Critical Care最新文献

{"title":"Commenting on baricitinib versus tocilizumab in mechanically ventilated patients with COVID-19: a nationwide cohort study","authors":"James Cheng Chung Wei, Poi Kuo, Po-Cheng Shih","doi":"10.1186/s13054-024-05116-6","DOIUrl":"https://doi.org/10.1186/s13054-024-05116-6","url":null,"abstract":"<p>We read with great interest the article by You et al., which provides valuable insights into the comparative efficacy of baricitinib and tocilizumab in mechanically ventilated COVID-19 patients [1]. While the study’s findings are important, especially regarding the lower 30-day mortality in the baricitinib group, we believe that the issue of confounding by indication was not sufficiently addressed and may have significantly influenced the results.</p><p>Confounding by indication occurs when treatment assignment is influenced by disease severity, leading to a bias in outcome comparison between treatment groups. In this study, patients in the tocilizumab group appeared to be more severely ill at baseline compared to those in the baricitinib group. Although the authors employed propensity score matching (PSM) to balance baseline characteristics, the data suggest that the tocilizumab group had a higher severity of illness, which could explain some of the observed differences in mortality. Notably, patients in the tocilizumab group had longer durations of mechanical ventilation prior to drug administration, higher use of extracorporeal membrane oxygenation (ECMO), and more severe comorbidities, as detailed in the supplementary tables. These factors strongly suggest that tocilizumab was more likely administered to patients in critical condition, potentially skewing the mortality comparison in favor of baricitinib.</p><p>Furthermore, while PSM is effective at balancing observable variables, it may not fully account for unmeasured or residual confounders, such as the timing of drug administration relative to disease progression or the specific clinical criteria that influenced treatment choices. Baricitinib was administered for a median of 8 days, while tocilizumab was often given as a single dose. This difference in treatment duration and pharmacodynamics could have further impacted the results. Baricitinib, with its broader anti-inflammatory effects and prolonged administration, may have provided a more sustained reduction in inflammation, whereas the single-dose nature of tocilizumab could have limited its efficacy in severely ill patients.</p><p>Additionally, the study does not provide sufficient detail regarding the criteria used to determine whether a patient received baricitinib or tocilizumab beyond the similar indications in general consideration [2]. Without understanding the clinical decision-making process, it is difficult to evaluate the extent to which confounding by indication may have influenced the results. If tocilizumab was preferentially administered to patients with more rapidly progressing or refractory disease, the higher mortality rate in this group might reflect underlying disease severity rather than a difference in drug efficacy [3]. </p><p>It may be beneficial to consider a subgroup analysis excluding patients requiring total parenteral nutrition (TPN), as those unable to tolerate enteral nutrition typically represent a mor","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"1 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What every intensivist needs to know about mpox","authors":"Siyao Zeng, Yue Li, Zhipeng Yao, Junbo Zheng, Hongliang Wang","doi":"10.1186/s13054-024-05114-8","DOIUrl":"https://doi.org/10.1186/s13054-024-05114-8","url":null,"abstract":"<p>The mpox virus is a zoonotic orthopoxvirus with a DNA genome. Based on genetic characteristics, the mpox virus is categorized into two main clades: clade I and clade II. Clade I is further subdivided into subclades Ia and Ib [1]. Clade I is predominantly found in Central Africa, while clade II primarily circulates in West Africa [2]. The clade IIb subclade of clade II caused the global mpox outbreak from 2022 to 2023, during which 86% of cases were among men who have sex with men (MSM) [1]. More than half of the reported mpox cases involve individuals who are co-infected with the human immunodeficiency virus (HIV) [3]. The 2024 mpox outbreak in the Democratic Republic of the Congo and neighboring countries is primarily caused by clade Ia [4]. Only in 2024, as of September 15, the Democratic Republic of the Congo has reported 25,757 cases of mpox, with 806 deaths [3]. In April 2024, scientists identified a new variant of clade I, named Ib, by analyzing samples collected in South Kivu Province, Democratic Republic of the Congo, from late 2023 to early 2024. Reports of infections caused by the Ib variant have increased over the past few months. The proportion of women infected with clade Ib was significantly higher (52%), with nearly one-third identifying as sex workers [1]. On August 15, Sweden reported its first case of mpox caused by the Ib variant. Thailand confirmed its first Ib variant mpox case on August 22 [4]. Compared to clade IIb, which caused the global mpox outbreak in 2022, clade Ia exhibits stronger human-to-human transmissibility and higher mortality and severity rates. As for the clade Ib, its characteristics remain unclear [5].