De Ritis Ratio to Predict Clinical Outcomes of Intermediate- and High-Risk Pulmonary Embolisms.

Background: Abnormal liver function tests can identify severe cardiopulmonary failure. The aspartate transaminase/alanine transaminase (AST/ALT) ratio, or the De Ritis ratio, is commonly used to evaluate acute liver damage. However, its prognostic value in pulmonary embolism (PE) is unknown. Methods: Two cohorts, including patients with intermediate- and high-risk PEs, were established: one with an abnormal baseline AST/ALT ratio (>1) and another with a normal baseline AST/ALT ratio (<1). The primary outcome was a 60-day mortality. Secondary outcomes included peak N-terminal pro-brain-natriuretic-peptide (NT-proBNP) levels, complications, and the need for critical care treatment. To assess the effect of abnormal AST/ALT ratios, inverse probability weighted (IPW) analyses were performed. Results: In total, 230 patients were included in the analysis, and 52 (23%) had an abnormal AST/ALT ratio. After the IPW correction, patients with an abnormal AST/ALT ratio had a significantly higher mortality rate and peak NT-proBNP levels. The relative risks of 60-day mortality, shock development, use of inotropes/vasopressors, mechanical ventilation, and extracorporeal life support were 9.2 (95% confidence interval: 3.3-25.3), 10.1 (4.3-24), 2.7 (1.4-5.2), 2.3 (1.4-3.7), and 5.7 (1.4-23.1), respectively. Conclusions: The baseline AST/ALT ratio can be a predictor of shock, multiorgan failure, and mortality in patients with a pulmonary embolism.

In vitro evaluation of the performance of an oxygenator depending on the non-standard gas content of the inlet blood with special regard on CO2 elimination.

INTRODUCTION: The performance of an oxygenator, as found in literature, is evaluated according to protocols that define standard values of the gas content in the inlet blood. However, when dealing with simulations of lung insufficiency, a more extensive evaluation is needed. This work aims to investigate and assess the gas exchange performance of an oxygenator for different input values of gas content in blood. METHODS: Three commercially available oxygenators with different membrane surfaces were investigated in a mock loop for three blood flow rates (0.5l/min, 1l/min, and 5l/min) and two gas-to-blood ratios (1:1, and 15:1). The initial CO2 and O2 partial pressures (pCO2 and pO2) in blood were set to ≥ 100 mmHg and ≤10 mmHg, respectively. For each ratio, the efficiency, defined as the ratio between the difference of pressure inlet and outlet and the inlet pCO2 (pCO2(i)), was calculated. RESULTS: The CO2 elimination in an oxygenator was higher for higher pCO2(i). While for a pCO2(i) of 100 mmHg, an oxygenator eliminated 80 mmHg, the same oxygenator at the same conditions eliminated 5 mmHg CO2 when pCO2(i) was 10 mmHg. The efficiency of the oxygenator decreased from 76,9% to 49,5%. For simulation reasons, the relation between the pCO2(i) and outlet (pCO2(o)) for each oxygenator at different blood and gas flows, was described as an exponential formula. CONCLUSION: The performance of an oxygenator in terms of CO2 elimination depends not only on the blood and gas flow, but also on the initial pCO2 value. This dependence is crucial for simulation studies in the future.

Oxygenation performance assessment of an artificial lung in different central anatomic configurations.

OBJECTIVES: Aim of this work was to characterize possible central anatomical configurations in which a future artificial lung (AL) could be connected, in terms of oxygenation performance. METHODS: Pulmonary and systemic circulations were simulated using a numerical and an in vitro approach. The in vitro simulation was carried out in a mock loop in three phases: (1) normal lung, (2) pulmonary shunt (50% and 100%), and (3) oxygenator support in three anatomical configurations: right atrium-pulmonary artery (RA-PA), pulmonary artery-left atrium (PA-LA), and aorta-left atrium (Ao-LA). The numerical simulation was performed for the oxygenator support phase. The oxygen saturation (SO2) of the arterial blood was plotted over time for two percentages of pulmonary shunt and three blood flow rates through the oxygenator. RESULTS: During the pulmonary shunt phase, SO2 reached a steady state value (of 68% for a 50% shunt and of nearly 0% for a 100% shunt) 20 min after the shunt was set. During the oxygenator support phase, physiological values of SO2 were reached for RA-PA and PA-LA, in case of a 50% pulmonary shunt. For the same conditions, Ao-LA could reach a maximum SO2 of nearly 60%. Numerical results were congruous to the in vitro simulation ones. CONCLUSIONS: Both in vitro and numerical simulations were able to properly characterize oxygenation properties of a future AL depending on its placement. Different anatomical configurations perform differently in terms of oxygenation. Right to right and right to left connections perform better than left to left ones.

