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Background: Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials.Methods: We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity.Results: We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined.Conclusions: These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.

This review focuses on the use of veno-venous extracorporeal membrane oxygenation for respiratory failure across all blood flow ranges. Starting with a short overview of historical development, aspects of the physiology of gas exchange (i.e., oxygenation and decarboxylation) during extracorporeal circulation are discussed. The mechanisms of phenomena such as recirculation and shunt playing an important role in daily clinical practice are explained. Treatment of refractory and symptomatic hypoxemic respiratory failure (e.g., acute respiratory distress syndrome [ARDS]) currently represents the main indication for high-flow veno-venous-extracorporeal membrane oxygenation. On the other hand, lower-flow extracorporeal carbon dioxide removal might potentially help to avoid or attenuate ventilator-induced lung injury by allowing reduction of the energy load (i.e., driving pressure, mechanical power) transmitted to the lungs during mechanical ventilation or spontaneous ventilation. In the latter context, extracorporeal carbon dioxide removal plays an emerging role in the treatment of chronic obstructive pulmonary disease patients during acute exacerbations. Both applications of extracorporeal lung support raise important ethical considerations, such as likelihood of ultimate futility and end-of-life decision-making. The review concludes with a brief overview of potential technical developments and persistent challenges.

Background: Sarcopenia (low skeletal muscle mass), myosteatosis (low skeletal muscle radiation-attenuation) and fitness are independently associated with postoperative outcomes in oesophago-gastric cancer. This study aimed to investigate (1) the effect of neoadjuvant therapy (NAT) on sarcopenia, myosteatosis and cardiopulmonary exercise testing (CPET), (2) the relationship between these parameters, and (3) their association with postoperative morbidity and survival.Methods: Body composition analysis used single slice computed tomography (CT) images from chest (superior to aortic arch) and abdominal CT scans (third lumbar vertebrae). Oxygen uptake at anaerobic threshold (VO2 at AT) and at peak exercise (VO2 Peak) were measured using CPET. Measurements were performed before and after NAT and an adjusted regression model assessed their association.Results: Of the 184 patients recruited, 100 underwent surgical resection. Following NAT skeletal muscle mass, radiation-attenuation and fitness reduced significantly (p < 0.001). When adjusted for age, sex, and body mass index, only pectoralis muscle mass was associated with VO2 Peak (p = 0.001). VO2 at AT and Peak were associated with 1-year survival, while neither sarcopenia nor myosteatosis were associated with morbidity or survival.Conclusion: Skeletal muscle and CPET variables reduced following NAT and were positively associated with each other. Cardiorespiratory function significantly contributes to short-term survival after oesophago-gastric cancer surgery.Keywords: body composition; myosteatosis; neoadjuvant therapy; oxygen uptake; physical fitness; sarcopenia.

OBJECTIVES To describe the distribution of high-sensitivity troponin in a consecutive cohort of patients in critical care units, regardless of clinical indication, and its association with clinical outcomes. DESIGN Prospective observational study. SETTING Single-center teaching hospital. PATIENTS Consecutive patients admitted to two adult critical care units (general critical care unit and neuroscience critical care unit) over a 6-month period. INTERVENTIONS All patients had high-sensitivity troponin tests performed at admission and tracked throughout their critical care stay, regardless of whether the supervising team felt there was a clinical indication. The results were not revealed to patients or clinicians unless clinically requested. MEASUREMENTS AND MAIN RESULTS There were 1,033 patients in the study cohort (general critical care unit 750 and neuroscience critical care unit 283). The median high-sensitivity troponin was 21 ng/L (interquartile range, 7-86 ng/L), with 560 patients (54.2%) above the upper limit of normal as defined by the manufacturer. Admission high-sensitivity troponin concentrations above the upper limit of normal in general critical care unit and neuroscience critical care unit were associated with increasing age, comorbidity, markers of illness severity, and the need for organ support. On adjusted analysis, the high-sensitivity troponin concentration remained an independent predictor of critical care mortality in general critical care unit and neuroscience critical care unit. CONCLUSIONS High-sensitivity troponin elevation, taken outside the context of conventional clinical indications, was common in the critically ill. Such elevations were associated with increasing age, comorbidity, illness severity, and the need for organ support. Admission high-sensitivity troponin concentration is an independent predictor of critical care mortality and as such may represent a novel prognostic biomarker at admission.

Background Acute kidney injury (AKI) is a common manifestation among patients critically ill with SARS-CoV-2 infection (Coronavirus 2019) and is associated with significant morbidity and mortality. The pathophysiology of renal failure in this context is not fully understood, but likely to be multifactorial. The intensive care unit outcomes of patients following COVID-19 acute critical illness with associated AKI have not been fully explored. We conducted a cohort study to investigate the risk factors for acute kidney injury in patients admitted to and intensive care unit with COVID-19, its incidence and associated outcomes. Methods We reviewed the medical records of all patients admitted to our adult intensive care unit suffering from SARS-CoV-2 infection from 14th March 2020 until 12th May 2020. Acute kidney injury was defined using the Kidney Disease Improving Global Outcome (KDIGO) criteria. The outcome analysis was assessed up to date as 3rd of September 2020. Results A total of 81 patients admitted during this period. All patients had acute hypoxic respiratory failure and needed either noninvasive or invasive mechanical ventilatory support. Thirty-six patients (44%) had evidence of AKI (Stage I-33%, Stage II-22%, Renal Replacement Therapy (RRT)-44%). All patients with AKI stage III had RRT. Age, diabetes mellitus, immunosuppression, lymphopenia, high D-Dimer levels, increased APACHE II and SOFA scores, invasive mechanical ventilation and use of inotropic or vasopressor support were significantly associated with AKI. The peak AKI was at day 4 and mean duration of RRT was 12.5 days. The mortality was 25% for the AKI group compared to 6.7% in those without AKI. Among those received RRT and survived their illness, the renal function recovery is complete and back to baseline in all patients. Conclusion Acute kidney injury and renal replacement therapy is common in critically ill patients presenting with COVID-19. It is associated with increased severity of illness on admission to ICU, increased mortality and prolonged ICU and hospital length of stay. Recovery of renal function was complete in all survived patients.

Background: Surgical resection remains the primary curative treatment for intra-cavity cancer. Low physical fitness and psychological factors such as depression are predictive of post–operative morbidity, mortality and length of hospital stay. Prolonged post-operative morbidity is associated with persistently elevated risk of premature death. We aim to investigate whether a structured, responsive exercise training programme, a psychological support programme or combined exercise and psychological support, delivered between treatment decision and major intra-cavity surgery for cancer, can reduce length of hospital stay, compared with standard care. Methods: WesFit is a pragmatic, 2x2 factorial-design, multi-centre, randomised-controlled trial, with planned recruitment of N=1560. Participants will be randomised to one of four groups. Group 1 (control) will receive usual pre-operative care, Group 2 (exercise) patients will undergo 2/3 aerobic, high-intensity interval training sessions per week supervised by personal trainers. Group 3 (psychological support) patients are offered 1 session per week at a local cancer support centre. Group 4 will receive both exercise and psychological support. All patients undergo baseline and pre-operative cardiopulmonary exercise testing, complete self-report questionnaires and will be followed up at 30 days, 12 weeks and 12 months post-operatively. Primary outcome is post-operative length-of-stay. Secondary outcomes include disability-adjusted survival at 1-year postoperatively, post-operative morbidity, and health-related quality of life. Exploratory investigations include objectively measured changes in physical fitness assessed by cardiopulmonary exercise test, disease-free and overall mortality at 1-year postoperatively, longer-term physical activity behaviour change, pre-operative radiological tumour regression, pathological tumour regression, pre and post-operative body composition analysis, health economics analysis and nutritional characterisation and its relationship to post-operative outcome. Conclusions: The WesFit trial will be a randomised controlled study investigating whether a high-intensity exercise training programme +/- psychological intervention results in improvements in clinical and patient reported outcomes in patients undergoing major inter-cavity resection of cancer. ClinicalTrials.gov registration: NCT03509428 (26/04/2018)