</p><p>As the mpox outbreak intensifies, by August 31, 2024, a total of 106,310 confirmed cases have been reported across 123 countries worldwide, resulting in 234 laboratory-confirmed deaths [3]. In Africa, the confirmed and suspected mpox cases in 2024 have surpassed 17,500, far exceeding the 15,000 cases reported in 2023. In response to this escalating situation, the Africa Centers for Disease Control and Prevention (Africa CDC) declared mpox a “Public Health Emergency of Security Concern” (PHESC) for the first time on August 13, 2024. The following day, the World Health Organization (WHO) declared the mpox outbreak a “Public Health Emergency of International Concern” (PHEIC), urging global cooperation to prevent further spread [5]. The current mpox outbreak may pose new challenges for intensivists worldwide.</p><p>Mpox mainly spreads through transmission between animals and humans or from person to person. Animal-to-human transmission can happen through direct contact with an infected animal, being bitten or scratched, or consuming undercooked meat from an infected animal. Human-to-human transmission primarily occurs through direct contact with an infected individual’s skin or mucous membrane lesions, oral secretions, upper respiratory secretions (such as nasal discharge and mucus), and items contamina","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"63 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transpulmonary pressure monitoring in critically ill patients: pros and cons—correction of description of the non-invasive PEEP-step method for separation of lung and chest wall mechanics","authors":"Ola Stenqvist","doi":"10.1186/s13054-024-05125-5","DOIUrl":"https://doi.org/10.1186/s13054-024-05125-5","url":null,"abstract":"<p>In a recent pro/con review on transpulmonary pressure by Ball, Talmor and Pelosi [1], the authors describe in detail positioning, inflation, and calibration of the esophageal balloon catheter and different interpretations of absolute esophageal and transpulmonary pressure measurements. They also briefly describe the only method that does not require esophageal pressure for separation of lung and chest wall mechanics, the PEEP-step method (PSM). However, they dismiss PSM invoking completely erroneous assumptions that the method “assumes implicitly that the end-expiratory transpulmonary pressure estimated with esophageal manometry is zero regardless of the applied PEEP level”. But PEEP causes an increase in EELV, and during inflation of the lung, transpulmonary pressure increases in relation to the volume inflated and the elastic properties of the lung, ΔV × EL. In five successful PSM validation studies, based strictly on tidal airway and esophageal pressure variations [2,3,4,5,6], we have shown that calculated end-expiratory transpulmonary pressure (PLEE) increases as much as PEEP (= PAWEE) is increased. Consequently, the change in end-expiratory esophageal pressure, calculated as ΔPAWEE - ΔPLEE , is zero, which proves that the chest wall does not impede PEEP inflation and therefore lung elastance can be determined as ΔPEEP/ΔEELV. Thus, it is not transpulmonary pressure, but tidally calculated esophageal pressure that remains zero and the dismissal statement is completely erroneous and misleading.</p><p>In data on absolute esophageal and transpulmonary pressure from the Brochard group, analysis of tidal variation in esophageal and transpulmonary pressure fully confirms the validity of PSM (for details, see, Figs. S2, S3, S4 in e-supplement).</p><p>Below, I give a correct description of the background physiology, validation, mathematical derivation and measurement procedure of the PEEP-step method.