Development of objective performance metrics for ultrasound-guided internal jugular vein cannulation on behalf of the College of Anaesthesiologists of Ireland and observation of scores amongst novice and experienced operators.

BACKGROUND: Ultrasound-guided, internal jugular venous (IJV) cannulation is a core technical skill for anaesthesiologists and intensivists. OBJECTIVES: At a modified Delphi panel meeting, to define and reach consensus on a set of objective ultrasound-guided IJV cannulation performance metrics on behalf of the College of Anaesthesiologists of Ireland (CAI). To use these metrics to objectively score video recordings of novice and experienced anaesthesiologists. DESIGN: An observational study. SETTING: CAI, March to June 2016 and four CAI training hospitals, November 2016 to July 2019. PARTICIPANTS: Metric development group: two CAI national directors of postgraduate training (specialist anaesthesiolgists), a behavioural scientist, a specialist intensivist and a senior CAI trainee. Scoring by two blinded assessors of video recordings of novice ( n  = 11) and experienced anaesthesiologists ( n  = 15) ultrasound-guided IJV cannulations. MAIN OUTCOME MEASURES: A set of agreed CAI objective performance metrics, that is, steps, errors, and critical errors characterising ultrasound-guided IJV cannulation. The difference in performance scores between novice and experienced anaesthesiologists as determined by skill level defined as being below or above the median total error score (errors plus critical errors): that is, low error (LoErr) and high error (HiErr), respectively. RESULTS: The study identified 47 steps, 18 errors and 13 critical errors through six phases.Variability was observed in the range of total error scores for both novice (1 to 3) and experienced (0 to 4.5) anaesthesiologists. This resulted in two further statistically different subgroups (LoErr and HiErr) for both novice ( P  = 0.011) and experienced practitioners ( P  < 0.000). The LoErr-experienced group performed the best in relation to steps, errors and total errors. Critical errors were only observed in the experienced group. CONCLUSION: A set of valid, reliable objective performance metrics has been developed for ultrasound-guided IJV cannulation. Considerable skill variability underlines the need to develop a CAI simulation-training programme using these metrics.

Breathlessness and Respiratory Disability After Kidney Transplantation.

BACKGROUND: Dyspnea is a common symptom in patients with end-stage kidney disease being treated with dialysis. This study aimed to ascertain the level of respiratory disability in patients after kidney transplantation through assessing a cohort of kidney allograft recipients for respiratory compromise and thereby identifying a potential target for therapeutic intervention. METHODS: Kidney transplant recipients who were under active observation in a single tertiary referral center were invited to take part in this prevalence study at the time of clinic follow-up. All patients agreed to take part in the study, which involved completing a Medical Research Council (MRC) dyspnea scale, completing the St George's Respiratory Questionnaire, and performing basic spirometry. An MRC score of ≥2 and/or a forced expiratory volume in 1 second <90% predicted prompted formal clinical assessment by a respiratory physician. RESULTS: This study enrolled 103 patients; 35% of all patients reported breathlessness, and 56% of all patients warranted formal respiratory medicine review. After completion of their investigations, 33 patients were found to have an underlying condition accounting for their symptoms. CONCLUSION: Our study highlights the issues of respiratory disability and breathlessness in patients who have undergone kidney transplantation. Although extensive cardiologic evaluation is performed routinely and can rule out many causes of dyspnea, respiratory assessment is not a preoperative prerequisite. This study could suggest that a formal pulmonological evaluation and basic spirometry should be part of the pretransplant evaluation of the kidney transplant recipient.

Hypersegmented neutrophils and oval macrocytes in the setting of B12 deficiency and pancytopaenia.

Vitamin B12 deficiency is a recognised pathology in several populations, with a particular prevalence in an older adult population. We present two cases whereby vitamin B12 deficiency is the causative factor in marked pancytopaenia. Oval macrocytosis and hypersegmented neutrophils were noted on both peripheral blood samples, which are a characteristic finding in macrocytic anaemia due to B12 deficiency. Distinct underlying pathologies were identified in both cases; food-cobalamin malabsorption and pernicious anaemia. Parenteral vitamin B12 supplementation resulted in a marked reticulocytosis and rapid improvement of haematological indices in both cases. We present this series to serve as a reminder that B12 deficiency can present as life-threatening pancytopaenia.It has has multiple underlying pathologies,defined risk populations and has characteristic blood film findings which can guide investigations, diagnosis and treatment.

Presenilins are novel substrates for TRAF6-mediated ubiquitination.

Mutations in presenilins (PS1 and PS2) have been linked to the pathogenesis of early onset familial Alzheimer's disease. Presenilins function as the catalytic component of the γ-secretase protease complexes responsible for the cleavage of the amyloid precursor protein (APP), subsequent generation of amyloid-ß and associated amyloid plaques in Alzheimer's disease. Biochemical and genetic studies have revealed that through interactions with several proteins, the presenilins are functionally involved in a range of cellular processes, including the regulation of intracellular calcium homeostasis. Our group has previously reported an association between presenilins and members of the tumour necrosis factor receptor-associated factor (TRAF) family of proteins. In this study we further investigated the association between TRAF6, an E3 ubiquitin ligase, and the presenilins. Here we show that the presenilin full-length holoproteins are novel substrates of TRAF6-mediated Lysine-63-linked ubiquitination. Interestingly, co-expression of catalytically active TRAF6 with the presenilins leads to decreased turnover of PS1 full-length holoprotein accompanying elevated presenilin protein levels. Similarly, while overexpression of TRAF6 increases presenilin holoprotein levels and ubiquitination in HEK293 cells, expression of catalytically deficient TRAF6 or TRAF6-deficiency leads to a reduction in presenilin protein levels and reduced PS1 ubiquitination. We also demonstrate that TRAF6 induces PS1 gene transcription in a JNK-dependent manner. Notably, we reveal that TRAF6-mediated ubiquitination of presenilin does not affect γ-secretase enzyme activity, but may regulate presenilin function in calcium signalling. Taken together, we propose that presenilins are novel substrates for TRAF6-mediated K63-linked ubiquitination and that ubiquitination of presenilins by TRAF6 increases presenilin holoprotein levels and in conditions in which TRAF6 ubiquitination of presenilins is reduced results in reduction of calcium release from the endoplasmic reticulum.