Background A multidisciplinary international working subgroup of the third Perioperative Quality Initiative consensus meeting appraised the evidence on the influence of preoperative arterial blood pressure and community cardiovascular medications on perioperative risk. Methods A modified Delphi technique was used, evaluating papers published in MEDLINE on associations between preoperative numerical arterial pressure values or cardiovascular medications and perioperative outcomes. The strength of the recommendations was graded by National Institute for Health and Care Excellence guidelines. Results Significant heterogeneity in study design, including arterial pressure measures and perioperative outcomes, hampered the comparison of studies. Nonetheless, consensus recommendations were that (i) preoperative arterial pressure measures may be used to define targets for perioperative management; (ii) elective surgery should not be cancelled based solely upon a preoperative arterial pressure value; (iii) there is insufficient evidence to support lowering arterial pressure in the immediate preoperative period to minimise perioperative risk; and (iv) there is insufficient evidence that any one measure of arterial pressure (systolic, diastolic, mean, or pulse) is better than any other for risk prediction of adverse perioperative events. Conclusions Future research should define which preoperative arterial pressure values best correlate with adverse outcomes, and whether modifying arterial pressure in the preoperative setting will change the perioperative morbidity or mortality. Additional research should define optimum strategies for continuation or discontinuation of preoperative cardiovascular medications.

Objectives The pattern of global COVID-19 has caused many to propose a possible link between susceptibility, severity and vitamin-D levels. Vitamin-D has known immune modulatory effects and deficiency has been linked to increased severity of viral infections. Methods We evaluated patients admitted with confirmed SARS-COV-2 to our hospital between March-June 2020. Demographics and outcomes were assessed for those admitted to the intensive care unit (ICU) with normal (>50 nmol/L) and low ( Results There were 646 SARS-COV-2 PCR positive hospitalisations and 165 (25.5%) had plasma vitamin-D levels. Fifty patients were admitted to ICU. There was no difference in vitamin-D levels of those hospitalised (34, IQR 18.5–66 nmol/L) and those admitted to the ICU (31.5, IQR 21–42 nmol/L). Higher proportion of vitamin-D deficiency ( Conclusions Despite the association of low vitamin-D levels with low CT values, there is no difference in clinical outcomes in this small cohort of critically ill COVID-19 patients. The complex relationship between vitamin-D levels and COVID-19 infection needs further exploration with large scale randomized controlled trials.

Objective:In autosomal recessive dystrophic Epidermolysis bullosa, repeat blistering results in finger webbing and severe contractures of the hands. The aim of this study was to codesign patient-reported outcome indicators for hand therapy with patients, carers and clinicians, and use these to proof-of-concept test a novel dressing glove for recessive dystrophic Epidermolysis bullosa, with cost analysis.Method:Qualitative interviews and focus groups with patients and carers generated content for the indicators. Validity and reliability were established through expert review, piloting and consensus between patients, carers and clinicians. The indicators were self-reported by patients before and while wearing the dressing glove in an N-of-1 study. Time for dressing changes and use of conventional products were also self-reported.Results:A total of 11 indicators were initially generated from the thematic analysis. Expert review, piloting and consensus involved six patients, five carers and eight clinicians (total n=19). Participants agreed 14 indicators, covering hand skin condition (n=4), webbing between the digits (n=4), experiences of wearing and changing dressings (n=2), hand function (n=2), wrist function (n=1) and hand pain (n=1). In Phase 3, 12 patients scored indicators before wearing the gloves and four patients completed scoring while wearing the gloves. Statistically significant improvements between pre-glove and with-glove periods were found for most participants' experience scores. Skin appearance also improved for most participants.Conclusions:The indicators generated useful data, differentiation between scores and participants demonstrating proof-of-concept for patients with recessive dystrophic Epidermolysis bullosa who could wear the dressing gloves. The indicators are being used in routine practice, supporting clinical follow up, commercialisation and regulatory governance of the dressing glove.

Some neurological complications following surgery have been related to a mismatch in cerebral oxygen supply and demand that may either lead to more subtle changes of brain function or overt complications like stroke or coma. Discovery of a perioperative neurological complication may be outside the treatment window, thereby making prevention an important focus. Early commercial devices used differential spectroscopy to measure relative changes from baseline of 2 chromophores: oxy- and deoxyhemoglobin. It was the introduction of spatially resolved spectroscopy techniques that allowed near-infrared spectroscopy (NIRS)-based cerebral oximetry as we know it today. Modern cerebral oximeters measure the hemoglobin saturation of blood in a specific "optical field" containing arterial, capillary, and venous blood, not tissue oxygenation itself. Multiple cerebral oximeters are commercially available, all of which have technical differences that make them noninterchangeable. The mechanism and meaning of these measurements are likely not widely understood by many practicing physicians. Additionally, as with many clinically used monitors, there is a lack of high-quality evidence on which clinicians can base decisions in their effort to use cerebral oximetry to reduce neurocognitive complications after surgery. Therefore, the Sixth Perioperative Quality Initiative (POQI-6) consensus conference brought together an international team of multidisciplinary experts including anesthesiologists, surgeons, and critical care physicians to objectively survey the literature on cerebral oximetry and provide consensus, evidence-based recommendations for its use in accordance with the GRading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria for evaluating biomedical literature. The group produced the following consensus recommendations: (1) interpreting perioperative cerebral oximetry measurements in the context of a preinduction baseline value; (2) interpreting perioperative cerebral oximetry measurements in the context of the physiologic variables that affect them; (3) using caution in comparing cerebral oximetry values between different manufacturers; (4) using preoperative cerebral oximetry to identify patients at increased risk of adverse outcomes after cardiac surgery; (5) using intraoperative cerebral oximetry indexed to preinduction baseline to identify patients at increased risk of adverse outcomes after cardiac surgery; (6) using cerebral oximetry to identify and guide management of acute cerebral malperfusion during cardiac surgery; (7) using an intraoperative cerebral oximetry-guided interventional algorithm to reduce intensive care unit (ICU) length of stay after cardiac surgery. Additionally, there was agreement that (8) there is insufficient evidence to recommend using intraoperative cerebral oximetry to reduce mortality or organ-specific morbidity after cardiac surgery; (9) there is insufficient evidence to recommend using intraoperative cerebral oximetry to improve outcomes after noncardiac surgery.

