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David C Rupp, David Canty, Catherine Rhéaume, Birgitte Sondergaard, Celina Niño, Ron S Broide, Amy D Brideau-Andersen Allergan Aesthetics, an AbbVie Company, Irvine, CA, USACorrespondence: David C Rupp, Allergan Aesthetics, an AbbVie Company, 2525 Dupont Drive, Irvine, CA, 92612, USA, Tel +1-714-246-4059, Email david.rupp@abbvie.comObjective: The goal of this study was to compare the unit-to-unit biological activity of the vacuum-dried formulation of prabotulinumtoxinA (prabotA) and onabotulinumtoxinA (onabotA) in preclinical assays.Methods: Reconstituted 100 U vials of prabotA and onabotA were tested in 3 distinct assays: plate-capture light chain activity (PC-LCA), measuringlight chain enzymatic activity after recovery of toxin from reconstituted product using a proprietary toxin capture step; cell-based potency assay (CBPA), measuring the intoxication steps of binding, translocation, and light chain activity (synaptosomal-associated protein 25 [SNAP25] cleavage); and mouse Digit Abduction Score (DAS), evaluating muscle paresis. Each assay tested 3 separate prabotA and onabotA lots on several independent test dates.Results: Multiple orthogonal assays established that when assessed on a unit-to-unit basis, the biological activity of prabotA is lower than that of onabotA. In the PC-LCA and CBPA assays, onabotA displayed 1.51 ± 0.14–fold higher (mean ± SD) and 1.33 ± 0.07–fold higher (mean of pooled lots ± SEM) activity than prabotA, respectively. Similarly, the mouse DAS data showed that onabotA had 1.4 ± 0.1–fold higher (mean ± SEM) potency than prabotA. Results of all 3 assays demonstrated differences in potency, efficacy, and duration of action between onabotA and prabotA on a unit-to-unit basis.Conclusion: Preclinical assays established differences in the biological activity of onabotA and prabotA, supporting that the units of biological activity are not interchangeable.Keywords: pharmaceutical preparations, biological assays, enzyme assays, animal studies, motor neurons, protein binding

Lung ultrasound is rapidly gaining popularity based on point of care ease of use, diagnostic fidelity and lack of ionizing radiation. This was particularly notable at the beginning of the COVID-19 pandemic, where concerns of contamination of the x-ray department led to a reluctance to order frequent chest x-rays. Early COVID-19 lung involvement is of a bronchopneumonia, and patches of consolidation adjacent to the chest wall were easily detectable by ultrasound. A large number of proposed scanning protocols were advocated and are often complex and largely based on traditional stethoscope examination or access points on the chest wall rather than the underlying lung anatomy. A surgical understanding of lung anatomy and related surface anatomy has led us to develop a simplified three zone scanning protocol in 2013. The anterior zone corresponds to the upper lobe, and the posterior zone is divided between upper lobe and lower lobe. The relationship between lung lobes and the surface of the chest wall provides the anatomical basis for a simple three scanning zone lung ultrasound protocol.

BackgroundBetween 1964 and 1996, the 10-year survival of patients having valve replacement surgery for rheumatic heart disease (RHD) in the Northern Territory, Australia, was 68%. As medical care has evolved since then, this study aimed to determine whether there has been a corresponding improvement in survival.MethodsA retrospective study of Aboriginal patients with RHD in the Northern Territory, Australia, having their first valve surgery between 1997 and 2016. Survival was examined using Kaplan-Meier and Cox regression analysis.FindingsThe cohort included 281 adults and 61 children. The median (IQR) age at first surgery was 31 (18–42) years; 173/342 (51%) had a valve replacement, 113/342 (33%) had a valve repair and 56/342 (16%) had a commissurotomy. There were 93/342 (27%) deaths during a median (IQR) follow-up of 8 (4–12) years. The overall 10-year survival was 70% (95% CI: 64% to 76%). It was 62% (95% CI: 53% to 70%) in those having valve replacement. There were 204/281 (73%) adults with at least 1 preoperative comorbidity. Preoperative comorbidity was associated with earlier death, the risk of death increasing with each comorbidity (HR: 1.3 (95% CI: 1.2 to 1.5), p50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death.InterpretationSurvival after valve replacement for RHD in this region of Australia has not improved. Although the patients were young, many had multiple comorbidities, which influenced long-term outcomes. The increasing prevalence of complex comorbidity in the region is a barrier to achieving optimal health outcomes.

Organ congestion from venous hypertension is an important pathophysiological mechanism mediating organ injury in several clinical contexts including critical illness, congestive heart failure and end-stage chronic kidney disease. However, the practical evaluation of venous congestion is often challenging at the bedside because of the limitations of traditional methods. Point-of-care ultrasound (POCUS) enables the clinician to assess venous velocity profiles during the cardiac cycle using Doppler modalities. Venous Doppler profile abnormalities at multiple sites are detected when elevated venous pressure results in hemodynamic changes within the systemic venous circulation. The detection of these abnormal Doppler profiles may identify patients with clinically significant systemic venous congestion. These patients have been reported to be at increased risk of medical complications. Improving the evaluation of venous congestion may lead to individualized treatment and improved patient outcomes. In this review, we describe the physiologic principles necessary to understand venous Doppler assessment. We also propose a nomenclature for the description of venous Doppler profiles. Finally, we provide a narrative review of the current clinical evidence related to use of venous Doppler assessment in various clinical contexts.

