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Literature Service
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March 2020

<<Briefanrede>> <<Last Name/Nachname>>,

Thank you for choosing to participate in our CytoSorb Literature Service where we regularly highlight publications and interesting CytoSorb treatment cases ("Case of the Week", published weekly online at www.cytosorb.com).

This month there are five new publications: two case reports looking at the use of CytoSorb in CAR T-cell associated cytokine release syndrome, two case reports in severe rhabdomyolysis, and an ex-vivo lung perfusion study.

The cases of the week include the use of CytoSorb in patients with:

  • Rat poison intoxication
  • Pediatric septic shock
  • Refractory septic shock
  • Liver and cardiac failure post cardiac surgery

For quick and easy access to the CytoSorb Literature Database, bookmark the following link: http://literature.cytosorb.com

Thank you very much for your interest. 
With kind regards from Berlin
 
Harriet Adamson
Senior Clinical Research Manager

Publication

Multimodal Therapeutic Approach of Cytokine Release Syndrome Developing in a Child Given Chimeric Antigen Receptor-Modified T Cell Infusion
Bottari G, Merli P, Guzzo I, Stoppa F, Ruggeri A, Di Nardo M, Del Bufalo F, Galaverna F, Corrado C, Locatelli F.
Critical Care Explorations 2020; 2(1): e0071
                
Summary
In this case report a 14-year-old boy with refractory B cell precursor acute lymphoblastic leukemia who was treated with chimeric antigen receptor (CAR) cells then developed severe (grade 4) cytokine release syndrome 7 days after the drug infusion, with progressive respiratory failure. He was admitted to the pediatric intensive care unit (PICU) with acute respiratory distress syndrome (ARDS) requiring mechanical ventilation, hemodynamic instability requiring vasopressors, and also secondary hemophagocytic lymphohistiocytosis (HLH) with extremely high ferritin levels. The patient was treated with five CytoSorb adsorbers (first two changed 12 hrly, then 24 hrly) in combination with continuous renal replacement therapy (CRRT). Tocilizumab was given 6 hours before admission to PICU and on the 3rd and 4th days after start of CytoSorb. This treatment resulted in a decrease of the inflammatory biomarkers over the first 96 hours (e.g. ferritin from 146,095 to 6,934 ng/mL and interleukin-6 from 4,048 – 247 pg/mL,) which was associated with progressive improvement in his ARDS (Pao2/Fio2 ratio). The patient was able to be discharged from PICU after 19 days. This case suggests that CytoSorb treatment with CRRT and tocilizumab is safe and potentially effective in pediatric patients with severe cytokine release syndrome.

Link to Pubmed

Publication

Extracorporeal cytokine removal in severe CAR-T cell associated cytokine release syndrome
Stahl K, Schmidt BMW, Hoeper MM, Skripuletz T, Mohn N, Beutel G, Eder M, Welte T, Ganser A, Falk CS, Koenecke C, David S.
J Crit Care 2020; 57: 124-129
 
Summary
In this case report a 65 yr old male with relapsed diffuse large B-cell lymphoma was admitted to ICU after he was treated with CD-19 Chimeric antigen receptor - T (CAR-T) cells and then developed grade 4 cytokine release syndrome (CRS) with refractory shock and severe capillary leakage. He was treated with IL-6 blockade (tocilizumab), methylprednisolone and additionally CytoSorb. During the next 24 hrs, the patient became more hemodynamically unstable, so the CytoSorb was then changed 8 hrly. Within hours the shock completely reversed, vasopressor dose could be decreased to 10% of the peak dose, and inotropic support stopped completely. Plasma was obtained before and 8 hrly following the start of CytoSorb treatment. While multiple soluble inflammatory factors were elevated and most of them decreased by more than 50% following Cytosorb, markers of endothelial injury increased steadily (e.g. Angpt-2/Angpt-1) leading to profound endothelial activation and leakage in ex vivo assays. This is the first reported use of cytokine adsorption for CRS showing efficacy in absorption of various cytokines but not endothelial growth factors. Findings suggest the possibility that removal of excessive circulating cytokines rather than pharmacological blockage of a single key cytokine alone might be a more effective treatment strategy for CRS. The authors are currently recruiting to a randomized controlled trial to evaluate additional CytoSorb treatment in CRS.

Link to Pubmed

Publication

Successful treatment of a severe case of rhabdomyolysis following heart transplantation by hemoadsorption
Immohr MB, Lichtenberg A, Boeken U, Akhyari P.
J Card Surg 2020; epub
 
Summary
This is a case reporting on a 61 yr old male patient, who post orthotopic heart transplantation developed cardiogenic shock and cardiac arrhythmias requiring support with veno-arterial extracorporeal membrane oxygenation (va-ECMO). The patient stabilized, however, 2 days later an enormous increase in plasma creatine kinase (CK) level was seen (>100,000U/L). His myoglobin concentration also increased to 380,000 mg/L and rhabdomyolysis most probably caused by the combination of statin and immunosuppressive therapies was diagnosed. Conventional therapies failed and the patient further developed acute renal failure requiring continuous veno-venous hemodialysis. A CytoSorb adsorber was then installed into the va-ECMO circuit and continued for the next 4 days. Plasma concentrations of immunosuppressive drugs and antibiotics were closely monitored (the patient received treatment with tacrolimus, mycophenolate mofetil, prednisolone, amphotericin, levofloxacin and cotrimoxazole). As soon as the CytoSorb adsorber was installed the patient stabilized. His CK and myoglobin rapidly and continuously decreased (at end of treatment CK 45,866U/L, myoglobin 53,700 μg/L). Plasma drug concentrations remained stable throughout the treatment period with no problems concerning pharmacokinetics seen. At six-month follow up there were no further postoperative complications, and he had full kidney function despite this episode of severe rhabdomyolysis. The authors state that CytoSorb was a safe and feasible technique (to purify the blood to preserve kidney function). 

