Automatic deep learning-based pleural effusion segmentation in lung ultrasound images.

BACKGROUND: Point-of-care lung ultrasound (LUS) allows real-time patient scanning to help diagnose pleural effusion (PE) and plan further investigation and treatment. LUS typically requires training and experience from the clinician to accurately interpret the images. To address this limitation, we previously demonstrated a deep-learning model capable of detecting the presence of PE on LUS at an accuracy greater than 90%, when compared to an experienced LUS operator. METHODS: This follow-up study aimed to develop a deep-learning model to provide segmentations for PE in LUS. Three thousand and forty-one LUS images from twenty-four patients diagnosed with PE were selected for this study. Two LUS experts provided the ground truth for training by reviewing and segmenting the images. The algorithm was then trained using ten-fold cross-validation. Once training was completed, the algorithm segmented a separate subset of patients. RESULTS: Comparing the segmentations, we demonstrated an average Dice Similarity Coefficient (DSC) of 0.70 between the algorithm and experts. In contrast, an average DSC of 0.61 was observed between the experts. CONCLUSION: In summary, we showed that the trained algorithm achieved a comparable average DSC at PE segmentation. This represents a promising step toward developing a computational tool for accurately augmenting PE diagnosis and treatment.

Three Zone Scanning Protocol For Lung Ultrasound: An Anatomical Basis.

Lung ultrasound is rapidly gaining popularity based on point of care ease of use, diagnostic fidelity and lack of ionising 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.

A Pilot Study of the Safety and Effectiveness of a Novel Device in Subjects With Axillary Hyperhidrosis.

BACKGROUND: One-third of U.S. adults are bothered by excessive sweating and 5% suffer from hyperhidrosis, both of which negatively affect quality-of-life (QoL). A single-use disposable patch using the novel targeted alkali thermolysis (TAT) technology is being developed to address this condition. OBJECTIVE: Assess the efficacy and safety of the TAT patch for the treatment of excessive sweating using a randomized, double-blind, sham-controlled study design. MATERIALS AND METHODS: Adults with Hyperhidrosis Disease Severity Scale (HDSS) scores of 3 or 4 ( n = 16) were treated with an active or sham patch for up to 3 minutes (as established in a previous unpublished feasibility study) and evaluated weekly for 6 weeks post-treatment. The primary effectiveness measure was improved HDSS at Week-4. RESULTS: The study met its objective. For the primary efficacy measure, 83% of TAT-treated subjects reported HDSS scores of 1 or 2 at Week-4 versus 0% of sham-treated subjects ( p = .0032). Furthermore, 67% of TAT-treated subjects had a 2-point improvement in HDSS scores versus 0% of sham-treated subjects ( p = .0123). Quality-of-life improvement correlated with HDSS. The TAT patch seemed to be well-tolerated; one transient moderate adverse event that resolved without sequelae was reported. CONCLUSION: The TAT patch successfully demonstrated efficacy and was well-tolerated.

The Impact on 30-Day Mortality From a Brief Focused Ultrasound-Guided Management Protocol Immediately Before Emergency Noncardiac Surgery in Critically Ill Patients: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To determine whether brief ultrasound-guided treatment of hemodynamic shock and respiratory failure immediately before emergency noncardiac surgery reduced 30-day mortality. DESIGN: Parallel, nonblinded, randomized trial with 1:1 allocation to control and intervention groups. SETTING: Twenty-eight major hospitals within China. PARTICIPANTS: Six-hundred sixty patients ≥14 years of age, scheduled for emergency noncardiac surgery with evidence of shock (heart rate >120 beat/min, systolic blood pressure< 90 mmHg or requiring inotrope infusion), or respiratory failure (Pulse Oxygen Saturation <92%, respiratory rate >20 beat/min, or requiring mechanical ventilation). INTERVENTIONS: 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. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Patency of conduits in patients who received internal mammary artery, radial artery and saphenous vein grafts.

