Interim analysis of the COSA (COVID-19 patients treated with the Seraph® 100 Microbind® Affinity filter) registry.

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.

Local-anesthetic like inhibition of the cardiac sodium channel Nav1.5 α-subunit by 5-HT3 receptor antagonists.

5-hydroxytryptamine 3 receptor (5-HT3 receptor) antagonists are administered for prevention and therapy of nausea and vomiting. Although regarded as safe therapeutics, they can also provoke arrhythmias by prolonging the QRS interval. However, the mechanisms mediating this cardiotoxicity are poorly understood. Here we investigated effects of 5-HT3 receptor antagonists on the cardiac Na(+) channel Nav1.5. We explored the interaction of dolasetron, tropisetron, granisetron and ondansetron on the human α-subunit Nav1.5 heterologously expressed in HEK293 cells. Sodium currents were explored by means of whole-cell patch clamp recordings. All four substances inhibited the Nav1.5 in a concentration and state-dependent manner. Dolasetron displayed the lowest blocking efficacy, and tropisetron was the most potent blocker with a half maximum blocking concentration of 18µM for tonic block of inactivated channels. Tropisetron was also the most potent use-dependent inhibitor, and it also induced a strong open -channel block. Both tonic and use-dependent block by tropisetron were abbreviated on the local-anesthetic insensitive mutant Nav1.5-F1760A. Co-administration of tropisetron and the local anesthetic bupivacaine or the hypnotic propofol augmented inhibition of Nav1.5. Our data demonstrate that 5-HT3 receptor antagonists induce a local-anesthetic like inhibition of Nav1.5, and that they display different blocking efficacies. Reports on a relevant cardiotoxicity of dolasetron as opposed to other 5-HT3 receptor antagonists do not seem to correlate with a block of Nav1.5. As inhibition of Nav1.5 was enhanced by propofol and bupivacaine however, it is possible that a combined administration of Na(+) channel blockers and 5-HT3 receptor antagonists can provoke arrhythmias.

[Childhood drowning in the Netherlands]. / Verdrinking bij kinderen in Nederland.

OBJECTIVE: To investigate susceptible groups and risk factors for childhood drowning in the Netherlands with the aim of improving prevention campaigns. DESIGN: Prospective and partly retrospective. METHOD: Information about drowning accidents in 2010 and 2011 was collected using two methods. Firstly, drowning - with or without a fatal outcome - was added to the list of conditions to be reported to the Netherlands Paediatric Surveillance Unit (NSCK). Paediatricians received a comprehensive questionnaire when they had reported on drowning. Additional information on drowning was collected from online media (news websites and online journals). RESULTS: A total of 82 reports of drowning were analysed (63 from the paediatricians' survey and 19 additional reports from online media). Twenty-three children died as a result of drowning in the Netherlands in 2010 and 2011. Fifty-four percent of all cases of drowning were in children younger than 4 years. Boys were victims in 71% of the cases. Half (51%) of the accidents happened because the parents or caregivers lost sight of the children. In 27% of cases the accident took place in or around the home. Twenty-one children (26%) were victims of drowning in a public swimming pool and 5 of these children died. CONCLUSION: Better and continuous supervision of young children could help prevent more cases of drowning. Open water in proximity to the home should be fenced off. Continuous good supervision is also essential in public swimming pools.

The Manchester triage system: improvements for paediatric emergency care.

OBJECTIVE: To improve the Manchester Triage System (MTS) in paediatric emergency care. METHODS: The authors performed a prospective observational study at the emergency departments of a university and teaching hospital in The Netherlands and included children attending in 2007 and 2008. The authors developed and implemented specific age-dependent modifications for the MTS, based on patient groups where the system's performance was low. Nurses applied the modified system in 11,481 (84%) patients. The reference standard for urgency defined five levels based on a combination of vital signs at presentation, potentially life-threatening conditions, diagnostic resources, therapeutic interventions and follow-up. The reference standard for urgency was previously defined and available in 11,260/11,481 (96%) patients. RESULTS: Compared with the original MTS specificity improved from 79% (95% CI 79% to 80%) to 87% (95% CI 86% to 87%) while sensitivity remained similar ((63%, 95% CI 59% to 66%) vs (64%, 95% CI 60% to 68%)). The diagnostic OR increased (4.1 vs 11). CONCLUSIONS: Modifications of the MTS for paediatric emergency care resulted in an improved specificity while sensitivity remained unchanged. Further research should focus on the improvement of sensitivity.