Immobilization of blood coagulant factor VII on polycaprolactone membrane through polydopamine grafting.

Postoperative bleeding following cardiac surgeries is still an issue that deranges the medical resources and cost. The oral and injection administrations of blood coagulation protein, Factor VII (FVII), is effective to stop the bleeding. However, its short half-life has limited the effectiveness of this treatment and frequent FVII intake may distress the patients. Instead, incorporating FVII into synthetic biodegradable polymers such as polycaprolactone (PCL) that is commonly used in drug delivery applications should provide a solution. Therefore, this study aimed to immobilize FVII on PCL membranes through a cross-linkage polydopamine (PDA) grafting as an intermediate layer. These membranes are intended to provide a solution for cardiac bleeding in coagulating blood and sealing the sutured region. The membranes were evaluated in terms of its physio-chemical properties, thermal behavior, FVII release profile and biocompatibility properties. The ATR-FTIR was used to analyze the chemical functionalities of the membranes. Further validation was done with XPS where the appearances of 0.45 ± 0.06% sulfur composition and C-S peak have confirmed the immobilization of FVII on the PCL membranes. The cross-linked FVIIs were viewed in spherical immobilization on the PCL membranes with a size range between 30 and 210 nm. The surface roughness and hydrophilicity of the membranes were enhanced with a slight shift of melting temperature. The PCL-PDA-FVII0.03 and PCL-PDA-FVII0.05 membranes, with wide area of FVII immobilization released approximately only 22% of FVII into the solution within 60 days period and, it is found that the PCL-PDA-FVIIx membranes projected the Higuchi release model with non-Fickian anomalous transport. While the cytotoxic and hemocompatibility analyses showed advance cell viability, identical coagulation time and low hemolysis ratio on the PCL-PDA-FVIIx membranes. The erythrocytes were viewed in polyhedrocyte coagulated structure under SEM visualization. These results validate the biocompatibility of the membranes and its ability to prolong blood coagulation, thus highlighting its potential application as cardiac bleeding sealant.

Effect of Circadian Rhythm Disturbance on the Human Musculoskeletal System and the Importance of Nutritional Strategies.

The circadian system in the human body responds to daily environmental changes to optimise behaviour according to the biological clock and also influences various physiological processes. The suprachiasmatic nuclei are located in the anterior hypothalamus of the brain, and they synchronise to the 24 h light/dark cycle. Human physiological functions are highly dependent on the regulation of the internal circadian clock. Skeletal muscles comprise the largest collection of peripheral clocks in the human body. Both central and peripheral clocks regulate the interaction between the musculoskeletal system and energy metabolism. The skeletal muscle circadian clock plays a vital role in lipid and glucose metabolism. The pathogenesis of osteoporosis is related to an alteration in the circadian rhythm. In the present review, we discuss the disturbance of the circadian rhythm and its resultant effect on the musculoskeletal system. We also discuss the nutritional strategies that are potentially effective in maintaining the system's homeostasis. Active collaborations between nutritionists and physiologists in the field of chronobiological and chrononutrition will further clarify these interactions. This review may be necessary for successful interventions in reducing morbidity and mortality resulting from musculoskeletal disturbances.

Biodegradable and antithrombogenic chitosan/elastin blended polyurethane electrospun membrane for vascular tissue integration.

Current commercialized vascular membranes to treat coronary heart disease (CHD) such as Dacron and expanded polytetrafluoroethylene (ePTFE) have been associated with biodegradable and thrombogenic issues that limit tissue integration. In this study, biodegradable vascular membranes were fabricated in a structure of electrospun nanofibers composed of polyurethane (PU), chitosan (CS) and elastin (0.5%, 1.0%, and 1.5%). The physicochemical properties of the membranes were analyzed, followed by the conduction of several test analyses. The blending of CS and elastin has increased the fiber diameter, pore size and porosity percentage with the appearance of identical chemical groups. The wettability of PU membranes was enhanced up to 39.6%, demonstrating higher degradation following the incorporation of both natural polymers. The PU/CS/elastin electrospun membranes exhibited a controlled release of CS (Higuchi and first-order mechanisms) and elastin (Higuchi and Korsmeyer-Peppas mechanisms). Delayed blood clotting time was observed through both activated partial thromboplastin time (APTT) and partial thromboplastin time (PT) analyses where significantly delay of 26.8% APTT was recorded on the PU membranes blended with CS and elastin, in comparison with the PU membranes, supporting the membrane's antithrombogenic properties. Besides, these membranes produced a minimum of 2.6 ± 0.1 low hemolytic percentage, projecting its hemocompatibility to be used as vascular membrane.

