A Comparison of Germany and the United Kingdom Indicates That More SARS-CoV-2 Circulation and Less Restrictions in the Warm Season Might Reduce Overall COVID-19 Burden.

(1) Background: Between March 2020 and January 2022 severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) caused five infection waves in Europe. The first and the second wave was caused by wildtype SARS-CoV-2, while the following waves were caused by the variants of concern Alpha, Delta, and Omicron respectively. (2) Methods: In the present analysis, the first four waves were compared in Germany and the UK, in order to examine the COVID-19 epidemiology and its modulation by non-pharmaceutical interventions (NPI). (3) Results: The number of COVID-19 patients on intensive care units and the case fatality rate were used to estimate disease burden, the excess mortality to assess the net effect of NPI and other measures on the population. The UK was more severely affected by the first and the third wave while Germany was more affected by the second wave. The UK had a higher excess mortality during the first wave, afterwards the excess mortality in both countries was nearly identical. While most NPI were lifted in the UK in July 2021, the measures were kept and even aggravated in Germany. Nevertheless, in autumn 2021 Germany was much more affected, nearly resulting in a balanced sum of infections and deaths compared to the UK. Within the whole observation period, in Germany the number of COVID-19 patients on ICUs was up to four times higher than in the UK. Our results show that NPI have a limited effect on COVID-19 burden, seasonality plays a crucial role, and a higher virus circulation in a pre-wave situation could be beneficial. (4) Conclusions: Although Germany put much more effort and resources to fight the pandemic, the net balance of both countries was nearly identical, questioning the benefit of excessive ICU treatments and of the implementation of NPI, especially during the warm season.

Association of Three-Dimensional Mesh-Derived Right Ventricular Strain with Short-Term Outcomes in Patients Undergoing Cardiac Surgery.

BACKGROUND: Three-dimensional (3D) right ventricular (RV) strain analysis is not routinely performed perioperatively. Although 3D RV strain adds incrementally to outcome prediction in various cardiac diseases, its role in the perioperative setting is not sufficiently understood. The aim of this study was to investigate the association between 3D RV strain measured on RV meshes created from 3D transesophageal echocardiographic data and short-term outcomes among patients undergoing cardiac surgery. METHODS: A total of 496 patients undergoing cardiac surgery who underwent intraoperative 3D transesophageal echocardiography (under general anesthesia, before sternotomy) were retrospectively selected, and RV meshes were generated using commercially available speckle-tracking software. Custom-made software automatically quantified longitudinal and circumferential RV strains on the mesh surfaces. Echocardiographic and clinical parameters were entered into logistic regression models to determine their associations with the primary (in-hospital death or need for extracorporeal life support) and secondary (postoperative ventilation > 48 hours) end points. RESULTS: Mesh-derived RV strain analysis was feasible in 94% of patients and revealed distinct regional patterns with basal-apical gradients for both longitudinal and circumferential strain. Thirty-seven patients (7.6%) reached the primary end point, and 118 patients (23.8%) reached the secondary end point. In a multivariable logistic regression model, serum lactate (P < .01), an emergency indication for surgery (P < .01), tricuspid regurgitation (P < .001), and mesh-derived RV global longitudinal strain (RV-GLS; P < .01) were independently associated with the primary end point, while established measures of RV function (3D RV ejection fraction, fractional area change, tricuspid annular plane systolic excursion) and left ventricular (LV) function (3D-derived LV ejection fraction and LV-GLS) were not independently associated. Hematocrit (P < .01), serum lactate (P < .001), pulmonary hypertension (P = .04), tricuspid regurgitation (P < .01), emergency procedures (P = .02), LV-GLS (P = .02), and RV-GLS (P < .001) were associated with the secondary end point. CONCLUSIONS: RV-GLS measured on RV meshes derived from 3D transesophageal echocardiography was independently associated with short-term outcomes in patients undergoing cardiac surgery and might be helpful for identifying patients at risk for adverse postoperative events.

Specific Risk Factors for Fatal Outcome in Critically Ill COVID-19 Patients: Results from a European Multicenter Study.

(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06-1.10), cardiovascular disease (OR 1.64, CI 1.06-2.55), pulmonary disease (OR 1.87, CI 1.16-3.03), baseline Statin treatment (0.54, CI 0.33-0.87), oxygen saturation (unit = 1%, OR 0.94, CI 0.92-0.96), leukocytes (unit 1000/µL, OR 1.04, CI 1.01-1.07), lymphocytes (unit 100/µL, OR 0.96, CI 0.94-0.99), platelets (unit 100,000/µL, OR 0.70, CI 0.62-0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05-1.18), kidney failure (OR 1.68, CI 1.05-2.70), congestive heart failure (OR 2.62, CI 1.11-6.21), severe liver failure (OR 4.93, CI 1.94-12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14-2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.