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 < 0.001. Patency RA 93.5% was also not different to IMA 96.8%, 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 < 0.001, and patency, 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.

A proposed lung ultrasound and phenotypic algorithm for the care of COVID-19 patients with acute respiratory failure.

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.

Comparison of Cardiac Output of Both 2-Dimensional and 3-Dimensional Transesophageal Echocardiography With Transpulmonary Thermodilution During Cardiac Surgery.

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.

Patency When Grafted to Coronary Stenosis More Than 50% in LIMA-RA-Y Grafts.

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<0.001 for each 10% increase in stenosis. CONCLUSIONS: Late patency of composite arterial grafts is acceptable when grafted to coronary arteries of greater than 50% stenosis.

The Feasibility and Impact of Routine Combined Limited Transthoracic Echocardiography and Lung Ultrasound on Diagnosis and Management of Patients Admitted to ICU: A Prospective Observational Study.

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.

A Pilot Assessment of 3 Point-of-Care Strategies for Diagnosis of Perioperative Lung Pathology.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Assessment of Image Quality of Repeated Limited Transthoracic Echocardiography After Cardiac Surgery.

OBJECTIVES: The use of limited transthoracic echocardiography (TTE) has been restricted in patients after cardiac surgery due to reported poor image quality. The authors hypothesized that the hemodynamic state could be evaluated in a high proportion of patients at repeated intervals after cardiac surgery. DESIGN: Prospective observational study. SETTING: Tertiary university hospital. PARTICIPANTS: The study comprised 51 patients aged 18 years or older presenting for cardiac surgery. INTERVENTIONS: Patients underwent TTE before surgery and at 3 time points after cardiac surgery. Images were assessed offline using an image quality scoring system by 2 expert observers. Hemodynamic state was assessed using the iHeartScan protocol, and the primary endpoint was the proportion of limited TTE studies in which the hemodynamic state was interpretable at each of the 3 postoperative time points. MEASUREMENTS AND MAIN RESULTS: Hemodynamic state interpretability varied over time and was highest before surgery (90%) and lowest on the first postoperative day (49%) (p<0.01). This variation in interpretability over time was reflected in all 3 transthoracic windows, ranging from 43% to 80% before surgery and from 2% to 35% on the first postoperative day (p<0.01). Image quality scores were highest with the apical window, ranging from 53% to 77% across time points, and lowest with the subcostal window, ranging from 4% to 70% across time points (p< 0.01). CONCLUSIONS: Hemodynamic state can be determined with TTE in a high proportion of cardiac surgery patients after extubation and removal of surgical drains.

Repeated Monitoring With Transthoracic Echocardiography and Lung Ultrasound After Cardiac Surgery: Feasibility and Impact on Diagnosis.

OBJECTIVES: Cardiorespiratory complications are common after cardiac surgery and current monitors used to diagnose these are invasive and have limitations. Transthoracic echocardiography and lung ultrasound are noninvasive and frequently improve diagnosis in critically ill patients but have not been reported for routine postoperative monitoring after coronary, valve, and aortic surgery. The aim was to determine whether both repeated postoperative transthoracic echocardiography and lung ultrasound revealed or excluded clinically important cardiac and respiratory disorders compared to conventional monitoring and chest x-ray. DESIGN: Prospective observational study. SETTING: Tertiary university hospital. PARTICIPANTS: Ninety-one patients aged older than 18 undergoing cardiac surgery INTERVENTIONS: Postoperative clinical patient assessment for significant cardiac and respiratory disorders by the treating physician was recorded at 3 time points (day after surgery, after extubation and removal of chest drains and at discharge) using conventional monitoring and chest x-ray. After each assessment, transthoracic echocardiography and lung ultrasound were performed, and differences in diagnosis from conventional assessment were recorded. MEASUREMENTS AND MAIN RESULTS: Transthoracic echocardiography was interpretable in at least 1 echocardiographic window in 99% of examinations. Transthoracic echocardiography and/or lung ultrasound changed the diagnosis of important cardiac and/or respiratory disorders in 61 patients (67%). New cardiac findings included cardiac dysfunction (38 patients), pericardial effusion (5), mitral regurgitation (2), and hypovolemia (1). New respiratory findings included pleural effusion (30), pneumothorax (4), alveolar interstitial syndrome (3) and consolidation (1). CONCLUSIONS: Routine repeated monitoring with cardiac and lung ultrasound after cardiac surgery is feasible and frequently alters diagnosis of clinically important cardiac and respiratory pathology.

