Programmed intermittent bolus versus continuous infusion for catheter-based erector spinae plane block on quality of recovery in thoracoscopic surgery: a single-centre randomised controlled trial.

BACKGROUND: Regional anaesthesia techniques, including the erector spinae fascial plane (ESP) block, reduce postoperative pain after video-assisted thoracoscopic surgery (VATS). Fascial plane blocks rely on spread of local anaesthetic between muscle layers, and thus, intermittent boluses might increase their clinical effectiveness. We tested the hypothesis that postoperative ESP analgesia with a programmed intermittent bolus (PIB) regimen is better than a continuous infusion (CI) regimen in terms of quality of recovery after VATS. METHODS: We undertook a prospective, double-blinded, randomised, controlled trial involving 60 patients undergoing VATS. All participants received ESP block catheters and were randomly assigned to CI or PIB of local anaesthetic regimen for postoperative analgesia. The primary outcome was Quality of Recovery-15 (QoR-15) score 24 h after surgery. Secondary outcomes included postoperative respiratory function, opioid consumption, verbal rating pain score, time to first mobilisation, nausea, vomiting, and length of hospital stay. RESULTS: Overall QoR-15 scores at 24 h after VATS were similar (PIB 115.5 [interquartile range 107-125] vs CI 110 [93-128]; Δ<6, P=0.29). The only quality of recovery descriptor showing a significant difference was nausea and vomiting, which was favourable in the PIB group (10 [10-10] vs 10 [7-10]; P=0.03). Requirement for rescue antiemetics up to 24 h after surgery was lower in the PIB group (4 [14%] vs 11 [41%]; P=0.04). There were no differences in other secondary outcomes between groups. CONCLUSIONS: Delivering ESP block analgesia after VATS via a PIB regimen resulted in similar QoR-15 at 24 h compared with a CI regimen.

Management of Severe Influenza.

Influenza infection causes severe illness in 3 to 5 million people annually, with up to an estimated 650,000 deaths per annum. As such, it represents an ongoing burden to health care systems and human health. Severe acute respiratory infection can occur, resulting in respiratory failure requiring intensive care support. Herein we discuss diagnostic approaches, including development of CLIA-waived point of care tests that allow rapid diagnosis and treatment of influenza. Bacterial and fungal coinfections in severe influenza pneumonia are associated with worse outcomes, and we summarize the approach and treatment options for diagnosis and treatment of bacterial and Aspergillus coinfection. We discuss the available drug options for the treatment of severe influenza, and treatments which are no longer supported by the evidence base. Finally, we describe the supportive management and ventilatory approach to patients with respiratory failure as a result of severe influenza in the intensive care unit.

N-glycosylation is important for the correct intracellular localization of HFE and its ability to decrease cell surface transferrin binding.

HFE is a type 1 transmembrane protein that becomes N-glycosylated during transport to the cell membrane. It influences cellular iron concentrations through multiple mechanisms, including regulation of transferrin binding to transferrin receptors. The importance of glycosylation in HFE localization and function has not yet been studied. Here we employed bioinformatics to identify putative N-glycosylation sites at residues N110, N130 and N234 of the human HFE protein, and used site-directed mutagenesis to create combinations of single, double or triple mutants. Compared with the wild-type protein, which co-localizes with the type 1 transferrin receptor in the endosomal recycling compartment and on distributed punctae, the triple mutant co-localized with BiP in the endoplasmic reticulum. This was similar to the localization pattern described previously for the misfolding HFE-C282Y mutant that causes type 1 hereditary haemachromatosis. We also observed that the triple mutant was functionally deficient in beta2-microglobulin interactions and incapable of regulating transferrin binding, once again, reminiscent of the HFE-C282Y variant. Single and double mutants that undergo limited glycosylation appeared to have a mixed phenotype, with characteristics primarily of the wild-type, but also some from the glycosylation-deficient protein. Therefore, although they displayed an endosomal recycling compartment/punctate localization like the wild-type protein, many cells simultaneously displayed additional reticular localization. Furthermore, although the majority of cells expressing these single and double mutants showed decreased surface binding of transferrin, a number appeared to have lost this ability. We conclude that glycosylation is important for the normal intracellular trafficking and functional activity of HFE.