Microarray Profiling of Differentially Expressed Genes in Coronary Artery Bypass Grafts of High-Risk Patients with Postoperative Cognitive Dysfunctions.

Postoperative cognitive dysfunction (POCD) is cognitive decline after surgery. The authors hypothesized that gene-level changes could be involved in the pathogenesis of POCD. The present study evaluated the incidence of POCD and its associated differentially expressed genes. This was a prospective cohort study conducted on high-risk coronary artery bypass graft patients aged 40 to 75 years. POCD classification was based on a one standard deviation decline in the postoperative scores compared to the preoperative scores. The differentially expressed genes were identified using microarray analysis and validated using quantitative RT-PCR. Forty-six patients were recruited and completed the study. The incidence of POCD was identified using a set of neurocognitive assessments and found to be at 17% in these high-risk CABG patients. Six samples were selected for the gene expression analyses (3 non-POCD and 3 POCD samples). The findings showed five differentially expressed genes in the POCD group compared to the non-POCD group. The upregulated gene was ERFE, whereas the downregulated genes were KIR2DS2, KIR2DS3, KIR3DL2, and LIM2. According to the results, the gene expression profiles of POCD can be used to find potential proteins for POCD diagnostic and predictive biomarkers. Understanding the molecular mechanism of POCD development will further lead to early detection and intervention to reduce the severity of POCD, and hence, reduce the mortality and morbidity rate due to the condition.

Dexmedetomidine and Propofol Sedation in Critically Ill Patients and Dose-associated 90-Day Mortality: A Secondary Cohort Analysis of a Randomized Controlled Trial (SPICE III).

Rationale: The SPICE III (Sedation Practice in Intensive Care Evaluation) trial reported significant heterogeneity in mortality with dexmedetomidine treatment. Supplemental propofol was commonly used to achieve desirable sedation. Objectives: To quantify the association of different infusion rates of dexmedetomidine and propofol, given in combination, with mortality and to determine if this is modified by age. Methods: We included 1,177 patients randomized in SPICE III to receive dexmedetomidine and given supplemental propofol, stratified by age (>65 or ⩽65 yr). We used double stratification analysis to produce quartiles of steady infusion rates of dexmedetomidine while escalating propofol dose and vice versa. We used Cox proportional hazard and multivariable regression adjusted for relevant clinical variable to evaluate the association of sedative dose with 90-day mortality. Measurements and Main Results: Younger patients (598 of 1,177 [50.8%]) received significantly higher doses of both sedatives compared with older patients to achieve comparable sedation depth. On double stratification analysis, escalating infusion rates of propofol to 1.27 mg/kg/h at a steady dexmedetomidine infusion rate (0.54 µg/kg/h) was associated with reduced adjusted mortality in younger but not older patients. This was consistent with multivariable regression modeling (hazard ratio, 0.59; 95% confidence interval, 0.43-0.78; P < 0.0001) adjusted for baseline risk and interaction with dexmedetomidine dose. In contrast, among younger patients, using multivariable regression, escalating dexmedetomidine infusion rate was associated with increased adjusted mortality (hazard ratio, 1.30; 95% confidence interval, 1.03-1.65; P = 0.029). Conclusions: In patients ⩽65 years of age sedated with dexmedetomidine and propofol combination, preferentially increasing the dose of propofol was associated with decreased adjusted 90-day mortality. Conversely, increasing dexmedetomidine may be associated with increased mortality. Clinical trial registered with www.clinicaltrials.gov (NCT01728558).

The Effectiveness of Simulation in Education 4.0: Application in a Transesophageal Echocardiography Training Program in Malaysia.