Transesophageal Echocardiography Guidance of Antegrade Cardioplegia Delivery for Cardiac Surgery.

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.

Interatrial septum motion but not Doppler assessment predicts elevated pulmonary capillary wedge pressure in patients undergoing cardiac surgery.

BACKGROUND: Left atrial pressure and its surrogate, pulmonary capillary wedge pressure (PCWP), are important for determining diastolic function. The role of transthoracic echocardiography (TTE) in assessing diastolic function is well established in awake subjects. The objective was to assess the accuracy of predicting PCWP by TTE and transesophageal echocardiography (TEE) during coronary artery surgery. METHODS: In 27 adult patients undergoing on-pump coronary artery surgery, simultaneous echocardiographic and hemodynamic measurements were obtained immediately before anesthesia (TTE), after anesthesia and mechanical ventilation (TTE and TEE), during conduit harvest (TEE), and after separation from cardiopulmonary bypass (TEE). RESULTS: Twenty patients had an ejection fraction (EF) of 0.5 or greater. With the exception of E/e' and S/D ratios, echocardiographic values changed over the echocardiographic studies. In patients with low EF, E velocity, deceleration time, pulmonary vein D, S/D, and E/e' ratios correlated well with PCWP before anesthesia. After induction of anesthesia using TTE or TEE, correlations were poor. In normal EF patients, correlations were poor for both TEE and TTE at all five stages. The sensitivity and specificity of echocardiographic values were not high enough to predict raised PCWP except for a fixed curve pattern of interatrial septum (area under the curve 0.89 for PCWP ≥ 17, and 0.98 for ≥ 18 mmHg) and S/D less than 1 (area under the curve 0.74 for PCWP ≥ 17, and 0.78 for ≥ 18 mmHg). CONCLUSION: Doppler assessment of PCWP was neither sensitive nor specific enough to be clinically useful in anesthetized patients with mechanical ventilation. The fixed curve pattern of the interatrial septum was the best predictor of raised PCWP.

Hepatic cholesteryl ester accumulation in lysosomal acid lipase deficiency: non-invasive identification and treatment monitoring by magnetic resonance.

BACKGROUND & AIMS: Lysosomal Acid Lipase (LAL) deficiency is a rare metabolic storage disease, caused by a marked reduction in activity of LAL, which leads to accumulation of cholesteryl esters (CE) and triglycerides (TG) in lysosomes in many tissues. We used (1)H magnetic resonance (MR) spectroscopy to characterize the abnormalities in hepatic lipid content and composition in patients with LAL deficiency, and in ex vivo liver tissue from a LAL deficiency rat model. Secondly, we used MR spectroscopy to monitor the effects of an enzyme replacement therapy (ERT), sebelipase alfa (a recombinant human lysosomal acid lipase), on hepatic TG and CE content in the preclinical model. METHODS: Human studies employed cohorts of LAL-deficient patients and NAFLD subjects. Rat experimental groups comprised ex vivo liver samples of wild type, NAFLD, LAL-deficient, and LAL-deficient rats receiving 4weeks of sebelipase alfa treatment. Hepatic (1)H MR spectroscopy was performed using 3T (human) and 7T (preclinical) MRI scanners to quantify hepatic cholesterol and triglyceride content. RESULTS: CE accumulation was identified in LAL deficiency in both human and preclinical studies. A significant decrease in hepatic CE was observed in LAL-deficient rats following treatment with sebelipase alfa. CONCLUSIONS: We demonstrate an entirely non-invasive method to identify and quantify the hepatic lipid signature associated with a rare genetic cause of fatty liver. The approach provides a more favorable alternative to repeated biopsy sampling for diagnosis and disease progression / treatment monitoring of patients with LAL deficiency and other disorders characterised by increased free cholesterol and/or cholesteryl esters.

