Prehospital triage of acute aortic syndrome using a machine learning algorithm.

BACKGROUND: Acute aortic syndrome (AAS) comprises a complex and potentially fatal group of conditions requiring emergency specialist management. The aim of this study was to build a prediction algorithm to assist prehospital triage of AAS. METHODS: Details of consecutive patients enrolled in a regional specialist aortic network were collected prospectively. Two prediction algorithms for AAS based on logistic regression and an ensemble machine learning method called SuperLearner (SL) were developed. Undertriage was defined as the proportion of patients with AAS not transported to the specialist aortic centre, and overtriage as the proportion of patients with alternative diagnoses but transported to the specialist aortic centre. RESULTS: Data for 976 hospital admissions between February 2010 and June 2017 were included; 609 (62·4 per cent) had AAS. Overtriage and undertriage rates were 52·3 and 16·1 per cent respectively. The population was divided into a training cohort (743 patients) and a validation cohort (233). The area under the receiver operating characteristic (ROC) curve values for the logistic regression score and the SL were 0·68 (95 per cent c.i. 0·64 to 0·72) and 0·87 (0·84 to 0·89) respectively (P < 0·001) in the training cohort, and 0·67 (0·60 to 0·74) and 0·73 (0·66 to 0·79) in the validation cohort (P = 0·038). The logistic regression score was associated with undertriage and overtriage rates of 33·7 (bootstrapped 95 per cent c.i. 29·3 to 38·3) and 7·2 (4·8 to 9·8) per cent respectively, whereas the SL yielded undertriage and overtriage rates of 1·0 (0·3 to 2·0) and 30·2 (25·8 to 34·8) per cent respectively. CONCLUSION: A machine learning prediction model performed well in discriminating AAS and could be clinically useful in prehospital triage of patients with suspected AAS.

ANTECEDENTES: Los síndromes aórticos agudos (aortic acute syndromes, AAS) constituyen un grupo complejo y potencialmente letal de entidades que requieren un tratamiento especializado en emergencias. El objetivo de este estudio fue construir un algoritmo de predicción para ayudar a la selección prehospitalaria de los AAS. MÉTODOS: Se recogieron prospectivamente una serie de pacientes consecutivos inscritos en una red regional especializada en patología aórtica. Se desarrollaron dos algoritmos de predicción para AAS basados en una regresión logística y en un método de aprendizaje automático denominado Super Learner (SL). Undertriage (infra-selección) se definió como la proporción de pacientes con AAS no transportados al centro especializado en patología aórtica y el overtriage (sobre-selección) como la proporción de pacientes con diagnósticos alternativos al AAS pero transportados al centro especializado en patología aórtica. RESULTADOS: Se incluyeron los datos de 976 ingresos hospitalarios entre febrero de 2010 y junio de 2017, con 609 (62,4%) AAS. Las tasas de overtriage y undertriage fueron del 52,3% y del 16,1%, respectivamente. La población se dividió en una cohorte de entrenamiento (n = 743) y en una cohorte de validación (n = 233). El área bajo la curva ROC para la puntuación de regresión logística y el SL fueron de 0,68 (0,64, 0,72) y de 0,87 (0,84, 0,89), respectivamente (P < 0,001) en la cohorte de entrenamiento, y de 0,67 (0,60, 0,74) y de 0,73 (0,66, 0,79) en la cohorte de validación (P = 0,038). La puntuación de regresión logística se asoció con tasas de undertriage y overtriage de 33,7% (i.c. del 95% bootstrapped 29,3%, 38,3%) y de 7,2% (4,8%, 9,8%), respectivamente, mientras que el SL presentó tasas de undertriage y overtriage de 1,0% (0,3%, 2,0%) y de 30,2% (25,8%, 34,8%), respectivamente. CONCLUSIÓN: El modelo de predicción de aprendizaje automático funcionó bien para discriminar AAS y podría ser clínicamente útil en la selección prehospitalaria de pacientes con sospecha de síndrome aórtico agudo.

Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.