Ascent to high altitude triggers a wide range of physiological changes. However, ascent is also associated with three acute pathologies: acute mountain sickness, high-altitude cerebral oedema (HACE) and high-altitude pulmonary oedema (HAPE). Awareness and understanding of these conditions allows measures to be taken to reduce the risk of them developing through careful planning and, where appropriate, pharmacological prophylaxis. Both HACE and HAPE are life threatening, necessitating prompt diagnosis and management. Acute mountain sickness, although usually benign, may progress, to HACE or HAPE, if not managed appropriately. This review examines each pathology providing options for risk reduction, diagnosis and management, as well as considering comorbidity at altitude, drawing upon recent advances and consensus guidelines in the field.

Introduction Scapular fractures are relatively rare injuries usually associated with high-energy trauma and multiple concomitant injuries. Most of scapular fractures do not require surgical intervention. Patient and clinical history A 42-year-old male sustained an extra-articular scapular body fracture along with multiple rib fractures with flail segments and right pneumothorax treated with intercostal drain. The scapula fracture was treated non-operatively initially, which resulted in very poor outcome. Operative intervention was planned following scans which showed a bony spike from the ventral surface impinging on the chest wall. Surgical technique Bony spur was approached from dorsal side using a three-dimensional anatomical model as a guide for accurate localization. Results The patient’s symptoms including shoulder stiffness and pain on deep inspiration settled down completely following removal of the spur. Discussion This case presents a new indication for surgical intervention in scapular body fracture which has not been published before. All the relevant measurements related to the fracture namely gleno-polar angle, lateral border offset and angulation were within published limits of indications for conservative treatment. Despite this, it resulted in poor outcome necessitating surgical intervention.

Acute mountain sickness (AMS) occurs when there is failure of acclimatisation to high altitude. The aim of this study was to describe the relationship between physiological variables and the incidence of AMS during ascent to 5300 m. A total of 332 lowland‐dwelling volunteers followed an identical ascent profile on staggered treks. Self‐reported symptoms of AMS were recorded daily using the Lake Louise score (mild 3–4; moderate‐severe ≥5), alongside measurements of physiological variables (heart rate, respiratory rate (RR), peripheral oxygen saturation (SpO2) and blood pressure) before and after a standardised Xtreme Everest Step‐Test (XEST). The overall occurrence of AMS among participants was 73.5% (23.2% mild, 50.3% moderate–severe). There was no difference in gender, age, previous AMS, weight or body mass index between participants who developed AMS and those who did not. Participants who had not previously ascended >5000 m were more likely to get moderate‐to‐severe AMS. Participants who suffered moderate‐to‐severe AMS had a lower resting SpO2 at 3500 m (88.5 vs. 89.6%, p = 0.02), while participants who suffered mild or moderate‐to‐severe AMS had a lower end‐exercise SpO2 at 3500 m (82.2 vs. 83.8%, p = 0.027; 81.5 vs. 83.8%, p 5000 m (OR 2.740, p‐value 0.003) predicted the development of moderate‐to‐severe AMS. The Xtreme Everest Step‐Test offers a simple, reproducible field test to help predict AMS, albeit with relatively limited predictive precision., We evaluated the performance of a simple exercise challenge at altitude (the Xtreme Everest Step‐Test) in predicting acute mountain sickness (AMS) on a trek to Everest Base Camp (5300 m). The overall occurrence of AMS during the trek was high (73.5%). Lower peripheral oxygen saturation (SpO2) following the Xtreme Everest Step‐Test at 3500 m and no previous exposure to altitude >5000 m predicted the development of moderate to severe AMS (Lake Louise score ≥5) during the trek. The Xtreme Everest Step‐Test offers a simple, reproducible field test to contribute towards the prediction of AMS, albeit with relatively limited predictive precision.

Redox dysregulation and oxidative stress have been implicated in asthma pathogenesis. Exercise interventions improve symptoms and reduce inflammation in asthma patients, but the underlying mechanisms remain unclear. We hypothesized that a personalised exercise intervention would improve asthma control by reducing lung inflammation through modulation of local and systemic reactive species interactions, thereby increasing antioxidant capacity. We combined deep redox metabolomic profiling with clinical assessment in an exploratory cohort of six female patients with symptomatic asthma and studied their responses to a metabolically targeted exercise intervention over 12 weeks. Plasma antioxidant capacity and circulating nitrite levels increased following the intervention (p = 0.028) and lowered the ratio of reduced to oxidised glutathione (p = 0.029); this was accompanied by improvements in physical fitness (p = 0.046), symptoms scores (p = 0.020), quality of life (p = 0.046), lung function (p = 0.028), airway hyperreactivity (p = 0.043), and eosinophilic inflammation (p = 0.007). Increased physical fitness correlated with improved plasma antioxidant capacity (p = 0.019), peak oxygen uptake and nitrite changes (p = 0.005), the latter also associated with reductions in peripheral blood eosinophil counts (p = 0.038). Thus, increases in “redox resilience” may underpin the clinical benefits of exercise in asthma. An improved understanding of exercise-induced alterations in redox regulation offers opportunities for greater treatment personalisation and identification of new treatment targets.

Introduction The diagnosis and clinical implication of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) is contentious, especially given its importance in the interpretation of trial data. Two accepted definitions of PPMI yield discrepant results. Little is known about the association between the diagnosis of PPMI, using high sensitivity troponin (hs-cTn), and medium term mortality in patients who undergo CABG, either alone or in conjunction with another procedure. In addition, there are currently no criteria for the diagnosis of PPMI following non-CABG surgery. Method Consecutive patients admitted to a cardiothoracic critical care unit (CCCU) over a six month period following open cardiac surgery had hs-cTnI assay performed on admission and every day for forty-eight hours, regardless of whether there was a clinical indication. Patients were categorised as PPMI using both the Universal Definition of MI (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Comorbidity data, surgical details and clinical progress in CCCU were recorded. One year mortality data were obtained from NHS Digital. Results There were 245 CABG patients, of whom 20.4% met criteria for UDMI PPMI and 87.6% for SCAI UDMI (figure 1). The diagnosis of UDMI PPMI was independently associated with one year mortality (hazard ratio 4.175 (95% confidence interval 1.281 – 13.608)), whereas there was no association between SCAI PPMI and one year mortality (figure 2). Of the 243 patients who had non CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI (figure1) but neither was associated with one year mortality. Conclusions The incidence of SCAI PPMI in a real world cohort of cardiac surgery patients is so high as to be of limited clinical value. By contrast, a diagnosis of UDMI PPMI post CABG is independently associated with one year mortality, so may have clinical utility. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Beckman Coulter - supplied the assays used in the study but had no role in the study Figure 1. Frequency of PPMIFigure 2. Kaplan Meier curves

Purpose of Review Cardiopulmonary exercise testing (CPET) informs the preoperative evaluation process by providing individualised risk profiles; guiding shared decision-making, comorbidity optimisation and preoperative exercise training; and informing perioperative patient management. This review summarises evidence on the role of CPET in preoperative evaluation and explores the role of novel and emerging CPET variables and alternative testing protocols that may improve the precision of preoperative evaluation in the future. Recent Findings CPET provides a wealth of physiological data, and to date, much of this is underutilised clinically. For example, impaired chronotropic responses during and after CPET are simple to measure and in recent studies are predictive of both cardiac and noncardiac morbidity following surgery but are rarely reported. Exercise interventions are increasingly being used preoperatively, and endurance time derived from a high intensity constant work rate test should be considered as the most sensitive method of evaluating the response to training. Further research is required to identify the clinically meaningful difference in endurance time. Measuring efficiency may have utility, but this requires exploration in prospective studies. Summary Further work is needed to define contemporaneous risk thresholds, to explore the role of other CPET variables in risk prediction, to better characterise CPET’s role in combination with other tools in multifactorial risk stratification and increasingly to evaluate CPET’s utility for preoperative exercise prescription in prehabilitation.

