Die extrakorporale Therapie septischer Patienten

Zusammenfassung Trotz zahlreicher Fortschritte in der Intensivmedizin stellt die Behandlung von Patienten mit schwerer Sepsis und septischem Schock eine medizinische Herausforderung dar. In der Pathogenese der systemischen Inflammation (SIRS) kommt es zur exzessiven Freisetzung von multiplen endogenen und exogenen inflammatorischen Mediatoren [z. B. Lipopolysaccharid (LPS), Tumor-Nekrose-Faktor (TNF)-α, Interleukin (IL)-1, IL-6] und zur Entwicklung eines Multi- Organ-Versagen (MOV). Dies führt bekannterma?en zu schlechten überlebenszahlen septischer Patienten. Ein komplexes dynamisches Kontrollsystem führt in der Abfolge meist zur zeitnahen gegen-regulatorischen antiinflammatorischen Antwort mittels Induktion anti-inflammatorischer Mediatoren (IL-10, transforming growth factor-beta [TGF-β]). In einer gro?en Anzahl septischer Patienten kommt es durch eine Persistenz des inflammatorischen Reizes zu einer Deaktivierung von antigenpr?sentierenden Zellen bzw. zu einem Versagen des zellvermittelten Immunsystems („Immunparalyse“). Unselektive und selektive intermittierende und kontinuierliche extrakorporale Therapieverfahren wurden evaluiert, ob diese in der Lage sind, in inflammatorische durch den klinischen Verlauf günstig zu beeinflussen. Technologische Fortschritte im Hinblick auf die Entwicklung von extrakorporalen Plasmapherese- bzw. Adsorptionsverfahren bieten heute neue, effektive M?glichkeiten, Mediatoren aus der Blutbahn septischer Patienten zu entfernen. In der vorliegenden übersichtsarbeit werden aktuell verfügbare und zukünftige adjunktive extrakorporale Therapiestrategien vorgestellt und vor dem Hintergrund aktueller Studien diskutiert.      

Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...     

Interleukin-6 serum level assessment using a new qualitative point-of-care test in sepsis: A comparison with ELISA measurements

ObjectivesInterleukin-6 (IL-6) is involved in inflammatory diseases, provides prognostical information, and allows the early identification and monitoring of septic patients. We investigated whether IL-6 can be assessed using a new densitometric point-of-care (POC) bedside assay.Design and methods392 samples were prospectively collected from 57 intensive care unit patients (38 male, age: 45.2 ± 16.9years, APACHE II score: 25.4 ± 4.8). Blinded IL-6 measurements were performed using conventional semiautomatic enzyme-linked immunosorbent assays (ELISA) and the POC test.ResultsMean IL-6 levels were 102.9 ± 388.6pg/mL (ELISA) and 97.0 ± 535.5 (POC). A significant correlation was found (p < 0.0001, r = 0.92). The sensitivity/specificity for sepsis was 82.6%/86.5% (ELISA, AUC: 0.881), and 76.4%/95.0% (POC, AUC: 0.868).ConclusionsHere we demonstrate significant correlations of IL-6 levels determined using a POC test and semiautomatic ELISA. ROC analyses revealed no significant differences between the two tests. With a turn-around time of 20min, the bedside IL-6 test is a new tool that may help to initiate early goal-directed therapy.     

A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a

In sepsis, endotoxin, interleukin 6 (IL-6), and complement-activation product 5a (C5a) trigger inflammatory cascades resulting in monocytic deactivation. When this occurs, the outcome is often uncontrolled infection, multiple organ dysfunction, and death. We tested here whether simultaneous reduction of systemic endotoxin, IL-6, and C5a levels could be achieved via selective extracorporeal immunoadsorption (IA) and whether this would restore monocytic responsiveness and improve organ function. Therefore, 33 patients with severe sepsis or septic shock were enrolled in a prospective, 1:2 case-control matched, blinded endpoint evaluation trial. In addition to best supportive care, 11 of these patients (mean age, 57.8 +/- 2.2 years; Acute Physiology and Chronic Health Evaluation II score, 23.7 +/- 1.6) received simultaneous endotoxin IA, IL-6 IA, and C5a IA on 5 consecutive days for 7.5 h each. Our observational end points were the course of monocytic immunity (monocytic HLA-DR expression) and other indices of inflammation and disease severity. In patients receiving IA, the mean circulating level of IL-6 was reduced from 361.7 +/- 116.0 to 38.2 +/- 15.2 pg/mL (P = 0.02), and of C5a from 297.6 +/- 43.1 to 79.2 +/- 14.5 ng/mL (P < 0.001). Two indices of endotoxemia were reduced also. Treated patients had lower C-reactive protein and Acute Physiology and Chronic Health Evaluation II scores at day 7 (P = 0.004 and P = 0.0001, respectively). Monocytic HLA-DR improved in the treated patients but not in controls (P < 0.0001). Under treatment, HLA-DR was found to recover in all patients with immunoparalysis (4,993.6 +/- 1,162 to 15,295.3 +/- 2,197 molecules per cell; P = 0.002). Here, we demonstrate that simultaneously reducing circulating endotoxin, IL-6, and C5a levels by selective IA reverses monocytic deactivation and improves organ system functions. This novel strategy might open a new therapeutic avenue for an interventional extracorporeal treatment of patients with sepsis.     

Granulomatosis with polyangiitis (Wegener’s) complicated by splenic rupture and severe acute respiratory distress syndrome: A case report

Even in the absence of disease‐specific radiological signs of granulomatosis with polyangiitis (GPA), severe intrapulmonary GPA may be present. Rapidly establishing the diagnosis with a confirmatory biopsy is key to initiate lifesaving therapy.     

Impact of Obesity on Operative Morbidity and Clinical Outcome in Primary Epithelial Ovarian Cancer after Optimal Primary Tumor Debulking

Background  

Obesity is a common and increasing condition in Western countries and seems to be associated with increased carcinogenesis and tumor invasiveness. We evaluated operative and clinical outcome in patients operated to treat primary epithelial ovarian cancer (EOC) according to their body mass index (BMI).