Introduction: Our understanding of the COVID-19 disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperin ammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress.We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood puri cation, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 -4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Puri cation using the AN69ST (oXiris ® ) hemo lter. We administered heparin (300 U/kg) to counter suspected hypercoagulability (= elevated Fibrinogen or Ddimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease (= dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome. 8 Patients have been discharged -average ICU length-ofstay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion:Means to monitor COVID-19 disease severity during hospitalisation are crucial to control disease progression and prevent hyperin ammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging.The combination of systemic heparin anticoagulation regimens and blood puri cation may prevent hyperin ammation, thromboembolism during hospitalisation and thus support clinical recovery.
<b><i>Introduction:</i></b> Coronavirus disease 2019 (COVID-19) is characterized by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and with critical cases progressing to acute respiratory distress syndrome. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we evaluated the longitudinal changes of systemic inflammatory markers in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris®) haemofilter. <b><i>Methods:</i></b> We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris®) cytokine adsorbing haemofilter (CAH) according to local practice; we visualize longitudinal results of biochemical, inflammatory, blood gas, and vital sign parameters focussing on systemic levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. <b><i>Results:</i></b> All patients were treated with ≥1 cycle extracorporeal continuous venovenous haemofiltration (CVVH) with CAH; of these, 30 severe patients received CVVH-CAH within 4–12 h of admission after recognizing a hyper-inflammatory state. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and were placed on EBP during hospitalization. The treatment was associated with a reduction of ferritin, CRP, fibrinogen, several inflammatory markers, and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3%. <b><i>Conclusion:</i></b> EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.
Introduction: Our understanding of the COVID-19 disease has been steadily evolving since the original outbreak in December 2019. Advanced disease is characterised by a hyperinflammatory state, systemic coagulopathies and multiorgan involvement, in particular respiratory distress. We here describe our initial experience with treating of COVID-19 patients based on early initiation of extracorporeal blood purification, systemic heparinisation and respiratory support.Methods: 15 patients were included; 2 were females. We monitored real-time several biochemical, immunological and coagulation biomarkers associated with disease severity following admission to our dedicated COVID-19 intensive care unit. To guide personalised treatment, we monitored among others levels of IL-6, IL-8, TNF-α, C-Reactive Protein (CRP), Neutrophil-to-Lymphocyte ratios, Thrombocyte counts, D-Dimers, Fibrinogen, and Activation Clotting time (ACT).Treatment consisted of individualised respiratory support supplemented with 1 - 4 cycles of 24-hour Extracorporeal Organ Support (ECOS) and Blood Purification using the AN69ST (oXiris®) hemofilter. We administered heparin (300 U/kg) to counter suspected hypercoagulability (= elevated Fibrinogen or D-dimers) states to maintain ACT ≥ 180 seconds.Results: N = 10 presented with severe to critical disease (= dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). A single case was admitted with a critical condition (= respiratory failure). One patient died after 5 days of hospitalisation after developing Acute Respiratory Syndrome. 8 Patients have been discharged - average ICU length-of-stay was 9.9 ± 2.4 days. Clinical improvement was associated with normalisation (increase) of thrombocytes, white blood cells, stable levels of IL-6 (< 50 ng/mL) and a decrease of CRP and Fibrinogen. Conclusion: Means to monitor COVID-19 disease severity during hospitalisation are crucial to control disease progression and prevent hyperinflammation and irreversible multiorgan failure. We present here a real-time monitoring system accounting for biochemical, immunological, coagulation parameters and radiological imaging. The combination of systemic heparin anticoagulation regimens and blood purification may prevent hyperinflammation, thromboembolism during hospitalisation and thus support clinical recovery.
Introduction: COVID-19 is characterised by hyperinflammation and coagulopathy. Severe cases often develop respiratory distress, requiring mechanical ventilation and critical cases progressing to ARDS. Control of hyperinflammation has been proposed as a possible therapeutic avenue for COVID-19; extracorporeal blood purification (EBP) modalities offer an attractive mean to ameliorate maladaptive inflammation. With this work, we describe the longitudinal variation of parameters of systemic inflammation in critically ill COVID-19 patients treated with blood purification using AN69ST (oXiris) hemodiafilter. Methods: We performed a time-series analysis of 44 consecutive COVID-19 cases treated with the AN69ST (oXiris) cytokine adsorbing hemodiafilter; we visualise longitudinal results of biochemical, inflammatory, blood gas- and vital sign parameters. Results: Blood purification was indicated for suspected hyperinflammation or hypercoagulation, (= CRP > 100 mg/L and/or IL-6 > 40 pg/mL and/or Ferritin > 500 ng/mL and/or Lactate Dehydrogenase > 365 U/L or D-dimers > 2000 ng/mL). All patients were treated with at least 1 cycle extracorporeal continuous venovenous hemofiltration (CVVHF) with cytokine adsorbing hemodiafilter (CAH); of these, 30 severe patients received CVVHF-CAH within 4 - 12 hours of hospitalisation. Another 14 patients admitted with mild-to-moderate symptoms progressed to severe disease and placed on EBP during the course of hospitalisation. The treatment was associated with a reduction of Ferritin, C-reactive protein, Fibrinogen, several inflammatory markers and a resolution of numerous cytopenias. The observed mortality across the cohort was 36.3% across the cohort. Conclusion: Extracorporeal blood purification with cytokine adsorbing hemofilter was associated with a decrease in the acute phase proteins CRP, Ferritin, and resolution of numerous cytopenias. Repetitive hemofiltration has been associated with lower levels of IL-6 in COVID-19 patients.
AimsThe present observational cohort study evaluated the association between the AKR1D1*36 (rs1872930) allele and the risk of major adverse cardiovascular and cerebrovascular events (MACCE) in clopidogrel treated patients.MethodsWe screened 198 consecutive cardiovascular patients on clopidogrel therapy admitted in October to November 2010 with cardiovascular or cerebrovascular symptoms; of these 118 met the study protocol entry criteria; the median age of the cohort was 62.5 years (IQR 57–66 years), and 55% were females.ResultsThe median follow up time was 38.5 (IQR 24–48) months; Kaplan-Meier/Log-rank analysis showed that patients carrying the AKR1D1*36 allelic variant have a shorter event-free-survival compared to wild type patients, hazard ratio = 2.193 (95% CI, 1.091 to 4.406); p = 0.0155. Multivariable Cox regression analysis confirmed the AKR1D1*36 allele as an independent risk factor (HR = 2.36; 95% CI, 1.34 to 4.18) and identified 3 other risk factors for MACCE; previous percutaneous interventions (PCI), HR = 2.78; (95% CI, 1.34 to 5.78), and a history of myocardial infarction, HR = 2.62; (95% CI, 1.48 to 4.64) at baseline and the previously reported CYP2C19*2 polymorphism (HR = 2.33; 95% CI, 1.33 to 4.06).ConclusionThe AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.
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