Fumarate hydratase deficiency (FHD) is a rare metabolic disease caused by two defective copies of the FH gene, which encodes the Krebs cycle enzyme fumarase. FHD is associated with brain and developmental abnormalities, seizures, and high childhood mortality. We describe the symptoms and treatment of a patient with FHD. While infantile spasms are common in FHD, the patient presented with epileptic spasms later in childhood. Also unexpectedly, the patient responded excellently to lacosamide for her non-convulsive status epilepticus and epileptic spasms after three first-line medication trials failed. We biochemically analyzed the patient's two fumarase variants (E432Kfs*17 and D65G). While E432Kfs*17 was extremely enzymatically defective, D65G exhibited only a mild defect, possibly playing a role in the patient's longer survival.

BACKGROUND: ARDS is an overwhelming systemic inflammatory process associated with significant morbidity and mortality. Several trials have evaluated the effects of pharmaconutrients, given as part of a feeding formula or as a nutritional supplement, on clinical outcomes in critical illness and ARDS. The aim of this review is to assess the effects of immunonutrition on mechanically ventilated adults with ARDS compared to the standard feeding formula. METHODS: We searched MEDLINE, EMBASE, CENTRAL, conference proceedings, and trial registries for appropriate studies up to April 2018. We performed statistical analysis according to Cochrane methodological standards. We used the GRADE approach to assess the quality of evidence for each outcome. RESULTS: We identified 10 randomized controlled trials with 1,015 participants. All of the studies compared an enteral formula or additional supplemental omega-3 fatty acids (eg, eicosapentaenoic acid, docosahexaenoic acid), γ-linolenic acid, and antioxidants. All of the studies reported mortality. For the primary outcome, there was no difference in all-cause mortality (for the longest period reported) with the use of an immunonutrition enteral formula or additional supplements of omega-3 fatty acids, γ-linolenic acid, and antioxidants (risk ratio = 0.79, 95% CI 0.59–1.07; low-quality evidence). For the secondary outcomes, we are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ICU length of stay, ventilator days, and oxygenation or increases harm. CONCLUSIONS: This Cochrane meta-analysis of 10 studies of varying quality examined the effects of omega-3 fatty acids and antioxidants in adults with ARDS. This intervention may produce little or no difference in all-cause mortality between groups. We are uncertain whether immunonutrition with omega-3 fatty acids and antioxidants improves ventilator days, ICU length of stay, or oxygenation due to the very low quality of evidence.

Background : Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure. Methods We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004–13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin–angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds. Results Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05–3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09–3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17–0.75) and thiazides (aOR: 0.28; 95% CI: 0.10–0.78) were associated with lower mortality in patients with systolic hypertension. Conclusions These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship.

Persistent postoperative opioid use is thought to contribute to the ongoing opioid epidemic in the United States. However, efforts to study and address the issue have been stymied by the lack of a standard definition, which has also hampered efforts to measure the incidence of and risk factors for persistent postoperative opioid use. The objective of this systematic review is to (1) determine a clinically relevant definition of persistent postoperative opioid use, and (2) characterize its incidence and risk factors for several common surgeries. Our approach leveraged a group of international experts from the Perioperative Quality Initiative-4, a consensus-building conference that included representation from anesthesiology, surgery, and nursing. A search of the medical literature yielded 46 articles addressing persistent postoperative opioid use in adults after arthroplasty, abdominopelvic surgery, spine surgery, thoracic surgery, mastectomy, and thoracic surgery. In opioid-naive patients, the overall incidence ranged from 2% to 6% based on moderate-level evidence. However, patients who use opioids preoperatively had an incidence of >30%. Preoperative opioid use, depression, factors associated with the diagnosis of substance use disorder, preoperative pain, and tobacco use were reported risk factors. In addition, while anxiety, sex, and psychotropic prescription are associated with persistent postoperative opioid use, these reports are based on lower level evidence. While few articles addressed the health policy or prescriber characteristics that influence persistent postoperative opioid use, efforts to modify prescriber behaviors and health system characteristics are likely to have success in reducing persistent postoperative opioid use.

OBJECTIVES The intermediate-term all-cause mortality rate of real-world patients with multivessel disease (MVD) treated with percutaneous coronary intervention (PCI) with new-generation drug-eluting stents or coronary artery bypass grafting (CABG) remains unknown. We sought to compare the intermediate-term all-cause mortality rates of real-world patients with MVD including left main stem disease, treated with CABG or PCI. METHODS All consecutive all-comer patients with MVD undergoing CABG or PCI with second/third generation drug-eluting stents from 2007 to 2015 in Harefield Hospital, UK were included in this study. The revascularization modality was based on heart team discussions. Primary outcome was all-cause mortality. Mean follow-up of the study was 3.3 years. Cox regression analysis and propensity matching were used. RESULTS Of 6383 patients with MVD, 4230 underwent CABG, whereas 2153 had PCI with new-generation stents. In the CABG group, the mean age was 66.4 ± 10 years, whereas in the PCI group it was 65.3 ± 12.1 years (P CONCLUSIONS In this contemporary cohort of real-world patients with MVD, CABG was associated with increased intermediate-term survival compared to PCI with new-generation drug-eluting stents.

Background Body composition assessment, measured using single-slice computed tomography (CT) image at L3 level, and aerobic physical fitness, objectively measured using cardiopulmonary exercise testing (CPET), are each independently used for perioperative risk assessment. Sarcopenia (i.e. low skeletal muscle mass), myosteatosis [i.e. low skeletal muscle radiation attenuation (SM-RA)], and impaired objectively measured aerobic fitness (reduced oxygen uptake) have been associated with poor post-operative outcomes and survival in various cancer types. However, the association between CT body composition and physical fitness has not been explored. In this study, we assessed the association of CT body composition with selected CPET variables in patients undergoing hepatobiliary and pancreatic surgery. Methods A pragmatic prospective cohort of 123 patients undergoing hepatobiliary and pancreatic surgery were recruited. All patients underwent preoperative CPET. Preoperative CT scans were analysed using a single-slice CT image at L3 level to assess skeletal muscle mass, adipose tissue mass, and muscle radiation attenuation. Multivariate linear regression was used to test the association between CPET variables and body composition. Main outcomes were oxygen uptake at anaerobic threshold (V?O-2 at AT), oxygen uptake at peak exercise (V?O-2 peak), skeletal muscle mass, and SM-RA. Results Of 123 patients recruited [77 men (63%), median age 66.9 +/- 11.7, median body mass index 27.3 +/- 5.2], 113 patients had good-quality abdominal CT scans available and were included. Of the CT body composition variables, SM-RA had the strongest correlation with V?O-2 peak (r = 0.57, P

