{"title":"Endotoxin: A Bona Fide Treatable Sepsis Endotype?","authors":"Hernando Gómez","doi":"10.1159/000546294","DOIUrl":"10.1159/000546294","url":null,"abstract":"<p><strong>Background: </strong>The recognition of syndromes has been a pillar of medical education and knowledge. However, treatment of syndromes is challenging because there is a disconnect between the underlying mechanisms that lead to organ injury and the clinical expression of this injury. This is an important barrier to identifying effective treatments in sepsis which may be resolved by the identification of sepsis endotypes.</p><p><strong>Summary: </strong>In this review, we discuss the rationale for considering endotoxic septic shock as a true endotype; the mechanisms by which endotoxin induce cell and organ injury and dysfunction, the strategies to recognize when it occurs and the potential treatments, focusing on endotoxin removal through extracorporeal blood purification.</p><p><strong>Key messages: </strong>There is sufficient preclinical and clinical evidence to support the notion that endotoxin is a relevant mechanism of injury in human sepsis that drives poor patient outcomes that can be identified using clinical criteria and biomarkers and that may respond to specific targeted therapies, strongly suggesting that endotoxemic septic shock is a bona fide endotype.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-12"},"PeriodicalIF":2.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Haemoadsorption in Paediatric Critical Care: Current Insights and Future Perspectives.","authors":"Gabriella Bottari, Isabella Guzzo, Akash Deep","doi":"10.1159/000546240","DOIUrl":"10.1159/000546240","url":null,"abstract":"<p><strong>Background: </strong>Haemoadsorption (HA) is increasingly recognized as a valuable extracorporeal blood purification technique in paediatric intensive care. Although initially developed for adult patients, HA's application in paediatric critical care, particularly for conditions such as septic shock, liver failure, and rhabdomyolysis, has gained significant attention due to promising clinical outcomes.</p><p><strong>Summary: </strong>HA has demonstrated efficacy in managing paediatric septic shock by reducing vasopressor requirements and lowering inflammatory markers. In liver failure, HA complements continuous renal replacement therapy (CRRT) by removing albumin-bound toxins and cytokines, mitigating systemic inflammation. Emerging evidence also supports HA as a rescue therapy in rare paediatric conditions like rhabdomyolysis and acute intoxications, preventing organ damage and reducing morbidity. Despite its benefits, HA in paediatrics presents technical challenges, including concerns over extracorporeal circuit volumes, vascular access, and anticoagulation. Paediatric-specific devices, such as the HA60, BS80, and PMX-05R, are addressing these limitations by offering lower priming volumes suitable for small children. Recent studies have highlighted improvements in haemodynamic stability, cytokine reduction, and organ function, reinforcing HA's potential as a critical adjuvant therapy. This review underscores the evolving landscape of HA in paediatric critical care, advocating for further research to optimize its application across diverse clinical scenarios.</p><p><strong>Key messages: </strong>(1) HA shows significant promise in paediatric septic shock, liver failure, and rhabdomyolysis. (2) Technical advancements are expanding HAs applicability to neonates and small infants. (3) More multicentre studies are needed to establish HA's role in reducing mortality and improving quality of life post-PICU.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current Experience Using the Selective Cytopheretic Device for Continuous Immunomodulation in Acute Kidney Injury and Multiorgan Failure.","authors":"Stuart L Goldstein, H David Humes","doi":"10.1159/000546219","DOIUrl":"https://doi.org/10.1159/000546219","url":null,"abstract":"<p><p>Introduction Sepsis and sepsis-associated acute kidney injury (AKI) are associated with increased patient morbidity and mortality. The immediate host response aimed at combating infection can become dysregulated, leading to uncontrolled inflammation and multi-organ failure, including AKI. Therapies targeting one protein component of the sepsis pathway have largely failed to improve patient outcomes, and currently only organ support therapies are used clinically to provide time for innate organ recovery to occur. The Selective Cytopheretic Device (SCD) is a continuous cell processing immunomodulatory device that attracts activated