Introduction: A Malaysian Higher Education Provider has applied technology as part of its pedagogical approach, in alignment with Education 4. 0. The use of simulation, which aligns with the principles of Education 4.0, employs digital technologies and supports learning by bridging the classroom and the clinical areas. We reported the effectiveness of learning in our program that utilizes multimodal pedagogy, including interactive lectures, pre-recorded video lectures, simulation, and hands-on supervised clinical sessions, using the program's cumulative assessment data. Methodology: This program evaluation was based on Kirkpatrick's framework. End-points for learning (Kirkpatrick level 2) were analyzed based on improved overall post-test theoretical and clinical assessment performance. Quantitative data analysis of theoretical pre-test, theoretical post-test, clinical assessment, and post-test scores was performed to compare cohorts. Results: The performance of 19 trainees, over six cohorts from 2012 to 2019, were analyzed. All our trainees had equal opportunities to learn using the multimodal pedagogy, including a simulator. The analysis of pre- and post-theoretical test scores showed a significant improvement in the mean scores (pre-test 48.7% (± SD 9), post-test 64.1% (± SD11.5); p ≤ 0.001). Overall, 19 out of 21 trainees completed the clinical assessment and case presentation satisfactorily. Conclusion: The Kirkpatrick framework served as a useful framework to perform the evaluation of the TEE program. The significant improvement in post-test scores, when compared with pre-test scores, suggested that the program is effective with regard to learning. As part of a multimodal pedagogy, simulation has proven to be an added value to our training program, and this was reflected by the improvement in the clinical assessment scores when compared to the pre-test scores. This result aligned with the concept of technology-enhanced learning in Education 4.0, where simulation in TEE training is applicable in the Malaysian context.

Intraoperative cerebral oximetry in open heart surgeries reduced postoperative complications: A retrospective study.

Cardiothoracic surgeries are life-saving procedures but often it results in various complications. Intraoperative cerebral oximetry monitoring used to detect regional cerebral oxygen saturation (rScO2) is a non-invasive method that provides prognostic importance in cardiac surgery. The main aim of the present study was to evaluate the association of intraoperative cerebral oxygen monitoring during cardiac surgery on postoperative complications. This was a case-controlled retrospective study conducted on adult patients, who underwent open-heart surgery in National Heart Institute, Malaysia. The case group comprised patients on protocolized cerebral oximetry monitoring. They were treated using a standardized algorithm to maintain rScO2 not lower than 20% of baseline rScO2. The control group comprised patients with matched demographic background, preoperative risk factors, and type of surgical procedures. Propensity score stratification was utilized to contend with selection bias. Retrospective analysis was performed on 240 patients (case group) while comparing it to 407 patients (control group). The non-availability of cerebral oximetry monitoring during surgery was the prominent predictor for all outcome of complications; stroke (OR: 7.66), renal failure needing dialysis (OR: 5.12) and mortality (OR: 20.51). Postoperative complications revealed that there were significant differences for risk of mortality (p<0.001, OR = 20.51), renal failure that required dialysis (p<0.001, OR = 5.12) and stroke (p <0.05, OR = 7.66). Protocolized cerebral oximetry monitoring during cardiothoracic surgeries was found to be associated with lower incidence of stroke, renal failure requiring dialysis and mortality rate.

Early sedation with dexmedetomidine in ventilated critically ill patients and heterogeneity of treatment effect in the SPICE III randomised controlled trial.

PURPOSE: To quantify potential heterogeneity of treatment effect (HTE), of early sedation with dexmedetomidine (DEX) compared with usual care, and identify patients who have a high probability of lower or higher 90-day mortality according to age, and other identified clusters. METHODS: Bayesian analysis of 3904 critically ill adult patients expected to receive invasive ventilation > 24 h and enrolled in a multinational randomized controlled trial comparing early DEX with usual care sedation. RESULTS: HTE was assessed according to age and clusters (based on 12 baseline characteristics) using a Bayesian hierarchical models. DEX was associated with lower 90-day mortality compared to usual care in patients > 65 years (odds ratio [OR], 0.83 [95% credible interval [CrI] 0.68-1.00], with 97.7% probability of reduced mortality across broad categories of illness severity. Conversely, the probability of increased mortality in patients ≤ 65 years was 98.5% (OR 1.26 [95% CrI 1.02-1.56]. Two clusters were identified: cluster 1 (976 patients) mostly operative, and cluster 2 (2346 patients), predominantly non-operative. There was a greater probability of benefit with DEX in cluster 1 (OR 0.86 [95% CrI 0.65-1.14]) across broad categories of age, with 86.4% probability that DEX is more beneficial in cluster 1 than cluster 2. CONCLUSION: In critically ill mechanically ventilated patients, early sedation with dexmedetomidine exhibited a high probability of reduced 90-day mortality in older patients regardless of operative or non-operative cluster status. Conversely, a high probability of increased 90-day mortality was observed in younger patients of non-operative status. Further studies are needed to confirm these findings.

Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review.

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.

Early Sedation with Dexmedetomidine in Critically Ill Patients.

BACKGROUND: Dexmedetomidine produces sedation while maintaining a degree of arousability and may reduce the duration of mechanical ventilation and delirium among patients in the intensive care unit (ICU). The use of dexmedetomidine as the sole or primary sedative agent in patients undergoing mechanical ventilation has not been extensively studied. METHODS: In an open-label, randomized trial, we enrolled critically ill adults who had been undergoing ventilation for less than 12 hours in the ICU and were expected to continue to receive ventilatory support for longer than the next calendar day to receive dexmedetomidine as the sole or primary sedative or to receive usual care (propofol, midazolam, or other sedatives). The target range of sedation-scores on the Richmond Agitation and Sedation Scale (which is scored from -5 [unresponsive] to +4 [combative]) was -2 to +1 (lightly sedated to restless). The primary outcome was the rate of death from any cause at 90 days. RESULTS: We enrolled 4000 patients at a median interval of 4.6 hours between eligibility and randomization. In a modified intention-to-treat analysis involving 3904 patients, the primary outcome event occurred in 566 of 1948 (29.1%) in the dexmedetomidine group and in 569 of 1956 (29.1%) in the usual-care group (adjusted risk difference, 0.0 percentage points; 95% confidence interval, -2.9 to 2.8). An ancillary finding was that to achieve the prescribed level of sedation, patients in the dexmedetomidine group received supplemental propofol (64% of patients), midazolam (3%), or both (7%) during the first 2 days after randomization; in the usual-care group, these drugs were administered as primary sedatives in 60%, 12%, and 20% of the patients, respectively. Bradycardia and hypotension were more common in the dexmedetomidine group. CONCLUSIONS: Among patients undergoing mechanical ventilation in the ICU, those who received early dexmedetomidine for sedation had a rate of death at 90 days similar to that in the usual-care group and required supplemental sedatives to achieve the prescribed level of sedation. More adverse events were reported in the dexmedetomidine group than in the usual-care group. (Funded by the National Health and Medical Research Council of Australia and others; SPICE III ClinicalTrials.gov number, NCT01728558.).

Sedation Intensity in the First 48 Hours of Mechanical Ventilation and 180-Day Mortality: A Multinational Prospective Longitudinal Cohort Study.

OBJECTIVES: In the absence of a universal definition of light or deep sedation, the level of sedation that conveys favorable outcomes is unknown. We quantified the relationship between escalating intensity of sedation in the first 48 hours of mechanical ventilation and 180-day survival, time to extubation, and delirium. DESIGN: Harmonized data from prospective multicenter international longitudinal cohort studies SETTING:: Diverse mix of ICUs. PATIENTS: Critically ill patients expected to be ventilated for longer than 24 hours. INTERVENTIONS: Richmond Agitation Sedation Scale and pain were assessed every 4 hours. Delirium and mobilization were assessed daily using the Confusion Assessment Method of ICU and a standardized mobility assessment, respectively. MEASUREMENTS AND MAIN RESULTS: Sedation intensity was assessed using a Sedation Index, calculated as the sum of negative Richmond Agitation Sedation Scale measurements divided by the total number of assessments. We used multivariable Cox proportional hazard models to adjust for relevant covariates. We performed subgroup and sensitivity analysis accounting for immortal time bias using the same variables within 120 and 168 hours. The main outcome was 180-day survival. We assessed 703 patients in 42 ICUs with a mean (SD) Acute Physiology and Chronic Health Evaluation II score of 22.2 (8.5) with 180-day mortality of 32.3% (227). The median (interquartile range) ventilation time was 4.54 days (2.47-8.43 d). Delirium occurred in 273 (38.8%) of patients. Sedation intensity, in an escalating dose-dependent relationship, independently predicted increased risk of death (hazard ratio [95% CI], 1.29 [1.15-1.46]; p < 0.001, delirium hazard ratio [95% CI], 1.25 [1.10-1.43]), p value equals to 0.001 and reduced chance of early extubation hazard ratio (95% CI) 0.80 (0.73-0.87), p value of less than 0.001. Agitation level independently predicted subsequent delirium hazard ratio [95% CI], of 1.25 (1.04-1.49), p value equals to 0.02. Delirium or mobilization episodes within 168 hours, adjusted for sedation intensity, were not associated with survival. CONCLUSIONS: Sedation intensity independently, in an ascending relationship, predicted increased risk of death, delirium, and delayed time to extubation. These observations suggest that keeping sedation level equivalent to a Richmond Agitation Sedation Scale 0 is a clinically desirable goal.