["Stop the bleeding"-Acute bleeding control in injuries to the trunk and extremities]. / "Stop the bleeding" ­ akute Blutungskontrolle bei Verletzungen von Körperstamm und Extremitäten.

Trauma-related blood loss is still associated with a high mortality and is a major factor in the development of a deadly triad consisting of acidosis, hypothermia and coagulopathy. Sources of bleeding occur particularly in the thoracic, abdominal and pelvic regions as well as in the extremities. For control of bleeding a timely identification of the source of bleeding and the initiation of a targeted treatment are essential. The principles are to stop the blood loss as soon as possible and to restore the lost volume to avoid the complications associated with traumatic hemorrhage. Surgical treatment in the acute situation is especially important due to its efficiency. The present article focuses on the current literature with respect to the appropriate diagnostic and treatment measures in the thoracic, abdominal and pelvic regions as well as the extremities and describes the latest scientific insights and developments. Available trauma algorithms are presented and the value of various strategies regarding surgical hemostasis for the thorax and abdomen are shown, whereby organ preservation can increasingly be achieved, particularly in the abdomen. With respect to hemostasis in severe pelvic injuries and injuries to the extremities, the regularly used surgical techniques are described and their values are differentially classified.

First Ultrasound-Assisted Thrombolysis for Pulmonary Embolism after Lung Surgery.

Background Experience with early postoperative catheter-directed ultrasound-assisted thrombolysis (USAT) in high-risk pulmonary embolism (PE) is limited. A first case of USAT directly after pulmonary surgery is presented. Case Description A 60-year-old female patient with two malignancies (triple negative breast cancer and pulmonary squamous cell carcinoma) underwent video-assisted lobectomy. The second postoperative day, she developed PE with hemodynamic deterioration. Note that 24 mg of alteplase was applied by USAT. After 3 days she was successfully weaned from ventilation and vasopressors. Conclusion USAT for acute PE is possible after major pulmonary resections and seems promising if reperfusion is needed.

[Traumatic Tracheobronchial Injuries - Recommendation of the Interdisciplinary Working Group of the DGT and DGU to Establish a Uniform Classification for Diagnostics and Therapy]. / Traumatische tracheobronchiale Verletzungen ­ Empfehlung der interdisziplinären Arbeitsgruppe der DGT und DGU zur Etablierung einer einheitlichen Klassifikation für Diagnostik und Therapie.

Traumatic tracheobronchial injuries are extremely rare. In comparison, iatrogenic injuries are somewhat more common. A literature search revealed that there is a large number of case reports and small case series for this clinical entity. There are hardly any reviews and they usually have a low level of evidence. One reason for this is the lack of a classification to allow comparison of the individual cases with each other. There is only one classification for iatrogenic injuries of the posterior tracheal wall, which the authors modified and expanded with regard to traumatic tracheobronchial injuries. This classification was extended by the authors to also include traumatic injuries. A three-digit classification is presented here. The grading of the injury covers the entire spectrum of injury patterns, from peribronchial emphysema to wall injuries of different depths to subtotal and complete rupture of the bronchus. In addition, the anatomical location and the cause of the injury were added to the classification. The levels of injury in the tracheobronchial tree are distinguished anatomically. The third digit distinguishes traumatic, iatrogenic and spontaneous injuries. On the basis of the three-digit classification resulting from these parameters, it is possible to group individual cases together and to develop recommendations for diagnostics and therapy.

[Pathophysiology, Diagnostics and Therapy of Pulmonary Contusion - Recommendations of the Interdisciplinary Group on Thoracic Trauma of the Section NIS of the German Society for Trauma Surgery (DGU) and the German Society for Thoracic Surgery (DGT)]. / Pathophysiologie, Diagnostik und Therapie der Lungenkontusion ­ Empfehlungen der interdisziplinären Arbeitsgruppe der Sektion NIS der DGU und DGT zur Thoraxtraumaversorgung.