The adoption of point-of-care lung ultrasound for both suspected and confirmed COVID-19 patients highlights the issues of accessibility to ultrasound training and equipment. Lung ultrasound is more sensitive than chest radiography in detecting viral pneumonitis and preferred over computed tomography for reasons including its portability, reduced healthcare worker exposure and repeatability. The main lung ultrasound findings in COVID-19 patients are interstitial syndrome, irregular pleural line and subpleural consolidations. Consolidations are most likely found in critical patients in need of ventilatory support. Hence, lung ultrasound may be used to timely triage patients who may have evolving pneumonitis. Other respiratory pathology that may be detected by lung ultrasound includes pulmonary oedema, pneumothorax, consolidation and large effusion. A key barrier to incorporate lung ultrasound in the assessment of COVID-19 patients is adequate decontamination of ultrasound equipment to avoid viral spread. This tutorial provides a practical method to learn lung ultrasound and a cost-effective method of preventing contamination of ultrasound equipment and a practical method for performing and interpreting lung ultrasound.

Pulmonary complications are the most common clinical manifestations of coronavirus disease (COVID-19). From recent clinical observation, two phenotypes have emerged: a low elastance or L-type and a high elastance or H-type. Clinical presentation, pathophysiology, pulmonary mechanics, radiological and ultrasound findings of these two phenotypes are different. Consequently, the therapeutic approach also varies between the two. We propose a management algorithm that combines the respiratory rate and oxygenation index with bedside lung ultrasound examination and monitoring that could help determine earlier the requirement for intubation and other surveillance of COVID-19 patients with respiratory failure.RéSUMé: Les complications pulmonaires du coronavirus (COVID-19) constituent ses manifestations cliniques les plus fréquentes. De récentes observations cliniques ont fait émerger deux phénotypes : le phénotype à élastance faible ou type L (low), et le phénotype à élastance élevée, ou type H (high). La présentation clinique, la physiopathologie, les mécanismes pulmonaires, ainsi que les observations radiologiques et échographiques de ces deux différents phénotypes sont différents. L’approche thérapeutique variera par conséquent selon le phénotype des patients atteints de COVID-19 souffrant d’insuffisance respiratoire.

Background Where each patient has all three conduits of internal mammary artery (IMA), saphenous vein graft (SVG) and radial artery (RA), most confounders affecting comparison between conduits can be mitigated. Additionally, since SVG progressively fails over time, restricting patient angiography to the late period only can mitigate against early SVG patency that may have occluded in the late period. Methods Research protocol driven conventional angiography was performed for patients with at least one of each conduit of IMA, RA and SVG and a minimum of 7 years postoperative. The primary analysis was perfect patency and secondary analysis was overall patency including angiographic evidence of conduit lumen irregularity from conduit atheroma. Multivariable generalized linear mixed model (GLMM) was used. Patency excluded occluded or “string sign” conduits. Perfect patency was present in patent grafts if there was no lumen irregularity. Results Fifty patients underwent coronary angiography at overall duration postoperative 13.1 ± 2.9, and age 74.3 ± 7.0 years. Of 196 anastomoses, IMA 62, RA 77 and SVG 57. Most IMA were to the left anterior descending territory and most RA and SVG were to the circumflex and right coronary territories. Perfect patency RA 92.2% was not different to IMA 96.8%, P = 0.309; and both were significantly better than SVG 17.5%, P P = 0.169, and both arterial conduits were significantly higher than SVG 82.5%, P = 0.029. Grafting according to coronary territory was not significant for perfect patency, P = 0.997 and patency P = 0.289. Coronary stenosis predicted perfect patency for RA only, P = 0.030 and for patency, RA, P = 0.007, and SVG, P = 0.032. When both arterial conduits were combined, perfect patency, P P = 0.017, were superior to SVG. Conclusions All but one patent internal mammary artery or radial artery grafts had perfect patency and had superior perfect patency and overall patency compared to saphenous vein grafts.

Background Point-of-care ultrasound (POCUS) is emerging as a reliable and valid clinical tool that impacts diagnosis and clinical decision-making as well as timely intervention for optimal patient management. This makes its utility in patients admitted to internal medicine wards attractive. However, there is still an evidence gap in all the medical setting of how its use affects clinical variables such as length of stay, morbidity, and mortality. Methods/design A prospective randomized controlled trial assessing the effect of a surface POCUS of the heart, lungs, and femoral and popliteal veins performed by an internal medicine physician during the first 24 h of patient admission to the unit with a presumptive cardiopulmonary diagnosis. The University of Melbourne iHeartScan, iLungScan, and two-point venous compression protocols are followed to identify left and right ventricular function, significant valvular heart disease, pericardial and pleural effusion, consolidation, pulmonary edema, pneumothorax, and proximal deep venous thrombosis. Patient management is not commanded by the protocol and is at the discretion of the treating team. A total of 250 patients will be recruited at one tertiary hospital. Participants are randomized to receive POCUS or no POCUS. The primary outcome measured will be hospital length of stay. Secondary outcomes include the change in diagnosis and management, 30-day hospital readmission, and healthcare costs. Discussion This study will evaluate the clinical impact of multi-organ POCUS in internal medicine patients admitted with cardiopulmonary diagnosis on the hospital length of stay. Recruitment of participants commenced in September 2018 and is estimated to be completed by March 2020. Trial registration Australian and New Zealand Clinical Trial Registry, ACTRN12618001442291. Registered on 28 August 2018.