</p><h3>Background physiology</h3><p>The PEEP step method (PSM) is a non-invasive, esophageal pressure free method for separation of lung and chest wall mechanics, based on the physiological conditions at functional residual capacity (FRC), where the contra-directional forces of the elastic recoil of the lung, striving to lower lung volume, and the rib cage spring out force, striving to expand the chest wall, balance each other. Thus, the chest wall complex does not lean on, or squeeze the lung at end-expiration at FRC. In case of a pneumothorax, the chest wall expands to 70–80% of total lung capacity (TLC). If end-expiratory lung volume instead is increased by PEEP, the rib cage spring out force will move the chest wall complex outwards in parallel with the lung volume increase, i.e., the ΔPEEP (= ΔPAWEE) of the ventilator only has to overcome the recoil of the lung. Consequently, the end-expiratory transpulmonary pressure (PLEE) will increase as much as PEEP is increased and EELV will increase in relation to the size of ΔPEEP and the elastic properti","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"87 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biochemical analysis of soft tissue infectious fluids and its diagnostic value in necrotizing soft tissue infections: a 5-year cohort study","authors":"Kai-Hsiang Wu, Po-Han Wu, Hung-Sheng Wang, Hsiu-Mei Shiau, Yung-Sung Hsu, Chih-Yi Lee, Yin-Ting Lin, Cheng-Ting Hsiao, Leng-Chieh Lin, Chia-Peng Chang, Pey-Jium Chang","doi":"10.1186/s13054-024-05146-0","DOIUrl":"https://doi.org/10.1186/s13054-024-05146-0","url":null,"abstract":"Necrotizing soft tissue infections (NSTI) are rapidly progressing and life-threatening conditions that require prompt diagnosis. However, differentiating NSTI from other non-necrotizing skin and soft tissue infections (SSTIs) remains challenging. We aimed to evaluate the diagnostic value of the biochemical analysis of soft tissue infectious fluid in distinguishing NSTIs from non-necrotizing SSTIs. This cohort study prospectively enrolled adult patients between May 2023 and April 2024, and retrospectively included patients from April 2019 to April 2023. Patients with a clinical suspicion of NSTI in the limbs who underwent successful ultrasound-guided aspiration to obtain soft tissue infectious fluid for biochemical analysis were evaluated and classified into the NSTI and non-necrotizing SSTI groups based on their final discharge diagnosis. Common extravascular body fluid (EBF) criteria were applied. Of the 72 patients who met the inclusion criteria, 10 patients with abscesses identified via ultrasound-guided aspiration were excluded. Based on discharge diagnoses, 39 and 23 patients were classified into the NSTI and non-necrotizing SSTI groups, respectively. Biochemical analysis revealed significantly higher albumin, lactate, lactate dehydrogenase (LDH), and total protein levels in the NSTI group than in the non-necrotizing SSTI group, and the NSTI group had significantly lower glucose levels and pH in soft tissue fluids. In the biochemical analysis, LDH demonstrated outstanding discrimination (area under the curve (AUC) = 0.955; p < 0.001) among the biochemical markers. Albumin (AUC = 0.884; p < 0.001), lactate (AUC = 0.891; p < 0.001), and total protein (AUC = 0.883; p < 0.001) levels also showed excellent discrimination. Glucose level (AUC = 0.774; p < 0.001) and pH (AUC = 0.780; p < 0.001) showed acceptable discrimination. When the EBF criteria were evaluated, the total scores of Light’s criteria (AUC = 0.925; p < 0.001), fluid-to-serum LDH ratio (AUC = 0.929; p < 0.001), and fluid-to-serum total protein ratio (AUC = 0.927; p < 0.001) demonstrated outstanding discrimination. Biochemical analysis and EBF criteria demonstrated diagnostic performances ranging from acceptable to outstanding for NSTI when analyzing soft tissue infectious fluid. These findings provide valuable diagnostic insights into the recognition of NSTI. Further research is required to validate these findings.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"32 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and functional characterization of a novel respiratory mask with full accordion cushioning to prevent air leaks and pressure injuries during non-invasive ventilation","authors":"Masahiko Hara, Masatake Tamaki","doi":"10.1186/s13054-024-05133-5","DOIUrl":"https://doi.org/10.1186/s13054-024-05133-5","url":null,"abstract":"&lt;p&gt;Non-invasive ventilation (NIV) is critical in the treatment of several respiratory diseases [1, 2]. However, interface air leakage and resultant pressure injury from tight-fitting can lead to intolerance or unsuccessful implementation of NIV [3, 4]. In response to these challenges, we have developed a new type of oronasal mask with full accordion cushioning designed to achieve effective sealing at lower pressures (Fig. 1 and Video. S1). Our mask incorporates six innovations: full accordion cushioning, turtle shell cover, nasal groove, folding function, visual pressure indicator, and soft medical-grade silicone (Videos. S2, S3, and S4). The mask is tapered toward the face, and it also incorporates multiple elastic adjustment lines to improve adaptability and fit, allowing the mask to “fold” snugly around the face. These elements enhance the mask’s ability to evenly distribute pressure and conform to different facial shapes, providing a secure fit at low pressures. The thickness of the accordion cushion decreases toward the face side, providing a visual indication of pressure application through the compression of the accordion valleys.