Pulmonary contusion usually occurs in combination with other injuries and is indicative of a high level of force. Especially in multiply injured patients, pulmonary contusions are frequently detected. The injury is characterised by dynamic development, which might result in difficulties in recognising the actual extent of the injury at an early stage. Subsequently, correct classification of the extent of injury and appropriate initiation of therapeutic steps are essential to achieve the best possible outcome. The main goal of all therapeutic measures is to preserve lung function as best as possible and to avoid associated complications such as the development of pneumonia or Acute Respiratory Distress Syndrome (ARDS).The present report from the interdisciplinary working group "Chest Trauma" of the German Society for Trauma Surgery (DGU) and the German Society for Thoracic Surgery (DGT) includes an extensive literature review on the background, diagnosis and treatment of pulmonary contusion. Without exception, papers with a low level of evidence were included due to the lack of studies with large cohorts of patients or randomised controlled studies. Thus, the recommendations given in the present article correspond to a consensus of the aforementioned interdisciplinary working group.Computed tomography (CT) of the chest is recommended for initial diagnosis; the extent of pulmonary contusion correlates with the incidence and severity of complications. A conventional chest X-ray may initially underestimate the injury, but is useful during short-term follow-up.Therapy for pulmonary contusion is multimodal and symptom-based. In particular, intensive care therapy with lung-protective ventilation and patient positioning are key factors of treatment. In addition to invasive ventilation, non-invasive ventilation should be considered if the patient's comorbidities and compliance allows this. Furthermore, depending on the extent of the lung injury and the general patient's condition, ECMO therapy may be considered as an ultima ratio. In particular, this should only be performed at specialised hospitals, which is why patient assignment or anticipation of early transfer of the patient should be anticipated at an early time during the course.

Inflow from a Cardiopulmonary Assist System to the Pulmonary Artery and Its Implications for Local Hemodynamics-a Computational Fluid Dynamics Study.

When returning blood to the pulmonary artery (PA), the inflow jet interferes with local hemodynamics. We investigated the consequences for several connection scenarios using transient computational fluid dynamics simulations. The PA was derived from CT data. Three aspects were varied: graft flow rate, anastomosis location, and inflow jet path length from anastomosis site to impingement on the PA wall. Lateral anastomosis locations caused abnormal flow distribution between the left and right PA. The central location provided near-physiological distribution but induced higher wall shear stress (WSS). All effects were most pronounced at high graft flows. A central location is beneficial regarding flow distribution, but the resulting high WSS might promote detachment of local thromboembolisms or influence the autonomic nervous innervation. Lateral locations, depending on jet path length, result in lower WSS at the cost of an unfavorable flow distribution that could promote pulmonary vasculature changes. Case-specific decisions and further research are necessary.

Computational fluid dynamics analysis of endoluminal aortic perfusion.

INTRODUCTION: In peripheral percutaneous (VA) extracorporeal membrane oxygenation (ECMO) procedures the femoral arteries perfusion route has inherent disadvantages regarding poor upper body perfusion due to watershed. With the advent of new long flexible cannulas an advancement of the tip up to the ascending aorta has become feasible. To investigate the impact of such long endoluminal cannulas on upper body perfusion, a Computational Fluid Dynamics (CFD) study was performed considering different support levels and three cannula positions. METHODS: An idealized literature-based- and a real patient proximal aortic geometry including an endoluminal cannula were constructed. The blood flow was considered continuous. Oxygen saturation was set to 80% for the blood coming from the heart and to 100% for the blood leaving the cannula. 50% and 90% venoarterial support levels from the total blood flow rate of 6 l/min were investigated for three different positions of the cannula in the aortic arch. RESULTS: For both geometries, the placement of the cannula in the ascending aorta led to a superior oxygenation of all aortic blood vessels except for the left coronary artery. Cannula placements at the aortic arch and descending aorta could support supra-aortic arteries, but not the coronary arteries. All positions were able to support all branches with saturated blood at 90% flow volume. CONCLUSIONS: In accordance with clinical observations CFD analysis reveals, that retrograde advancement of a long endoluminal cannula can considerably improve the oxygenation of the upper body and lead to oxygen saturation distributions similar to those of a central cannulation.

Minimally Invasive Central Cannulation for Extracorporeal Life Support: The Uniportal and Subxiphoid Approach.