Background The EMPOWER trial aimed to assess the effects of a 9-week exercise prehabilitation programme on physical fitness compared with a usual care control group. Secondary aims were to investigate the effect of (1) the exercise prehabilitation programme on psychological health; and (2) neoadjuvant chemoradiotherapy (NCRT) on physical fitness and psychological health. Methods Between October 2013 and December 2016, adults with locally advanced rectal cancer undergoing standardised NCRT and surgery were recruited to a multi-centre trial. Patients underwent cardiopulmonary exercise testing (CPET) and completed HRQoL questionnaires (EORTC-QLQ-C30 and EQ-5D-5L) pre-NCRT and post-NCRT (week 0/baseline). At week 0, patients were randomised to exercise prehabilitation or usual care (no intervention). CPET and HRQoL questionnaires were assessed at week 0, 3, 6 and 9, whilst semi-structured interviews were assessed at week 0 and week 9. Changes in oxygen uptake at anaerobic threshold (VO2 at AT (ml kg−1 min−1)) between groups were compared using linear mixed modelling. Results Thirty-eight patients were recruited, mean age 64 (10.4) years. Of the 38 patients, 33 were randomised: 16 to usual care and 17 to exercise prehabilitation (26 males and 7 females). Exercise prehabilitation significantly improved VO2 at AT at week 9 compared to the usual care. The change from baseline to week 9, when adjusted for baseline, between the randomised groups was + 2.9 ml kg −1 min −1; (95% CI 0.8 to 5.1), p = 0.011. Conclusion A 9-week exercise prehabilitation programme significantly improved fitness following NCRT. These findings have informed the WesFit trial (NCT03509428) which is investigating the effects of community-based multimodal prehabilitation before cancer surgery. Trial registration ClinicalTrials.gov NCT01914068. Registered 1 August 2013.

Introduction The diagnosis and clinical implication of periprocedural myocardial infarction (PPMI) following coronary artery bypass grafting (CABG) is contentious, especially given its importance in the interpretation of trial data. Two accepted definitions of PPMI yield discrepant results. Little is known about the association between the diagnosis of PPMI, using high sensitivity troponin (hs-cTn), and medium term mortality in patients who undergo CABG, either alone or in conjunction with another procedure. Method Consecutive patients admitted to a cardiothoracic critical care unit (CCCU) over a six month period following open cardiac surgery had hs-cTnI assay performed on admission and every day for forty-eight hours, regardless of whether there was a clinical indication. Patients were categorised as PPMI using both the Universal Definition of MI (UDMI) and Society of Cardiovascular Angiography and Interventions (SCAI) criteria. Comorbidity data, surgical details and clinical progress in CCCU were recorded. One year mortality data were obtained from NHS Digital. Results There were 245 CABG patients, of whom 20.4% met criteria for UDMI PPMI and 87.6% for SCAI UDMI. The diagnosis of UDMI PPMI was independently associated with one year mortality (hazard ratio 4.175 (95% confidence interval 1.281 – 13.608)), whereas there was no association between SCAI PPMI and one year mortality (figure 1). Of the 243 patients who had non CABG cardiac surgery, 11.4% met criteria for UDMI PPMI and 85.2% for SCAI PPMI but neither was associated with one year mortality. Conclusions The incidence of SCAI PPMI in a real world cohort of cardiac surgery patients is so high as to be of limited clinical value. By contrast, a diagnosis of UDMI PPMI post CABG is independently associated with one year mortality, so may have clinical utility. Conflict of Interest Beckman Coulter provided the assays used in my research but had no other role in the studies

Introduction High-sensitivity troponin (hs-cTn) assays now form a key component of the diagnostic pathways for patients presenting to emergency medical services with chest pain. However, hs-cTn concentrations above the manufacturer-provided upper limit of normal (ULN) are now frequently reported in patients presenting with conditions not traditionally associated with type 1 myocardial infarction (T1MI). This is particularly true of severe illness states. We investigated the possible association between hs-cTn and one year mortality in critical care patients. Method Consecutive patients admitted to two adult critical care units (general critical care unit (GCCU) and neuroscience critical care unit (NCCU)) over a six month period had hs-cTnI assay performed on admission, regardless of whether there was a clinical indication, and the results nested unless a clinical request had been made. Comorbidity data, illness severity and critical care outcome were recorded and have been previously reported. One year mortality data were obtained from NHS Digital. Results After excluding patients diagnosed with T1MI by the clinical team, there were 1,033 patients remaining. At one year a total of 253 (24.5%) patients had died. The Kaplan-Meier curves in figure 1 demonstrate a positive association between mortality and increasing hs-cTnI concentrations relative to the ULN. Specifically, using the log-rank test, the mortality at one year was significantly higher (p Conclusions These data suggest that admission hs-cTnI is a biomarker for one year mortality in critical care patients. Further work is now required to assess whether any medical intervention can alter this risk. Conflict of Interest All of these assays used in our studies were provided by Beckman Coulter but they had no other role in the studies

Objective: To determine the relationship between body composition (BC), specifically low skeletal muscle mass (sarcopenia) and poor muscle quality (myosteatosis) and outcomes in emergency laparotomy patients. Background: Emergency laparotomy has one of the highest morbidity and mortality rates of all surgical interventions. BC objectively identifies patients at risk of adverse outcomes in elective cancer cohorts, however evidence is lacking in emergency surgery. Methods: An observational cohort study of patients undergoing emergency laparotomy at ten English hospitals was performed. BC analyses were performed at the third lumbar vertebrae level using pre-operative CT images to quantify skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SM-RA). Sex-specific SMI and SM-RA were determined, with the lower tertile splits defining sarcopenia (low SMI) and myosteatosis (low SM-RA). Accuracy of mortality risk prediction, incorporating SMI and SM-RA variables into risk models was assessed with regression modelling. Results: Six hundred and ten patients were included. Sarcopenia and myosteatosis were both associated with increased risk of morbidity (52.1% vs. 45.1%, p = 0.028; 57.5% vs. 42.6%, p = 0.014), 30-day (9.5% vs. 3.6%, p = 0.010; 14.9% vs. 3.4%, p < 0.001), and 1-year mortality (27.4% vs. 11.5%, p < 0.001; 29.7% vs.12.5%, p < 0.001). Risk-adjusted 30-day mortality was significantly increased by sarcopenia (OR 2.56 (95%CI 1.12-5.84), p = 0.026) and myosteatosis (OR 4.26 (2.01-9.06), p < 0.001), similarly at 1-year (OR 2.66 (95%CI 1.57-4.52), p < 0.001; OR 2.08 (95%CI 1.26-3.41), p = 0.004). BC data increased discrimination of an existing mortality risk-prediction model (AUC 0.838, 95%CI 0.835-0.84). Conclusion: Sarcopenia and myosteatosis are associated with increased adverse outcomes in emergency laparotomy patients.

Objective To identify interventions for the treatment of acute ischemic stroke after cardiac surgery and to report the efficacy of these treatments. Design Systematic review and narrative synthesis Participants Patients with ischemic stroke after cardiac surgery. Interventions Treatment efficacy of intra-arterial thrombolysis (IAT) and/or endovascular mechanical thrombectomy (EMT). Methods and Main Results The MEDLINE (Ovid), Embase (Ovid), Scopus (Elsevier), and Cochrane Central Register of Controlled Trials (Wiley) databases were searched from January 1, 1990, until September 20, 2018. After reviewing 5,231 records, 8 case reports/series and 2 retrospective studies were included (n = 33). Three of these reports (n = 19) published between 2001 and 2003 described IAT, and 6 studies (n = 14) published between 2015 and 2019 reported the use of EMT. In the 19 patients who received IAT, 3 (16%) had good, 8 (42%) had moderate, and 8 (42%) had poor neurologic outcomes. In the 14 patients who received EMT, 7 (50%) had good, 5 (36%) had moderate, and 2 (14%) had poor neurologic outcomes. Conclusions Endovascular thrombectomy, with or without IAT, is being used increasingly with success in patients presenting with postcardiac surgery stroke. However, the number of patients reported is too small to confidently understand its overall effect on neurologic outcomes in this setting.