Nine Months of COVID-19 Pandemic in Europe: A Comparative Time Series Analysis of Cases and Fatalities in 35 Countries.

(1) Background: to describe the dynamic of the pandemic across 35 European countries over a period of 9 months. (2) Methods: a three-phase time series model was fitted for 35 European countries, predicting deaths based on SARS-CoV-2 incidences. Hierarchical clustering resulted in three clusters of countries. A multiple regression model was developed predicting thresholds for COVID-19 incidences, coupled to death numbers. (3) Results: The model showed strongly connected deaths and incidences during the waves in spring and fall. The corrected case-fatality rates ranged from 2% to 20.7% in the first wave, and from 0.5% to 4.2% in the second wave. If the incidences stay below a threshold, predicted by the regression model (R2=85.0%), COVID-19 related deaths and incidences were not necessarily coupled. The clusters represented different regions in Europe, and the corrected case-fatality rates in each cluster flipped from high to low or vice versa. Severely and less severely affected countries flipped between the first and second wave. (4) Conclusions: COVID-19 incidences and related deaths were uncoupled during the summer but coupled during two waves. Once a country-specific threshold of infections is reached, death numbers will start to rise, allowing health care systems and countries to prepare.

Incidence and Death Rates from COVID-19 Are Not Always Coupled: An Analysis of Temporal Data on Local, Federal, and National Levels.

SARS-CoV-2 has caused a deadly pandemic worldwide, placing a burden on local health care systems and economies. Infection rates with SARS-CoV-2 and the related mortality of COVID-19 are not equal among countries or even neighboring regions. Based on data from official German health authorities since the beginning of the pandemic, we developed a case-fatality prediction model that correctly predicts COVID-19-related death rates based on local geographical developments of infection rates in Germany, Bavaria, and a local community district city within Upper Bavaria. Our data point towards the proposal that local individual infection thresholds, when reached, could lead to increasing mortality. Restrictive measures to minimize the spread of the virus could be applied locally based on the risk of reaching the individual threshold. Being able to predict the necessity for increasing hospitalization of COVID-19 patients could help local health care authorities to prepare for increasing patient numbers.

Extubation and Noninvasive Ventilation of Patients Supported by Extracorporeal Life Support for Cardiogenic Shock: A Single-Center Retrospective Observational Cohort Study.

BACKGROUND: Temporary extracorporeal life support (ECLS) by venoarterial extracorporeal membrane oxygenation is an emerging therapy for patients with severe, ongoing cardiogenic shock. After stabilization of the hemodynamic status and end-organ function, sedation weaning, extubation, and noninvasive ventilation (NIV) can be attempted. The goal of this study was to analyze the feasibility of extubation and NIV during versus after ECLS for cardiogenic shock. METHODS: Single-center retrospective observational study of 132 patients undergoing ECLS due to severe cardiogenic shock between January 2015 and December 2016 at a tertiary care university hospital. RESULTS: Patients received ECLS due to acute myocardial infarction (20.6%), ongoing cardiogenic shock (15.2%), postoperative low-cardiac-output syndrome (24.2%), and extracorporeal cardiopulmonary resuscitation (40.2%). Overall, intensive care unit survival was 44.7%. Sixty-nine (52.3%) patients could never be extubated. Forty-three (32.6%) were extubated while on ECLS support (group 1) and 20 (15.1%) were extubated after weaning from ECLS (group 2). Patients extubated during ECLS had a significantly shorter total time on ventilator (P = .003, mean difference: -284 hours [95% confidence limits: -83 to -484]) and more invasive ventilation free days (P = .0018; mean difference 8 days [95%CL: 2-14]). Mortality and NIV failure rates were similar between groups. CONCLUSIONS: Extubation and NIV are feasible in patients who stabilize during ECLS therapy. Further studies need to address whether extubation has the potential to improve patients outcome or if the feasibility to extubate is a surrogate for disease severeness.

The effects of anesthesia induction and positive pressure ventilation on right-ventricular function: an echocardiography-based prospective observational study.