OBJECTIVE: Extracorporeal life support (ECLS) for circulatory and/or respiratory failure is improving. Currently, invasive sternotomies or rib-spreading thoracotomies are used for central cannulation of the heart and great vessels. Although peripheral cannulation of the extremities is often used, this approach may result in immobility and unintentional dislodgement. Less invasive methods for central cannulation are needed to achieve long-term ECLS. The objective of this study was to develop 2 different minimally invasive approaches for central thoracic cannulation. METHODS: Porcine hearts were positioned in a plastic thoracic model. An endoscopic camera and multiple endoscopic instruments were used. Both access points, uniportal (lateral) and subxiphoidal, were simulatively investigated. A novel cannulation method using purse string sutures, a custom-made endoscopic puncture tool, guidewires, and dilator-assisted cannulas was developed. Simulations were tested in a closed circuit regarding leak tightness. RESULTS: The uniportal approach allowed a cannulation of the aorta, inferior vena cava, right atrium, and main pulmonary artery. Cannulation of the right branches of the pulmonary artery and vein was also possible. From the subxiphoid approach, cannulation of the aorta, main pulmonary artery, and both atria were possible. Subsequent evaluation and leakage tests revealed no damage to the surrounding structures and tightly sealed cannulation sites. The uniportal approach was also successfully performed in a human cadaver to connect the aorta and right atrium with cannulas from the subxiphoidal space. CONCLUSIONS: Both uniportal and subxiphoid central cannulation of potential sites for ECLS were feasible. This study encourages further investigation and potential clinical translation of minimally invasive central organ support.

Platelet-derived growth factor (PDGF)-BB regulates the airway tone via activation of MAP2K, thromboxane, actin polymerisation and Ca2+-sensitisation.

BACKGROUND: PDGFR-inhibition by the tyrosine kinase inhibitor (TKI) nintedanib attenuates the progress of idiopathic pulmonary fibrosis (IPF). However, the effects of PDGF-BB on the airway tone are almost unknown. We studied this issue and the mechanisms beyond, using isolated perfused lungs (IPL) of guinea pigs (GPs) and precision-cut lung slices (PCLS) of GPs and humans. METHODS: IPL: PDGF-BB was perfused after or without pre-treatment with the TKI imatinib (perfused/nebulised) and its effects on the tidal volume (TV), the dynamic compliance (Cdyn) and the resistance were studied. PCLS (GP): The bronchoconstrictive effects of PDGF-BB and the mechanisms beyond were evaluated. PCLS (human): The bronchoconstrictive effects of PDGF-BB and the bronchorelaxant effects of imatinib were studied. All changes of the airway tone were measured by videomicroscopy and indicated as changes of the initial airway area. RESULTS: PCLS (GP/human): PDGF-BB lead to a contraction of airways. IPL: PDGF-BB decreased TV and Cdyn, whereas the resistance did not increase significantly. In both models, inhibition of PDGFR-(ß) (imatinib/SU6668) prevented the bronchoconstrictive effect of PDGF-BB. The mechanisms beyond PDGF-BB-induced bronchoconstriction include activation of MAP2K and TP-receptors, actin polymerisation and Ca2+-sensitisation, whereas the increase of Ca2+ itself and the activation of EP1-4-receptors were not of relevance. In addition, imatinib relaxed pre-constricted human airways. CONCLUSIONS: PDGFR regulates the airway tone. In PCLS from GPs, this regulatory mechanism depends on the ß-subunit. Hence, PDGFR-inhibition may not only represent a target to improve chronic airway disease such as IPF, but may also provide acute bronchodilation in asthma. Since asthma therapy uses topical application. This is even more relevant, as nebulisation of imatinib also appears to be effective.

Video-Assisted Thoracoscopic Surgery Management of Subacute Retained Blood Syndrome after Cardiac Surgery.

