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Abstract Background There is limited information about the long-term outcome of patients suffering from acute respiratory distress syndrome (ARDS) supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Most studies focused on short- to mid-term follow-up. We aimed to investigate long-term survival and health-related quality of life (HRQL) in these patients. Methods We report retrospective data from a single-centre registry of patients with severe ARDS treated with VV ECMO at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 10/2010 and 06/2019. Follow-up data of all patients that survived the index hospitalisation were collected by telephone interviews from 02/2020 till 09/2020. Long-term survival, HRQL (Short-Form Health Survey-36 (SF-36), St. Georges Respiratory Questionnaire (SGRQ), Hospital Anxiety and Depression Scale (HADS)) and the return to work rate were documented. Results In total, 289 patients were treated with VV ECMO during the study period (median age 55 years, 67% males, hospital survival 45%). After a median duration of 3.9 years, follow-up assessment was complete in 94 of 129 hospital survivors (73%). Fifty-three patients completed the HRQL assessment. Hospital survivors showed a high 6- and 12-month survival rate (89% and 85%, respectively). Estimated survival rate of those discharged alive from ICU was 68.5% (95%-CI 56.9–80.1%) after 9.7 years. These patients reported high levels of HRQL (median SF-36 total score 73) and only few pulmonary (median SGRQ total score 19) and mental limitations (median HAD-D score 2 and HAD-A score 3). In total, 80% of the patients were able to resume employment. Conclusion This analysis of VV ECMO patients showed favourable long-term survival and high levels of HRQL suggesting promising prospects for VV ECMO survivors. Graphical Abstract

Abstract Background Typical lung ultrasound (LUS) findings in patients with a COVID-19 infection were reported early on. During the global SARS-CoV-2 pandemic, LUS was propagated as a useful instrument in triage and monitoring. We evaluated LUS as a rapid diagnostic triage tool for the management of patients with suspected COVID-19 in the emergency department (ED). Methods The study retrospectively enrolled patients with suspected COVID-19, who were admitted from 1st April to 25th of April 2020 to the ED of a tertiary care center in Germany. During clinical work-up, patients underwent LUS and polymerase chain reaction (PCR) testing for SARS-CoV-2. The recorded ultrasound findings were analyzed and judged regarding typical signs of viral pneumonia, blinded for clinical information of the patients. The results were compared with PCR test and chest computed tomography (CT). Results 2236 patients were treated in the ED during the study period. 203 were tested for SARS-CoV-2 using PCR, 135 (66.5%) underwent LUS and 39 (28.9%) of the patients were examined by chest CT scan. 39 (28.9%) of the 135 patients were tested positive for SARS-CoV-2 with PCR. In 52 (38.5%) COVID-19 was suspected from the finding of the LUS, resulting in a sensitivity of 76.9% and a specificity of 77.1% compared with PCR results. The negative predictive value reached 89.2%. The findings of the LUS had - compared to a positive chest CT scan for COVID-19 - a sensitivity of 70.6% and a specificity of 72.7%. Conclusions LUS is a rapid and useful triage tool in the work-up of patients with suspected COVID-19 infection during a pandemic scenario. Still, the results of the LUS depend on the physician’s experience and skills.

Abstract Background 3,4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) abuse is frequent, and overdosing might cause severe and eventually lethal multi-organ failure. To date, there is no causal therapy of MDMA intoxication and removal of MDMA from the circulation might be a reasonable measure to prevent adverse courses after overdosing. We present here first-in-man experience and in vitro data supporting a potential role of an adsorber device in severe MDMA overdosing. Results We applied a CytoSorb adsorber device in a 21-year-old male presenting with severe MDMA intoxication and multi-organ failure, including neurological impairment, hyperpyrexia, rhabdomyolysis, oliguric renal failure, liver failure, and coagulopathy with disseminated gastrointestinal and intramuscular bleeding. Use of the adsorber device was associated with a decline in MDMA concentrations in serum from 540 to 140 ng/ml within the first 24 h, a decrease of interleukin 6 and myoglobin levels, and subsequent clinical improvement. The patient was discharged from hospital after restoration of organ function and full neurological recovery. Effective elimination of MDMA by the adsorber device could be confirmed in vitro, when the device lowered MDMA concentrations to non-detectable levels. Conclusions We report here first-in-man experience and in vitro data showing the capacity of a CytoSorb adsorber device for MDMA removal. Early integration of CytoSorb use may enhance the management of severe MDMA intoxication, though we cannot prove whether clinical improvement was directly related to elimination of MDMA or beneficial effects on rhabdomyolysis, hyperinflammation, or liver failure. Our findings encourage further investigation of the CytoSorb adsorber device in a prospective study and to evaluate its use for other intoxications.

