[This corrects the article DOI: 10.1016/j.bioactmat.2022.04.015.].
Regenerative bone implants promote new bone formation and ideally degrade simultaneously to osteogenesis. Although clinically established calcium phosphate bone grafts provide excellent osseointegration and osteoconductive efficacy, they are limited in terms of bioresorption. Magnesium phosphate (MP) based ceramics are a promising alternative, because they are biocompatible, mechanically extremely stable, and degrade much faster than calcium phosphates under physiological conditions. Bioresorption of an implant material can include both chemical dissolution as well as cellular resorption. We investigated the bioresorption of 3D powder printed struvite and newberyite based MP ceramics in vitro by a direct human osteoclast culture approach. The osteoclast response and cellular resorption was evaluated by means of fluorescence and TRAP staining, determination of osteoclast activities (CA II and TRAP), SEM imaging as well as by quantification of the ion release during cell culture. Furthermore, the bioactivity of the materials was investigated via SBF immersion, whereas hydroxyapatite precipitates were analyzed by SEM and EDX measurements. This bioactive coating was resorbed by osteoclasts. In contrast, only chemical dissolution contributed to bioresorption of MP, while no cellular resorption of the materials was observed. Based on our results, we expect an increased bone regeneration effect of MP compared to calcium phosphate based bone grafts and complete chemical degradation within a maximum of 1.5–3.1 years.
In Sinorhizobium meliloti, the methionine biosynthesis genes metA and metZ are preceded by S-adenosyl-L-methionine (SAM) riboswitches of the SAM-II class. Upon SAM binding, structural changes in the metZ riboswitch were predicted to cause transcriptional termination, generating the sRNA RZ. By contrast, the metA riboswitch was predicted to regulate translation from an AUG1 codon. However, downstream of the metA riboswitch, we found a putative Rho-independent terminator and an in-frame AUG2 codon, which may contribute to metA regulation. We validated the terminator between AUG1 and AUG2, which generates the sRNA RA1 that is processed to RA2. Under high SAM conditions, the activities of the metA and metZ promoters and the steady-state levels of the read-through metA and metZ mRNAs were decreased, while the levels of the RZ and RA2 sRNAs were increased. Under these conditions, the sRNAs and the mRNAs were stabilized. Reporter fusion experiments revealed that the Shine-Dalgarno (SD) sequence in the metA riboswitch is required for translation, which, however, starts 74 nucleotides downstream at AUG2, suggesting a novel translation initiation mechanism. Further, the reporter fusion data supported the following model of RNA-based regulation: Upon SAM binding by the riboswitch, the SD sequence is sequestered to downregulate metA translation, while the mRNA is stabilized. Thus, the SAM-II riboswitches fulfil incoherent, dual regulation, which probably serves to ensure basal metA and metZ mRNA levels under high SAM conditions. This probably helps to adapt to changing conditions and maintain SAM homoeostasis.
Background Research results on the training intensity distribution (TID) in endurance athletes are equivocal. This non-uniformity appears to be partially founded in the different quantification methods that are implemented. So far, TID research has solely focused on sports involving the lower-body muscles as prime movers (e.g. running). Sprint kayaking imposes high demands on the upper-body endurance capacity of the athlete. As there are structural and physiological differences between upper- and lower-body musculature, TID in kayaking should be different to lower-body dominant sports. Therefore, we aimed to compare the training intensity distribution during an 8-wk macrocycle in a group of highly trained sprint kayakers employing three different methods of training intensity quantification. Methods Heart rate (HR) and velocity during on-water training of nine highly trained German sprint kayakers were recorded during the final 8 weeks of a competition period leading to the national championships. The fractional analysis of TID was based on three zones (Z) derived from either HR (TIDBla-HR) or velocity (TIDBla-V) based on blood lactate (Bla) concentrations (Z1 ≤ 2.5 mmol L⁻¹ Bla, Z2 = 2.5–4.0 mmol L⁻¹ Bla, Z3 ≥ 4.0 mmol L⁻¹ Bla) of an incremental test or the 1000-m race pace (TIDRace): Z1 ≤ 85% of race pace, Z2 = 86–95% and Z3 ≥ 95%. Results TIDBla-V (Z1: 68%, Z2: 14%, Z3: 18%) differed from TIDBla-HR (Z1: 91%, Z2: 6%, Z3: 3%) in each zone (all p < 0.01). TIDRace (Z1: 73%, Z2: 20%, Z3: 7%) differed to Z3 in TIDBla-V (p < 0.01) and all three TIDBla-HR zones (all p < 0.01). Individual analysis revealed ranges of Z1, Z2, Z3 fractions for TIDBla-HR of 85–98%, 2–11% and 0.1–6%. For TIDBla-V, the individual ranges were 41–82% (Z1), 6–30% (Z2) and 8–30% (Z3) and for TIDRace 64–81% (Z1), 14–29% (Z2) and 4–10% (Z3). Conclusion The results show that the method of training intensity quantification substantially affects the fraction of TID in well-trained sprint kayakers. TIDRace determination shows low interindividual variation compared to the physiologically based TIDBla-HR and TIDBla-V. Depending on the aim of the analysis TIDRace, TIDBla-HR and TIDBla-V have advantages as well as drawbacks and may be implemented in conjunction to maximize adaptation.
