Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study

Background & AimsIn acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure.MethodsPigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure.ResultsThe Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen.ConclusionsThe survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients

Appetite Stimulant and Anti-Emetic Effect of Mirtazapine Transdermal Ointment in Cats Affected by Lymphoma Following Chemotherapy Administration: A Multi-Centre Retrospective Study

In humans, mirtazapine can prevent chemotherapy-induced nausea and vomiting (CINV) and improve cancer patients’ quality of life (QoL). This drug is being increasingly used as an appetite stimulant in cats. The hypothesis of this retrospective study was that mirtazapine could reduce the incidence of CINV and weight loss in feline patients affected by lymphoma. The objectives were to report the use of mirtazapine transdermal ointment and assess the incidence of gastrointestinal (GI) toxicity and weight loss in cats diagnosed with lymphoma and receiving chemotherapy. Transdermal mirtazapine was topically administered to the inner surface of the pinna (2 mg/cat/daily) for 14 days following chemotherapy administration. Data recorded from 20 patients were collected. Different grades of GI toxicity were shown in 8/20 (40%) patients. Body weight (BW), body condition score (BCS), and muscle condition score (MCS) improved in 12/20 (60%), 6/20 (30%), and 2/20 (10%) cats, respectively. Mirtazapine-induced adverse events (AEs) occurred in 4/20 (20%) cats and did not require mirtazapine discontinuation. Substantial weight loss was not encountered, suggesting that patients had an adequate food intake after chemotherapy administration. Transdermal mirtazapine ointment was considered safe and well tolerated

Management and safety of intraoperative ventriculostomy during early surgery for ruptured intracranial aneurysms

Brain edema and/or acute hydrocephalus are common features that limit working space during early surgery of aneurysmal subarachnoid hemorrhage (aSAH). Intraoperative ventriculostomy offers an immediate brain relaxation. However, management and complications related to the routine use of intraoperative external ventricular drainage (iEVD) are not well investigated.Background: Brain edema and/or acute hydrocephalus are common features that limit working space during early surgery of aneurysmal subarachnoid hemorrhage (aSAH). Intraoperative ventriculostomy offers an immediate brain relaxation. However, management and complications related to the routine use of intraoperative external ventricular drainage (iEVD) are not well investigated. Methods: We retrospectively reviewed all patients who were treated with pterional craniotomy and clipping for ruptured anterior circulation aneurysms in our center between 2012 and 2019. We included in this study all patients submitted to iEVD using the Paine’s point on the side of craniotomy. Indication for positioning of an iEVD was given in all cases whenever initial cisternal dissection was hampered by the lack of cerebrospinal fluid (CSF) circulation due to SAH and/or hydrocephalus. Results: In the study period, 162 patients with aSAH underwent surgical clipping. In 103 patients, an iEVD was used. The overall rate of iEVD-related complications was 6.7%, including 3 cases of catheter misplacement, one case of catheter obstruction, one case of related hemorrhage, and 2 cases of infection. The rate of shunt-dependent hydrocephalus was 16.5% (17/103 patients). Conclusion: In our experience, iEVD is a safe technique that facilitates dissection during early surgery for intracranial ruptured aneurysms, without requiring an additional burr hole procedure

Primary afferent plasticity following deafferentation of the trigeminal brainstem nuclei in the adult rat

Alpha-tyrosinated tubulin is a cytoskeletal protein that is involved in axonal growth and is considered a marker of neuronal plasticity in adult mammals. In adult rats, unilateral ablation of the left facial sensorimotor cortical areas induces degeneration of corticotrigeminal projections and marked denervation of the contralateral sensory trigeminal nuclei. Western blotting and real-time-PCR of homogenates of the contralateral trigeminal ganglion (TG) revealed consistent overexpression of growth proteins 15 days after left decortication in comparison with the ipsilateral side. Immunohistochemical analyses indicated marked overexpression of α-tyrosinated tubulin in the cells of the ganglion on the right side. Cytoskeletal changes were primarily observed in the small ganglionic neurons. Application of HRP-CT, WGA-HRP, and HRP to infraorbital nerves on both sides 15 days after left decortication showed a significant degree of terminal sprouting and neosynaptogenesis from right primary afferents at the level of the right caudalis and interpolaris trigeminal subnuclei. These observations suggest that the adaptive response of TG neurons to central deafferentation, leading to overcrowding and rearrangement of the trigeminal primary afferent terminals on V spinal subnuclei neurons, could represent the anatomical basis for distortion of facial modalities, perceived as allodynia and hyperalgesia, despite nerve integrity