Abstract Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can be a rescue therapy for patients in cardiogenic shock or in refractory cardiac arrest. After cannulation, vasoplegia and cardiac depression are frequent. In literature, there are conflicting data on inotropic therapy in these patients. Methods Analysis of a retrospective registry of all patients treated with VA-ECMO in a university hospital center between October 2010 and December 2018 for cardiogenic shock or extracorporeal cardiopulmonary resuscitation (eCPR) with a focus on individual early inotropic therapy. Results A total of 231 patients (age 58.6 ± 14.3, 29.9% female, 58% eCPR, in-house survival 43.7%) were analyzed. Of these, 41.6% received no inotrope therapy within the first 24 h (survival 47.9%), 29.0% received an inodilator (survival 52.2%), and 29.0% received epinephrine (survival 25.0%). Survival of patients with epinephrine was significantly worse compared to other patient groups when evaluating 30-day survival (p = 0.034/p = 0.005) and cumulative incidence of in-hospital death (p = 0.001). In a multivariate logistic regression analysis, treatment with epinephrine was associated with mortality in the whole cohort (OR 0.38, p = 0.011) as well as after propensity score matching (OR 0.24, p = 0.037). We found no significant differences between patients with inodilator treatment and those without. Conclusion Early epinephrine therapy within the first 24 h after cannulation for VA-ECMO was associated with poor survival compared to patients with or without any inodilator therapy. Until randomized data are available, epinephrine should be avoided in patients on VA-ECMO.

Background: Patients supported with extracorporeal membrane oxygenation (ECMO) may develop elevated carboxyhemoglobin (CO-Hb), a finding described in the context of hemolysis. Clinical relevance of elevated CO-Hb in ECMO is unclear. We therefore investigated the prognostic relevance of CO-Hb during ECMO support. Methods: Data derives from a retrospective single-center registry study. All ECMO patients in a medical ICU from October 2010 through December 2019 were considered. Peak arterial CO-Hb value during ECMO support and median CO-Hb values determined by point-of-care testing for distinct time intervals were determined. Groups were divided by CO-Hb (p < 0.001, respectively). Hospital survival was significantly higher in patients with CO-Hb < 2% compared to CO-Hb ≥ 2%, evaluating time periods 24–48 h (48.6% vs. 35.2%, p = 0.003), 48–72 h (51.5% vs. 36.8%, p = 0.003), or >72 h (56.9% vs. 31.1%, p < 0.001) after ECMO cannulation. Peak CO-Hb was independently associated with lower hospital survival after adjustment for confounders. Conclusions: In ECMO, CO-Hb correlates with hemolysis and hospital survival. If high CO-Hb measured should trigger a therapeutic intervention in order to reduce hemolysis has to be investigated in prospective trials.

We report here on a 61-year-old patient with acute right heart failure of unclear etiology. Echocardiography revealed a myocardial mass infiltrating the heart, though, we assumed a cardiac lymphoma. A VA-ECMO was implanted as bridging for diagnosis and therapy. Our patient received chemotherapy, under which the tumor (of unknown etiology at this point) reached a partial remission. Nine months after first admission the patient developed acute myeloid leukemia with DNMT3a and TET2 mutations. Retrospective analysis of the cardiac biopsy revealed the identical mutations and matched with the diagnosis of an extremely rare primary extramedullary manifestation of an AML (myelosarcoma). The patient received induction-chemotherapy and was planned for consolidating allogeneic stem cell transplantation. From this case, we conclude that an extracorporeal therapy should be discussed in selected patients even in case of an initially fatal appearing prognosis. In selected cases, extracorporeal support can generate enough time for diagnosis and therapy. However, transparent planning, including discussion of best supportive care strategies involving the patient's family are indispensable requirements for starting ECMO in such patients.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) might be a lifesaving therapy for patients with cardiac arrest and no return of spontaneous circulation during advanced life support. However, even with ECPR, mortality of these severely sick patients is high. Little is known on the exact mode of death in these patients. Methods: Retrospective registry analysis of all consecutive patients undergoing ECPR between May 2011 and May 2020 at a single center. Mode of death was judged by two researchers. Results: A total of 274 ECPR cases were included (age 60.0 years, 47.1% shockable initial rhythm, median time-to-extracorporeal membrane oxygenation (ECMO) 53.8min, hospital survival 25.9%). The 71 survivors had shorter time-to-ECMO durations (46.0 ± 27.9 vs. 56.6 ± 28.8min, p < 0.01), lower initial lactate levels (7.9 ± 4.5 vs. 11.6 ± 8.4 mg/dL, p < 0.01), higher PREDICT-6h (41.7 ± 17.0% vs. 25.3 ± 19.0%, p < 0.01), and SAVE (0.4 ± 4.8 vs. −0.8 ± 4.4, p < 0.01) scores. Most common mode of death in 203 deceased patients was therapy resistant shock in 105/203 (51.7%) and anoxic brain injury in 69/203 (34.0%). Comparing patients deceased with shock to those with cerebral damage, patients with shock were significantly older (63.2 ± 11.5 vs. 54.3 ± 16.5 years, p < 0.01), more frequently resuscitated in-hospital (64.4% vs. 29.9%, p < 0.01) and had shorter time-to-ECMO durations (52.3 ± 26.8 vs. 69.3 ± 29.1min p < 0.01). Conclusions: Most patients after ECPR decease due to refractory shock. Older patients with in-hospital cardiac arrest might be prone to development of refractory shock. Only a minority die from cerebral damage. Research should focus on preventing post-CPR shock and treating the shock in these patients.