neutrophils and monocytes its biomimetic membrane surface. The activated leukocytes are transformed to a less pro-inflammatory phenotype and released back into the circulation when exposed to low ionized calcium concentration established in the SCD by standard regional citrate anticoagulation protocols used in continuous renal replacement therapy. Review In this review, we detail the history of the SCD and our experience with it, from discovery to pre-clinical testing to translational research application at the bedside. We discuss the SCD mechanism of action, its immunomodulatory effect, and the human studies involving critically ill adult pediatric patients with AKI who require continuous renal replacement therapy as part of the standard of care. We conclude discussing ongoing and future application of the SCD in both acute and chronic inflammatory states that would benefit from immunomodulation.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Saif Al-Chalabi, Smeeta Sinha, Philip A Kalra, Dawn Evans, Darren Green, Leon Schurgers, Dimitrios Poulikakos
{"title":"A Randomised Prospective Crossover Study on the Effects of Medium Cut-Off Membranes on FGF-23 and Inflammatory Mediators in Patients Receiving Regular Haemodialysis.","authors":"Saif Al-Chalabi, Smeeta Sinha, Philip A Kalra, Dawn Evans, Darren Green, Leon Schurgers, Dimitrios Poulikakos","doi":"10.1159/000545745","DOIUrl":"10.1159/000545745","url":null,"abstract":"<p><strong>Introduction: </strong>In contrast to high-flux dialysis (HFD) membranes, medium cut-off membranes (MCO) can potentially remove a wide range of middle molecules. Our study aimed to compare the clearance rate (CR) of fibroblast growth factor 23 (FGF-23) and other selected inflammatory cytokines between medium MCO and HFD membranes and investigate the intrasubject stability of these biomarkers.</p><p><strong>Methods: </strong>This prospective randomised case-crossover study recruited 20 adult patients who were randomised into two groups: group A: to start with 1 week of thrice-weekly dialysis using HFD membrane followed by a 3-week washout period and then 1 week of dialysis with an MCO membrane. Group B followed the reverse sequence. Blood samples were taken before and after each dialysis session for the analysis of the assessed biomarkers (FGF-23, interleukin-6 [IL-6], interleukin-18 [IL-18], high-sensitivity C-reactive protein [hsCRP], and dephosphorylated uncarboxylated matrix Gla protein [dp-ucMGP]). Wilcoxon signed rank and paired t tests were used for comparison between the membranes. One-way repeated measures ANOVA or Friedman tests were used for the intrasubject stability of the biomarkers.</p><p><strong>Results: </strong>The use of both MCO and HFD membranes resulted in a significant reduction of FGF-23 levels and other selected inflammatory cytokines. However, there was no significant difference in the CR: FGF-23 (0.31 vs. 0.23], p = 0.242), IL-6 (0.19 vs. 0.12, p = 0.215), IL-18 (-0.05 vs. -0.03, p = 0.704), dp-ucMGP (0.33 vs. 0.33, p = 0.903), and hsCRP (-0.05 vs. -0.08, p = 0.107). There was no significant intrasubject variability for all assessed biomarkers except in pre-dialysis high hsCRP levels when using HFD membrane.</p><p><strong>Conclusion: </strong>The use of both MCO and HFD membranes resulted in a significant reduction of FGF-23 levels and other selected inflammatory cytokines. However, the MCO membrane did not demonstrate a significant advantage over the HFD in the short term. There was no significant intrasubject variability for all assessed biomarkers apart from hsCRP.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12105827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ilona Lemagnen, Céline Monard, Maxime Palluau, Layla Bergamaschi, Taku Furukawa, Rinaldo Bellomo, Antoine Schneider
{"title":"Drug Removal by Hemoadsorption.","authors":"Ilona Lemagnen, Céline Monard, Maxime Palluau, Layla Bergamaschi, Taku Furukawa, Rinaldo Bellomo, Antoine Schneider","doi":"10.1159/000545804","DOIUrl":"10.1159/000545804","url":null,"abstract":"<p><strong>Background: </strong>There is growing interest in hemoadsorption (HA) therapies in critically ill patients although their precise indications remain to be established. Several devices are available on the market with heterogeneous properties and capabilities.</p><p><strong>Summary: </strong>Due to the nonspecific removal associated with most HA techniques, concerns have been raised on their unintended removal of drugs such as anti-infectives in sepsis. On the other hand, drug removal might be beneficial in certain situations for instance antithrombotic medications in patients requiring emergency surgery or in case of accidental or self-induced intoxication. In this review, we summarize available in vitro, in vivo, and clinical studies reporting on the influence of various HA techniques on drugs pharmacokinetics.</p><p><strong>Key message: </strong>We conclude that further studies should aim at providing drug dosing recommendations during HA and confirm its safety, efficacy, and practicalities when used for intoxications.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-13"},"PeriodicalIF":2.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stefano Romagnoli, Gianluca Villa, Francesco Barbani, Zaccaria Ricci