Key Points Question Does integrating multiorgan focused clinical ultrasonography with clinical evaluation of patients admitted with cardiopulmonary symptoms reduce the hospital length of stay? Findings In a randomized clinical trial of 250 participants allocated to undergo multiorgan focused clinical ultrasonography or standard management at admission to the hospital, the hospital length of stay was not different compared with control patients. Meaning These findings suggest that integration of multiorgan focused clinical ultrasonography with the initial evaluation does not reduce hospital length of stay by more than 24 hours., This randomized clinical trial examines whether adding multiorgan focused clinical ultrasonography (FCU) to the initial clinical evaluation of patients admitted with cardiopulmonary symptoms reduces hospital length of stay, hospital readmissions, and in-hospital costs., Importance There are accumulating data about the utility of diagnostic multiorgan focused clinical ultrasonography (FCU) in the assessment of patients admitted with cardiopulmonary symptoms. Objective To determine whether adding multiorgan FCU to the initial clinical evaluation of patients admitted with cardiopulmonary symptoms reduces hospital length of stay, hospital readmissions, and in-hospital costs. Design, Setting, and Participants This is a prospective, parallel-group, superiority, randomized clinical trial with a 1:1 allocation ratio. The study was conducted at The Royal Melbourne Hospital, a tertiary public hospital located in Melbourne, Victoria, Australia. Adults aged 18 years or older admitted to the internal medicine ward with a cardiopulmonary diagnosis were enrolled between September 2018 and December 2019 and were followed up until hospital discharge. Data analysis was performed from August 2020 to January 2021. Interventions The intervention involved an internal medicine physician–performed heart, lung, and 2-point vein compression FCU in addition to standard clinical evaluation. Main Outcomes and Measures The primary outcome was the difference in the mean length of hospital stay, defined as the number of hours from admission to the internal medicine ward to hospital discharge. A difference of 24 hours was defined as clinically important. Secondary outcomes included hospital readmissions at 30 days and hospital care costs. Results A total of 250 participants were enrolled and 2 were excluded, leaving 248 participants (mean [SD] age, 80.1 [11.0] years; 121 women [48.7%]) in the final analysis. There were 124 patients in the intervention group and 124 patients in the control group. The most common initial diagnoses were acute decompensated heart failure (113 patients [45.5%]), pneumonia (45 patients [18.1%]), and exacerbated chronic pulmonary disease (32 patients [12.9%]). The length of hospital stay was 113.4 hours (95% CI, 91.7-135.1 hours) in the FCU group and 125.3 hours (95% CI, 101.7-148.8 hours) in the control group (P = .53). The 30-day readmission rate was not different between groups (FCU vs control, 20 of 124 patients [16.1%] vs 15 of 124 patients [12.0%]), nor were total in-hospital costs (FCU vs control, A$7831.1 [95% CI, A$5586.1-A$10 076.1] vs A$7895.7 [95% CI, A$6385.9-A$9.405.5]). Conclusions and Relevance In this randomized clinical trial, adult patients admitted to an internal medicine ward with a cardiopulmonary diagnosis, who underwent multiorgan FCU of the heart, lungs, and lower extremities veins during their initial clinical assessment, did not have a shorter hospital length of stay by more than 24 hours, compared with patients who received standard care. Trial Registration Australian New Zealand Clinical Trials Registry Identifier: ACTRN12618001442291

Focused cardiac ultrasound (FCU) training in critical care is restricted by availability of instructors. Supervised training may be substituted by self-directed learning with an ultrasound simulator guided by automated electronic learning, enabling scalability.We prospectively compared learning outcomes in novice critical care physicians after completion of a supervised one-and-a-half-day workshop model with a self-guided course utilizing a simulator over four weeks. Both groups had identical pre-workshop on-line learning (20h). Image quality scores were compared using FCU performed on humans without pathology. Interpretive knowledge was compared using 20MCQ tests.Of 161 eligible, 145 participants consented. Total Image quality scores were higher in the Simulator group (95.2% vs. 66.0%, P .001) and also higher for each view (all P .001). Interpretive knowledge was not different before (78.6% vs. 79.0%) and after practical training (74.7% vs. 76.1%) and at 3 months (81.0% vs. 77.0%, all P .1). Including purchase of the simulator and ultrasound equipment, the simulator course required lower direct costs (AUD$796 vs. $1724 per participant) and instructor time (0.5 vs.1.5 days) but similar participant time (2.8 vs. 3.0 days).Self-directed learning with ultrasound simulators may be a scalable alternative to conventional supervised teaching with human models.

The aim in this systematic review was to determine the effect of point-of-care ultrasound (POCUS) on the clinical decision-making process and patient outcomes in adults admitted to the general medicine ward. A comprehensive search was performed in MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library, ClinicalTrials.gov, Scopus, LILACS and Cinahl. Articles had to fulfill the inclusion criteria of randomised or non-randomised studies assessing the impact of POCUS on the diagnosis, management, length of hospital stay or mortality of patients admitted to the internal medicine ward. Six studies were included involving a total of 1836 patients. The influence of POCUS on the diagnosis was reported as a change in the main diagnosis or the addition of a relevant diagnosis in up to 18% and 24% of the cases, respectively. Impact on the management plan was reported in 37% to 52.1% of the participants. Three studies documented the impact of POCUS on the length of stay. Two of them reported no difference between groups, and the other reported a significant reduction of 1 d of the hospital stay. In conclusion, POCUS appears to have positive effects on the clinical decision-making process with impacts on optimal patient management and possible reduction in the hospital length of stay.

To determine whether brief ultrasound-guided treatment of hemodynamic shock and respiratory failure immediately before emergency noncardiac surgery reduced 30-day mortality.Parallel, nonblinded, randomized trial with 1:1 allocation to control and intervention groups.Twenty-eight major hospitals within China.Six-hundred sixty patients ≥14 years of age, scheduled for emergency noncardiac surgery with evidence of shock (heart rate120 beat/min, systolic blood pressure90 mmHg or requiring inotrope infusion), or respiratory failure (Pulse Oxygen Saturation92%, respiratory rate20 beat/min, or requiring mechanical ventilation).A brief (15 minutes) focused ultrasound of ventricular filling and function, lung, and peritoneal spaces, with predefined treatment recommendation based on the ultrasound was performed before surgery or standard care.The primary outcome was 30-day mortality. Secondary outcomes included changes in medical or surgical diagnosis and management due to ultrasound, intensive care unit, and hospital stay and cost, and Short Form-8 quality-of-life scores. Although there were frequent changes in diagnosis (82%) and management (49%) after the ultrasound, mortality at 30 days was not different between groups (50 [15.7%] v 53 [16.3%]; odds ratio 1.05, 0.69-1.6, p = 0.826). There were no differences in the secondary outcomes of the days spent in the hospital (mean 13.8 days, 95% confidence interval [CI] 12.1-15.6 v 14.4 d, 11.8-17.1, p = 0.718) or intensive care unit (mean 9.3 days, 95% CI 7.7-11.0 v 8.7 d, 7.2-10.2, p = 0.562), hospital cost (USD$14.5K, 12.2-16.7 v 13.7, 11.5-15.9, p = 0.611) or Short Form-8 scores at one year (mean 80.9, 95% CI 78.4-83.3 v 79.7, 76.9-82.5, p = 0.54) between participants allocated to the ultrasound and control groups.In critically ill patients with hemodynamic shock or respiratory failure, a focused ultrasound-guided management did not reduce 30-day mortality but led to frequent changes in diagnosis and patient management.

