic injury and can be quantified clinically by measuring the plasma concentration of syndecan-1 (SDC-1). Tranexamic acid (TXA) attenuates endothelial damage in animal and cell culture models and has been associated with lower SDC-1 levels after prehospital TXA administration. The aim of this study was to assess the association of prehospital TXA on SDC-1 levels in a more severely injured prehospital cohort.</p><p><strong>Methods: </strong>The PATCH-Trauma trial randomised patients to receive pre-hospital TXA or placebo. In this sub-cohort, SDC-1 was measured in blood samples collected on hospital admission, at 8 and 24 h. Relationships between SDC-1 levels over time, treatment groups, and outcomes were analyzed using regression modelling controlling for potential confounding factors.</p><p><strong>Results: </strong>There were 89 patients included, with 57 administered TXA and 32 administered placebo (per protocol). SDC-1 levels were available in 87 patients on arrival to hospital, 70 at 8 h, and 69 at 24 h. Patients had a median SDC-1 on admission of 106 ng/mL (IQR 88-137). There was no effect of TXA treatment on SDC-1 levels over the first 24 h of hospital admission, even after controlling for known confounders. There was no association between SDC-1 level at any time point and the development of deep vein thrombosis or sepsis, mortality at 28-days, or days alive and out of hospital, even after adjustment for confounding factors.</p><p><strong>Conclusion: </strong>Administration of TXA, initiated pre-hospital, did not affect SDC-1 levels in the first 24 h of hospital admission in this severely injured cohort. Further research is required to elucidate the mechanisms of the effect of TXA on the endothelium as well as the utility of SDC-1 as an endothelial biomarker.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"72"},"PeriodicalIF":2.8,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12254099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608288","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}
Taku Furukawa, Alemayehu H Jufar, Clive N May, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Sally G Hood, Ian E Birchall, Jaishankar Raman, Pei Chen Connie Ow, Anton Trask-Marino, Lachlan F Miles, Rinaldo Bellomo, Yugeesh R Lankadeva
{"title":"Recruitment of renal functional reserve by intravenous amino acid loading in a sheep model of cardiopulmonary bypass.","authors":"Taku Furukawa, Alemayehu H Jufar, Clive N May, Roger G Evans, Andrew D Cochrane, Bruno Marino, Peter R McCall, Sally G Hood, Ian E Birchall, Jaishankar Raman, Pei Chen Connie Ow, Anton Trask-Marino, Lachlan F Miles, Rinaldo Bellomo, Yugeesh R Lankadeva","doi":"10.1186/s40635-025-00774-4","DOIUrl":"10.1186/s40635-025-00774-4","url":null,"abstract":"<p><strong>Background: </strong>Cardiopulmonary bypass (CPB) may decrease the renal functional reserve (RFR). However, the temporal changes in RFR after during the recovery period after CPB remains unknown. We assessed RFR before and then weekly after CPB over four weeks following CPB in non-anaesthetised sheep.</p><p><strong>Methods: </strong>In 10 Merino ewes, amino acids were infused before CPB and weekly for four weeks to assess RFR. At each assessment, we measured renal blood flow (RBF), renal oxygen delivery (RDO<sub>2</sub>), creatinine clearance and medullary and cortical oxygenation. Histological assessment was performed at 4 weeks.</p><p><strong>Results: </strong>Before CPB, amino acid infusion increased RBF from (mean ± SD) 6.60 ± 1.64 to 8.56 ± 1.80 mL/kg/min, and RDO<sub>2</sub> from 0.80 ± 0.28 to 1.12 ± 0.37 mL O<sub>2</sub>/kg/min. These renal macro-circulatory responses remained consistent across all weekly assessments after CPB. Amino acid infusion also increased creatinine clearance (from 62.5 ± 15.0 to 110 ± 30.6 mL/h pre-CPB) throughout the study period. RFR remained unchanged over time (P = 0.53). However, compared with pre-CPB values, medullary (33.9 ± 9.0 pre-CPB to 15.1 ± 13.2 mmHg at 4 weeks, P = 0.0068) and cortical tissue PO<sub>2</sub> (46.0 ± 14.2 to 17.2 ± 6.5 mmHg, P = 0.0029) decreased over time. Furthermore, the response of the medullary (but not cortical) PO₂ to amino acid infusion changed over time (P = 0.0064). While medullary PO₂ did not change in response to amino acid infusion pre-CPB and at one week after CPB, it appeared to fall from two weeks thereafter (P = 0.039 and 0.091 at weeks 2 and 3, respectively). Despite preserved RFR, sheep exposed to CPB showed greater peritubular inflammation, interstitial fibrosis and tubular casts compared with healthy controls (P = 0.007, 0.021, 0.007, respectively).