Background: Perioperative infection and sepsis are of fundamental concern to perioperative clinicians. However, standardised endpoints are either poorly defined or not routinely implemented. The Standardised Endpoints in Perioperative Medicine (StEP) initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials.Methods: We undertook a systematic review to identify measures of infection and sepsis used in the perioperative literature. A multi-round Delphi consensus process that included more than 60 clinician researchers was then used to refine a recommended list of outcome measures.Results: A literature search yielded 1857 titles of which 255 met inclusion criteria for endpoint extraction. A long list of endpoints, with definitions and timescales, was generated and those potentially relevant to infection and sepsis circulated to the theme subgroup and then the wider StEP-COMPAC working group, undergoing a three-stage Delphi process. The response rates for Delphi rounds 1, 3, and 3 were 89% (n=8), 67% (n=62), and 80% (n=8), respectively. A set of 13 endpoints including fever, surgical site, and organ-specific infections as defined by the US Centres for Disease Control and Sepsis-3 are proposed for future use.Conclusions: We defined a consensus list of standardised endpoints related to infection and sepsis for perioperative trials using an established and rigorous approach. Each endpoint was evaluated with respect to validity, reliability, feasibility, and patient centredness. One or more of these should be considered for inclusion in future perioperative clinical trials assessing infection, sepsis, or both, thereby permitting synthesis and comparison of future results.

Background High sensitivity troponin (hs-cTn) concentrations above the manufacturer's upper limit of normal (ULN) are frequently seen outside the context of MI, particularly in critical care units. The current evidence regarding the prognostic value of hs-cTn in critical care settings is discrepant. Purpose To describe the distribution of hs-cTn in a consecutive cohort of patients in critical care units, regardless of whether there is a conventional clinical indication, and the association of this distribution with clinical outcomes. Methods Consecutive patients admitted to three adult critical care units (cardiothoracic (CCU), general (GCU), neuroscience (NCU)) over a six month period had hs-cTnI tests performed serially throughout the admission, regardless of whether the supervising team felt there was a clinical indication. The results were nested and not revealed to patients or clinicians unless they were requested as part of routine care. The hs-cTnI results were correlated with parameters of clinical outcome. Results After excluding those diagnosed with a type 1 MI, there were 1,563 patients remaining in the study cohort (CCU 530, GCU 750, NCU 283). The median hs-cTnI was 77ng/L (IQR 11–1932ng/L, with 1081 (69.2%) patients above the manufacturer-provided ULN. Overall there was a bimodal distribution; GCU and NCU were positively skewed and CCU negatively skewed. Hs-cTnI concentrations above the ULN were associated with age, comorbidity, illness severity and need for organ support (table 1). The degree by which the hs-cTnI concentration was above the ULN remained an independent predictor of critical care mortality (figure 1) in NCU and GCU. Conclusion Hs-cTnI elevation taken outside the context of conventional clinical indications is common in the critically ill and is associated with age, comorbidity and illness severity. Admission hs-cTnI is an independent predictor of mortality and provides additional discriminative ability to the APACHE II score alone. This assay may represent a novel prognostic biomarker on admission in non-CCU critical care settings. Mortality relative to ULN Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Beckman Coulter

Loss-of-function mutations in both alleles of the human insulin receptor gene (INSR) cause extreme insulin resistance (IR) and usually death in childhood, with few therapeutic options. Bivalent anti-receptor antibodies can elicit insulin-like signaling by mutant INSR in cultured cells, but whether this translates into meaningful metabolic benefitsin vivo, where dynamics of insulin signaling and receptor recycling are more complex, is unknown. To address this we adopted a strategy to model human insulin receptoropathy in mice, usingCrerecombinase delivered by adeno-associated virus to knock out endogenous hepaticInsracutely in floxedInsrmice (L- IRKO+GFP), before adenovirus-mediated ‘add-back’ of wild-type (WT) or mutant humanINSR. Two murine anti-INSR monoclonal antibodies, previously shown to be surrogate agonists for mutant INSR, were then tested by intraperitoneal injections. As expected, L-IRKO+GFP mice showed glucose intolerance and severe hyperinsulinemia, and this was fully corrected by add-back of WT but neither D734A nor S350L mutant INSR. Antibody injection improved glucose tolerance in D734A INSR-expressing mice and reduced hyperinsulinemia in both S350L and D734A INSR-expressing animals, and did not cause hypoglycemia in WT INSR-expressing mice. Antibody treatment also downregulated both wild-type and mutant INSR protein, attenuating its beneficial metabolic effects. Anti-INSR antibodies thus improve IR in an acute model of insulin receptoropathy, but these findings imply a narrow therapeutic window determined by competing effects of antibodies to stimulate receptors and induce their downregulation.One Sentence SummaryBivalent anti-insulin receptor antibodies improve glycaemic control, but downregulate receptor expression, in a novel mouse model of lethal human insulin receptoropathy.

Background: supplemental oxygen is frequently administered to patients with acute respiratory distress syndrome (ARDS), including ARDS secondary to viral illness such as coronavirus disease 19 (COVID-19). An up-to-date understanding of how best to target this therapy (e.g. arterial partial pressure of oxygen (PaO2) or peripheral oxygen saturation (SpO2) aim) in these patients is urgently required.Objectives: to address how oxygen therapy should be targeted in adults with ARDS (particularly ARDS secondary to COVID-19 or other respiratory viruses) and requiring mechanical ventilation in an intensive care unit, and the impact oxygen therapy has on mortality, days ventilated, days of catecholamine use, requirement for renal replacement therapy, and quality of life.Search methods: we searched the Cochrane COVID-19 Study Register, CENTRAL, MEDLINE, and Embase from inception to 15 May 2020 for ongoing or completed randomized controlled trials (RCTs).Selection criteria: two review authors independently assessed all records in accordance with standard Cochrane methodology for study selection. We included RCTs comparing supplemental oxygen administration (i.e. different target PaO2 or SpO2 ranges) in adults with ARDS and receiving mechanical ventilation in an intensive care setting. We excluded studies exploring oxygen administration in patients with different underlying diagnoses or those receiving non-invasive ventilation, high-flow nasal oxygen, or oxygen via facemask.Data collection and analysis: one review author performed data extraction, which a second review author checked. We assessed risk of bias in included studies using the Cochrane 'Risk of bias' tool. We used the GRADE approach to judge the certainty of the evidence for the following outcomes; mortality at longest follow-up, days ventilated, days of catecholamine use, and requirement for renal replacement therapy.Main results: we identified one completed RCT evaluating oxygen targets in patients with ARDS receiving mechanical ventilation in an intensive care setting. The study randomized 205 mechanically ventilated patients with ARDS to either conservative (PaO2 55 to 70 mmHg, or SpO2 88% to 92%) or liberal (PaO2 90 to 105 mmHg, or SpO2 ≥ 96%) oxygen therapy for seven days. Overall risk of bias was high (due to lack of blinding, small numbers of participants, and the trial stopping prematurely), and we assessed the certainty of the evidence as very low. The available data suggested that mortality at 90 days may be higher in those participants receiving a lower oxygen target (odds ratio (OR) 1.83, 95% confidence interval (CI) 1.03 to 3.27). There was no evidence of a difference between the lower and higher target groups in mean number of days ventilated (14.0, 95% CI 10.0 to 18.0 versus 14.5, 95% CI 11.8 to 17.1); number of days of catecholamine use (8.0, 95% CI 5.5 to 10.5 versus 7.2, 95% CI 5.9 to 8.4); or participants receiving renal replacement therapy (13.7%, 95% CI 5.8% to 21.6% versus 12.0%, 95% CI 5.0% to 19.1%). Quality of life was not reported.Authors' conclusion: we are very uncertain as to whether a higher or lower oxygen target is more beneficial in patients with ARDS and receiving mechanical ventilation in an intensive care setting. We identified only one RCT with a total of 205 participants exploring this question, and rated the risk of bias as high and the certainty of the findings as very low. Further well-conducted studies are urgently needed to increase the certainty of the findings reported here. This review should be updated when more evidence is available.