The SPICE III study protocol and analysis plan: a randomised trial of early goaldirected sedation compared with standard care in mechanically ventilated patients.

BACKGROUND: Sedation strategy in critically ill patients who are mechanically ventilated is influenced by patient-related factors, choice of sedative agent and the intensity or depth of sedation prescribed. The impact of sedation strategy on outcome, in particular when delivered early after initiation of mechanical ventilation, is uncertain. OBJECTIVES: To present the protocol and analysis plan of a large randomised clinical trial investigating the effect of a sedation strategy, in critically ill patients who are mechanically ventilated, based on a protocol targeting light sedation using dexmedetomidine as the primary sedative, termed "early goal-directed sedation", compared with usual practice. METHODS: This is a multinational randomised clinical trial in adult intensive care patients expected to require mechanical ventilation for longer than 24 hours. The main exclusion criteria include suspected or proven primary brain pathology or having already been intubated or sedated in an intensive care unit for longer than 12 hours. Randomisation occurs via a secured website with baseline stratification by site and suspected or proven sepsis. The primary outcome is 90-day all-cause mortality. Secondary outcomes include death, institutional dependency, cognitive function and health-related quality of life 180 days after randomisation, as well as deliriumfree, coma-free and ventilation-free days at 28 days after randomisation. A predefined subgroup analysis will also be conducted. Analyses will be on an intention-to-treat basis and in accordance with this pre-specified analysis plan. CONCLUSION: SPICE III is an ongoing large scale clinical trial. Once completed, it will inform sedation practice in critically ill patients who are ventilated.

Modified rapid shallow breathing index adjusted with anthropometric parameters increases predictive power for extubation failure compared with the unmodified index in postcardiac surgery patients.

OBJECTIVE: The aim of this study was to determine the best predictors of successful extubation after cardiac surgery, by modifying the rapid shallow breathing index (RSBI) based on patients' anthropometric parameters. DESIGN: Single-center prospective observational study. SETTING: Two general intensive care units at a single research institute. PARTICIPANTS: Patients who had undergone uncomplicated cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following parameters were investigated in conjunction with modification of the RSBI: Actual body weight (ABW), predicted body weight, ideal body weight, body mass index (BMI), and body surface area. Using the first set of patient data, RSBI threshold and modified RSBI for extubation failure were determined (threshold value; RSBI: 77 breaths/min (bpm)/L, RSBI adjusted with ABW: 5.0 bpm×kg/mL, RSBI adjusted with BMI: 2.0 bpm×BMI/mL). These threshold values for RSBI and RSBI adjusted with ABW or BMI were validated using the second set of patient data. Sensitivity values for RSBI, RSBI modified with ABW, and RSBI modified with BMI were 91%, 100%, and 100%, respectively. The corresponding specificity values were 89%, 92%, and 93%, and the corresponding receiver operator characteristic values were 0.951, 0.977, and 0.980, respectively. CONCLUSIONS: Modified RSBI adjusted based on ABW or BMI has greater predictive power than conventional RSBI.

A Hybrid Method for Endocardial Contour Extraction of Right Ventricle in 4-Slices from 3D Echocardiography Dataset.

