ABSTRACT
Background
The Seraph® 100 Microbind® Affinity Blood Filter is a haemoperfusion device that is licensed for the reduction of pathogens, including several viruses, in the blood. It received ...Emergency Use Authorization for the treatment of severe coronavirus disease 2019 (COVID-19) by the Food and Drug Administration (FDA). Several studies have shown that the blood viral load of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) correlates with adverse outcomes and removal of the nucleocapsid of the SARS-CoV-2 virus by the Seraph® 100 has been recently demonstrated. The aim of this registry was to evaluate the safety and efficacy of Seraph® 100 treatment for COVID-19 patients.
Methods
Twelve hospitals from six countries representing two continents documented patient and treatment characteristics as well as outcome parameters without reimbursement. Additionally, mortality and safety results of the device were reported. A total of 102 treatment sessions in 82 patients were documented in the registry. Four patients were excluded from mortality analysis due to incomplete outcome data, which were available in the other 78 patients.
Results
Overall, a 30-day mortality rate of 46.2% in the 78 patients with complete follow-up was reported. The median treatment time was 5.00 h (4.00–13.42) and 43.1% of the treatments were performed as haemoperfusion only. Adverse events of the Seraph® 100 treatment were reported in 8.8% of the 102 treatments and represented the premature end of treatment due to circuit failure. Patients who died were treated later in their intensive care unit (ICU) stay and onset of COVID symptoms. They also had higher ferritin levels. Multivariate Cox regression revealed that delayed Seraph® 100 treatment after ICU admission (>60 h), as well as bacterial superinfection, were associated with mortality. While average predicted mortality rate according to Sequential Organ Failure Assessment (SOFA) score in ICU patients was 56.7%, the observed mortality was 50.7%. In non-ICU patients, Coronavirus Clinical Characterisation Consortium (4C) score average predicted a mortality rate of 38.0%, while the observed mortality rate was 11.1%.
Conclusions
The treatment of COVID-19 patients with Seraph® 100 is well tolerated and the circuit failure rate was lower than previously reported for kidney replacement therapy (KRT) in COVID-19 patients. Mortality correlated with late initiation of Seraph treatment after ICU admission and bacterial superinfection. Compared with predicted mortality according to 4C and SOFA scores, mortality of Seraph® 100-treated patients reported in the registry was lower.
Graphical Abstract
Graphical Abstract
Puumala hantavirus (PUUV) infections usually show a mild or moderate clinical course, but may sometimes also lead to life-threatening disease. Here, we report on a 60-year-old female patient with ...common variable immunodeficiency (CVID) who developed a fatal PUUV infection with persistent renal failure, thrombocytopenia, and CNS infection with impaired consciousness and tetraparesis. Hantavirus-specific antibodies could not be detected due to the humoral immunodeficiency. Diagnosis and virological monitoring were based on the quantitative detection of PUUV RNA in blood, cerebrospinal fluid, bronchial lavage, and urine, where viral RNA was found over an unusually extended period of one month. Due to clinical deterioration and virus persistence, treatment with ribavirin was initiated. Additionally, fresh frozen plasma (FFP) from convalescent donors with a history of PUUV infection was administered. Despite viral clearance, the clinical condition of the patient did not improve and the patient died on day 81 of hospitalization. This case underlines the importance of the humoral immune response for the course of PUUV disease and illustrates the need for PCR-based virus diagnostics in those patients. Due to its potential antiviral activity, convalescent plasma should be considered in the therapy of severe hantavirus diseases.