BACKGROUND: General anesthesia induction with the initiation of positive pressure ventilation creates a vulnerable phase for patients. The impact of positive intrathoracic pressure on cardiac performance has been studied but remains controversial. 3D echocardiography is a valid and MRI-validated bed-side tool to evaluate the right ventricle (RV). The aim of this study was to assess the impact of anesthesia induction (using midazolam, sufentanil and rocuronium, followed by sevoflurane) with positive pressure ventilation (PEEP 5, tidal volume 6-8 ml/kg) on 2D and 3D echocardiography derived parameters of RV function. METHODS: A prospective observational study on fifty-three patients undergoing elective cardiac surgery in a tertiary care university hospital was designed. Transthoracic echocardiography exams were performed before and immediately after anesthesia induction and were recorded together with hemodynamic parameters and ventilator settings. RESULTS: After anesthesia induction TAPSE (mean difference - 1.6 mm (95% CI - 2.6 mm to - 0.7 mm; p = 0.0013) as well as the Tissue Doppler derived tricuspid annulus peak velocity (TDITVs') were significantly reduced (mean difference - 1.9% (95% CI: - 2.6 to - 1.2; p < 0.0001), but global right ventricular ejection fraction (RVEF; p = 0.1607) and right ventricular stroke volume (RVSV; p = 0.1838) did not change. CONCLUSIONS: This data shows a preserved right ventricular ejection fraction and right ventricular stroke volume after anesthesia induction and initiation of positive pressure ventilation. However, the baso-apical right ventricular function is significantly reduced. Larger studies are needed in order to determine the clinical impact of these findings especially in patients presenting with impaired right ventricular function before anesthesia induction. TRIAL REGISTRATION: Retrospecitvely registered, 6th June 2016, ClinicalTrials.gov Identifier NCT02820727 .

Detection of early incomplete heparin reversal following congenital cardiac surgery: A single-center retrospective observational study.

BACKGROUND: The monitoring of unfractionated heparin (UFH) reversal with protamine plays a crucial role for bleeding management after cardio-pulmonary bypass (CPB) in congenital cardiac surgery. The current standard for the monitoring of UFH and its reversal is the activated clotting time (ACT). While the ACT is affected by other CPB-associated pathologies a bedside technique with more specific heparin-related results would be very helpful. The new point-of-care viscoelastic test Haemonetics TEG® 6s, which is based on small blood samples may fulfill these requirements. This study aimed to compare the new TEG with laboratory assays. METHODS: A retrospective observational study was performed on 40 children with a median age of 130 days (interquartile range 13 to 310 days) undergoing congenital cardiac surgery. After separation of CPB, test results of the TEG® 6s, ACT, anti-Xa for UFH and PTT were compared and correlated with each other. RESULTS: No clinically relevant correlation was found for heparin specific TEG-derived parameters (CK/CKH R-time ratio) with ACT, PTT and anti-Xa measurements. After grouping in dependence to the CK/CKH R-time in patients with and without successful heparin reversal again no significant difference of anti-Xa-UFH-levels, post-/pre-CPB ratio of the PTT and ACT was observed. CONCLUSIONS: In pediatric patients undergoing cardiac surgery using CPB there is no association of conventional coagulation tests and TEG-derived results. While bedside viscoelastic tests deliver rapid results, further studies are needed to compare whether the TEG based management of incomplete heparin reversal is sufficient to monitor heparin reversal and to reduce blood loss.

Novel mesh-derived right ventricular free wall longitudinal strain analysis by intraoperative three-dimensional transoesophageal speckle-tracking echocardiography: a comparison with conventional parameters.

Longitudinal right ventricular (RV) function is substantial and might be reflected by free wall longitudinal strain (FWLS). Software solutions for FWLS analysis by two-dimensional (2D) and three-dimensional (3D) transesophageal echocardiography (TEE) are available, but data on validation are sparse. In this study, a novel method for FWLS analysis on 3D meshes ("mesh surface", MS-FWLS,) was tested for feasibility and compared to available parameters. 80 patients undergoing left-sided cardiac valve surgery with intraoperative TEE were included retrospectively. 2D-FWLS, 3D-derived (3Dd)-FWLS (assessed in optimized four-chamber views after volume analysis) and MS-FWLS were measured and compared to conventional parameters (3Dd-TAPSE, FAC and RVEF). The mean FWLS values did not differ significantly between methods (- 19.0 ± 6.1%, - 20.0 ± 7.3%, - 19.5 ± 7.3% for 2D-, 3Dd- and MS-FWLS, respectively). No significant differences in the mean FWLS between patients with normal or increased pulmonary artery pressures as well as normal or reduced left ventricular ejection fraction were observed. Agreement was best between 3Dd- and MS-FWLS (r = 0.89, bias = - 1.0%, LOA ± 6.9%). Conventional echocardiographic parameters yielded poorer intermodality agreement. In patients with discrepant results between 2D- and 3Dd-FWLS, 3Dd-FWLS and MS-FWLS yielded similar results (r = 0.82, bias = - 0.3%, LOA ± 8.6%), while 2D-FWLS and MS-FWLS did not. Intra- and interobserver variabilities of strain analyses were low. MS-FWLS might represent a promising method to overcome artefacts associated with 2D analysis. Its prognostic relevance needs to be investigated in prospective studies.

