Plasma exchange improves outcome of sepsis-associated liver failure

Ye, Xiaolin; Wang, Fei; Ding, Yueping; Ma, Dannv; Lv, Bin

doi:10.1097/md.0000000000015307

Cited by 5 publications

(4 citation statements)

References 20 publications

(20 reference statements)

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“…Since sepsis‐associated liver failure is linked with poor survival (Yan et al , 2014; Ye et al , 2019), targeted delivery of AS605240 through T‐LipoAS improved liver function and overall outcome (Fig 5). The chosen sepsis model aimed to mimic a clinical situation.…”

Section: Resultsmentioning

confidence: 99%

Targeted delivery of a phosphoinositide 3‐kinase γ inhibitor to restore organ function in sepsis

et al. 2021

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Jaundice, the clinical hallmark of infection‐associated liver dysfunction, reflects altered membrane organization of the canalicular pole of hepatocytes and portends poor outcomes. Mice lacking phosphoinositide 3‐kinase‐γ (PI3Kγ) are protected against membrane disintegration and hepatic excretory dysfunction. However, they exhibit a severe immune defect that hinders neutrophil recruitment to sites of infection. To exploit the therapeutic potential of PI3Kγ inhibition in sepsis, a targeted approach to deliver drugs to hepatic parenchymal cells without compromising other cells, in particular immune cells, seems warranted. Here, we demonstrate that nanocarriers functionalized through DY‐635, a fluorescent polymethine dye, and a ligand of organic anion transporters can selectively deliver therapeutics to hepatic parenchymal cells. Applying this strategy to a murine model of sepsis, we observed the PI3Kγ‐dependent restoration of biliary canalicular architecture, maintained excretory liver function, and improved survival without impairing host defense mechanisms. This strategy carries the potential to expand targeted nanomedicines to disease entities with systemic inflammation and concomitantly impaired barrier functionality.

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Section: Resultsmentioning

confidence: 99%

Targeted delivery of a phosphoinositide 3‐kinase γ inhibitor to restore organ function in sepsis

et al. 2021

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“…Since sepsis-associated liver failure is linked with poor survival, 25,26 targeted delivery of AS605240 through T-LipoAS improved not only liver function but also overall outcome ( Figure 5 ). The chosen sepsis model aimed to mimic a clinical situation.…”

Section: Resultsmentioning

confidence: 99%

Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis through dye-functionalized lipid nanocarriers

Press

Babic

Hoffmann

et al. 2021

Preprint

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Jaundice, the clinical hallmark of infection-associated liver dysfunction, reflects altered membrane organization of the canalicular pole of hepatocytes and portends poor outcomes. Mice lacking phosphoinositide 3-kinase-γ (PI3Kγ) are protected against membrane disintegration and hepatic excretory dysfunction. However, they exhibit a severe immune defect that hinders neutrophil recruitment to sites of infection. To exploit the therapeutic potential of PI3Kγ inhibition in sepsis, a targeted approach to deliver drugs to hepatic parenchymal cells without compromising other cells, in particular immune cells, seems warranted. Here we demonstrate that nanocarriers functionalized through DY-635, a fluorescent polymethine dye and a ligand of organic anion transporters can selectively deliver therapeutics to hepatic parenchymal cells. Applying this strategy to a murine model of sepsis, we observed PI3Kγ-dependent restoration of biliary canalicular architecture, maintained excretory liver function, and improved survival without impairing host defense mechanisms. This strategy carries the potential to expand targeted nanomedicines to disease entities with systemic inflammation and concomitantly impaired barrier functionality.One-Sentence SummaryDye-functionalized liposomes allow delivery of a PI3Kγ inhibitor to hepatocytes to resolve sepsis-related liver failure without ‘off-target’ effects on immunity.Graphical AbstractTargeting PI3Kγ in hepatocytes by dye-functionalized liposomes to resolve sepsis-related liver failure without ‘off-target’ effects on immunity.

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“…Larsen et al showed in their study of adults that plasmapheresis was effective in the treatment of patients with acute liver failure without the need for liver transplantation [ 15 ]. In another study, it was reported that TPE can be applied in cases where there is no response to other treatments in hepatic failure due to sepsis [ 16 ]. In our study, two of the 5 patients who underwent TPE due to liver failure were discharged, two were transferred to the transplantation center, and one patient died.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the results of the patients who underwent plasmapheresis in the pediatric intensive care unit

TALAY,

ORHAN,

KANĞIN

et al. 2024

Turkish Journal of Medical Sciences

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Background/aim Therapeutic plasma exchange (TPE) is an extracorporeal treatment method that removes large molecular weight substances from plasma. In our study, we aimed to retrospectively examine the indications and procedural methods of the patients who had undergone TPE, and the complications that occurred during the procedure. Materials and methods Forty-one patients who were monitored in thePICU of Gazi Yaşargil Training and Research Hospital and had indications for TPE between 2017 and 2021 were included in the study. Laboratory parameters were checked before and after the TPE procedure. In addition to these, patients’ diagnosis, weight, type of procedure and type of device, where the procedure was performed, duration of the procedure, amount of blood and plasma processed, complications, number of procedures, and death during the procedure or independent of the procedure were evaluated. Results The median age was 93.0 (14.0–167.0) months. Hemolytic uremic syndrome (HUS) was the most common TPE indication with nine patients. The most common complication related to TPE was fever (11 patients), while no complication was observed in 18 patients. When laboratory results were evaluated according to American Society for Apheresis (ASFA) categories, a significant improvement was observed in the values of platelet, AST, ALT, LDH, urea, and creatinine in ASFA1 after TPE. No significant improvement was observed in ASFA2 (p > 0.05). In ASFA3, a significant improvement was observed in INR, AST, ALT, LDH, total bilirubin, creatinine, pH, and lactate values after TPE (p < 0.05). Five patients died from ASFA1, one from ASFA2, and three patients from ASFA3. Conclusion Since significant adjustments are observed in clinical and laboratory values in sepsis-MOF, which is in the ASFA3 category, we believe that it should be evaluated in the ASFA2 or ASFA1 category in the early treatment of these diseases. In addition, we think that MIS-C cases, which have not been in any category according to ASFA, should be included in the ASFA2 or ASFA3 category, considering our TPE results.

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Plasma exchange improves outcome of sepsis-associated liver failure

Cited by 5 publications

References 20 publications

Targeted delivery of a phosphoinositide 3‐kinase γ inhibitor to restore organ function in sepsis

Targeted delivery of a phosphoinositide 3‐kinase γ inhibitor to restore organ function in sepsis

Targeted delivery of a phosphoinositide 3-kinase γ inhibitor to restore organ function in sepsis through dye-functionalized lipid nanocarriers

Evaluation of the results of the patients who underwent plasmapheresis in the pediatric intensive care unit

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