Venous Doppler to Assess Congestion: A Comprehensive Review of Current Evidence and Nomenclature.

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.

Impact of focused cardiac and lung ultrasound screening performed by a junior doctor during admission to the surgical ward on patients before emergency non-cardiac surgery: A pilot prospective observational study.

Purpose: To assess whether pre-operative focused cardiac ultrasound and lung ultrasound screening performed by a junior doctor can change diagnosis and clinical management of patients aged ≥65 years undergoing emergency, non-cardiac surgery. Method: This pilot prospective observational study included patients scheduled for emergency, non-cardiac surgery. The treating team completed a diagnosis and management plan before and after focused cardiac and lung ultrasound, which was performed by a junior doctor. Changes to diagnosis and management after ultrasound were recorded. Ultrasound images were assessed for image and diagnostic interpretation by an independent expert. Results: There was a total of 57 patients at age 77 ± 8 years. Cardiopulmonary pathology was suspected after clinical assessment in 28% vs. 72% after ultrasound (including abnormal haemodynamic state in 61%, valvular lesions in 32%, acute pulmonary oedema/interstitial syndrome in 9% and bilateral pleural effusions in 2%). In 67% of patients, the perioperative management was changed. The changes were in fluid therapy in 30%, cardiology consultation in 7%, formal in- or out-patient, transthoracic echocardiography in 11% and 30% respectively. Discussion: The impact of pre-operative focused cardiac and lung ultrasound on diagnosis and management of patients on the hospital ward before emergency non-cardiac surgery by a junior doctor was comparable to previous studies of anaesthetists experienced in focused ultrasound. However, the ability to recognise when image quality is insufficient for diagnosis is an important consideration for novice sonographers. Conclusions: Focused cardiac and lung ultrasound examination by a junior doctor is feasible and may change preoperative diagnosis and management in patients of 65 years or older, admitted for emergency non-cardiac surgery.

A Preclinical Study Comparing the Activity and Potency of OnabotulinumtoxinA and PrabotulinumtoxinA.

Objective: 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.

Surgery for rheumatic heart disease in the Northern Territory, Australia, 1997-2016: what have we gained?

BACKGROUND: Between 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. METHODS: A 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. FINDINGS: The 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), p<0.001). Preoperative chronic kidney disease (HR 6.5 (95% CI: 3.0 to 14.0) p≤0.001)), coronary artery disease (HR 3.3 (95% CI: 1.3 to 8.4) p=0.012) and pulmonary artery systolic pressure>50 mm Hg before surgery (HR 1.9 (95% CI: 1.2 to 3.1) p=0.007) were independently associated with death. INTERPRETATION: Survival 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.

Core review: physician-performed ultrasound: the time has come for routine use in acute care medicine.

The use of ultrasound in the acute care specialties of anesthesiology, intensive care, emergency medicine, and surgery has evolved from discrete, office-based echocardiographic examinations to the real-time or point-of-care clinical assessment and interventions. "Goal-focused" transthoracic echocardiography is a limited scope (as compared with comprehensive examination) echocardiographic examination, performed by the treating clinician in acute care medical practice, and is aimed at addressing specific clinical concerns. In the future, the practice of surface ultrasound will be integrated into the everyday clinical practice as ultrasound-assisted examination and ultrasound-guided procedures. This evolution should start at the medical student level and be reinforced throughout specialist training. The key to making ultrasound available to every physician is through education programs designed to facilitate uptake, rather than to prevent access to this technology and education by specialist craft groups. There is evidence that diagnosis is improved with ultrasound examination, yet data showing change in management and improvement in patient outcome are few and an important area for future research.