Regional Right Ventricular Volume and Function Analysis Using Intraoperative 3-Dimensional Echocardiography-Derived Mesh Models.

OBJECTIVES: In daily echocardiographic practice, the right ventricle (RV) is assessed using mostly 2-dimensional (2D) echocardiography. Parameters measuring longitudinal shortening (eg, tricuspid annular plane systolic excursion) or changes in areas (eg, fractional area change) are used as surrogates for right ventricular function. Three-dimensional (3D) echocardiography-based techniques allow for cardiac magnetic resonance imaging-validated assessment of the RV. Depiction of regional right ventricular function is of increasing clinical interest. This study aimed to calculate regional volumetric changes in the right ventricular inlet, apical section, and outflow tract. Correlations between traditional parameters and regional right ventricular function were studied. DESIGN: Retrospective cohort study on patients scheduled for cardiac surgery. SETTING: Tertiary care university hospital. PARTICIPANTS: The study comprised 80 patients scheduled for cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Based on 3D echocardiographic datasets, mesh models of the RV were generated on a vendor-independent platform. The meshes were further cut into the following 3 regions: the inlet part, the apical section, and the outflow tract. The regional volumes and ejection fractions were compared with the global right ventricular and left ventricular functions. Regional volumes were correlated linearly with the global end-diastolic volume. The right ventricular outflow tract demonstrated a significantly lower ejection fraction than the inlet part (34% ± 11% v 28% ± 11%; p = 0.0054). The function in the right ventricular outflow tract was reduced significantly compared with the global right ventricular function in patients with severely reduced left ventricular ejection fraction (<20%). CONCLUSION: The different parts of the RV seem to have different ejection fractions. Different regions of the RV are affected differently by reduced left ventricular ejection fraction. Regional right ventricular analyses could help clinicians better understand pathologic states of the RV.

3D echocardiography derived right ventricular function is associated with right ventricular failure and mid-term survival after left ventricular assist device implantation.

BACKGROUND: Right heart failure remains a major cause of morbidity and mortality after left ventricular assist device (LVAD) implantation. Multiple 2D echocardiography derived parameters are associated with right ventricular failure (RV failure), but none of them has been proven to be a reliable predictor to date. We hypothesized that novel 3D-echocardiography (3DE) based parameters are associated with RV failure and predict long term outcome in patients undergoing LVAD implantation. METHODS: This single-center study retrospectively enrolled 26 patients undergoing continuous-flow LVAD implantation. RV failure was defined as prolonged inotropic support for >14 days after LVAD implantation or consecutive implantation of a right ventricular assist device. Based on transesophageal 3DE datasets acquired prior to surgery right ventricular size, ejection fraction and longitudinal strains were calculated. RESULTS: The overall RV failure rate was 19.2%. Patients suffering from RV failure had a significantly impaired 3D-right ventricular ejection fraction (3D-RVEF; 28 ±â€¯2% vs. 19 ±â€¯3%, p = 0.0145) and 3D derived RV free wall longitudinal strain (3D-RV-fws; -13.2 ±â€¯0.97% vs. -6.4 ±â€¯1.98%; p = 0.0056) when compared to patients without RV failure. ROC analysis for 3D-RV-fws (AUC 0.914) and 3D-RVEF (AUC 0.876) showed high discriminative capabilities in regard to detection of RV failure. Kaplan-Meier analysis showed an improved long-term survival of patients with a 3D-RV-fws <-11.9%. CONCLUSIONS: 3D-echocardiography derived RV ejection fraction and RV free wall strain are associated with right ventricular failure and long term outcome in patients undergoing LVAD implantation. These parameters have the potential to be future predictors for right heart failure in LVAD surgery.