The field of cancer survivorship has significantly advanced person-centered care throughout the cancer continuum. Within cancer survivorship, the last decade has seen remarkable growth in the investigation of prehabilitation comprising pre-treatment interventions to prevent or attenuate the burden of oncologic therapies. While the majority of evidence remains in the surgical setting, prehabilitation is being adapted to target modifiable risk factors that predict poor treatment outcomes in patients receiving other systemic and localized anti-tumor treatments. Here, we propose a multiphasic approach for prehabilitation across the cancer continuum, as a conceptual framework, to encompass the variability in cancer treatment experiences while adopting the most inclusive definition of the cancer survivor.

Background High sensitivity troponin (hs-cTn) concentrations above the manufacturer’s upper limit of normal (ULN) are frequently seen outside the context of MI, particularly in critical care patients. The potential value of hs-cTn as a biomarker for prognosis in CC patients has never before been systematically explored. Aims 1. To describe both the distribution of hs-cTn in critical care and 2. the association of this distribution with clinical outcomes, including in hospital mortality. Methods Consecutive patients admitted to the three adult CC units (cardiothoracic (CCCU), general (GCCU), neuroscience (NCCU)) over a six month period had hs-cTnI tests performed serially throughout the admission, regardless of whether the supervising team had identified a clinical indication. Except when requested for clinical reasons, the results were nested and not revealed to patients or clinicians. The association between hs-cTnI concentration and clinical outcome was evaluated. Results After excluding patients diagnosed with a type 1 MI, there were 1,563 patients remaining in the study cohort (CCCU 530, GCCU 750, NCCU 283). The median hs-cTnI was 77ng/L (IQR 11-1932ng/L), with 1081 (69.2%) patients above the manufacturer-provided ULN. Overall there was a bimodal distribution; GCCU and NCCU were positively skewed and CCCU negatively skewed (figure 1). Concentrations above the ULN were associated with increasing age, comorbidity, markers of illness severity and need for organ support (table 1). On multivariate analysis the degree by which the admission hs-cTnI concentration was above the ULN remained an independent predictor of critical care mortality (figure 2), but not length of stay for patients in NCCU and GCCU. Furthermore, the addition of the degree by which the hs-cTnI concentration was above the ULN to the Acute Physiology and Chronic Health Evaluation (APACHE) II score improved the area under the curve for critical care mortality (from 0.828 to 0.846 (p Conclusion Admission hs-cTnI concentration, taken regardless of a clinical indication, is an independent predictor of ICU mortality and provides additional discriminative ability to the APACHE II score alone. This assay may represent a novel prognostic biomarker on admission in critical care settings. Conflict of Interest Unrestricted research grant from Beckman Coulter (who had no role in the study design, data collection, analysis or interpretation).

Summary The COVID‐19 pandemic is causing a significant increase in the number of patients requiring relatively prolonged invasive mechanical ventilation and an associated surge in patients who need a tracheostomy to facilitate weaning from respiratory support. In parallel, there has been a global increase in guidance from professional bodies representing staff who care for patients with tracheostomies at different points in their acute hospital journey, rehabilitation, and recovery. Of concern are the risks to healthcare staff of infection arising from tracheostomy insertion and subsequent management. Hospitals are also facing extraordinary demands on critical care services such that many patients who require a tracheostomy will be managed outside established intensive care or head and neck units, cared for by staff with little tracheostomy experience. These concerns led NHS England and NHS Improvement to expedite the National Patient Safety Improvement Programme’s ‘Safe Tracheostomy Care’ workstream as part of the NHS COVID‐19 response. Supporting this workstream, UK stakeholder organisations involved in tracheostomy care were invited to develop consensus guidance based on the available literature and existing multidisciplinary guidelines. Topics with direct relevance for frontline staff were identified. The consensus guidance includes: infectivity of patients with respect to tracheostomy indications and timing; aerosol‐generating procedures and risks to staff; insertion procedures; and management following tracheostomy. These consensus recommendations are based on expert opinion and informed by the best available evidence and published guidance where possible.

Objective:Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disorder which requires intensive hand therapy to delay fusion of the digits. Existing dressings do not conform to the complex structure of the hand and are applied in patches held with additional bandages, leading to an occlusive environment. The aim was to co-design with patients a dressing glove based on their user experiences and needs.Method:Qualitative interviews and focus groups with children and adults with RDEB, and their carers, were conducted. Iterative feedback of design cues, bench and surrogate testing of materials and prototype refinement were achieved through collaborative codesign with patients, carers, clinicians and manufacturers.Results:Thematic analysis generated eight user needs and corresponding design cues, addressing issues of absorbency, adherence, comfort, adaptability, ease of application and removal, breathability, protection, and hand hygiene. A prototype was selected for proof of concept testing.Conclusion:This novel dressing glove design met the patient's requirements for a dressing, which conformed to the hand structure and sat in the web spaces to keep fingers separated. Proof of concept testing has since been undertaken with patients to determine performance, value for money and whether further developments are required.

Objective: To describe demographic characteristics, current local clinical management and outcomes for patients with familial hypercholesterolaemia (FH) managed at the Royal Brompton and Harefield NHS Foundation Trust (RBHT), a specialist UK tertiary cardiac centre. Research design and methods: A local service evaluation of patients with FH was conducted by RBHT. Patients were identified from local FH databases and medical records based on pre-defined eligibility criteria. Descriptive statistics were performed. Main outcome measures: Proportion of patients with cardiovascular (CV) events during the period of follow-up; per cent change in low-density lipoprotein cholesterol (LDL-C) between highest untreated and most recent measurement; description of patient characteristics and treatment pathways. Results: The final evaluation sample included 306 patients whose first contact with the RBHT FH service was between November 1991 and February 2015. Patients were followed up until 2016 (median 4.4 years, range 1.2–24.9). Forty-three per cent (131/306) of patients had genetically confirmed FH and 56% (172/306) did not but meet a modified Simon Broome criteria. One fifth (20%, 60/306) had at least one CV event prior to their first contact with the service, mainly angioplasty (15%, 45/306) and MI (10%, 32/306). Thirty-five patients (11%) had CV events during the period of follow-up, occurring at a mean of 5.2 years after first contact. Of 269 “current” patients (i.e. patients with at least one contact with the service in the previous 3 years) 90% (241/269) were prescribed statins, with adverse events experienced by 30% (73/241). Eleven patients received lipoprotein apheresis. Only 34% (49/143) of patients had a reduction of ≥50% between the highest untreated and most recent LDL-C measurement. Conclusions: Results highlight the challenges of diagnosing and management of this high risk patient group whilst reducing CV events. Future work should focus on characterisation of patient subgroups and optimising treatment with novel therapeutic agents.