Link to Pubmed

Publication

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb(R))
Dilken O, Ince C, van der Hoven B, Thijsse S, Ormskerk P, de Geus HRH.
Blood Purif 2020: epub
 
Summary
This case describes a 56-year-old man with severe traumatic rhabdomyolysis of the lower extremities and abdominal wall due to a crush injury (initial myoglobin and creatinine kinase – CK levels 79,931mg/l and 15,032 U/L respectively). As he was unresponsive to high dose continuous renal replacement therapy (CRRT) with a high cut off EMiC-2 dialysis filter, a CytoSorb adsorber was added into the circuit on the 2nd ICU day. Within 4 hours myoglobin and CK levels had reduced from 110,000 to 90,000 mg/l and 115,000 – 65,000 U/L respectively. The adsorber was changed after 12 hours due to evidence of saturation. This reduced myoglobin and creatine kinase levels further despite ongoing tissue ischemia. Treatment with CytoSorb improved the microcirculatory perfusion despite abnormal macro-hemodynamic parameters, however, this was not enough, resulting in the eventual demise of the patient due to severity of the injury. This report indicates that myoglobin was efficiently removed with CytoSorb following exchange with the conventional high cut-off filter in continuous venovenous hemodialysis in severe traumatic rhabdomyolysis. The authors emphasise the need to install CytoSorb early for removal of inflammatory cytokines and myoglobin.

Link to Pubmed

Publication

Perfusate-adsorption during ex vivo lung perfusion improves early post-transplant lung function  
Iskender I, Arni S, Maeyashiki T, Citak N, Sauer M, Monné Rodriguez J, Frauenfelder T,Opitz I, Weder W, Inci I.
Journal of Thoracic and Cardiovascular Surgery 2020; epub
 
Summary
In this ex vivo lung perfusion study (EVLP), the effect of ischemia-reperfusion injury after lung transplantation was studied in donor pig lungs. In the treatment group, the perfusate was also adsorbed through a CytoSorb adsorber, whereas the control lungs were perfused according to the standard protocol (n = 5, each). Variables of EVLP physiology and biochemistry were monitored. Cytokine concentrations in the perfusate were markedly lower with Cytosorb, resulting in improved EVLP physiology and biochemistry during the 6-hour ex-vivo perfusion period. After the subsequent transplant, dynamic lung compliance was markedly better during the 4-hour reperfusion period in the treatment group, as was isolated allograft oxygenation function and dynamic compliance at the end of reperfusion which was accompanied by a markedly decreased local inflammatory response. The authors conclude that the implementation of CytoSorb has refined the standard EVLP protocol. Furthermore, cytokine removal during EVLP improved immediate post-transplant graft function together with a less intense inflammatory response as a consequence of reperfusion in this pig model.

Link to Article

Case of the Week 09 / 2020

Use of CytoSorb in a patient with rat poison intoxication with multiple organ failure
Ganapathy N.
Dhanavatri Multi Speciality Hospital, Erode, India

Summary
This case reports on a 52-year-old male patient who was admitted unconscious into the emergency department with signs of hypotension, tachycardia, fever and arrhythmia most probably due to imbibement of aluminium phosphide in a suicide attempt.

Link to full Case of the Week (pdf)

Case of the Week 10 / 2020

Use of CytoSorb in a pediatric patient with septic shock in the setting of a non-controlled infectious focus
Burov АI, Tchaschukhina АB, Brunova ОY, Makulova АI, Kostritca NS, Savin IА. 

Burdenko National Scientific and Practical Center for Neurosurgery of The Russian Federation Healthcare Ministry, Moscow, The Russian Federation Children city hospital #9 named after G.N. Speransky, Moscow, The Russian Federation

Summary

The case study reports on a 16-year-old girl, who presented to the hospital with syncope and fever (39°C), tachycardia, complaints of chest pain and coughing after fainting at home.

Link to full Case of the Week (pdf)

Case of the Week 11 / 2020

Use of CytoSorb in a patient with fecal peritonitis secondary to sigmoid diverticula perforation with refractory septic shock 
Sathe P, Sakhavalkar P.
Ruby Hall Clinic, Pune, India

Summary 
This case reports on a 61-year-old male with no comorbidities, who was hospitalized for an elective orthopedic procedure.

Link to full Case of the Week (pdf)

Case of the Week 12 / 2020

Use of CytoSorb in a patient with acute liver failure and acute exacerbation of heart failure after cardiac surgery
Zagorski M, Wypych P, Kozak M.
ICU Department of Cardiac Surgery, Medical University of Łódź, Central University Hospital in Łódź, Poland

Summary
This case reports on a 42-year-old male patient (known pre-existing conditions: small intestine resection in 2019, mitral valve regurgitation grade IV and tricuspid valve regurgitation grade III), who was transferred from a peripheral hospital to the Central University Hospital in Łódź with acute heart failure due to progressive mitral valve regurgitation.

Link to full Case of the Week (pdf)
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