[Impact of Cardiac Anaesthesia on Patient Outcome]. / Einfluss der Kardioanästhesie auf das Patientenoutcome.

The perioperative management of complex patients in a highly technical and subspecialized environment is the domain of the cardiac anesthesiologist. Evidence suggests that hemodynamic management using goal directed hemodynamic therapy (GDHT) improves patient outcome. Organ protection remains a main concern during cardiac surgery using extracorporeal circulation. Mortality can be decreased when remote ischemic preconditioning techniques (RIPC) are being used. Neurological outcomes can be improved with near-infrared-spectometry (NIRS), volatile anesthetics increase myocardial protection through preconditioning and perioperative echocardiography increases overall patient survival.

Catheter-based tricuspid valve replacement: first experimental data of a newly designed bileaflet stent graft prosthesis.

OBJECTIVES: Moderate or severe degree tricuspid valve regurgitation (TVR) is associated with high rates of morbidity and mortality. Surgical correction as the only therapeutic option offers unsatisfactory results. Recently, several interventional procedures have been introduced clinically in a limited cohort. We present our initial experiments with an innovative interventional valved stent graft for treatment of TVR. METHODS: A newly designed porcine pericardium-covered nitinol stent graft with a lateral bicuspid valve was adapted to size in a cadaver study. After haemodynamic testing in an ex vivo perfusion setup, vascular access, valve delivery and function were investigated in an ovine animal model ( n = 7). RESULTS: The device was implanted successfully in all animals. Vascular access was established surgically via the femoral vein without any vascular complications. Angiography demonstrated the correct position of the device with proper sealing of both venae cavae in 6 animals. In 1 extremely large animal, the position of the device was considered too cranial but still acceptable. Correct valve function was verified in all animals by both angiography and echocardiography. There were no persistent arrhythmias other than during valve implant. All animals survived the implant procedure and were sacrificed electively. CONCLUSIONS: This study demonstrated that this new valved stent graft could be delivered safely with correct positioning and valve function in this ovine model. Further long-term studies in animals implanted with the device after creation of tricuspid regurgitation are necessary to prove the haemodynamic benefit of this procedure.

2D Echocardiographic Evaluation of Right Ventricular Function Correlates With 3D Volumetric Models in Cardiac Surgery Patients.

OBJECTIVES: The early diagnosis and treatment of right ventricular (RV) dysfunction are of critical importance in cardiac surgery patients and impact clinical outcome. Two-dimensional (2D) transesophageal echocardiography (TEE) can be used to evaluate RV function using surrogate parameters due to complex RV geometry. The aim of this study was to evaluate whether the commonly used visual evaluation of RV function and size using 2D TEE correlated with the calculated three-dimensional (3D) volumetric models of RV function. DESIGN AND SETTING: Retrospective study, single center, University Hospital. PARTICIPANTS AND INTERVENTION: Seventy complete datasets were studied consisting of 2D 4-chamber view loops (2-3 beats) and the corresponding 4-chamber view 3D full-volume loop of the right ventricle. RV function and RV size of the 2D loops then were assessed retrospectively purely qualitatively individually by 4 clinician echocardiographers certified in perioperative TEE. Corresponding 3D volumetric models calculating RV ejection fraction and RV end-diastolic volumes then were established and compared with the 2D assessments. MEASUREMENTS AND MAIN RESULTS: 2D assessment of RV function correlated with 3D volumetric calculations (Spearman's rho -0.5; p<0.0001). No correlation could be established between 2D estimates of RV size and actual 3D volumetric end-diastolic volumes (Spearman's rho 0.15; p = 0.25). CONCLUSION: The 2D assessment of right ventricular function based on visual estimation as frequently used in clinical practice appeared to be a reliable method of RV functional evaluation. However, 2D assessment of RV size seemed unreliable and should be used with caution.

Echocardiography for Less-Invasive Implantation of Left Ventricular Assist Devices.

New surgical techniques aim for less-invasive implantation of left ventricular assist devices (LVADs) via small surgical incision sites. Echocardiography plays an important role during patient selection and guidance of the procedure. The surgical incision site can be identified preoperatively by transthoracic echocardiography. Intraoperative identification of left ventricular apex, de-airing, and monitoring heart function is performed by transesophageal echocardiography. This article highlights special echocardiographic considerations during less-invasive LVAD implantation surgeries.

The role of transesophageal echocardiography in aortic surgery.