&lt;/p&gt;&lt;figure&gt;&lt;figcaption&gt;&lt;b data-test=\"figure-caption-text\"&gt;Fig. 1&lt;/b&gt;&lt;/figcaption&gt;&lt;picture&gt;&lt;source srcset=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05133-5/MediaObjects/13054_2024_5133_Fig1_HTML.png?as=webp\" type=\"image/webp\"/&gt;&lt;img alt=\"figure 1\" aria-describedby=\"Fig1\" height=\"433\" loading=\"lazy\" src=\"//media.springernature.com/lw685/springer-static/image/art%3A10.1186%2Fs13054-024-05133-5/MediaObjects/13054_2024_5133_Fig1_HTML.png\" width=\"685\"/&gt;&lt;/picture&gt;&lt;p&gt;Structural and Functional Features of Our Novel Respiratory Mask with Full Accordion Cushioning. Overview of the mask (&lt;b&gt;A&lt;/b&gt;). The rear view of the mask from the face side shows the nasal groove (&lt;b&gt;B&lt;/b&gt;). Elastic adjustment lines are symmetrically aligned with six on the nasal side and eight on the chin side (&lt;b&gt;C&lt;/b&gt;). An illustration of the mask in clinical use (&lt;b&gt;D&lt;/b&gt;). A detailed view of the accordion structure, showing the five outermost ridges defined as accordion lines (&lt;b&gt;E&lt;/b&gt;). These ridges are sequentially labeled from the face side (first line, purple) to the cover side (fifth line, blue). Mechanical testing provided visual cues for the estimated pressure at which the mask would adhere to the skin (&lt;b&gt;F&lt;/b&gt;). See Video. S1 for the 3-dimensional computer-aided design data of the mask, Video. S2 for a frontal view of the mask in use, Video. S3 for a visualization of the nasal groove, and Video. S4 for the folding function&lt;/p&gt;&lt;span&gt;Full size image&lt;/span&gt;&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-chevron-right-small\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/figure&gt;&lt;p&gt;To assess the mask’s performance, a mechanical bench test was conducted to evaluate sealing efficiency and to estimate skin pressure at various visual pressure ind","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"112 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142562091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: nationwide multicenter retrospective study in Japan.","authors":"Akira Kawauchi, Yohei Okada, Makoto Aoki, Akihiko Inoue, Toru Hifumi, Tetsuya Sakamoto, Yasuhiro Kuroda, Mitsunobu Nakamura","doi":"10.1186/s13054-024-05086-9","DOIUrl":"10.1186/s13054-024-05086-9","url":null,"abstract":"<p><strong>Background: </strong>Previous studies examining sex differences in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) have indicated that women have favorable outcomes; however, detailed evidence remains lacking. We aimed to investigate sex differences in the backgrounds and outcomes of patients undergoing ECPR for OHCA.</p><p><strong>Methods: </strong>This study was a secondary analysis of the registry from the SAVE-J II study, a retrospective multicenter study conducted in Japan from 2013 to 2018. Adult patients without external causes who underwent ECPR for OHCA were included. The primary outcome was a favorable neurological outcome (Cerebral Performance Status 1 or 2) at hospital discharge. We used multilevel logistic regression to evaluate the association of sex differences, adjusting for center-level (hospital) and individual-level variables (patient background, cardiac arrest situation, and in-hospital intervention factors). For sensitivity analyses, we performed three models of multilevel logistic regression when selecting confounders.</p><p><strong>Results: </strong>Among the 1819 patients, 1523 (83.7%) were men, and 296 (16.3%) were women. The median age (61.0 vs. 58.0 years), presence of a witness (78.8% vs. 79.2%), and occurrence of bystander CPR (57.5% vs. 61.6%) were similar between groups. Women were more likely to present with an initial non-shockable rhythm (31.7% vs. 49.7%), as well as a non-shockable rhythm at hospital arrival (52.1% vs. 61.5%) and at ECMO initiation (48.1% vs. 57.1%). The proportion of favorable neurological outcomes was 12.3% in males and 15.9% in females (p = 0.10). Multilevel logistic regression analysis showed that the female sex was significantly associated with a favorable neurologic outcome at discharge (adjusted odds ratio: 1.60 [95% confidence interval: 1.05-2.43]; p = 0.03). This advantage in women was consistently observed in the sensitivity analyses.</p><p><strong>Conclusions: </strong>The female sex is significantly associated with favorable neurological outcomes at hospital discharge in patients who received ECPR for OHCA.