Lung ultrasound (LUS) imaging as a point-of-care diagnostic tool for lung pathologies has been proven superior to X-ray and comparable to CT, enabling earlier and more accurate diagnosis in real-time at the patient's bedside. The main limitation to widespread use is its dependence on the operator training and experience. COVID-19 lung ultrasound findings predominantly reflect a pneumonitis pattern, with pleural effusion being infrequent. However, pleural effusion is easy to detect and to quantify, therefore it was selected as the subject of this study, which aims to develop an automated system for the interpretation of LUS of pleural effusion. A LUS dataset was collected at the Royal Melbourne Hospital which consisted of 623 videos containing 99,209 2D ultrasound images of 70 patients using a phased array transducer. A standardized protocol was followed that involved scanning six anatomical regions providing complete coverage of the lungs for diagnosis of respiratory pathology. This protocol combined with a deep learning algorithm using a Spatial Transformer Network provides a basis for automatic pathology classification on an image-based level. In this work, the deep learning model was trained using supervised and weakly supervised approaches which used frame- and video-based ground truth labels respectively. The reference was expert clinician image interpretation. Both approaches show comparable accuracy scores on the test set of 92.4% and 91.1%, respectively, not statistically significantly different. However, the video-based labelling approach requires significantly less effort from clinical experts for ground truth labelling.

Introduction Mild cognitive impairment is considered a precursor to dementia and significantly impacts upon quality of life. The prevalence of mild cognitive impairment is higher in the post-surgical cardiac population than in the general population, with older age and comorbidities further increasing the risk of cognitive decline. Exercise improves neurogenesis, synaptic plasticity and inflammatory and neurotrophic factor pathways, which may help to augment the effects of cognitive decline. However, the effects of resistance training on cognitive, functional and overall patient-reported recovery have not been investigated in the surgical cardiac population. This study aims to determine the effect of early moderate-intensity resistance training, compared to standard care, on cognitive recovery following cardiac surgery via a median sternotomy. The safety, feasibility and effect on functional recovery will also be examined. Methods This study will be a prospective, pragmatic, pilot randomised controlled trial comparing a standard care group (low-intensity aerobic exercise) and a moderate-intensity resistance training group. Participants aged 18 years and older with coronary artery and/or valve disease requiring surgical intervention will be recruited pre-operatively and randomised 1:1 to either the resistance training or standard care group post-operatively. The primary outcome, cognitive function, will be assessed using the Alzheimer’s Disease Assessment Scale and cognitive subscale. Secondary measures include safety, feasibility, muscular strength, physical function, multiple-domain quality of recovery, dynamic balance and patient satisfaction. Assessments will be conducted at baseline (pre-operatively) and post-operatively at 2 weeks, 8 weeks, 14 weeks and 6 months. Discussion The results of this pilot study will be used to determine the feasibility of a future large-scale randomised controlled trial that promotes the integration of early resistance training into existing aerobic-based cardiac rehabilitation programs in Australia. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001430325p. Registered on 9 October 2017. Universal Trial Number (UTN): U1111-1203-2131.

Differences in botulinum neurotoxin manufacturing, formulation, and potency evaluation can impact dose and biological activity, which ultimately affect duration of action. The potency of different labeled vials of incobotulinumtoxinA (Xeomin&reg, 50 U, 100 U, or 200 U vials, incobotA) versus onabotulinumtoxinA (BOTOX&reg, 100 U vial, onabotA) were compared on a unit-to-unit basis to assess biological activity using in vitro (light-chain activity high-performance liquid chromatography (LCA-HPLC) and cell-based potency assay (CBPA)) and in vivo (rat compound muscle action potential (cMAP) and mouse digit abduction score (DAS)) assays. Using LCA-HPLC, incobotA units displayed approximately 54% of the protease activity of label-stated equivalent onabotA units. Lower potency, reflected by higher EC50, ID50, and ED50 values (pooled mean &plusmn, SEM), was displayed by incobotA compared to onabotA in the CBPA (EC50: incobotA 7.6 &plusmn, 0.7 U/mL, onabotA 5.9 &plusmn, 0.5 U/mL), cMAP (ID50: incobotA 0.078 &plusmn, 0.005 U/rat, onabotA 0.053 &plusmn, 0.004 U/rat), and DAS (ED50: incobotA 14.2 &plusmn, 0.5 U/kg, onabotA 8.7 &plusmn, 0.3 U/kg) assays. Lastly, in the DAS assay, onabotA had a longer duration of action compared to incobotA when dosed at label-stated equivalent units. In summary, onabotA consistently displayed greater biological activity than incobotA in two in vitro and two in vivo assays. Differences in the assay results do not support dose interchangeability between the two products.

