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Blood flow through left ventricular assist devices (LVAD) may induce activation and dysfunction of platelets. Dysfunctional platelets cause coagulation disturbances and form platelet-neutrophil conjugates (PNC), which contribute to inflammatory tissue damage. This prospective observational cohort study investigated patients, who underwent implantation of a LVAD (either HeartMate II (HM II) (n = 7) or HeartMate 3 (HM 3) (n = 6)) and as control patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement (AVR) (n = 10). We performed platelet and leukocyte flow cytometry, analysis of platelet activation markers, and platelet aggregometry. Platelet CD42b expression was reduced at baseline and perioperatively in HM II/3 compared to CABG/AVR patients. After surgery the platelet activation marker β-thromboglobulin and platelet microparticles increased in all groups while platelet aggregation decreased. Platelet aggregation was more significantly impaired in LVAD compared to CABG/AVR patients. PNC were higher in HM II compared to HM 3 patients. We conclude that LVAD implantation is associated with platelet dysfunction and proinflammatory platelet-leukocyte binding. These changes are less pronounced in patients treated with the newer generation LVAD HM 3. Future research should identify device-specific LVAD features, which are associated with the least amount of platelet activation to further improve LVAD therapy. [ABSTRACT FROM AUTHOR]

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 endorgan 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. Fortythree (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. [ABSTRACT FROM AUTHOR]

Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality.Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled.Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy.Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections.Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.Trial Registration: ClinicalTrials.gov Identifier: NCT02669589. [ABSTRACT FROM AUTHOR]

Background: Right ventricular (RV) function is an important prognostic indicator. The acute effects of cardiac interventions or cardiac surgery on global and longitudinal RV function are not entirely understood. In this study, acute changes of RV function during mitral valve surgery (MVS), percutaneous mitral valve repair (PMVR) and off-pump coronary artery bypass surgery (OPCAB) were investigated employing 3D echocardiography.Methods: Twenty patients scheduled for MVS, 23 patients scheduled for PMVR and 25 patients scheduled for OPCAB were included retrospectively if patients had received 3D transesophageal echocardiography before and immediately after MVS, PMVR or OPCAB, respectively. RV global and longitudinal function was assessed using a 3D multiparameter set consisting of global right ventricular ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), longitudinal contribution to RVEF (RVEFlong) and free wall longitudinal strain (FWLS).Results: Longitudinal RV function was significantly depressed immediately after MVS, as reflected by all parameters (RVEFlong: 20 ± 5% vs. 13 ± 6%, p <  0.001, TAPSE: 13.1 ± 5.1 mm vs. 11.0 ± 3.5 mm, p = 0.04 and FWLS: -20.1 ± 7.1% vs. -15.4 ± 5.1%, p <  0.001, respectively). The global RVEF was slightly impaired, but the difference did not reach significance (37 ± 13% vs. 32 ± 9%, p = 0.15). In the PMVR group, both global and longitudinal RV function parameters were unaltered, whereas the OPCAB group showed a slight reduction of RVEFlong only (18 ± 7% vs. 14 ± 5%, p <  0.01). RVEFlong yielded moderate case-to-case but good overall reproducibility.Conclusions: TAPSE, FWLS and RVEFlong reflect the depression of longitudinal compared to global RV function initially after MVS. PMVR alone had no impact, while OPCAB had a slight impact on longitudinal RV function. The prognostic implications of these phenomena remain unclear and require further investigation. [ABSTRACT FROM AUTHOR]

Background: With the following report we want to present an unusual case of a patient suffering from acute respiratory distress syndrome with early discovery of bacterial pathogens in bronchoalveolar liquid samples that developed a fatal undiscovered disseminated fungal infection. Case presentation: A 67-year-old man was admitted to our university hospital with dyspnea. Progressive respiratory failure developed leading to admission to the intensive care unit, intubation and prone positioning was necessary. To ensure adequate oxygenation and lung protective ventilation veno-venous extracorporeal membrane oxygenation was established. Despite maximal therapy and adequate antiinfective therapy of all discovered pathogens the condition of the patient declined further and he deceased. Postmortem autopsy revealed Mucor and Aspergillus mycelium in multiple organs such as lung, heart and pancreas as the underlying cause of his deterioration and death. Conclusion: Routine screening re-evaluation of every infection is essential for adequate initiation and discontinuation of every antiinfective therapy. In cases with unexplained deterioration and unsuccessful sampling the possibility for diagnostic biopsies should be considered. [ABSTRACT FROM AUTHOR]

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet–neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet–neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury. Reperfusion injury following myocardial ischemia is aggravated by inflammation and platelet–neutrophil complex formation. Here the authors show that semaphorin 7A binds to platelet GPIb, enhancing platelet–neutrophil interaction and increasing post-ischemic myocardial tissue injury, and that blockage of semaphorin 7A is protective. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) is caused by rapid-onset (within hours) acute inflammatory processes in lung tissue, and it is a life-threatening condition with high mortality. The treatment of ARDS to date is focused on the prevention of further iatrogenic damage of the lung rather than the treatment of the initial inflammatory process. Several preclinical studies have revealed a beneficial effect of iloprost on the control of pulmonary inflammation, and in a small number of patients with ARDS, iloprost treatment resulted in improved oxygenation. Therefore, we plan to conduct a large multicenter trial to evaluate the effect of iloprost on ARDS.Methods: The Therapeutic Iloprost during ARDS trial (ThIlo trial) is a multicenter, randomized, single blinded, clinical phase II trial assessing the efficacy of inhaled iloprost for the prevention of the development and progression of ARDS in critically ill patients. One hundred fifty critically ill patients suffering from acute ARDS will be treated either by nebulized iloprost or NaCl 0.9% for 5 days. Blood samples will be drawn at defined time points to elucidate the serum levels of iloprost and inflammatory markers during treatment. Mechanical ventilation will be standardized. In follow-up visits at days 28 and 90 as well as 6 months after enrollment, functional status according to the Barthel Index and a health care-related questionnaire, and frailty (Vulnerable Elders Survey) will be evaluated. The primary endpoint is the improvement of oxygenation, defined as the ratio of PaO2/FiO2. Secondary endpoints include 90-day all-cause mortality, Sequential Organ Failure Assessment scores during the study period up to day 90, the duration of mechanical ventilation, the length of intensive care unit (ICU) stay, ventilator-associated pneumonia, delirium, ICU-acquired weakness, and discharge localization. The study will be conducted in three university ARDS centers in Germany.Discussion: The results of the ThIlo trial will highlight the anti-inflammatory effect of iloprost on early inflammatory processes during ARDS, resulting in the improvement of outcome parameters in patients with ARDS.Trial Registration: EUDRA-CT: 2016-003168-37. Registered on 12 April 2017. ClinicalTrials.gov: NCT03111212. Registered on 4 June 2017. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]