PURPOSE: The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. MATERIAL AND METHODS: This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18FDG-PET-CT tumor uptake at 6months. RESULTS: Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18FDG-PET CT follow-up. CONCLUSION: Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance.

Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion.

In cardiac surgery, postoperative low cardiac output has been shown to correlate with increased rates of organ failure and mortality. Catecholamines have been the standard therapy for many years, although they carry substantial risk for adverse cardiac and systemic effects, and have been reported to be associated with increased mortality. On the other hand, the calcium sensitiser and potassium channel opener levosimendan has been shown to improve cardiac function with no imbalance in oxygen consumption, and to have protective effects in other organs. Numerous clinical trials have indicated favourable cardiac and non-cardiac effects of preoperative and perioperative administration of levosimendan. A panel of 27 experts from 18 countries has now reviewed the literature on the use of levosimendan in on-pump and off-pump coronary artery bypass grafting and in heart valve surgery. This panel discussed the published evidence in these various settings, and agreed to vote on a set of questions related to the cardioprotective effects of levosimendan when administered preoperatively, with the purpose of reaching a consensus on which patients could benefit from the preoperative use of levosimendan and in which kind of procedures, and at which doses and timing should levosimendan be administered. Here, we present a systematic review of the literature to report on the completed and ongoing studies on levosimendan, including the newly commenced LEVO-CTS phase III study (NCT02025621), and on the consensus reached on the recommendations proposed for the use of preoperative levosimendan.

Psychiatric consequences of intraoperative awareness: short review and case series.

Intraoperative awareness is an unwanted outcome that consists of an explicit recall of events during a surgical procedure performed under general anesthesia. Despite its relatively infrequent occurrence, intraoperative awareness is of significant concern due to frequent adverse psychiatric sequelae. We present three patients who developed posttraumatic sequelae following an episode of awareness under anesthesia and discuss the importance of early detection and specific care.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

[Respiratory support using veno-venous ECMO during lung resection for aspergilloma]. / Assistance ventilatoire par ECMO veino-veineuse pour résection d'aspergillome pulmonaire.

Respiratory support using extra corporeal membrane oxygenation (ECMO) is rarely used in the setting of adult lung surgery, with the exception of lung transplantation. We report the case of a patient with pulmonary aspergilloma, for whom selective bronchial intubation was required to facilitate surgery. Intolerance to unilateral ventilation was anticipated due to poor underlying lung function. Intra-operatively, an attempt to lung exclusion was responsible for severe hypoxemia. The use of veno-venous ECMO allowed to improve oxygenation and lung resection was carried out successfully at the expense of major intra-operative bleeding.

Comparison of two versions of the Vigileo-FloTrac system (1.03 and 1.07) for stroke volume estimation: a multicentre, blinded comparison with oesophageal Doppler measurements.

BACKGROUND: Our aim was to evaluate the validity of stroke volume measurements obtained using the Vigileo-FloTrac system in comparison with those obtained using oesophageal Doppler considered as a reference. METHODS: Prospective, multicentre study (four university hospitals), in which investigators were blinded to stroke volume values acquired simultaneously with the other technique. Two different versions of the Vigileo software (1.03 and 1.07) were studied and compared over two consecutive periods of time. Forty critically ill patients (three ICUs) and 20 high-risk surgical patients (one operating theatre) were studied over a 6-month period. RESULTS: Two hundred and forty paired stroke volume values obtained using the second version of the Vigileo (1.07) yielded better correlation and agreement (R=0.48, P<0.001; bias=4 ml, limits of agreement: +/- 41 ml) than the 207 paired values obtained using version 1.03 (R=0.12, P=0.1; bias=1 ml, limits of agreement: +/- 75 ml). However, even with the second version, the percentage error in stroke volume measurement was 58%, a value still above the range considered clinically acceptable (30%). CONCLUSIONS: The precision of stroke volume estimation using Vigileo-FloTrac has improved with the second version of the software (1.07), but remains insufficient to allow the replacement of the reference technique in the population studied.

Diastolic heart failure in anaesthesia and critical care.