PURPOSE: Blood loss along with inadequate evacuation after cardiac surgery leads to retained blood syndrome (RBS) in the pleural and/or pericardial cavity. Re-sternotomy is often needed for clot evacuation. Video-assisted thoracoscopic surgery (VATS) evacuation is a less-invasive procedure. However, sufficient evidence on safety and outcomes is lacking. METHODS: Thirty patients who developed hemothorax and/or hemopericardium after cardiac surgery and underwent VATS evacuation between April 2015 and September 2020 were included in this retrospective single-center analysis. RESULTS: The median patient age was 70 (interquartile range: IQR 62-75) years, body mass index (BMI) was 24.7 (IQR 22.8-29) kg/m2, time between initial cardiac surgery and VATS was 17 (IQR 11-21) days, 30% of the patients were female, 60% resided in the ICU, and 17% were nicotine users. Coronary artery bypass graft was the most frequent initial cardiac procedure. Median operation time was 120 (IQR 90-143) min, 23% of the patients needed an additional VATS, and the median length of hospital stay after VATS was 8 (IQR 5-14) days. All patients survived VATS, and we experienced no mortality related to the VATS procedure. CONCLUSION: In our study, VATS for evacuation of RBS after cardiac surgery was a feasible, safe, and efficient alternative approach to re-sternotomy in selected patients.

Extracorporeal membrane oxygenation in patients with COVID-19: 1-year experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) in patients with coronavirus disease 2019 (COVID-19) showed reasonable outcomes. However, recent studies indicated a negative trend and analysis is needed. METHODS: Baseline characteristics, laboratory parameters, and outcomes of ECMO-supported patients with COVID-19 were analyzed in a retrospective single-center study. We included hospital admissions until February 28, 2021; patients were followed until discharge/death. Eventually, we compared data between patients hospitalized before and after September 1, 2020. RESULTS: Median age of patients treated with ECMO (n=39) was 56 years; most patients were males (n=28, 72%). Median mechanical ventilation time (prior to ECMO) was 6 days, while the median ECMO duration was 19 days. Overall survival rate was 41%. In the sub-analysis, survival until discharge in the first and second epidemic waves was 53% (n=19) and 30% (n=20), respectively (P=0.2). At baseline, compared with patients of the first wave, those of the second wave had higher median body mass index (28.2 vs. 31.1 kg/m2, respectively, P=0.02), bicarbonate (27 vs. 31.8 mmol/L, respectively, P=0.033), plasma free hemoglobin (36 vs. 58 mg/L, respectively, P=0.013), alanine aminotransferase (33 vs. 52 U/L, respectively, P=0.018), and pH (7.29 vs. 7.42, respectively, P=0.005), lower rate of pulmonary hypertension (32% vs. 0%, respectively, P=0.008), lower positive end-expiratory pressure (14 vs. 12 cmH2O, respectively, P=0.04), longer median ECMO duration (16 vs. 24.5 days, respectively, P=0.074), and more frequent major bleeding events (42% vs. 80%, respectively, P=0.022). CONCLUSIONS: ECMO-supported patients with COVID-19 had an overall survival rate of 41%. Similar to international registries, we observed less favorable outcomes during the second wave. Further research is needed to confirm this signal and find predictors for mortality.

Outcomes of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome in COVID-19 Patients: A Propensity-Matched Analysis.

It remains unclear to what extent the outcomes and complications of extracorporeal membrane oxygenation (ECMO) therapy in COVID-19 patients with acute respiratory distress syndrome (ARDS) differ from non-COVID-19 ARDS patients. In an observational, propensity-matched study, outcomes after ECMO support were compared between 19 COVID-19 patients suffering from ARDS (COVID group) and 34 matched non-COVID-19 ARDS patients (NCOVID group) from our historical cohort. A 1:2 propensity matching was performed based on respiratory ECMO survival prediction (RESP) score, age, gender, bilirubin, and creatinine levels. Patients' characteristics, laboratory parameters, adverse events, and 90-day survival were analyzed. Patients' characteristics in COVID and NCOVID groups were similar. Before ECMO initiation, fibrinogen levels were significantly higher in the COVID group (median: 493 vs. 364 mg/dL, p < 0.001). Median ECMO support duration was similar (16 vs. 13 days, p = 0.714, respectively). During ECMO therapy, patients in the COVID group developed significantly more thromboembolic events (TEE) than did those in the NCOVID group (42% vs. 12%, p = 0.031), which were mainly pulmonary artery embolism (PAE) (26% vs. 0%, p = 0.008). The rate of major bleeding events (42% vs. 62%, p = 0.263) was similar. Fibrinogen decreased significantly more in the COVID group than in the NCOVID group (p < 0.001), whereas D-dimer increased in the COVID group (p = 0.011). Additionally, 90-day mortality did not differ (47% vs. 74%; p = 0.064) between COVID and NCOVID groups. Compared with that in non-COVID-19 ARDS patients, ECMO support in COVID-19 patients was associated with comparable in-hospital mortality and similar bleeding rates but a higher incidence of TEE, especially PAE. In contrast, coagulation parameters differed between COVID and NCOVID patients.