This paper presents a hybrid method to extract endocardial contour of the right ventricular (RV) in 4-slices from 3D echocardiography dataset. The overall framework comprises four processing phases. In Phase I, the region of interest (ROI) is identified by estimating the cavity boundary. Speckle noise reduction and contrast enhancement were implemented in Phase II as preprocessing tasks. In Phase III, the RV cavity region was segmented by generating intensity threshold which was used for once for all frames. Finally, Phase IV is proposed to extract the RV endocardial contour in a complete cardiac cycle using a combination of shape-based contour detection and improved radial search algorithm. The proposed method was applied to 16 datasets of 3D echocardiography encompassing the RV in long-axis view. The accuracy of experimental results obtained by the proposed method was evaluated qualitatively and quantitatively. It has been done by comparing the segmentation results of RV cavity based on endocardial contour extraction with the ground truth. The comparative analysis results show that the proposed method performs efficiently in all datasets with overall performance of 95% and the root mean square distances (RMSD) measure in terms of mean ± SD was found to be 2.21 ± 0.35 mm for RV endocardial contours.

Numerical investigation of the effect of cannula placement on thrombosis.

Despite the rapid advancement of left ventricular assist devices (LVADs), adverse events leading to deaths have been frequently reported in patients implanted with LVADs, including bleeding, infection, thromboembolism, neurological dysfunction and hemolysis. Cannulation forms an important component with regards to thrombus formation in assisted patients by varying the intraventricular flow distribution in the left ventricle (LV). To investigate the correlation between LVAD cannula placement and potential for thrombus formation, detailed analysis of the intraventricular flow field was carried out in the present study using a two way fluid structure interaction (FSI), axisymmetric model of a passive LV incorporating an inflow cannula. Three different cannula placements were simulated, with device insertion near the LV apex, penetrating one-fourth and mid-way into the LV long axis. The risk of thrombus formation is assessed by analyzing the intraventricular vorticity distribution and its associated vortex intensity, amount of stagnation flow in the ventricle as well as the level of wall shear stress. Our results show that the one-fourth placement of the cannula into the LV achieves the best performance in reducing the risk of thrombus formation. Compared to cannula placement near the apex, higher vortex intensity is achieved at the one-fourth placement, thus increasing wash out of platelets at the ventricular wall. One-fourth LV penetration produced negligible stagnation flow region near the apical wall region, helping to reduce platelet deposition on the surface of the cannula and the ventricular wall.

Sedation depth and long-term mortality in mechanically ventilated critically ill adults: a prospective longitudinal multicentre cohort study.

PURPOSE: To ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality. METHODS: We conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤-3. RESULTS: The cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7%) and 110/237 (46.4%). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93%) versus 72 (28%) patients (P < 0.0001) for 966 (39.6%) versus 183 (7.5%) study days respectively. Deep sedation occurred in (182/257) 71% patients at first assessment and in 159 (61%) patients and 1,658 (59%) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.97, P = 0.003], hospital death (HR 1.11, 95% CI 1.05-1.18, P < 0.001) and 180-day mortality (HR 1.09, 95% CI 1.04-1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44%) of patients. CONCLUSION: Irrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.

An accessory mitral valve leaflet causing left ventricular outflow tract obstruction and associated with severe aortic incompetence.

This case report describes a 20-year-old woman with Turner's syndrome who presented with reduced effort tolerance limited by dyspnea. She had previously been on pediatric cardiology follow-up for congenital subvalvular aortic stenosis first diagnosed at age 7. Unfortunately she defaulted after two visits before any intervention could be done. Transthoracic echocardiography demonstrated severe aortic incompetence (AI) with a membrane-like structure in the left ventricular outflow tract (LVOT). The mean pressure gradient across the LVOT on continuous wave Doppler was 41 mmHg. The membranous interventricular septum appeared aneurysmal and it was observed that the "subaortic membrane" had a connection to the anterolateral papillary muscle via a strand of chordal tissue. Further images were captured using two-dimensional and three-dimensional transthoracic and transesophageal echocardiography (iE33, Philips Medical Systems, Andover, MA, USA). After a review of the literature it was concluded that this appeared to be an accessory mitral valve (AMV) leaflet causing LVOT obstruction associated with AI. AMV tissue is a rare congenital malformation causing LVOT obstruction. Because it is so unusual, it may not be immediately recognizable even in a high volume echocardiography laboratory. The clue which helped with the diagnosis was the strand of chordal tissue which connected the mass to the papillary muscle. This anomaly is often associated with LVOT obstruction.