In the context of the coronavirus disease 2019 (COVID-19) pandemic, lung ultrasound has emerged as an accurate and reliable alternative for assessment of lung pathology. The main lung ultrasound findings in COVID-19 patients are interstitial syndrome, irregular and broken aspect of the pleural line, and sub-pleural consolidation. Consolidations are usually a late finding appearing during the second week since symptoms onset. Translating into the practice, lung ultrasound can improve diagnostic accuracy and contribute with relevant information to the triage of these patients. It can be used as part of the routinely assessment of patients admitted to the medical ward allowing early identification of disease progression. Among patients mechanically ventilated, it is useful evaluating response to prone position and/or recruiting maneuvers. Finally, in all the previous scenarios, lung ultrasound may also detect common complications seen in these patients such as cardiogenic pulmonary edema and pulmonary embolism. In this review, we have summarized the information available and suggest simple algorithm to incorporate lung ultrasound into the assessment of COVID-19 patients.

Ultrasound is increasingly being adopted into anaesthesia and intensive care practice. The range of ultrasound examination has also increased from transoesophageal echocardiography in cardiac surgery and ultrasound-guided nerve blocks and vascular access, to examination of the heart, lungs, abdomen and deep veins. Typically, the use of ultrasound is focused or basic, designed to be performed by the anaesthetist at the patient's bedside in real time to answer clinical questions and to direct therapy. Ultrasound is not performed in isolation, but used to complement clinical evaluation, and accordingly can be considered as 'ultrasound-assisted perioperative evaluation'. Whilst there is good evidence that ultrasound improves diagnostic accuracy and in turn alters management, there are few data examining whether ultrasound leads to improved clinical outcomes. This review will examine multiple uses of perioperative ultrasound with case studies to illustrate potential utility.

Background Failed extubation from mechanical ventilation in critically ill patients is multifactorial, complex and not well understood. We aimed to identify whether combined transthoracic echocardiography, lung and diaphragmatic ultrasound can predict extubation failure in critically ill patients. Results Fifty-three participants who were intubated > 48 h and deemed by the treating intensivist ready for extubation underwent a 60-min pre-extubation weaning trial (pressure support ≤ 10 cmH2O and positive end expiratory pressure 5 cmH2O). Prior to extubation, data collected included ultrasound assessment of left ventricular ejection fraction, left atrial area, early diastolic trans-mitral flow velocity wave (E), early diastolic trans-mitral flow velocity wave/late diastolic trans-mitral flow velocity wave (E/A), early diastolic trans-mitral flow velocity wave/early diastolic mitral annulus velocity (E/E′), interatrial septal motion, lung loss of aeration score and diaphragm movement. At the end of the weaning trial, the rapid shallow breathing index and serum B-type natriuretic peptide concentration were measured. Success and failure of weaning was assessed by defined criteria. Decision to extubate was at the discretion of the treating intensivist. Failure of extubation was defined as re-intubation, non-invasive ventilation or death within 48 h after extubation. Of 53 extubated participants, 11 failed extubation. Failed extubation was associated with diabetes, ischaemic heart disease, higher E/E′ (OR 1.27, 95% CI 1.05–1.54), left atrial area (OR 1.14, CI 1.02–1.28), fixed rightward curvature of the interatrial septum (OR 12.95, CI 2.73–61.41), and higher loss of aeration score of anterior and lateral regions of the lungs (OR 1.41, CI 1.01–1.82). Conclusions Failed extubation in mechanically ventilated patients is more prevalent if markers of left ventricular diastolic dysfunction and loss of lung aeration are present.

OBJECTIVES: Saphenous vein graft (SVG) remains the predominant conduit used in coronary surgery. The internal mammary artery has higher later term patency and confers superior survival. Current debate focuses on the increased use of arterial conduits rather than eradication of venous conduits. METHODS: Patient data extracted from the Australian and New Zealand Society of Cardiothoracic Surgeons database from 2001-2013 were linked to the national death registry held by the Australian Institute of Health and Welfare for all-cause mortality with censor date 7 October 2014. The dataset was divided according to use of SVG rather than the arterial conduit. Analyses of SVG ≥ 1 or SVG = 1 were compared to SVG = 0. Additionally, groups of 3, 4 or 5 grafts were subjected to multiple analyses testing the mortality hazard with increasing use of SVG. Propensity score matched analyses were conducted using 24 variables. RESULTS: Of 51 113 primary coronary surgery patients, unmatched survival at up to 12.5 years was significantly lower for SVG ≥ 1, n = 33 359, mortality hazard ratio (HR) 1.24 [95% confidence interval (CI) 1.18-1.30], P

Hip fracture surgery is common, usually occurs in elderly patients who have multiple comorbidities, and is associated with high morbidity and mortality. Pre-operative focused cardiac ultrasound can alter diagnosis and management, but its impact on outcome remains uncertain. This pilot study assessed feasibility and group separation for a proposed large randomised clinical trial of the impact of pre-operative focused cardiac ultrasound on patient outcome after hip fracture surgery. Adult patients requiring hip fracture surgery in four teaching hospitals in Australia were randomly allocated to receive focused cardiac ultrasound before surgery or not. The primary composite outcome was any death, acute kidney injury, non-fatal myocardial infarction, cerebrovascular accident, pulmonary embolism or cardiopulmonary arrest within 30 days of surgery. Of the 175 patients screened, 100 were included as trial participants (screening:recruitment ratio 1.7:1), 49 in the ultrasound group and 51 as controls. There was one protocol failure among those recruited. The primary composite outcome occurred in seven of the ultrasound group patients and 12 of the control group patients (relative group separation 39%). Death, acute kidney injury and cerebrovascular accident were recorded, but no cases of myocardial infarction, pulmonary embolism or cardiopulmonary arrest ocurred. Focused cardiac ultrasound altered the management of 17 participants, suggesting an effect mechanism. This pilot study demonstrated that enrolment and the protocol are feasible, that the primary composite outcome is appropriate, and that there is a treatment effect favouring focused cardiac ultrasound – and therefore supports a large randomised clinical trial.