Objective Portable gas exchange instruments allow the assessment of peak oxygen uptake (V̇O 2peak ) but are often bulky, expensive and require wearing a face mask thereby limiting their routine application. A newly developed miniaturized headset (VitaScale, Nuremberg, Germany) may overcome these barriers and allow measuring V̇O 2peak without applying a face mask. Here we aimed (i) to disclose the technical setup of a headset incorporating a gas and volume sensor to measure volume flow and expired oxygen concentration and (ii) to assess the concurrent criterion-validity of the headset to measure V̇O 2peak in 44 individuals exercising on a stationary cycle ergometer in consideration of the test–retest reliability of the criterion measure. Results The coefficient of variation (CV%) while measuring V̇O 2peak during incremental cycling with the headset was 6.8%. The CV% for reliability of the criterion measure was 4.0% for V̇O 2peak . Based on the present data, the headset might offer a new technology for V̇O 2peak measurement due to its low-cost and mask-free design.
Background Artistic gymnastics is a popular Olympic discipline where female athletes compete in four and male athletes in six events with floor exercise having the longest competition duration in Women’s and Men’s artistic gymnastics (WAG, MAG). To date no valid information on the energetics of floor gymnastics is available although this may be important for specific conditioning programming. This study evaluated the metabolic profile of a simulated floor competition in sub-elite gymnasts. Methods 17 (9 male, 8 female) sub-elite gymnasts aged 22.5 ± 2.6y took part in a floor-training-competition where oxygen uptake was measured during and until 15 min post-exercise. Additionally, resting and peak blood lactate concentration after exercise were obtained. The PCr-LA-O2 method was used to calculate the metabolic energy and the relative aerobic (WAER), anaerobic alactic (WPCr) and anaerobic lactic (WBLC) energy contribution. Further, the athletes completed a 30 s Bosco-jumping test, a countermovement jump and a drop jump. Results The competition scores were 9.2 (CI:8.9–9.3) in WAG and 10.6 (CI:10.4–10.9) in MAG. The metabolic profile of the floor routine was mainly aerobic (58.9%, CI: 56.0–61.8%) followed by the anaerobic alactic (24.2%, CI: 21.3–27.1%) and anaerobic lactic shares (16.9%, CI:14.9–18.8%). While sex had a significant (p = .010, d = 1.207) large effect on energy contribution, this was not the case for competition duration (p = .728, d = 0.061). Relative energy contribution of WAG and MAG differed in WAER (64.0 ± 4.7% vs. 54.4 ± 6.8%, p = .004, d = 1.739) but not in WPCr (21.3 ± 6.1% vs. 26.7 ± 8.0%, p = .144, d = 0.801) and WBLC (14.7 ± 5.4% vs. 18.9 ± 4.2%, p = .085, d = 0.954). Further no correlation between any energy share and performance was found but between WPCr and training experience (r = .680, p = .044) and WBLC and competition level (r = .668, p = .049). Conclusion The results show a predominant aerobic energy contribution and a considerable anaerobic contribution with no significant difference between anaerobic shares. Consequently, gymnastic specific aerobic training should not be neglected, while a different aerobic share in WAG and MAG strengthens sex-specific conditioning. All in all, the specific metabolic share must secure adequate energy provision, while relative proportions of the two anaerobic pathways seem to depend on training and competition history.