Abstract
Background and Aims
The COVID-19 pandemic has serious impact on health and economics worldwide. Despite the recent advent of SARS-Cov-2 vaccines, treatment options are needed, yet ...pharmacologic interventions remain limited. Several extracorporeal treatments are currently explored concerning their potential to improve the clinical course and outcome of critically ill patients with COVID-19. The Seraph® 100 Microbind® Affinity adsorber (Exthera Medical, CA, USA) has recently been introduced for the elimination of several pathogens from the blood and an emergency authorization in patients with COVID-19 was granted by the FDA. Bacteria, viruses (including the SARS-CoV-2 spike glycoprotein), fungi and toxins have been shown to bind to the immobilized heparin on the ultra-high molecular weight polyethylene beads of the device in a similar way to the interaction with heparan sulfate on the cell-surface and are thereby removed from the bloodstream. Here we report the interim analysis of the COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter (COSA) registry. The goal of the registry is to gather data regarding the safety and efficacy of the Seraph® 100 in the treatment of COVID-19 patients.
Method
Participating sites were advised to insert patient data of COVID-19 patients, treated with the Seraph® 100, during their hospital stay into the COSA registry (ClinicalTrials.gov Identifier: NCT04361500). A total of 66 items were asked in a web-based platform.
Results
Until January 2021, 33 patients with 39 treatment sessions form six different hospitals were reported to the register (seven female, median age 61 years, Table 1). The patients were treated between March and December 2020. Eleven patients with a hospital admission between March and August and 22 between September and December 2020. The Seraph® 100 treatment was initiated 9 days after symptom onset, without any difference between survivors and non-survivors. Overall, a mortality of 27% was reported. Serious comorbidities (as preadmission immunosuppressive therapy, lung fibrosis or CKD5T) were reported in all of the non-survivors. Invasive ventilation was needed in 67% of these patients when Seraph treatment was initiated. A non-significant trend towards higher Ferritin levels in non-survivors (2000 (1963 – 8326) vs. 989 (644 – 2000), p=0.09) was reported. All treatments were well tolerated, three clotting events were reported.
Conclusion
Viral SARS-CoV-2 RNA is frequently (up to 78%) seen in the blood of critically ill COVID-19 patients and correlates with the severity of the disease. The Seraph® 100 can bind to viral spike protein, proinflammatory cytokines may be reduced by the device and hemodynamic stabilization has been reported during the Seraph®100 treatment of COVID-19 patients. Platelets can be hyperactivated in association with SARS-CoV-2 proteins and thus presumably trigger the hypercoagulation and thrombosis. In this context, the removal of SARS-CoV-2 proteins to prevent hyperactivated platelets appears to be a sensible approach.
All reported deaths were associated with serious preexisting comorbidities, immunosuppression, dialysis dependent renal failure, or a combination of these factors. Hence, Seraph® 100 treatment may be most beneficial in COVID-19 courses of patients without multi organ failure. More clinical data is needed to describe possible benefits of the Seraph®100 in the treatment of COVID-19 patients.
spp. are frequently encountered in specimens from ICUs. However, most of these detections represent colonization. Nevertheless, clinical practice shows that a considerable proportion of these ...patients will receive antifungal therapy (AT). β-(1→3)-D-glucan (BDG) and mannan are fungal biomarkers with high negative predictive values. We aimed to examine whether biomarker-guided discontinuation of AT can reduce the antifungal consumption. Therefore, we conducted a prospective, randomized intervention study between 1 April 2019 and 31 March 2020. All adult ICU patients with a newly started systemic AT but without fungal infection were eligible for inclusion. Enrolled patients were randomized into an intervention and a control group. In both groups, serum BDG and mannan were determined on days 1 and 2 of AT. If all measurements were negative, AT was discontinued in the intervention group. The primary endpoint was antifungal use. The study was terminated after 12 months. Until this time-point, 41 patients had been included. In the intervention group (
= 19), AT was stopped in only two patients because all others showed either positive BDG and/or mannan levels. One of these two patients developed candidemia and AT had to be restarted. There was no significant difference in the primary and secondary endpoints. In summary, the strategy of using two negative BDG and mannan levels to stop AT failed to reduce antifungal consumption in our cohort. Indeed, there will inevitably be patients with invasive candidiasis in whom necessary AT is discontinued. The optimal patient population, biomarker set, and termination criteria are critical to the success of biomarker-based termination strategies.