Aortic disease, when left untreated, is still associated with major morbidity and mortality. Aortic dissection and aortic aneurysm are the main reasons for performing aortic surgery procedures in the adult. Imaging techniques such as computed tomography and magnetic resonance imaging play a key role in the preoperative evaluation. Transesophageal echocardiography (TEE) has become a safe and invaluable perioperative imaging tool for aortic disease over the past decade with high sensitivity and specificity. TEE can increase patient safety and improve overall patient outcome in aortic surgery. Especially during endovascular aortic repair, TEE is more sensitive than other imaging modalities in diagnosing complications such as graft endoleaks. Newer echocardiographic techniques such as three-dimensional (3D) TEE and contrast-enhanced TEE are emerging and seem to have a valuable role especially in aortic dissection repair and endovascular aortic stent procedures. In the absence of contraindications, TEE should generally be performed during aortic surgery and endovascular aortic procedures.

Safety of transesophageal echocardiography during extracorporeal life support.

INTRODUCTION:: Use of extracorporeal life support (ECLS) has significantly increased in critically ill patients refractory to medical management. ECLS requires systemic anticoagulation to avoid thromboembolic complications and superimposed coagulopathies are common. Transesophageal echocardiography (TEE) is frequently employed to assess cannula position and cardiac function during extracorporeal therapy. The goal of this study was to assess whether TEE probe insertion and removal in systemically anticoagulated ECLS patients was safe compared to patients without ECLS and normal coagulation studies. METHODS:: Eighty-seven separate TEE examinations in 53 adult ECLS patients were analyzed. Detailed complication profiles were logged for each patient from initiation through discontinuation of ECLS. Routine coagulation testing was recorded within two hours prior to the TEE exams. Controls consisted of age- and gender-matched patients undergoing perioperative TEE without ECLS and normal coagulation (N=87). RESULTS:: Overall TEE-associated morbidity in ECLS patients was 2.3% and consisted of minor oropharyngeal bleeding (2/87 TEE exams) exclusively. The patients presenting with oropharyngeal bleeding received heparin for anticoagulation and had two or more abnormal coagulation studies at the time of TEE. Seventy-nine percent of ECLS patients received intravenous heparin infusions, 6.8% argatroban and 3.4% epoprostenol. Ten-point-eight percent of patients were not anticoagulated at the time of TEE because of pre-existing bleeding complications and/or deranged plasmatic coagulation profiles. No major complications (e.g., esophageal perforation, gastrointestinal bleeding, accidental extubation) were recorded in either group. CONCLUSIONS:: TEE remained safe in critically ill patients under ECLS, despite systemic anticoagulation, during probe insertion, manipulation and removal. TEE-related complications pertained solely to oropharyngeal bleeding amenable to conservative management.

Lysophosphatidic acid generation by pulmonary NKT cell ENPP-2/autotaxin exacerbates hyperoxic lung injury.

Hyperoxia is still broadly used in clinical practice in order to assure organ oxygenation in critically ill patients, albeit known toxic effects. In this present study, we hypothesize that lysophosphatidic acid (LPA) mediates NKT cell activation in a mouse model of hyperoxic lung injury. In vitro, pulmonary NKT cells were exposed to hyperoxia for 72 h, and the induction of the ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP-2) was examined and production of lysophosphatidic acid (LPA) was measured. In vivo, animals were exposed to 100 % oxygen for 72 h and lungs and serum were harvested. Pulmonary NKT cells were then incubated with the LPA antagonist Brp-LPA. Animals received BrP-LPA prior to oxygen exposure. Autotaxin (ATX, ENPP-2) was significantly up-regulated on pulmonary NKT cells after hyperoxia (p < 0.01) in vitro. LPA levels were increased in supernatants of hyperoxia-exposed pulmonary NKT cells. LPA levels were significantly reduced by incubating NKT cells with LPA-BrP during oxygen exposure (p < 0,05) in vitro. Hyperoxia-exposed animals showed significantly increased serum levels of LPA (p ≤ 0,05) as well as increased pulmonary NKT cell numbers in vivo. BrP-LPA injection significantly improved survival as well as significantly decreased lung injury and lowered pulmonary NKT cell numbers. We conclude that NKT cell-induced hyperoxic lung injury is mediated by pro-inflammatory LPA generation, at least in part, secondary to ENPP-2 up-regulation on pulmonary NKT cells. Being a potent LPA antagonist, BrP-LPA prevents hyperoxia-induced lung injury in vitro and in vivo.