Extracorporeal Blood Purification in Moderate and Severe COVID-19 Patients: A Prospective Cohort Study.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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%. CONCLUSION: EBP with CAH was associated with a decrease in CRP, and control of IL-6 and procalcitonin.

Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris®) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series.

INTRODUCTION: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. METHODS: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. RESULTS: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. CONCLUSION: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.

Minimally Invasive Surgical Repair of Vertebral Artery Ostium Stenosis in Patients with Ischemic Stroke: A Single-Center Case Series.

BACKGROUND: Ischemic stroke is the second leading cause of death in North Macedonia. Posterior circulation disease, caused by vertebral artery (VA) ostium (VAo) stenosis, is a common cause of ischemic stroke. We established a treatment approach using surgical revascularization of posterior circulation disease. In the present observational study, we assessed the outcome after surgical revascularization of the posterior circulation ischemia caused by VAo stenosis. METHODS: A retrospective analysis of 20 consecutive patients who had undergone surgery from January 2017 to December 2019. The VA was accessed through a 3-cm incision in the upper medial clavicle. The corrective procedures consisted of resection and anastomosis (15 of 20), VA to subclavian artery transposition (16 of 20), endarterectomy (10 of 20), vein graft interposition techniques (4 of 20), and vein graft bypass (1 of 20). RESULTS: The cohort included 9 acute cases. The mean patient age was 66.5 years (range 46-77). Of the 20 patients, 8 were women and 12 were men. Left-sided VA pathology was present in 75% of the cases. We observed rapid clinical improvement in 19 patients (95%). The total study period was 321 patient-months, with a median follow-up of 18 months (interquartile range, 5-24 months). One patient had died of an unknown cause after 12 months. During the follow-up period, 15 patients (75%) had reported permanent clinical improvement with no significant relapse of symptoms. CONCLUSIONS: Minimally invasive surgical revascularization of the posterior brain circulation is a clinically effective therapeutic approach to manage ischemia caused by VAo stenosis. It can be performed safely, promote long-lasting symptom relief, and prevent recurrent strokes.

The AKR1D1*36 (rs1872930) Allelic Variant Is Independently Associated With Clopidogrel Treatment Outcome.

AIMS: The 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. METHODS: We 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. RESULTS: The 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). CONCLUSION: The AKR1D1*36 (rs1872930) variant is independently associated with a higher risk for MACCE and shorter event-free survival time.

Early Initiation of Extracorporeal Blood Purification Using the AN69ST (oXiris®) Hemofilter as a Treatment Modality for COVID-19 Patients: a Single-Centre Case Series

Abstract Introduction: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. Methods: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. Results: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. Conclusion: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.