We discover three-dimensional intertwined Weyl phases, by developing a theory to create topological phases. The theory is based on intertwining existing topological gapped and gapless phases protected by the same crystalline symmetry. The intertwined Weyl phases feature both unconventional Weyl semimetallic (monopole charge>1) and higher-order topological phases, and more importantly, their exotic intertwining. While the two phases are independently stabilized by the same symmetry, their intertwining results in the specific distribution of them in the bulk. The construction mechanism allows us to combine different kinds of unconventional Weyl semimetallic and higher-order topological phases to generate distinct phases. Remarkably, on 2D surfaces, the intertwining causes the Fermi-arc topology to change in a periodic pattern against surface orientation. This feature provides a characteristic and feasible signature to probe the intertwining Weyl phases. Moreover, we provide guidelines for searching candidate materials, and elaborate on emulating the intertwined double-Weyl phase in cold-atom experiments.
The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hard scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.
Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. Trial registration ClinicalTrials.gov; Identifier: NCT03563677; First posted: June 20, 2018, https://clinicaltrials.gov/ct2/show/NCT03563677 .
The UK House of Commons Science and Technology Committee has called for evidence on the roles that different stakeholders play in reproducibility and research integrity. Of central priority are proposals for improving research integrity and quality, as well as guidance and support for researchers. In response to this, we argue that there is one important component of research integrity that is often absent from discussion: the pedagogical consequences of how we teach, mentor, and supervise students through open scholarship. We justify the need to integrate open scholarship principles into research training within higher education and argue that pedagogical communities play a key role in fostering an inclusive culture of open scholarship. We illustrate these benefits by presenting the Framework for Open and Reproducible Research Training (FORRT) , an international grassroots community whose goal is to provide support, resources, visibility, and advocacy for the adoption of principled, open teaching and mentoring practices, whilst generating conversations about the ethics and social impact of higher-education pedagogy. Representing a diverse group of early-career researchers and students across specialisms, we advocate for greater recognition of and support for pedagogical communities, and encourage all research stakeholders to engage with these communities to enable long-term, sustainable change.
Cancer therapies with anthracyclines have been shown to induce cardiovascular complications. The aims of this study were to establish an in vitro induced pluripotent stem cell model (iPSC) of anthracycline-induced cardiotoxicity (ACT) from patients with an aggressive form of B-cell lymphoma and to examine whether doxorubicin (DOX)-treated ACT-iPSC cardiomyocytes (CM) can recapitulate the clinical features exhibited by patients, and thus help uncover a DOX-dependent pathomechanism. ACT-iPSC CM generated from individuals with CD20⁺ B-cell lymphoma who had received high doses of DOX and suffered cardiac dysfunction were studied and compared to control-iPSC CM from cancer survivors without cardiac symptoms. In cellular studies, ACT-iPSC CM were persistently more susceptible to DOX toxicity including augmented disorganized myofilament structure, changed mitochondrial shape, and increased apoptotic events. Consistently, ACT-iPSC CM and cardiac fibroblasts isolated from fibrotic human ACT myocardium exhibited higher DOX-dependent reactive oxygen species. In functional studies, Ca²⁺ transient amplitude of ACT-iPSC CM was reduced compared to control cells, and diastolic sarcoplasmic reticulum Ca²⁺ leak was DOX-dependently increased. This could be explained by overactive CaMKIIδ in ACT CM. Together with DOX-dependent augmented proarrhythmic cellular triggers and prolonged action potentials in ACT CM, this suggests a cellular link to arrhythmogenic events and contractile dysfunction especially found in ACT engineered human myocardium. CamKIIδ inhibition prevented proarrhythmic triggers in ACT. In contrast, control CM upregulated SERCA2a expression in a DOX-dependent manner, possibly to avoid heart failure conditions. In conclusion, we developed the first human patient-specific stem cell model of DOX-induced cardiac dysfunction from patients with B-cell lymphoma. Our results suggest that DOX-induced stress resulted in arrhythmogenic events associated with contractile dysfunction and finally in heart failure after persistent stress activation in ACT patients.