Lung ultrasonography is superior to clinical examination and chest X-ray (CXR) in diagnosis of acute respiratory pathology in the emergency and critical care setting and after cardiothoracic surgery in intensive care. Lung ultrasound may be useful before cardiothoracic surgery and after discharge from intensive care, but the proportion of significant respiratory pathology in this setting is unknown and may be too low to justify its routine use. The aim of this study was to determine the proportion of clinically significant respiratory pathology detectable with CXR, clinical examination, and lung ultrasound in patients on the ward before and after cardiothoracic surgery.In this prospective observational study, patients undergoing elective cardiothoracic surgery who received a CXR as part of standard care preoperatively or after discharge from the intensive care unit received a standardized clinical assessment and then a lung ultrasound examination within 24 hours of the CXR by 2 clinicians. The incidence of collapse/atelectasis, consolidation, alveolar-interstitial syndrome, pleural effusion, and pneumothorax were compared between clinical examination, CXR, and lung ultrasound (reference method) based on predefined diagnostic criteria in 3 zones of each lung.In 78 participants included, presence of any pathology was detected in 56% of the cohort by lung ultrasound; 24% preoperatively and 94% postoperatively. With lung ultrasound as a reference, the sensitivity of the 5 different pathologies ranged from 7% to 69% (CXR), 7% to 76% (clinical examination), and 14% to 94% (combined); the specificity of the 5 different pathologies ranged from 91% to 98% (CXR), from 90% to 99% (clinical examination), and from 82% to 97% (combined). For clinical examination and lung ultrasound, intraobserver agreements beyond chance ranged from 0.28 to 0.70 and from 0.84 to 0.97, respectively. The agreements beyond chance of pathologic diagnoses between modalities ranged from 0.11 to 0.64 (CXR and lung ultrasound), from 0.08 to 0.7 (CXR and lung ultrasound), and from 0 to 0.58 (clinical examination and CXR).Clinically important respiratory pathology is detectable by lung ultrasound in a substantial number of noncritically ill, pre or postoperative cardiothoracic surgery participants with high estimate of interobserver agreement beyond that expected by chance, and we showed clinically significant diagnoses may be missed by the contemporary practice of clinical examination and CXR.

OBJECTIVES We sought to compare the effects of conventional wire cerclage with that of the band and plate fixation of the sternum. METHODS A parallel randomized open-label trial with 1:1 allocation ratio compared healing after adult cardiac surgery using ‘figure-of-8’ stainless steel wire cerclage or a band and plate system (plates). The primary end point was maximal sternal edge displacement during active coughing of ≥2 mm in ≥2 of 4 sites measured with ultrasound by 2 assessors blinded to the other at 6 weeks postoperatively. Secondary end points at 12 weeks included ultrasound assessment, computed tomography (CT) scan and multidimensional assessment of quality of recovery using the Postoperative Quality of Recovery Scale. RESULTS Of 50 patients, 26 received plates and 24 wires. Two patients died and 1 withdrew consent leaving 25 plates and 22 wires for primary end point analysis. Operations included 37 coronary, 5 valve and 8 combined coronary and valve procedures. At 6 weeks, less sternal movement was observed in patients with plates than those with wires, 4% (1/25) vs 32% (7/22), P = 0.018. Agreement between observers was high, kappa = 0.850. At 12 weeks, less ultrasound motion was seen in patients with plates, 0% (0/23) than those with wires, 25% (5/20), P = 0.014. Recovery from pain was higher for patients with plates 92% (22/24) than those with wires 67% (14/21), P = 0.004. CT bone edge separation was less for plates 38% (9/24) than wires 71% (15/21), P = 0.036. CT mild bone synthesis or greater was similar between patients with plates 21% (5/24) and wires 14% (3/21), P = 0.71. CONCLUSIONS Patients receiving the band and plate system had significantly less sternal edge motion than those receiving wires, 6 and 12 weeks after cardiac surgery and experienced less pain. Clinical trial registration clinicaltrials.gov NCT03282578.

Introduction: Mild cognitive impairment is considered a precursor to dementia and significantly impacts upon quality of life. The prevalence of mild cognitive impairment is higher in the post-surgical cardiac population than the general population, with older age and co-morbidities further increasing the risk of cognitive decline. This significantly impacts upon quality of life. Exercise improves neurogenesis, synaptic plasticity and inflammatory and neurotrophic factor pathways, which may help to augment the effects of cognitive decline. However, the effects of resistance training on cognitive, functional and overall patient-reported recovery have not been investigated in the surgical cardiac population. This study aims to determine the safety and feasibility of early moderate intensity resistance training in people undergoing cardiac surgery via a median sternotomy, compared to standard care. The effect of this exercise program on cognitive and functional recovery will also be examined. Methods: This study will be a prospective, pragmatic, pilot randomised controlled trial comparing a standard care group (low-intensity aerobic exercise) and a moderate-intensity resistance training group. Participants aged 18 years and older with coronary artery and/or valve disease requiring surgical intervention will be recruited pre-operatively and randomised 1:1 to either the resistance training or standard care group post-operatively. Feasibility and safety will be assessed through recruitment and retention rates; exercise program adherence; dropout rate; exercise and session stoppages due to pain, any adverse event or incident; and, any major adverse cardiac and cerebral events. Secondary measures include cognitive function, muscular strength, physical function, multiple-domain recovery, balance and patient satisfaction. Assessments will be conducted at baseline (pre-operatively) and post-operatively at 2 weeks, 8 weeks, 14 weeks and 6 months. Discussion: The results of this study will inform the safety and feasibility of early intervention resistance training for patients following cardiac surgery. In addition, this study will provide insights into the effect of resistance training on postoperative cognitive recovery to inform rehabilitation guidelines. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry (ANZCTR), ID: ACTRN12617001430325p. Registered on 9 October 2017. Universal Trial Number (UTN):U1111-1203-2131. Keywords: Median sternotomy, resistance training, cognition, cardiac surgery, recovery, rehabilitation, exercise