</p>","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"28 1","pages":"302"},"PeriodicalIF":8.8,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review on lung injury: mechanisms, biomarkers, and monitoring","authors":"Wenping Fan, Biyu Gui, Xiaolei Zhou, Li Li, Huaiyong Chen","doi":"10.1186/s13054-024-05149-x","DOIUrl":"https://doi.org/10.1186/s13054-024-05149-x","url":null,"abstract":"Lung injury is closely associated with the heterogeneity, severity, mortality, and prognosis of various respiratory diseases. Effective monitoring of lung injury is crucial for the optimal management and improved outcomes of patients with lung diseases. This review describes acute and chronic respiratory diseases characterized by significant lung injury and current clinical tools for assessing lung health. Furthermore, we summarized the mechanisms of lung cell death observed in these diseases and highlighted recently identified biomarkers in the plasma indicative of injury to specific cell types and scaffold structure in the lung. Last, we propose an artificial intelligence-driven lung injury monitoring model to assess disease severity, and predict mortality and prognosis, aiming to achieve precision and personalized medicine.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"6 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of therapeutic plasma exchange on tissue factor and tissue factor pathway inhibitor in septic shock.","authors":"Klaus Stahl, Georg F Lehner, Pedro David Wendel-Garcia, Benjamin Seeliger, Thorben Pape, Bernhard M W Schmidt, Heiko Schenk, Julius Schmitt, Andrea Sauer, Lennart Wild, Konrad Peukert, Christian Putensen, Christian Bode, Michael Joannidis, Sascha David","doi":"10.1186/s13054-024-05142-4","DOIUrl":"10.1186/s13054-024-05142-4","url":null,"abstract":"<p><strong>Background: </strong>Coagulopathy is part of the pathological host response to infection in sepsis. Higher plasma concentrations of both tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are associated with occurrence of disseminated intravascular coagulation (DIC), multi-organ dysfunction and increased mortality in patients with sepsis. Currently no treatment approaches specifically targeting this axis are available. We hypothesize that therapeutic plasma exchange (TPE) might limit this coagulopathy by restoring the balance of plasma proteins.</p><p><strong>Methods: </strong>This was a pooled post-hoc biobank analysis including 51 patients with early (shock onset < 24 h) and severe (norepinephrine dose > 0.4 μg/kg/min) septic shock, who were either receiving standard of care treatment (SOC, n = 14) or SOC + one single TPE (n = 37). Plasma concentrations of TF and TFPI were measured both at- and 6 h after study inclusion. The effect of TPE on concentrations of TF and TFPI was investigated and compared to SOC patients. Further, baseline TF and TFPI concentrations were used to modulate and predict clinical response to adjunctive TPE, indicated by longitudinal reduction of lactate concentrations over the first 24 h following study inclusion.</p><p><strong>Results: </strong>TPE led to a significant reduction in circulating concentrations of both TF and TFPI while no difference was observed in the SOC group. Relative change of TF within 6 h was + 14 (-0.8 to + 30.4) % (p = 0.089) in the SOC and -18.3 (-32.6 to -2.2) % (p < 0.001) in the TPE group (between group p < 0.001). Similarly, relative change of TFPI was + 14.4 (-2.3 to + 30.9) % (p = 0.076) in the SOC and -20 (-32.8 to -7.9) % (p < 0.001) in the TPE group (between group p = 0.022). The ratio of TF to TFPI remained unchanged in both SOC and TPE groups. SOC patients exhibited an increase in lactate over the initial 24 h when TF and TFPI concentrations were higher at baseline. In contrast, patients undergoing TPE experienced a sustained longitudinal reduction of lactate concentrations across all levels of baseline TF and TFPI elevations. In a multivariate mixed-effects model, higher baseline TF (p = 0.003) and TFPI (p = 0.053) levels led to greater longitudinal lactate concentration reduction effects in the TPE group.</p><p><strong>Conclusions: </strong>Adjunctive TPE in septic shock is associated with a significant removal of both TF and TFPI, which may contribute to the early hemodynamic improvement observed in septic shock patients receiving TPE. Higher baseline TF (and TFPI) plasma concentrations were identified as a putative predictor of treatment response that could be useful for predictive enrichment strategies in future clinical trials.</p>","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"28 1","pages":"351"},"PeriodicalIF":8.