The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed to meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.
Purpose Despite much improved preoperative planning techniques accurate intraoperative assessment of the high tibial valgus osteotomy (HTO) remains challenging and often results in coronal over- and under-corrections as well as unintended changes of the posterior tibial slope. Noyes et al. reported a novel method for accurate intraoperative coronal and sagittal alignment correction based on a three-dimensional mathematical model. This is the first study examining preliminary data via the proposed Noyes approach for accurate intraoperative coronal and sagittal alignment correction during HTO. Methods From 2016 to 2020 a total of 24 patients (27 knees) underwent HTO applying the proposed Noyes method (Noyes-Group). Radiographic data was analyzed retrospectively and matched to patients that underwent HTO using the conventional method, i.e., gradual medial opening using a bone spreader under fluoroscopic control (Conventional-Group). All operative procedures were performed by an experienced surgeon at a single orthopaedic university center. Results From the preoperative to the postoperative visit no statistically significant changes of the posterior tibial slope were noted in the Noyes-Group compared to a significant increase in the Conventional-Group ( p = 0.01). Regarding the axial alignment no significant differences between both groups were observed pre- and postoperatively. The number of over- and under-corrections did not differ significantly between both groups. Linear regression analysis showed a significant correlation of the postoperative medial proximal tibial angle (MPTA) with the position of the weightbearing line on the tibial plateau. Conclusion The 3-triangle method by Noyes seems to be a promising approach for preservation of the posterior tibial slope during HTO.
Background In severe cases, SARS-CoV-2 infection leads to acute respiratory distress syndrome (ARDS), often treated by extracorporeal membrane oxygenation (ECMO). During ECMO therapy, anticoagulation is crucial to prevent device-associated thrombosis and device failure, however, it is associated with bleeding complications. In COVID-19, additional pathologies, such as endotheliitis, may further increase the risk of bleeding complications. To assess the frequency of bleeding events, we analyzed data from the German COVID-19 autopsy registry (DeRegCOVID). Methods The electronic registry uses a web-based electronic case report form. In November 2021, the registry included N = 1129 confirmed COVID-19 autopsy cases, with data on 63 ECMO autopsy cases and 1066 non-ECMO autopsy cases, contributed from 29 German sites. Findings The registry data showed that ECMO was used in younger male patients and bleeding events occurred much more frequently in ECMO cases compared to non-ECMO cases (56% and 9%, respectively). Similarly, intracranial bleeding (ICB) was documented in 21% of ECMO cases and 3% of non-ECMO cases and was classified as the immediate or underlying cause of death in 78% of ECMO cases and 37% of non-ECMO cases. In ECMO cases, the three most common immediate causes of death were multi-organ failure, ARDS and ICB, and in non-ECMO cases ARDS, multi-organ failure and pulmonary bacterial ± fungal superinfection, ordered by descending frequency. Interpretation Our study suggests the potential value of autopsies and a joint interdisciplinary multicenter (national) approach in addressing fatal complications in COVID-19.