Diastolic heart failure is an underestimated pathology with a high risk of acute decompensation during the perioperative period. This article reviews the epidemiology, risk factors, pathophysiology, and treatment of diastolic heart failure. Although frequently underestimated, diastolic heart failure is a common pathology. Diastolic heart failure involves heart failure with preserved left ventricular (LV) function, and LV diastolic dysfunction may account for acute heart failure occurring in critical care situations. Hypertensive crisis, sepsis, and myocardial ischaemia are frequently associated with acute diastolic heart failure. Symptomatic treatment focuses on the reduction in pulmonary congestion and the improvement in LV filling. Specific treatment is actually lacking, but encouraging data are emerging concerning the use of renin-angiotensin-aldosterone axis blockers, nitric oxide donors, or, very recently, new agents specifically targeting actin-myosin cross-bridges.

Quantification of left ventricular modification in weightlessness conditions from the spatio-temporal analysis of 2D echocardiographic images.

Two-dimensional echocardiography (2DE) performed during flights with a parabolic trajectory to simulate weightlessness provides a unique means to study left ventricular (LV) modifications to prevent post-flight orthostatic intolerance in astronauts. However, conventional analysis of 2DE is based on manual tracings and depends on experience. Accordingly, the aim was objectively to quantify, from 2DE images, the LV modifications related to different gravity levels, by applying a semi-automated level-set border detection technique. The algorithm validation was performed by the comparison of manual tracing results, obtained by two independent observers with 20 images, with the semi-automated measurements. To quantify LV modifications, three consecutive cardiac cycles were analysed for each gravity phase (1 Gz, 1.8 Gz, 0 Gz). The level-set procedure was applied frame-by-frame to detect the LV endocardial contours and obtain LV area against time curves, from which end-diastolic (EDA) and end-systolic (ESA) areas were computed and averaged to compensate for respiratory variations. Linear regression (y = 0.91x + 1.47, r = 0.99, SEE:0.80cm2) and Bland-Altman analysis (bias = -0.58 cm2, 95% limits of agreement= +/- 2.14cm2) showed excellent correlation between the semi-automatic and manually traced values. Inter-observer variability was 5.4%, and the inter-technique variability was 4.1%. Modifications in LV dimensions during the parabola were found: compared with 1 Gz values, EDA and ESA were significantly reduced at 1.8 Gz by 8.8 +/- 5.5% and 12.1 +/- 10.1%, respectively, whereas, during 0 Gz, EDA and ESA increased by 13.3 +/- 7.3% and 11.6 +/- 5.1%, respectively, owing to abrupt changes in venous return. The proposed method resulted in fast and reliable estimations of LV dimensions, whose changes caused by different gravity conditions were objectively quantified.

Changes in Doppler mitral inflow patterns during parabolic flight.

Aim of the study was to evaluate by transthoracic Doppler the alterations in mitral inflow velocity pattern caused by acute changes in loading conditions occurring during parabolic flights. Each parabola included normogravity (1 Gz, 1 min), mild hypergravity (1.8 Gz, 20 sec), microgravity (0 Gz, 24 sec) and mild hypergravity (1.8 Gz, 20 sec) phases. Pulsed-Doppler images were digitally acquired in 11 unmedicated subjects (46 +/- 5 years), in standing upright position and supine resting. Doppler profiles were semi-automatically traced and inflow parameters extracted and averaged onto three consecutive beats. Only in standing position, significant alterations during microgravity (p<0.05) were noted in several parameters.

[In vitro effects of antiallergic eyedrops on complement activation induced by particulate matter]. / Effets modulateurs de collyres anti-allergiques sur l'activation du complément induite in vitro par des polluants particulaires.