Efficacy of a Novel Medical Adhesive for Sealing Lung Parenchyma: An in vitro Study in Rabbit Lungs.

INTRODUCTION: During thoracic resection procedures, complete hemostasis and aerostasis are priorities. A persistent alveolar air leak is associated with increased morbidity and mortality rates. This study aimed to evaluate whether the novel medical adhesive VIVO (Adhesys Medical GmbH Aachen, Germany) is a reliable alternative sealing technique to routine surgical procedures. METHODS: We conducted an in vitro animal study by analyzing 21 lungs of New Zealand (n = 19) and Chinchilla Bastard (n = 2) rabbits (age, 11-18 weeks; weight, 2,400-3,600 g). Three groups, each comprising 7 animals, were evaluated. VIVO (VIVO-group) was compared with standard surgical lung parenchymal lesion closure with a polypropylene suture (Suture-group) and TachoSil® (TachoSil-group). We adopted a stable, pressure-controlled ventilation protocol. After explantation, a surgical incision 0.5-cm deep and 1.5-cm wide was made in the lungs using a customized template. Air leak was measured quantitatively (mL/min) using a respirator and visualized qualitatively by 2 observers who made independent judgments. Next, the leak was closed using VIVO, suture, or TachoSil® as specified by the manufacturer. Subsequently, positive end-expiratory pressure (PEEP) and inspiratory pressure were gradually increased until a maximum of 15 and 30 mbar were attained, respectively. RESULTS: At PEEPs of 8, 10, and 15 mbar, VIVO achieved complete sealing of the profound parenchymal defect in all (n = 7) lungs. After closure of the incision, we observed an air leak variation of 127 ± 114 mL/min (Suture-group), 31 ± 49 mL/min (VIVO-group), and 114 ± 134 mL/min (TachoSil-group). VIVO showed a significantly lower air leak than surgical sutures (p = 0.031) and TachoSil® (p = 0.046). CONCLUSION: VIVO offers sufficient closure of the lung parenchymal lesions. The novel adhesive enabled significantly better sealing with lower persistent air leakage than TachoSil® or surgical sutures. Further investigation using in vivo models is strongly encouraged to confirm our findings.

Thromboembolic and Bleeding Events in COVID-19 Patients receiving Extracorporeal Membrane Oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential treatment option in critically ill COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) if mechanical ventilation (MV) is insufficient; however, thromboembolic and bleeding events (TEBE) during ECMO treatment still need to be investigated. METHODS: We conducted a retrospective, single-center study including COVID-19 patients treated with ECMO. Additionally, we performed a univariate analysis of 85 pre-ECMO variables to identify factors influencing incidences of thromboembolic events (TEE) and bleeding events (BE), respectively. RESULTS: Seventeen patients were included; the median age was 57 years (interquartile range [IQR]: 51.5-62), 11 patients were males (65%), median ECMO duration was 16 days (IQR: 10.5-22), and the overall survival was 53%. Twelve patients (71%) developed TEBE. We observed 7 patients (41%) who developed TEE and 10 patients (59%) with BE. Upper respiratory tract (URT) bleeding was the most frequent BE with eight cases (47%). Regarding TEE, pulmonary artery embolism (PAE) had the highest incidence with five cases (29%). The comparison of diverse pre-ECMO variables between patients with and without TEBE detected one statistically significant value. The platelet count was significantly lower in the BE group (n = 10) than in the non-BE group (n = 7) with 209 (IQR: 145-238) versus 452 G/L (IQR: 240-560), with p = 0.007. CONCLUSION: This study describes the incidences of TEE and BE in critically ill COVID-19 patients treated with ECMO. The most common adverse event during ECMO support was bleeding, which occurred at a comparable rate to non-COVID-19 patients treated with ECMO.

Role of extracorporeal membrane oxygenation in critically Ill COVID-19 patients and predictors of mortality.