</p><p><strong>Conclusions: </strong>In this large mammalian model of CPB, weekly amino acid administration consistently recruited RFR over four weeks, despite the presence of histological injury. However, it was associated with the development of renal medullary hypoxia after two weeks. These findings highlight the complexity of the pathophysiological response of the kidney to CPB.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"71"},"PeriodicalIF":2.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144600327","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}
Emma Rademaker, Daan F L Filippini, Jelle L G Haitsma Mulier, Marleen A Slim, Rombout B E van Amstel, Sivasubramanium V Bhavani, Nicole P Juffermans, Harm-Jan S de Grooth, Lennie P G Derde, Olaf L Cremer, Lieuwe D J Bos
{"title":"Immunobiological effects of tocilizumab across respiratory subphenotypes in COVID-19 ARDS.","authors":"Emma Rademaker, Daan F L Filippini, Jelle L G Haitsma Mulier, Marleen A Slim, Rombout B E van Amstel, Sivasubramanium V Bhavani, Nicole P Juffermans, Harm-Jan S de Grooth, Lennie P G Derde, Olaf L Cremer, Lieuwe D J Bos","doi":"10.1186/s40635-025-00779-z","DOIUrl":"10.1186/s40635-025-00779-z","url":null,"abstract":"<p><strong>Background: </strong>Two distinct longitudinal respiratory subphenotypes have recently been described in COVID-19-related acute respiratory distress syndrome (ARDS). These subphenotypes exhibit dynamic immunobiological changes that may help guide immunomodulatory interventions. However, the extent to which the immune response is determined by respiratory subphenotype in the presence of concurrent immunomodulatory treatment remains unclear. We investigated the independent and combined effects of respiratory subphenotype and tocilizumab on inflammatory response and clinical outcomes.</p><p><strong>Methods: </strong>We analyzed patients from existing COVID-19 biobanks who were consecutively admitted to the ICU and received more than 4 days of invasive mechanical ventilation between March 2020 and May 2022. Patients were classified into two previously described longitudinal respiratory subphenotypes-characterized by mechanical power, minute volume and ventilatory ratio-referred to as 'low-power' and 'high-power' subphenotypes. We analyzed how tocilizumab treatment and respiratory subphenotype were associated with endothelial and inflammatory plasma biomarkers on days 0, 4 and 7, as well as with mortality.</p><p><strong>Results: </strong>720 patients were included, of whom 464 (64%) and 256 (36%) were assigned to the low- and high-power subphenotypes, respectively. 108 (23%) of the low-power subphenotype patients received tocilizumab, and 43 (17%) of the high-power subphenotype. 427 patients had plasma samples available. The high-power subphenotype was associated with slightly higher SP-D, thrombomodulin and TNF-RI plasma concentrations on the day of intubation compared to the low-power subphenotype, along with a more rapid increase in IL-6 and TNF-RI levels in subjects who had received tocilizumab treatment (β = 0.14 log ng/ml, p = 0.022, and β = 0.06 log ng/ml, p = 0.014, respectively). Tocilizumab treatment accounted for four times more variance in IL-6 and angiopoietin-2 levels than subphenotype, while subphenotype explained only a small proportion of the variance and slightly more than tocilizumab for TNF-RI and thrombomodulin. Subphenotype did not modify the association between tocilizumab and mortality (IPTW adjusted hazard ratio 1.18; 95%CI 0.60-2.33).</p><p><strong>Conclusion: </strong>Respiratory subphenotypes showed varying TNF-RI and IL-6 responses to tocilizumab, but these differences were only minor compared to the drug's overall immunobiological effect. This suggests that respiratory subphenotype should not determine tocilizumab treatment decisions.</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"70"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591107","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}