BACKGROUND: Recent decades have been marked by an increasing number of patients suffering from ocular allergic-like symptoms without being associated with an increase in IgE levels. These symptoms include heaviness of the lid, foreign body sensation, burning, stinging and photophobia. Both epidemiological studies and controlled human exposure clinical studies have shown cause-effect relationships between allergic-like symptoms and environmental factors such as outdoor air pollutants or poor indoor air quality. An ocular surface subclinical inflammation is thought to be responsible for pseudoallergic, pollution-related conjunctivitis. The complement system is considered as one of the major effector mechanisms involved in initiation of the subclinical inflammation that leads to IgE-independent eye irritation. PURPOSE: To study the capability of nine antiallergic eyedrops commonly used in the treatment of allergic conjunctivitis to inhibit complement activation induced in vitro by pollutants. METHODS: Normal human serum obtained from healthy individuals was used as a source of complement. Activation of complement was assessed using the complement hemolytic 50% (CH50) assay, in the absence or the presence of antiallergic eyedrops and in the absence or the presence of various stimuli, including sand, common house dust, eye mascara, and Dactylis glomerata pollen extract. Zymosan was used as a standardized complement activator. The following eyedrops were studied: Naabak (4.9% N-acetyl aspartic acid-glutamic acid, NAAGA, sodium salt), Almide (lodoxamide 0.1%), Levophta (0.05% levocabastine), Emadine (0.05% emedastine), Tilavist (2% nedocromil), Allergodil (0.05% azelastine), Patanol (olopatadine), and Zaditen (0.025% ketotifen). Effects of preservative-free lodoxamide and ketotifen were also assessed and compared to those of the preserved formulations. A solution of 0.01% benzalkonium chloride (BAC), the most widely used preservative in topical eyedrops, was also tested. RESULTS: Zymosan-induced activation of complement (30+/-6%) was significantly lowered by preincubation of serum with unpreserved NAAGA (16.6+/-4%, p=0.0026) or benzalkonium-preserved nedocromil (20+/-2%, p=0.022). Preserved levocabastine, emedastine, olopatadine and ketotifen did not interfere with zymosan-induced complement activation, whereas preserved azelastine, lodoxamide and benzalkonium chloride significantly aggravated complement activation induced by zymosan. Similar results were obtained when complement activation was triggered by sand, common house dust, mascara, or by an allergenic extract of Dactylis glomerata pollen. In the absence of complement activator, none of the antiallergic eyedrops induced a significant change in CH50 titer, indicating that the deleterious pro-inflammatory effect of preserved azelastine and lodoxamide may occur only once complement activation has been initiated, i.e., on an inflamed ocular surface. CONCLUSION: Among the antiallergic eyedrops tested in this study, only Naabak and Tilavist were found to significantly inhibit complement activation triggered by particulate matters or pollen allergenic extract. Such an anticomplement activity confers these two molecules a potential in the therapeutic management of pollution-related pseudoallergic conjunctivitis.

Changes in left ventricular size during parabolic flights by two-dimensional echocardiography and level set method.

This study aims to evaluate changes on cardiac chambers size, induced by gravitational stresses. During parabolic flight, seven subjects underwent 2-D transthoracic echocardiography at three different gravity phases (1 Gz, 1.8 Gz, and 0 Gz). LV endocardial borders were detected applying a semi-automatic segmentation procedure based on level set methods. LV cavity area was computed frame-by-frame for a whole cardiac cycle during each gravity phase. Expected modifications in LV area with different gravity were found: at 1.8 Gz, end-diastolic (ED) and end-systolic (ES) areas were significantly (p<0.05) reduced of 10.7 +/- 5.4% and 21.6 +/- 11.1% respectively, compared to 1 Gz values, while they were increased of 11.2 +/- 5.4% and 11.1 +/- 6% during 0 Gz. Fractional area change was augmented of 20.9 +/- 29.1% at 1.8 Gz, while it remained unchanged at 0 Gz, compared with 1 Gz values. Furthermore, LV filling due to atrial contraction was increased at 0 Gz of 39 +/- 35.6%.

Time-variant spectral analysis of heart rate variability during parabolic flight with and without LBNP.