Background Performance of high-intensity interval training (HIIT) by children and adolescents improves physical and health-related fitness, as well as cardiometabolic risk factors. Objectives To assess the impact of HIIT performed at school, i.e. both in connection with physical education (intra-PE) and extracurricular sports activities (extra-PE), on the physical fitness and health of children and adolescents. Methods PubMed and SPORTDiscus were searched systematically utilizing the following criteria for inclusion: (1) healthy children and adolescents (5–18 years old) of normal weight; (2) HIIT performed intra- and/or extra-PE for at least 5 days at an intensity ≥ 80% of maximal heart rate (HR max ) or peak oxygen uptake (VO 2peak ) or as Functional HIIT; (3) comparison with a control (HIIT versus alternative interventions); and (4) pre- and post-analysis of parameters related to physical fitness and health. The outcomes with HIIT and the control interventions were compared utilizing Hedges’ g effect size (ES) and associated 95% confidence intervals. Results Eleven studies involving 707 participants who performed intra-PE and 388 participants extra-PE HIIT were included. In comparison with the control interventions, intra-PE HIIT improved mean ES for neuromuscular and anaerobic performance (ES jump performance: 5.89 ± 5.67 (range 1.88–9.90); ES number of push-ups: 6.22 (range n.a.); ES number of sit-ups: 2.66 ± 2.02 (range 1.24–4.09)), as well as ES fasting glucose levels (− 2.68 (range n.a.)) more effectively, with large effect sizes. Extra-PE HIIT improved mean ES for neuromuscular and anaerobic performance (ES jump performance: 1.81 (range n.a.); ES number of sit-ups: 2.60 (range n.a.)) to an even greater extent, again with large effect sizes. Neither form of HIIT was more beneficial for parameters related to cardiorespiratory fitness than the control interventions. Conclusion Compared to other forms of exercise (e.g. low-to-moderate-intensity running or walking), both intra- and extra-PE HIIT result in greater improvements in neuromuscular and anaerobic performance, as well as in fasting levels of glucose in school children.
Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.
Background Fast and accurate T 1ρ mapping in myocardium is still a major challenge, particularly in small animal models. The complex sequence design owing to electrocardiogram and respiratory gating leads to quantification errors in in vivo experiments, due to variations of the T 1ρ relaxation pathway. In this study, we present an improved quantification method for T 1ρ using a newly derived formalism of a T 1ρ * relaxation pathway. Methods The new signal equation was derived by solving a recursion problem for spin-lock prepared fast gradient echo readouts. Based on Bloch simulations, we compared quantification errors using the common monoexponential model and our corrected model. The method was validated in phantom experiments and tested in vivo for myocardial T 1ρ mapping in mice. Here, the impact of the breath dependent spin recovery time T rec on the quantification results was examined in detail. Results Simulations indicate that a correction is necessary, since systematically underestimated values are measured under in vivo conditions. In the phantom study, the mean quantification error could be reduced from − 7.4% to − 0.97%. In vivo, a correlation of uncorrected T 1ρ with the respiratory cycle was observed. Using the newly derived correction method, this correlation was significantly reduced from r = 0.708 (p < 0.001) to r = 0.204 and the standard deviation of left ventricular T 1ρ values in different animals was reduced by at least 39%. Conclusion The suggested quantification formalism enables fast and precise myocardial T 1ρ quantification for small animals during free breathing and can improve the comparability of study results. Our new technique offers a reasonable tool for assessing myocardial diseases, since pathologies that cause a change in heart or breathing rates do not lead to systematic misinterpretations. Besides, the derived signal equation can be used for sequence optimization or for subsequent correction of prior study results.
Background Electrically evoked auditory brainstem response (E-ABR) is an evoked potential recorded from the auditory nerve in response to electric stimulation. It is considered a short latency evoked potential. It plays a vital role, especially after the increased number of cochlear implant receivers. Body of abstract E-ABR is characterized by three positive peaks (eII, eIII, and eV) generated from the auditory nerve, cochlear nucleus, and perhaps from neurons in the lateral lemniscus or inferior colliculus. The largest is corresponding to wave V of the acoustic one. There are differences between both acoustic auditory brainstem response (A-ABR) and E-ABR. E-ABR is characterized by larger amplitudes and shorter latencies than the acoustic, and it has a steeper latency-intensity function. There are many variables affecting the E-ABR waveform, including recording-related variables, stimulus-related variables, and subject-related variables. E-ABR has potential clinical applications in cochlear implants (pre, inter, and postoperative). Conclusion After the increase in the number of cochlear implant receivers, E-ABR provides a promising new tool that can be used to evaluate auditory nerve functions. A lot of factors affect its waveform, including recording-related factors and stimulus-related and subject-related variables. E-ABR has many clinical applications, not only in post-implantation situations but also in preimplantation.
Background Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. Methods 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. Results Most patients were between 50 and 70 years of age. PaO 2 /FiO 2 ratio prior to ECMO was 72 mmHg (IQR: 58–99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) ( p = 0.0014, OR 0.64 (CI 0.41–0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively ( p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28–1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. Conclusions Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. Trial registration Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 . Graphical abstract
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