Healthcare providers are facing a coronavirus disease pandemic. This pandemic may last for many months, stressing the Canadian healthcare system in a way that has not previously been seen. Keeping healthcare providers safe, healthy, and available to work throughout this pandemic is critical. The consistent use of appropriate personal protective equipment (PPE) will help assure its availability and healthcare provider safety. The purpose of this communique is to give both anesthesiologists and other front-line healthcare providers a framework from which to understand the principles and practices surrounding PPE decision-making. We propose three types of PPE including: 1) PPE for droplet and contact precautions, 2) PPE for general airborne, droplet, and contact precautions, and 3) PPE for those performing or assisting with high-risk aerosol-generating medical procedures.

Background Anemia is common in liver cirrhosis. This generally infers a fall in total hemoglobin mass (tHb‐mass). However, hemoglobin concentration ([Hb]) may fall due to an expansion in plasma volume (PV). The “optimized carbon monoxide rebreathing method” (oCOR) measures tHb‐mass directly and PV (indirectly using hematocrit). It relies upon carboxyhemoglobin (COHb) distribution throughout the entire circulation. In healthy subjects, such distribution is complete within 6–8 min. Given the altered circulatory dynamics in cirrhosis, we sought in this pilot study, to assess whether this was true in cirrhosis. The primary aim was to ascertain if the standard timings for the oCOR were applicable to patients with chronic liver disease and cirrhosis. The secondary aim was to explore the applicability of standard CO dosing methodologies to this patient population. Methods Sixteen patients with chronic liver parenchymal disease were studied. However, tHb‐mass was determined using the standard oCOR technique before elective paracentesis. Three subjects had an inadequate COHb% rise. In the remaining 13 (11 male), mean ± standard deviation (SD) age was 52 ± 13.8 years, body mass 79.1 ± 11.4 kg, height 175 ± 6.8 cm. To these, mean ± SD dose of carbon monoxide (CO) gas administered was 0.73 ± 0.13 ml/kg COHb values at baseline, 6 and 8 min (and “7‐min value”) were compared to those at 10, 12, 15 and 20 min after CO rebreathing. Results The “7‐min value” for median COHb% (IQR) of 6.30% (6.21%–7.47%) did not differ significantly from those at subsequent time points (8 min: 6.30% (6.21%–7.47%), 10 min: 6.33% (6.00%–7.50%), 12 min: 6.33% (5.90%–7.40%), 15 min: 6.37% (5.80%–7.33%), 20 min: 6.27% (5.70%–7.20%)). Mean difference in calculated tHb‐mass between minute 7 and minute 20 was only 4.1 g, or 0.6%, p = .68. No subjects reported any adverse effects. Conclusions The oCOR method can be safely used to measure tHb‐mass in patients with chronic liver disease and ascites, without adjustment of blood sample timings. Further work might refine and validate appropriate dosing regimens.

Complications after major surgery account for a disproportionate amount of in-hospital morbidity and mortality. Recent efforts have focused on preoperative optimization in an attempt to modify the risk associated with major surgery. Underaddressed, but important, modifiable risk factors are physical fitness and nutritional status. Surgical patients are particularly at risk of 3 related, but distinct, conditions: frailty, sarcopenia, and reduced physical fitness. Exercise-based prehabilitation strategies have shown promise in terms of improving aerobic fitness, although their impact on key clinical perioperative outcome measures have not been fully determined. Preoperative nutritional status also has a strong bearing on perioperative outcome.

Angelman syndrome (AS) is a neurogenetic imprinting disorder caused by loss of the maternally inherited Ube3a gene and is characterized by generalized epilepsy, limited expressive speech, sleep dysfunction, and movement disorders. Myoclonic seizures are often the first seizure type to appear, and myoclonic status, associated with developmental regression, may occur in the first few years of life. Additionally, there have been rare reports of prolonged episodes of myoclonus without electrographic correlate in adults with AS. The medical records of 200 individuals seen in the Angelman Syndrome Clinic at the Massachusetts General Hospital and the Lurie Center for Autism were retrospectively reviewed to identify and characterize myoclonic seizures and episodes of nonepileptic myoclonus. Myoclonic seizures were reported in 14% of individuals with age of onset occurring before 8years. These are brief events, unless the individual was experiencing myoclonic status, and electroencephalographs show interictal generalized spike and wave activity. Nonepileptic myoclonus occurred in 40% of individuals over 10years of age, and prevalence appears to increase with age. The episodes of nonepileptic myoclonus arise during puberty or later, with age of onset ranging from 10 to 26years. These events were captured on 5 video electroencephalographs and had no electrographic correlate. They can last from seconds to hours, always occurring in the hands and spreading to the face and all extremities in some individuals. Episodes of nonepileptic myoclonus have a discrete beginning and end, lacks a postictal period, and are not associated with significant alteration of consciousness or developmental regression. These episodes can be difficult to treat and are often refractory to medication; however, levetiracetam, clobazam, and clonazepam appear to be effective for some individuals. Myoclonic seizures are common in AS, typically occurring in young children and associated with epileptiform changes on electroencephalographs. Prolonged episodes are associated with developmental regression. In contrast, nonepileptic myoclonus typically begins in adolescence or early adulthood and has no electroencephalogram (EEG) correlate, alteration in consciousness, or regression but can significantly impact quality of life.

Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the cytidine diphosphocholine (CDP):choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways. Here, we used ESI-MS/MS both to characterize plasma PC compositions and to quantify metabolic fluxes of both pathways using stable isotopes in patients with severe ARDS and in healthy controls. Direct incorporation of methyl-D9-choline estimated CDP:choline pathway flux, while PEMT flux was determined from incorporations of one and two methyl-D3 groups derived from methyl-D9-choline. The results of MS/MS analysis showed significant alterations in plasma PC composition in patients with ARDS versus healthy controls. In particular, the increased overall methyl-D9-PC enrichment and, most importantly, the much lower methyl-D3-PC and methyl-D6-PC enrichments suggest increased flux through the CDP:choline pathway and reduced flux through the PEMT pathway in ARDS. To our knowledge, this study is the first to demonstrate significant plasma PC molecular compositional changes combined with associated alterations in the dynamics of PC synthetic pathways in patients with ARDS.

Objectives To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. Design Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). Setting Eligible patients were randomized prior to surgery in a 1:1 ratio. Participants Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. Interventions Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. Measurements and Main Results The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. Conclusion By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Background: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance.Methods: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician–researchers was then used to refine a recommended list of endpoints.Results: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival).Conclusion: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia–analgesia technique on oncological outcomes.