Modifications of autonomic activity during parabolic flight were studied by a time-variant model able to estimate low (LF, 0.04-0.14 Hz) and high (HF, 0.14-0.35 Hz) frequency spectral components on a beat-to-beat basis. Ten subjects were studied with and without lower body negative pressure (LBNP). ECG and Gz load were digitized (500 Hz) and RR interval variability series extracted. Beat-to-beat mean RR, variance, LF and HF power were obtained. One-way ANOVA (p<0.01) was used to compare values obtained during starting 1Gz (I), first 1.8Gz (II), 0Gz (III), second 1.8Gz (IV), ending 1Gz (V). Without LBNP, total and LF power increased during 0Gz to 1.69 +/- 1.41 and 2.87 +/- 4.66 respectively (mean +/- SD, normalized by phase I value). With LBNP, their change during 0Gz (1.38 +/- 1.37 and 1.54 +/- l.04 respectively) reached significance only with phase II and phase V. Phase I HF power was higher than in the other phases, both without and with LBNP.

Gram-positive and gram-negative bacteria do not trigger monocytic cytokine production through similar intracellular pathways.

Toll-like receptors (TLRs) are involved in human monocyte activation by lipopolysaccharide (LPS) and Staphylococcus aureus Cowan (SAC), suggesting that gram-positive and gram-negative bacteria may trigger similar intracellular events. Treatment with specific kinase inhibitors prior to cell stimulation dramatically decreased LPS-induced cytokine production. Blocking of the p38 pathway prior to LPS stimulation decreased interleukin-1alpha (IL-1alpha), IL-1ra, and tumor necrosis factor alpha (TNF-alpha) production, whereas blocking of the ERK1/2 pathways inhibited IL-1alpha, IL-1beta, and IL-1ra but not TNF-alpha production. When cells were stimulated by SAC, inhibition of the p38 pathway did not affect cytokine production, whereas only IL-1alpha production was decreased in the presence of ERK kinase inhibitor. We also demonstrated that although LPS and SAC have been shown to bind to CD14 before transmitting signals to TLR4 and TLR2, respectively, internalization of CD14 occurred only in monocytes triggered by LPS. Pretreatment of the cells with SB203580, U0126, or a mixture of both inhibitors did not affect internalization of CD14. Altogether, these results suggest that TLR2 signaling does not involve p38 mitogen-activated protein kinase signaling pathways, indicating that divergent pathways are triggered by gram-positive and gram-negative bacteria, thereby inducing cytokine production.

Smooth muscle relaxation and local hydraulic impedance properties of the aorta.

Smooth muscle relaxation is expected to yield beneficial effects on hydraulic impedance properties of large vessels. We investigated the effects of intravenous diltiazem infusion on aortic wall stiffness and local hydraulic impedance properties. In seven anesthetized, closed-chest dogs, instantaneous cross-sectional area and pressure of the descending thoracic aorta were measured using transesophageal echocardiography combined with acoustic quantification and a micromanometer, respectively. Data were acquired during a vena caval balloon inflation, both at the control condition and with diltiazem infusion. At the operating point, diltiazem reduced blood pressure in all dogs but did not alter aortic dimensions or wall stiffness. Over the observed pressure range, aortic area-pressure relationships were linear. Whereas diltiazem affected the slope of this relationship variably (no change in 3 dogs, increase in 1 dog, decrease in 3 dogs), the zero-pressure area intercept was significantly increased in every case such that higher area was observed at any given pressure. When comparisons were made at a common level of wall stress, wall stiffness was either increased or unchanged during diltiazem infusion. In contrast, diltiazem decreased wall stiffness in every case when comparisons were made at a common level of aortic midwall radius. Aortic characteristic impedance and pulse wave velocity, components of left ventricular hydraulic load that are determined by aortic elastic and geometric properties, were affected variably. A comparison of wall stiffness at matched wall stress appears inappropriate for assessing changes in smooth muscle tone. Because of the competing effects of changes in vessel diameter and wall stiffness, smooth muscle relaxation is not necessarily accompanied by the expected beneficial changes in local aortic hydraulic impedance. These results can be reconciled by recognizing that components other than vascular smooth muscle (e.g., elastin, collagen) contribute to aortic wall stiffness.