L Felipe Damiani, Roque Basoalto, Vanessa Oviedo, Leyla Alegria, Dagoberto Soto, M Consuelo Bachmann, Yorschua Jalil, Cesar Santis, David Carpio, Rodrigo Ulloa, Daniel Valenzuela, Magdalena Vera, Marcus J Schultz, Jaime Retamal, Alejandro Bruhn, Guillermo Bugedo
{"title":"Effect of decreasing respiratory rate on the mechanical power of ventilation and lung injury biomarkers: a randomized cross-over clinical study in COVID-19 ARDS patients.","authors":"L Felipe Damiani, Roque Basoalto, Vanessa Oviedo, Leyla Alegria, Dagoberto Soto, M Consuelo Bachmann, Yorschua Jalil, Cesar Santis, David Carpio, Rodrigo Ulloa, Daniel Valenzuela, Magdalena Vera, Marcus J Schultz, Jaime Retamal, Alejandro Bruhn, Guillermo Bugedo","doi":"10.1186/s40635-025-00782-4","DOIUrl":"10.1186/s40635-025-00782-4","url":null,"abstract":"<p><strong>Background: </strong>The respiratory rate (RR) is a key determinant of the mechanical power of ventilation (MP). The effect of reducing the RR on MP and its potential to mitigate ventilator-induced lung injury remains unclear.</p><p><strong>Objectives: </strong>To compare invasive ventilation using a lower versus a higher RR with respect to MP and plasma biomarkers of lung injury in COVID-19 ARDS patients.</p><p><strong>Methods: </strong>In a randomized cross-over clinical study in COVID-19 ARDS patients, we compared ventilation using a lower versus a higher RR in time blocks of 12 h. Patients were ventilated with tidal volumes of 6 ml/kg predicted body weight, and positive-end-expiratory pressure and fraction of inspired oxygen according to an ARDS network table. Respiratory mechanics and hemodynamics were assessed at the end of each period, and blood samples were drawn for measurements of inflammatory cytokines, epithelial and endothelial lung injury markers. In a subgroup of patients, we performed echocardiography and esophageal pressure measurements.</p><p><strong>Results: </strong>We enrolled a total of 32 patients (26 males [81%], aged 52 [44-64] years). The median respiratory rate during ventilation with a lower and a higher RR was 20 [16-22] vs. 30 [26-32] breaths/min (p < 0.001), associated with a lower median minute ventilation (7.3 [6.5-8.5] vs. 11.6 [10-13] L/min [p < 0.001]) and a lower median MP (15 [11-18] vs. 25 [21-32] J/min [p < 0.001]). No differences were observed in any inflammatory (IL-6, IL-8, and TNF-R1), epithelial (s-RAGE and SP-D), endothelial (Angiopoietin-2), or pro-fibrotic activity (TGF-ß) marker between high or low RR. Cardiac function by echocardiography, and respiratory mechanics using esophageal pressure measurements were also not different.</p><p><strong>Conclusions: </strong>Reducing the respiratory rate decreases mechanical power in COVID-19 ARDS patients but does not reduce plasma lung injury biomarkers levels in this cross-over study. Study registration This study is registered at clinicaltrials.gov (study identifier NCT04641897).</p>","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"69"},"PeriodicalIF":2.8,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144591195","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":"What can the machine teach us?","authors":"Edward J Schenck","doi":"10.1186/s40635-025-00775-3","DOIUrl":"10.1186/s40635-025-00775-3","url":null,"abstract":"","PeriodicalId":13750,"journal":{"name":"Intensive Care Medicine Experimental","volume":"13 1","pages":"68"},"PeriodicalIF":2.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575387","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}
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
{"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<sup>™</sup>, 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<sup>™</sup> 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}