High-flow nasal oxygen vs. standard oxygen therapy for patients undergoing transcatheter aortic valve replacement with conscious sedation: a randomised controlled trial.

BACKGROUND: Minimally invasive surgery is becoming more common and transfemoral transcatheter aortic valve replacement is offered to older patients with multiple comorbidities. Sternotomy is not required but patients must lie flat and still for up to 2-3 h. This procedure is increasingly being performed under conscious sedation with supplementary oxygen, but hypoxia and agitation are commonly observed. METHODS: In this randomised controlled trial, we hypothesised that high-flow nasal oxygen would provide superior oxygenation as compared with our standard practice, 2 l min-1 oxygen by dry nasal specs. This was administered using the Optiflow THRIVE Nasal High Flow delivery system (Fisher and Paykel, Auckland, New Zealand) at a flow rate of 50 l min-1 and FiO2 0.3. The primary endpoint was the change in arterial partial pressure of oxygen (pO2) during the procedure. Secondary outcomes included the incidence of oxygen desaturation, airway interventions, the number of times the patient reached for the oxygen delivery device, incidence of cerebral desaturation, peri-operative oxygen therapy duration, hospital length of stay and patient satisfaction scores. RESULTS: A total of 72 patients were recruited. There was no difference in change in pO2 from baseline using high-flow compared with standard oxygen therapy: median [IQR] increase from 12.10 (10.05-15.22 [7.2-29.8]) to 13.69 (10.85-18.38 [8.5-32.3]) kPa vs. decrease from 15.45 (12.17-19.33 [9.2-22.8]) to 14.20 (11.80-19.40 [9.7-35.1]) kPa, respectively. The percentage change in pO2 after 30 min was also not significantly different between the two groups (p = 0.171). There was a lower incidence of oxygen desaturation in the high-flow group (p = 0.027). Patients in the high-flow group assigned a significantly higher comfort score to their treatment (p ≤ 0.001). CONCLUSION: This study has demonstrated that high flow, compared with standard oxygen therapy, does not improve arterial oxygenation over the course of the procedure. There are suggestions that it may improve the secondary outcomes studied. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number (ISRCTN) 13,804,861. Registered on 15 April 2019. https://doi.org/10.1186/ISRCTN13804861.

Clinical utility of the Quantra® point-of-care haemostasis analyser during urgent cardiac surgery.

Coagulopathic bleeding during and after cardiac surgery is associated with increased morbidity and mortality. Viscoelastic testing is increasingly used instead of laboratory testing. Our aim was to compare a new viscoelastic point-of-care device, the Quantra® System, with thromboelastography and standard laboratory testing. After ethical approval and with written informed consent, we prospectively recruited adult patients undergoing urgent cardiac surgery at increased risk of bleeding. Clot time and clot stiffness values were compared before, during and after cardiopulmonary bypass. We prospectively recruited 52 patients, of whom 34 (65%) were transfused with red blood cells. Our usual transfusion thresholds for fibrinogen (1.5 g.l-1 ), platelets (100,000.µl-1 ), prothrombin time (20 s), activated partial thromboplastin time (48 s) and maximum amplitude on thromboelastography (50 mm) corresponded to Quantra values of fibrinogen clot stiffness 2.0 hPa, platelet clot stiffness 13.5 hPa, clot time 159 s, clot time 183 s and clot stiffness 17.0 hPa, respectively. These Quantra thresholds showed high negative predictive value for low platelets (platelet clot stiffness, 97.4%), prolonged activated partial thromboplastin time (clot time, 92.6%) and reduced maximum amplitude on thromboelastography (clot stiffness, 93.6%). The Quantra predicted clinical need for transfusion of platelets (area under the curve 0.71, p = 0.001) but all tests performed poorly at predicting the need for fresh frozen plasma transfusion. We have shown that point-of-care testing using the novel Quantra system provides useful data for guiding transfusion management.

Relationship between fetal head station established using an open magnetic resonance imaging scanner and the angle of progression determined by transperineal ultrasound.

OBJECTIVE: We investigated the correlation between the angle of progression measured by transperineal ultrasound and fetal head station measured by open magnetic resonance imaging (MRI), the gold standard, in pregnant women at full term. METHODS: Thirty-one pregnant women at full term with a fetus in the occipitoanterior position were enrolled. First, the distance between the leading part of the skull and the interspinal plane was obtained using an open MRI system with the patient in a supine position. Immediately after MRI, the angle of progression was obtained by transperineal ultrasound without changing the woman's posture. RESULTS: There was a significant correlation between the angle of progression determined by transperineal sonography and the distance between the presenting fetal part and the level of the maternal ischial spines (y = - 0.51x + 60.8, r(2) = 0.38, P < 0.001). None of the fetal heads was engaged at the time of MRI and ultrasound examinations. CONCLUSIONS: The present study demonstrated a predictable relationship between the angle of progression obtained by transperineal ultrasound and the traditional scale used to quantify fetal head descent. Based on our results, station 0 would correspond to a 120° angle of progression. However, this correlation is based on statistical assumptions only and has to be proven in future studies.

Homodimerization of amyloid precursor protein and its implication in the amyloidogenic pathway of Alzheimer's disease.

We reported previously that the carbohydrate domain of the amyloid precursor protein is involved in amyloid precursor protein (APP)-APP interactions. Functional in vitro studies suggested that this interaction occurs through the collagen binding site of APP. The physiological significance remained unknown, because it is not understood whether and how APP dimerization occurs in vivo. Here we report that cellular APP exists as homodimers matching best with a two-site model. Consistent with our published crystallographic data, we show that a deletion of the entire sequence after the kunitz protease inhibitor domain did not abolish APP homodimerization, suggesting that two domains are critically involved but that neither is essential for homodimerization. Finally, we generated stabilized dimers by expressing mutant APP with a single cysteine in the ectodomain juxtamembrane region. Mutation of Lys(624) to cysteine produced approximately 6-8-fold more A beta than cells expressing normal APP. Our results suggest that amyloid A beta production can in principle be positively regulated by dimerization in vivo. We suggest that dimerization could be a physiologically important mechanism for regulating the proposed signal activity of APP.

Characterization of growth/differentiation factor 5 (GDF-5) as a neurotrophic factor for cultured neurons from chicken dorsal root ganglia.

Growth/differentiation factor-5 (GDF-5), a morphogenetic protein, has previously been shown to act as a neurotrophic factor for midbrain dopaminergic neurons. To further elucidate the neurotrophic potential of GDF-5, serum free cultures of dorsal root ganglionic (DRG) neurons from developing chick embryos were treated with GDF-5 with or without the simultaneous addition of other trophic factors. Our results show that GDF-5 has a minor promoting effect on its own, but it can enhance the survival promoting effect of neurotrophin-3 (NT-3) and nerve growth factor (NGF) on cultured DRG neurons. Our finding fits well into the concept that neurotrophic factors may act synergistically in ensuring survival of different neuronal populations. The capacity of GDF-5 to reduce the requirement of a subpopulation of sensory neurons for NT-3 may have implications for the treatment of peripheral neuropathies.