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Airway epithelium damage in acute respiratory distress syndrome","authors":"Ludovic Gerard, Marylene Lecocq, Bruno Detry, Caroline Bouzin, Delphine Hoton, Joao Pinto Pereira, François Carlier, Thomas Plante-Bordeneuve, Sophie Gohy, Valérie Lacroix, Pierre-François Laterre, Charles Pilette","doi":"10.1186/s13054-024-05127-3","DOIUrl":"https://doi.org/10.1186/s13054-024-05127-3","url":null,"abstract":"The airway epithelium (AE) fulfils multiple functions to maintain pulmonary homeostasis, among which ensuring adequate barrier function, cell differentiation and polarization, and actively transporting immunoglobulin A (IgA), the predominant mucosal immunoglobulin in the airway lumen, via the polymeric immunoglobulin receptor (pIgR). Morphological changes of the airways have been reported in ARDS, while their detailed features, impact for mucosal immunity, and causative mechanisms remain unclear. Therefore, this study aimed to assess epithelial alterations in the distal airways of patients with ARDS. We retrospectively analyzed lung tissue samples from ARDS patients and controls to investigate and quantify structural and functional changes in the small airways, using multiplex fluorescence immunostaining and computer-assisted quantification on whole tissue sections. Additionally, we measured markers of mucosal immunity, IgA and pIgR, alongside with other epithelial markers, in the serum and the broncho-alveolar lavage fluid (BALF) prospectively collected from ARDS patients and controls. Compared to controls, airways of ARDS were characterized by increased epithelial denudation (p = 0.0003) and diffuse epithelial infiltration by neutrophils (p = 0.0005). Quantitative evaluation of multiplex fluorescence immunostaining revealed a loss of ciliated cells (p = 0.0317) a trend towards decreased goblet cells (p = 0.056), and no change regarding cell progenitors (basal and club cells), indicating altered mucociliary differentiation. Increased epithelial permeability was also shown in ARDS with a significant decrease of tight (p < 0.0001) and adherens (p = 0.025) junctional proteins. Additionally, we observed a significant decrease of the expression of pIgR, (p < 0.0001), indicating impaired mucosal IgA immunity. Serum concentrations of secretory component (SC) and S-IgA were increased in ARDS (both p < 0.0001), along other lung-derived proteins (CC16, SP-D, sRAGE). However, their BALF concentrations remained unchanged, suggesting a spillover of airway and alveolar proteins through a damaged AE. The airway epithelium from patients with ARDS exhibits multifaceted alterations leading to altered mucociliary differentiation, compromised defense functions and increased permeability with pneumoproteinemia.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"43 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpretable machine learning model for new-onset atrial fibrillation prediction in critically ill patients: a multi-center study","authors":"Chengjian Guan, Angwei Gong, Yan Zhao, Chen Yin, Lu Geng, Linli Liu, Xiuchun Yang, Jingchao Lu, Bing Xiao","doi":"10.1186/s13054-024-05138-0","DOIUrl":"https://doi.org/10.1186/s13054-024-05138-0","url":null,"abstract":"New-onset atrial fibrillation (NOAF) is the most common arrhythmia in critically ill patients admitted to intensive care and is associated with poor prognosis and disease burden. Identifying high-risk individuals early is crucial. This study aims to create and validate a NOAF prediction model for critically ill patients using machine learning (ML). The data came from two non-overlapping datasets from the Medical Information Mart for Intensive Care (MIMIC), with MIMIC-IV used for training and subset of MIMIC-III used as external validation. LASSO regression was used for feature selection. Eight ML algorithms were employed to construct the prediction model. Model performance was evaluated based on identification, calibration, and clinical application. The SHapley Additive exPlanations (SHAP) method was used for visualizing model characteristics and individual case predictions. Among 16,528 MIMIC-IV patients, 1520 (9.2%) developed AF post-ICU admission. A model with 23 variables was built, with XGBoost performing best, achieving an AUC of 0.891 (0.873–0.888) in validation and 0.769 (0.756–0.782) in external validation. Key predictors included age, mechanical ventilation, urine output, sepsis, blood urea nitrogen, percutaneous arterial oxygen saturation, continuous renal replacement therapy and weight. A risk probability greater than 0.6 was defined as high risk. A friendly user interface had been developed for clinician use. We developed a ML model to predict the risk of NOAF in critically ill patients without cardiac surgery and validated its potential as a clinically reliable tool. SHAP improves the interpretability of the model, enables clinicians to better understand the causes of NOAF, helps clinicians to prevent it in advance and improves patient outcomes.","PeriodicalId":10811,"journal":{"name":"Critical Care","volume":"31 1","pages":""},"PeriodicalIF":15.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}