{"title":"Hemoadsorption: One Name, Varied Techniques.","authors":"Stefano Romagnoli, Gianluca Villa, Francesco Barbani, Zaccaria Ricci","doi":"10.1159/000545741","DOIUrl":"10.1159/000545741","url":null,"abstract":"<p><strong>Background: </strong>Despite significant efforts to improve outcomes for patients with sepsis and septic shock, mortality rates remain alarmingly high.</p><p><strong>Summary: </strong>Beyond standard management, novel adjuvant treatments seek to improve outcomes through a personalized approach. Among these, immunomodulation strategies aim to reestablish a balance in the dysregulated immune system, managing both pro-inflammatory and anti-inflammatory mediators. In recent years, various techniques utilizing extracorporeal circuits equipped with filters or cartridges, collectively referred to as blood purification therapies, have been developed and introduced to the market. Hemoadsorption, whether used alone or in conjunction with hemofiltration, may clear a broad range of substances from the blood, including inflammatory mediators, drugs, trace elements, bacteria, and viruses.</p><p><strong>Key messages: </strong>Understanding the fundamental principles of blood purification techniques is essential for enhancing survival probabilities, keeping in mind the principle of primum non nocere as a guiding tenet of our daily practice. This review aimed to give an overview of hemoadsorption techniques by presenting current evidence and highlighting key areas that require further investigation.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-9"},"PeriodicalIF":2.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Venous Chamber Design: A Comparative Analysis of Retention Characteristics.","authors":"Osamu Yamaga, Masafumi Fukuda, Kei Fukami, Nobuhisa Hirayu, Masakazu Nabeta, Tetsurou Imai, Gaku Sugihara, Osamu Takasu, Norio Yamashita","doi":"10.1159/000545779","DOIUrl":"10.1159/000545779","url":null,"abstract":"<p><strong>Introduction: </strong>The air trap chamber used in continuous renal replacement therapy (CRRT) often causes clot formation due to gas interface, blood stasis and turbulent flow. The designs of this chamber vary widely. Few studies have quantitatively evaluated ex vivo quasi-blood stasis for different chamber types.</p><p><strong>Methods: </strong>Flow retention characteristics at 20, 30, 40, 50, and 60 s in a top-feed chamber (where blood flow enters vertically from the top and passes through a mesh within the air trap chamber with a chamber 12 mL in volume) and a side-feed chamber (where blood flow enters from the side and bottom, without a mesh filter, with a flow deviator and 6 mL chamber volume) were evaluated using a 30% glycerin and iodine povidone-solution. Still images of the chambers at each time point were converted to 8-bit grayscale using Image J software (ver.1.54, Maryland, USA), with a brightness threshold in the range of 1-80 to compare the two chamber designs.</p><p><strong>Results: </strong>Both chambers showed a decrease in the values of the highlighted areas over time; however, from 20 s, the side-feed chamber showed significantly lower values of the highlighted areas compared with the top-feed chamber. Similar to the findings at 20 s, significant differences in the values of the highlighted areas favored the side-feed chamber and persisted at 30, 40, 50, and 60 s. Furthermore, pseudo blood remained superficially in the top-feed chamber, while the side-feed chamber exhibited vortex flow, less stasis, turbulence, and stagnation.</p><p><strong>Conclusion: </strong>The two chambers tested emptied of pseudo blood at different rates, with varying retention characteristics, with the side-feed chamber showing less pseudo-blood retention at all-time points assessed.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-8"},"PeriodicalIF":2.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lucia Cattin, Sergio Lassola, Eleonora Balzani, Maria Salinas Rojo, Nicola Marchionna, Anna Lorenzin, Massimo De Cal, Monica Zanella, Claudio Ronco, Vinicio Danzi, Silvia De Rosa