Oral anticoagulants and painkillers, some with an additional effect on the coagulation system, are widely used and are therefore prone to abuse and (intentional) overdose. We report the case of a ...patient with a massive mixed anticoagulant intoxication.
The patient had ingested 1960 mg rivaroxaban, 31.5 mg phenprocoumon, 1425 mg diclofenac, and 21,000 mg metamizole in suicidal intention.
Massive mixed anticoagulant overdose.
The patient was closely monitored. The phenprocoumon overdose was treated by the administration of vitamin K and PCC.
Despite the massive inhibition of the coagulation system, the patient did not experience bleeding apart from a slight gross hematuria.
Despite the ingestion of a massive amount of rivaroxaban, the plasma levels were not as high as feared, due to the ceiling effect of rivaroxaban absorption. Elimination occurred according to the half-life of rivaroxaban and was not unduly prolonged by the ingested quantity.
About 50% of all critically ill patients develop acute kidney injury (AKI) and approximately 15% receive renal replacement therapy (RRT). Although RRT is frequently used in intensive care units in ...Germany, it is currently unknown which RRT procedures are available, which qualification the involved staff has, which anticoagulation strategies are used and how RRT doses are prescribed. To investigate quality and structural characteristics of the performance of RRT in intensive care units throughout Germany, the German Interdisciplinary Society of Intensivists (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin DIVI) performed an inquiry among their members. A total of 897 members participated in the survey in which practical aspects were queried. In 69.1% of the cases, RRT was performed in hospitals with more than 400 beds and in 74.5% in university hospitals or other primary care hospitals. Furthermore, 93.3% of clinics are equipped with continuous and 75.8% with intermittent renal replacement devices. In 91.9%, indication for initiation of RRT was performed by trained physicians specialized in intensive care medicine or nephrologists. Intermittent as well as continuous modalities are both present in three-quarters of cases, which allows for individualized therapy. However, the documentation of dialysis dose needs to be improved.
Zusammenfassung
Eine akute Nierenschädigung (AKI) tritt heute bei 50 % aller kritisch kranken Patienten auf und etwa 15 % müssen mit einer Nierenersatztherapie (NET) behandelt werden. Obwohl eine NET ...ein häufiges und essenzielles Organersatzverfahren in der deutschen Intensivmedizin darstellt, ist es ist nicht bekannt, in welchem Umfang Nierenersatzverfahren zur Verfügung stehen, wer mit welcher Qualifikation eine NET durchführt, welche Formen der Antikoagulation verwendet werden und wie die Dosis der NET verschrieben wird. Die Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin (DIVI) hat deshalb Ende 2019 unter ihren Mitgliedern eine Umfrage zu den strukturellen Gegebenheiten der NET in ihrem Arbeitsumfeld durchgeführt. Es konnten 897 Datensätze erfasst werden (31,1 % der Befragten), anhand derer die aktuellen strukturellen und prozeduralen Gegebenheiten bei der Durchführung der NET auf deutschen Intensivstationen beschrieben werden können. Es waren Krankenhäuser aller Versorgungsstufen vertreten, allerdings waren Krankenhäuser mit einer Bettenzahl von > 400 Betten (69,1 %) und Krankenhäuser der Schwerpunkt- und Maximalversorgung und Unikliniken (74,5 %) verstärkt vertreten. Kontinuierliche Nierenersatzverfahren stehen auf 93,3 % und intermittierende Verfahren auf 75,8 % der Intensivstationen in Deutschland zur Verfügung. Die Indikation zur NET wird in 91,9 % durch eine/n Facharzt/Fachärztin oder einen Facharzt/Fachärztin mit Zusatzweiterbildung Intensivmedizin und/oder Nephrologie gestellt. In Fragen der Therapiedurchführung sind jedoch Aspekte der Dialysedosis besser zu implementieren und dokumentieren.
Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses ...on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes.
This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7-1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months.
This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications.
ClinicalTrials.gov NCT05726825 , Registered on 14 February 2023.
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