Background Recent coronary surgery practice is to graft arterial conduits to more severely stenosed coronary targets than in the past. We aimed to investigate postoperative arterial graft patency with native coronary stenosis at the time of surgery, using the left internal mammary artery and radial artery (RA) as a composite Y graft (LIMA-RA-Y). In the study timeframe, it was routine clinical practice to graft coronary arteries with >50% stenosis. Methods Of 464 patients previously reported 1996–1999, 346 who underwent LIMA-RA-Y at the Royal Melbourne Hospital, 76 had postoperative angiograms at the same institution. Each anastomosis was considered separately. For arterial grafts a “string sign” was analysed as being occluded. Predictor of patency was performed with a generalised linear mixed model (GLMM). Results Seventy-six (76) patients had postoperative angiograms at 5.8±5.4 years (range 0.23–19.4; interquartile range 1.7–10.0) years postoperative; with age at operation 62.5±10.7 years and 3.4±0.8 grafts per patient, 82% were male. Of 256 anastomoses, 230 were to coronary targets >50% stenosis. Overall patency was 84.0% (214/256). For coronary stenosis >50%, patency was 88% (201/230) and varied by coronary territory left anterior descending (LAD) 94% (87/93), circumflex 90% (71/79) and right coronary artery (RCA) 74% (43/58). Interaction for coronary territory was significant (p=0.022). Higher preoperative coronary stenosis predicted higher patency; with odds ratio for improved patency of 1.83 (95% CI 1.51, 2.22), p Conclusions Late patency of composite arterial grafts is acceptable when grafted to coronary arteries of greater than 50% stenosis.

Objectives To compare agreement and variability of cardiac output measurement of 2-dimensional (2D) and 3D transesophageal echocardiography (TEE) with thermodilution before and after bypass. Design Prospective observational study. Setting Two tertiary hospitals. Interventions Cardiac output (CO) was measured simultaneously with thermodilution and TEE by multiplying either the left ventricular outflow tract area (LVOTA) or aortic valve area (AVA), the velocity-time integral (VTI) of flow at the same site, and heart rate. The LVOTA was calculated using diameter for 2D TEE. Planimetry was used for 3D TEE. The AVA was measured using planimetry. Participants The study comprised 82 adult patients undergoing coronary or valve surgery. Measurements and Main Results One hundred fifty-four complete sets of measurements were obtained (82 prebypass and 72 postbypass). All TEE methods had acceptable correlation and absence of proportional or fixed bias except for the left ventricular outflow tract (LVOT) VTI modal trace method, which had poor correlation and proportional but not fixed bias (regression coefficient [95% confidence interval], bias [percentage of mean CO]): 2D LVOT VTI modal trace 0.67 (0.54-0.80), –36.4%; 2D LVOT VTI outer edge trace 0.96 (0.80-1.12), –15.3%; 2D AVA planimetry 0.96 (0.75-1.18), +4.9%; 3D LVOT area planimetry 1.18 (0.96-1.41), +0.8%; 3D AVA planimetry 1.20 (0.93-1.46), +0.4%. All TEE methods had wide levels of agreement compared with thermodilution (–3.94 to +0.23 L/min, –2.83 to +1.28 L/min, –2.23 to +2.73 L/min, –2.35 to +2.42 L/min, and –2.57 to +2.61 L/min, respectively). Measurement variability was superior for all TEE methods compared with thermodilution before but not after bypass. Conclusions Although limits of agreement of CO measurement with 3D TEE and thermodilution are wide, 2D planimetry of the AVA and continuous wave Doppler may be substituted for thermodilution before and after bypass.

David J Canty, Johan Heiberg, Yang Yang, Alistair G Royse, Swaroop Margale, Nagesh Nanjappa ... et al.

Background: Ultrasound-assisted examination of the cardiovascular system with focused cardiac ultrasound by the treating physician is non-invasive and changes diagnosis and management of patient’s with suspected cardiac disease. This has not been reported in a general practice setting. Aim: To determine whether focused cardiac ultrasound performed on patients aged over 50 years changes the diagnosis and management of cardiac disease by a general practitioner. Design and setting: A prospective observational study of 80 patients aged over 50years and who had not received echocardiography or chest CT within 12months presenting to a general practice. Method: Clinical assessment and management of significant cardiac disorders in patients presenting to general practitioners were recorded before and after focused cardiac ultrasound. Echocardiography was performed by a medical student with sufficient training, which was verified by an expert. Differences in diagnosis and management between conventional and ultrasound-assisted assessment were recorded. Results and conclusion: Echocardiography and interpretation were acceptable in all patients. Significant cardiac disease was detected in 16 (20%) patients, including aortic stenosis in 9 (11%) and cardiac failure in 7 (9%), which were missed by clinical examination in 10 (62.5%) of these patients. Changes in management occurred in 12 patients (15% overall and 75% of those found to have significant cardiac disease) including referral for diagnostic echocardiography in 8 (10%), commencement of heart failure treatment in 3 (4%) and referral to a cardiologist in 1 patient (1%). Routine focused cardiac ultrasound is feasible and frequently alters the diagnosis and management of cardiac disease in patients aged over 50years presenting to a general practice.

The diaphragm is the most important muscle of respiration. At equilibrium, the load imposed on the diaphragmatic muscles from transdiaphragmatic pressure balances the force generated by diaphragmatic muscles. However, procedural and nonprocedural thoracic and abdominal conditions may disrupt this equilibrium and impair diaphragmatic function. Diaphragmatic dysfunction is associated with respiratory insufficiency and poor outcome. Therefore, rapid diagnosis and early intervention may be useful. Ultrasound imaging provides quick and accurate bedside assessment of the diaphragm. Various imaging techniques have been suggested, using 2-dimensional and M-mode technology. Diaphragm viewing depends on the degree of robe movement, determined by the angle of incidence of the ultrasound beam and by the direction of probe movement. In this review, we will discuss the function of the diaphragm focusing on clinically important anatomical and physiological properties of the diaphragm. We will review the literature regarding various sonographic techniques for diaphragm assessment. We will also explore the evidence for the role of the tidal displacement of subdiaphragmatic organs as a surrogate for diaphragm movement.