{"title":"Impact of Fluid Management on Outcomes in Sequential Extracorporeal Support: A Post Hoc Analysis.","authors":"Lucia Cattin, Sergio Lassola, Eleonora Balzani, Maria Salinas Rojo, Nicola Marchionna, Anna Lorenzin, Massimo De Cal, Monica Zanella, Claudio Ronco, Vinicio Danzi, Silvia De Rosa","doi":"10.1159/000545728","DOIUrl":"10.1159/000545728","url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a life-threatening condition characterized by dysregulated inflammatory responses, often leading to multiple organ dysfunction and high mortality rates. Continuous renal replacement therapy (CRRT) and extracorporeal blood purification therapies have emerged as vital adjuncts to manage fluid overload and modulate immune responses in septic shock. This study evaluates the impact of daily fluid balance variation on 90-day mortality and hospital length of stay in ICU patients undergoing CRRT for septic shock with endotoxin activity.</p><p><strong>Methods: </strong>A post hoc analysis of the EUPHAS 2 project was conducted on 61 ICU patients with nonresponsive endotoxin shock at San Bortolo Hospital (2016-2021). Bayesian joint models assessed the relationship between fluid balance and mortality. Mediation analysis explored the impact of CRRT on mechanical ventilation duration and hospital stay.</p><p><strong>Results: </strong>Fluid overload and excessive ultrafiltration were associated with prolonged mechanical ventilation and extended hospital stays. Targeted fluid balance management reduced 90-day mortality risk by 50%. CRRT reduced hospital length of stay directly by 5.31 days but indirectly extended it by 11.78 days due to mechanical ventilation. Optimal fluid balance was critical for minimizing mortality and complications.</p><p><strong>Conclusions: </strong>Careful and tailored fluid management in CRRT is essential for improving survival rates and clinical outcomes in septic shock patients. Continuous monitoring of fluid dynamics is necessary to optimize hemodynamic stability and avoid complications. Future multicenter studies are needed to validate these findings and refine fluid management protocols.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-10"},"PeriodicalIF":2.2,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Eleonora Balzani, Sergio Lassola, Hannah Wozniak, Giacomo Bellani, Silvia De Rosa
{"title":"Advances in Renal Replacement Therapy: The Role of Polymethyl Methacrylate Membranes in Acute Critically Ill Patients.","authors":"Eleonora Balzani, Sergio Lassola, Hannah Wozniak, Giacomo Bellani, Silvia De Rosa","doi":"10.1159/000543856","DOIUrl":"10.1159/000543856","url":null,"abstract":"<p><strong>Background: </strong>Polymethyl methacrylate (PMMA) membranes are increasingly recognized for their effectiveness in treating acute kidney injury (AKI) due to their strong adsorption capabilities, particularly for inflammatory mediators like β2-microglobulin and IL-6. These membranes ensure mechanical stability and chemical inertness, minimizing adverse reactions during blood filtration.</p><p><strong>Summary: </strong>In acute conditions such as sepsis and acute respiratory distress syndrome (ARDS), PMMA membranes show promising findings. In sepsis, they may help reduce multiorgan failure by modulating immune responses, although further research is needed to confirm their routine use. For ARDS, PMMA membranes could mitigate \"cytokine storms\" by adsorbing key cytokines, improving oxygenation and hemodynamic stability, which may reduce ICU stays and reliance on mechanical ventilation. Monitoring biomarkers like IL-6, TNF-α is critical for tracking efficacy and tailoring therapy to individual needs. In chronic conditions, such as hemodialysis for chronic kidney disease, PMMA membranes help lower oxidative stress and β2-microglobulin levels, reducing complications such as amyloidosis. By decreasing oxidative damage, they provide long-term protective benefits for dialysis patients.</p><p><strong>Key message: </strong>While these advantages are notable, large-scale studies are needed to establish PMMA's efficacy, refine treatment protocols, and confirm its broader role in acute and chronic disease management. The potential of PMMA membranes highlights their value, but standardized clinical evidence is necessary for widespread adoption.</p>","PeriodicalId":8953,"journal":{"name":"Blood Purification","volume":" ","pages":"1-11"},"PeriodicalIF":2.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}