Evidence has arisen in recent years suggesting that a tissue renin-angiotensin system (tRAS) is involved in the progression of various human diseases. This system contains two regulatory pathways: a pathological pro-inflammatory pathway containing the Angiotensin Converting Enzyme (ACE)/Angiotensin II (AngII)/Angiotensin II receptor type 1 (AGTR1) axis and a protective anti-inflammatory pathway involving the Angiotensin II receptor type 2 (AGTR2)/ACE2/Ang1–7/MasReceptor axis. Numerous studies reported the positive effects of pathologic tRAS pathway inhibition and protective tRAS pathway stimulation on the treatment of cardiovascular, inflammatory, and autoimmune disease and the progression of neuropathic pain. Cell senescence and aging are known to be related to RAS pathways. Further, this system directly interacts with SARS-CoV 2 and seems to be an important target of interest in the COVID-19 pandemic. This review focuses on the involvement of tRAS in the progression of the mentioned diseases from an interdisciplinary clinical perspective and highlights therapeutic strategies that might be of major clinical importance in the future.

BackgroundReported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied.MethodsThis retrospective observational monocenter cohort study was performed after implementation of a non-restricted, dynamic tertiary care model at the University Medical Center Freiburg, an experienced acute respiratory distress syndrome (ARDS) and extracorporeal membrane-oxygenation (ECMO) referral center. All hospitalised patients with PCR-confirmed SARS-CoV-2 infection were included. The primary endpoint was in-hospital mortality, secondary endpoints included major complications and modes of death. A multistate analysis and a Cox regression analysis for competing risk models were performed. Modes of death were determined by two independent reviewers.ResultsBetween February 25, and May 8, 213 patients were included in the analysis. The median age was 65 years, 129 patients (61%) were male. 70 patients (33%) were admitted to the intensive care unit (ICU), of which 57 patients (81%) received mechanical ventilation and 23 patients (33%) ECMO support. Using multistate methodology, the estimated probability to die within 90 days after COVID-19 onset was 24% in the whole cohort. If the levels of care at time of study entry were accounted for, the probabilities to die were 16% if the patient was initially on a regular ward, 47% if in the intensive care unit (ICU) and 57% if mechanical ventilation was required at study entry. Age ≥65 years and male sex were predictors for in-hospital death. Predominant complications-as judged by two independent reviewers-determining modes of death were multi-organ failure, septic shock and thromboembolic and hemorrhagic complications.ConclusionIn a dynamic care model COVID-19-related in-hospital mortality remained very high. In the absence of potent antiviral agents, strategies to alleviate or prevent the identified complications should be investigated. In this context, multistate analyses enable comparison of models-of-care and treatment strategies and allow estimation and allocation of health care resources.

Aims: Strain rate imaging techniques have been proposed for the detection of ischemic or viable myocardium in coronary artery disease, which is still a challenge in clinical cardiology. This retrospective comparative study analyzed regional left ventricular function and scaring with two-dimensional strain (2DS) in the first 4 to 10 days after acute anterior myocardial infarction (AMI).Methods and results: The study population consisted of 32 AMI patients with an LAD occlusion and successful reperfusion. The assessment of peak systolic 2DS and peak systolic strain rate (SR) was performed segment-oriented with the angle-independent speckle tracking algorithm Velocity Vector Imaging (VVI). The infarcted, adjacent and non-infarcted segments were revealed by late enhancement MRI (LE-MRI), which was used as reference for the comparison with 2DS. The infarcted segments showed a significant decrease of tissue velocities, 2DS and SR in comparison to the non-affected segments.Conclusion: 2DS and SR as assessed by VVI seem to be a suitable approach for echocardiographic quantification of global and regional myocardial function as well as a promising tool for multimodal risk stratification after anterior AMI.