Focused echocardiography is becoming a widely used tool to aid clinical assessment by anaesthetists and critical care physicians. At the present time, most physicians are not yet trained in focused echocardiography or believe that it may result in adverse outcomes by delaying, or otherwise interfering with, time-critical patient management. We performed a systematic review of electronic databases on the topic of focused echocardiography in anaesthesia and critical care. We found 18 full text articles, which consistently reported that focused echocardiography may be used to identify or exclude previously unrecognised or suspected cardiac abnormalities, resulting in frequent important changes to patient management. However, most of the articles were observational studies with inherent design flaws. Thirteen prospective studies, including two that measured patient outcome, were supportive of focused echocardiography, whereas five retrospective cohort studies, including three outcome studies, did not support focused echocardiography. There is an urgent requirement for randomised controlled trials.

Objectives The initial volume of antegrade cardioplegia used to induce asystole during aortic cross-clamp still is based on empiric methods and may be excessive, potentially leading to hyperkalemia, myocardial edema, and acute left ventricular distention from aortic regurgitation. The objectives were to determine whether the volume of cardioplegia required to induce asystole is proportional to left ventricular mass, and whether the degree of left ventricular distention is proportional to the severity of aortic regurgitation. Design Prospective observational study. Setting Two tertiary university hospitals. Interventions Transesophageal echocardiography was used to estimate left ventricular mass (prolate ellipse revolution formula), quantify aortic regurgitation, and monitor for distention during initial antegrade cardioplegia delivery. The volume of cardioplegia required for asystole was recorded. Participants Fifty-eight patients aged over 18 years scheduled for cardiac surgery requiring aortic cross-clamping. Measurements and Main Results There was a weak correlation of left ventricular mass and antegrade cardioplegia volume required for asystole (r = 0.35, p = 0.047). The degree of left ventricular distention correlated moderately with the severity of aortic regurgitation (r = 0.55, p = 0.007) and was excessive and stopped early (aborted) in 24% of all patients, including 18% of 39 patients without aortic regurgitation. An aortic regurgitation vena contracta of 0.3 cm predicted aborted cardioplegia with modest accuracy (AUC 0.81, 0.66-0.99, p = 0.02, sensitivity 71%, specifity 81%). Conclusions Estimated left ventricular mass is not a useful predictor of the initial volume of antegrade cardioplegia required to induce asystole. However transesophageal echocardiography can predict and monitor for left ventricular distention, which is common.

In 1999, Royse et al. reported on the left internal mammary artery, radial artery, Y-graft technique (LIMA-RA-Y), which achieves total arterial revascularization (TAR). However, the most common coronary reconstruction remains LIMA and supplementary saphenous vein grafts (LIMA + SVG).The goal of this study was to conduct a survival comparison of LIMA-RA-Y versus the conventional LIMA + SVG.Of the original 464 LIMA-RA-Y patients reported (1996 to 1998), 346 were from the Royal Melbourne Hospital. Survival at June 2017 was compared with a group of 534 patients from 1996 to 2003 from the same institution who received LIMA + SVG, or 5,800 patients who received TAR with different grafting configurations. Propensity score matching (PSM) was performed with 1:1 matching using 26 variables. Comparisons used Kaplan-Meier (KM) and Cox proportional hazards methods. LIMA-RA-Y was compared with LIMA + SVG in which all non-left anterior descending artery grafts were performed with either composite RA or aorta-coronary SVG with no use of right internal mammary artery. We also conducted a comparison of LIMA-RA-Y versus TAR.Baseline characteristics of the LIMA-RA-Y group (n = 346) compared with LIMA + SVG (n = 534) after PSM (n = 232 pairs) did not differ (3.3 ± 0.8 grafts per patient). Survival was worse for LIMA + SVG in the unmatched groups (KM, p 0.001) and for PSM groups (KM, p = 0.043; Cox proportional hazards ratio: 1.3; 95% confidence interval: 1.0 to 1.6; p = 0.038). Survival did not differ between LIMA-RA-Y and other TAR (n = 5,800) patients before, or after, PSM (n = 332 pairs).Use of LIMA + SVG has worse survival than LIMA-RA-Y in achieving total arterial revascularization.

Objectives Limited transthoracic echocardiography (TTE) and lung ultrasound increasingly is performed in the intensive care unit (ICU), though used in a goal-directed rather than routine manner. Design Prospective observational study. Settings Tertiary ICU. Participants Ninety-three critically ill participants within 24 hours of admission to ICU. Methods A treating intensivist documented a clinical diagnosis and management plan before and after combined limited TTE and lung ultrasound. Ultrasound was performed by an independent intensivist and checked for accuracy offline by a second reviewer. Results Ultrasound images were interpretable in 99%, with good interobserver agreement. The hemodynamic diagnosis was altered in 66% of participants, including new (14%) or altered (25%) abnormal states or exclusion of clinically diagnosed abnormal state (27%). Valve pathology of at least moderate severity was diagnosed for mitral regurgitation (7%), aortic stenosis (1%), aortic stenosis and mitral regurgitation (1%), tricuspid regurgitation (3%), and 1 case of mitral regurgitation was excluded. Lung pathology diagnosis was changed in 58% of participants including consolidation (13%), interstitial syndrome (4%), and pleural effusion (23%), and exclusion of clinically diagnosed consolidation (6%), interstitial syndrome (3%), and pleural effusion (9%). Management changed in 65% of participants including increased (12%) or decreased (23%) fluid therapy, initiation (10%), changing (6%) or cessation (9%) of inotropic, vasoactive or diuretic drugs, non-invasive ventilation (3%), and pleural drainage (2%). Conclusion Routine screening of patients with combined limited TTE and lung ultrasound on admission to ICU is feasible and frequently alters diagnosis and management.