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill COVID-19 patients remains unclear. Our study aims to analyze the outcomes and risk factors from patients treated with ECMO. This retrospective, single-center study includes 17 COVID-19 patients treated with ECMO. Univariate and multivariate parametric survival regression identified predictors of survival. Nine patients (53%) were successfully weaned from ECMO and discharged. The incidence of in-hospital mortality was 47%. In a univariate analysis, only four out of 83 pre-ECMO variables were significantly different; IL-6, PCT, and NT-proBNP were significantly higher in non-survivors than in survivors. The Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) score was significantly higher in survivors. After a multivariate parametric survival regression, IL-6, NT-proBNP and RESP scores remained significant independent predictors, with hazard ratios (HR) of 1.069 [95%-CI: 0.986-1.160], P = .016 1.001 [95%-CI: 1.000-1.001], P = .012; and .843 [95%-CI: 0.564-1.260], P = .040, respectively. A prediction model comprising IL-6, NT-proBNP, and RESP score showed an area under the curve (AUC) of 0.87, with a sensitivity of 87.5% and 77.8% specificity compared to an AUC of 0.79 for the RESP score alone. The present study suggests that ECMO is a potentially lifesaving treatment for selected critically ill COVID-19 patients. Considering IL-6 and NT-pro-BNP, in addition to the RESP score, may enhance outcome predictions.

Levosimendan reduces segmental pulmonary vascular resistance in isolated perfused rat lungs and relaxes human pulmonary vessels.

INTRODUCTION: Levosimendan is approved for acute heart failure. Within this context, pulmonary hypertension represents a frequent co-morbidity. Hence, the effects of levosimendan on segmental pulmonary vascular resistance (PVR) are relevant. So far, this issue has been not studied. Beyond that the relaxant effects of levosimendan in human pulmonary vessel are unknown. We addressed these topics in rats' isolated perfused lungs (IPL) and human precision-cut lung slices (PCLS). MATERIAL AND METHODS: In IPL, levosimendan (10 µM) was perfused in untreated and endothelin-1 pre-contracted lungs. The pulmonary arterial pressure (PPA) was continuously recorded and the capillary pressure (Pcap) was determined by the double-occlusion method. Thereafter, segmental PVR, expressed as precapillary (Rpre) and postcapillary resistance (Rpost) and PVR were calculated. Human PCLS were prepared from patients undergoing lobectomy. Levosimendan-induced relaxation was studied in naïve and endothelin-1 pre-contracted PAs and PVs. In endothelin-1 pre-contracted PAs, the role of K+-channels was studied by inhibition of KATP-channels (glibenclamide), BKCa2+-channels (iberiotoxin) and Kv-channels (4-aminopyridine). All changes of the vascular tone were measured by videomicroscopy. In addition, the increase of cAMP/GMP due to levosimendan was measured by ELISA. RESULTS: Levosimendan did not relax untreated lungs or naïve PAs and PVs. In IPL, levosimendan attenuated the endothelin-1 induced increase of PPA, PVR, Rpre and Rpost. In human PCLS, levosimendan relaxed pre-contracted PAs or PVs to 137% or 127%, respectively. In pre-contracted PAs, the relaxant effect of levosimendan was reduced, if KATP- and Kv-channels were inhibited. Further, levosimendan increased cGMP in PAs/PVs, but cAMP only in PVs. DISCUSSION: Levosimendan reduces rats' segmental PVR and relaxes human PAs or PVs, if the pulmonary vascular tone is enhanced by endothelin-1. Regarding levosimendan-induced relaxation, the activation of KATP- and Kv-channels is of impact, as well as the formation of cAMP and cGMP. In conclusion, our results suggest that levosimendan improves pulmonary haemodynamics, if PVR is increased as it is the case in pulmonary hypertension.

Prolonged Survival of a Patient with Advanced-Stage Combined Hepatocellular-Cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC/CCA) represents a rare type of primary liver cancer with a very limited prognosis. Although just recently genomic studies have contributed to a better understanding of the disease's genetic landscape, therapeutic options, especially for advanced-stage patients, are limited and often experimental, as no standardized treatment protocols have been established to date. Here, we report the case of a 38-year-old male patient who was diagnosed with extensive intrahepatic cHCC/CCA in an otherwise healthy liver without signs of chronic liver disease. An interdisciplinary stepwise therapeutic approach including locoregional liver-targeted therapy, systemic chemotherapy, liver transplantation, surgical pulmonary metastasis resection, and next-generation sequencing-based targeted therapy led to a prolonged overall survival beyond 5 years with an excellent quality of life. This case report comprises several provocative treatment decisions that are extensively discussed in light of the existing literature on this rare but highly aggressive malignancy.