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Background: The number of advanced heart failure patients with left ventricular assist devices (LVAD) is increasing. Despite guideline-recommendations, little is known about specialist palliative care involvement in LVAD-patients, especially in Europe. This study aims to investigate timing and setting of specialist palliative care in LVAD-patients., Methods: We conducted a retrospective multicenter study in 2022. Specialist palliative care services in German LVAD-centers were identified and invited to participate. Forty adult LVAD-patients (mean age 65 years (SD 7.9), 90% male) from seven centers that received a specialist palliative care consultation during hospitalization were included., Results: In 37 (67.3%) of the 55 LVAD-centers, specialist palliative care was available. The median duration between LVAD-implantation and first specialist palliative care contact was 17 months (IQR 6.3-50.3 months). Median duration between consultation and death was seven days (IQR 3-28 days). 65% of consults took place in an intensive/intermediate care unit with half of the patients having a Do-Not-Resuscitate order. Care planning significantly increased during involvement (advance directives before: n = 15, after: n = 19, p < 0.001; DNR before: n = 20, after: n = 28, p < 0.001). Symptom burden as assessed at first specialist palliative care contact was higher compared to the consultation requests (request: median 3 symptoms (IQR 3-6); first contact: median 9 (IQR 6-10); p < 0.001) with a focus on weakness, anxiety, overburdening of next-of-kin and dyspnea. More than 70% of patients died during index hospitalization, one third of these in a palliative care unit., Conclusions: This largest European multicenter investigation of LVAD-patients receiving specialist palliative care shows a late integration and high physical and psychosocial symptom burden. This study highlights the urgent need for earlier integration to identify and address poorly controlled symptoms. Further studies and educational efforts are needed to close the gap between guideline-recommendations and the current status quo., (© 2024. The Author(s).)

Purpose: Triggers have been developed internationally to identify intensive care patients with palliative care needs. Due to their work, nurses are close to the patient and their perspective should therefore be included. In this study, potential triggers were first identified and then a questionnaire was developed to analyse their acceptance among German intensive care nurses., Methods: For the qualitative part of this mixed methods study, focus groups were conducted with intensive care nurses from different disciplines (surgery, neurosurgery, internal medicine), which were selected by convenience. Data were analysed using the "content-structuring content analysis" according to Kuckartz. For the quantitative study part, the thus identified triggers formed the basis for questionnaire items. The questionnaire was tested for comprehensibility in cognitive pretests and for feasibility in a pilot survey., Results: In the qualitative part six focus groups were conducted at four university hospitals. From the data four main categories (prognosis, interprofessional cooperation, relatives, patients) with three to 15 subcategories each could be identified. The nurses described situations requiring palliative care consults that related to the severity of the disease, the therapeutic course, communication within the team and between team and patient/relatives, and typical characteristics of patients and relatives. In addition, a professional conflict between nurses and physicians emerged. The questionnaire, which was developed after six cognitive interviews, consists of 32 items plus one open question. The pilot had a response rate of 76.7% (23/30), whereby 30 triggers were accepted with an agreement of ≥ 50%., Conclusion: Intensive care nurses see various triggers, with interprofessional collaboration and the patient's prognosis playing a major role. The questionnaire can be used for further surveys, e.g. interprofessional triggers could be developed., (© 2024. The Author(s).)

Importance: Cardiopulmonary resuscitation (CPR) is an exceptional physical situation and may lead to significant psychological, spiritual, and social distress in patients and their next of kin. Furthermore, clinicians might experience distress related to a CPR event. Specialist palliative care (sPC) integration could address these aspects but is not part of routine care., Objectives: This study aimed to explore perspectives on sPC integration during and after CPR. A needs assessment for sPC, possible triggers indicating need, and implementation strategies were addressed., Design Setting and Participants: A multiprofessional qualitative semistructured focus group study was conducted in a German urban academic teaching hospital. Participants were clinicians (nursing staff, residents, and consultants) working in the emergency department and ICUs (internal medicine and surgical)., Analysis: The focus groups were recorded and subsequently transcribed. Data material was analyzed using the content-structuring content analysis according to Kuckartz., Results: Seven focus groups with 18 participants in total were conducted online from July to November 2022. Six main categories (two to five subcategories) were identified: understanding (of palliative care and death), general CPR conditions (e.g., team, debriefing, and strains), prognosis (e.g., preexisting situation, use of extracorporeal support), next of kin (e.g., communication, presence during CPR), treatment plan (patient will and decision-making), and implementation of sPC (e.g., timing, trigger factors)., Conclusions: Perceptions about the need for sPC to support during and after CPR depend on roles, areas of practice, and individual understanding of sPC. Although some participants perceive CPR itself as a trigger for sPC, others define, for example, pre-CPR-existing multimorbidity or complex family dynamics as possible triggers. Suggestions for implementation are multifaceted, especially communication by sPC is emphasized. Specific challenges of extracorporeal CPR need to be explored further. Overall, the focus groups show that the topic is considered relevant, and studies on outcomes are warranted., Competing Interests: Dr. Tenge has received a grant (Walter Benjamin Fellowship, TE 1567/1-1) from the German Research Foundation. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Background: The desire to die can occur in palliative care patients with a prevalence of up to 22%. Not every desire to die is accompanied by a pressure to act, but usually by a burden that can arise from various factors. To address this burden appropriately, health care workers should be trained. Based on an evaluated course on handling the desire to die, an elective course for medical students was developed and evaluated. In order to identify the impact of the elective course's content, a comparison of attitudes towards assisted dying with two other participant groups was conducted. Therefore, three questions from the evaluation of the elective course were used., Method: Online evaluation of the elective and questions addressing attitude were assessed using a five-point Likert scale. The specific outcome-based assessment was determined using the Comparative Self-Assessment Gain. The main participant group (group 1) were students who took the elective. The additional survey on attitudes towards assisted dying included undergraduate medical students who had taken compulsory palliative care courses (group 2) and physicians who had taken an introductory course in intensive care or emergency medicine (group 3)., Results: Group 1 (n = 13, response rate rr = 86.7%) was very satisfied with the blended learning format (100%) and the course itself (100%). They were able to deepen their knowledge (81.0%) and train skills (71.2%) through the course. In the additional surveys, there were 37 students in group 2 (rr = 66.1%) and 258 physicians in group 3 (rr = 73.6%). Willingness to assist with or accompany the various options for assisted dying varied according to the type of assistance. Among the participants, it can be summarised that the highest willingness was shown by the students of group 2 followed by the physicians of group 3 and the students of group 1., Conclusions: A course on handling the desire to die of palliative patients can deepen knowledge and train communication skills and thus support self-confidence. Dealing with the background of the desire to die, knowledge about assisted dying, but also one's own attitudes and responsibilities can influence the attitude towards assisted dying., (© 2024. The Author(s).)

Hemodynamic stabilization plays a crucial role in the treatment of patients suffering from severe trauma. Current guidelines recommend the early administration of tranexamic acid (TXA) for bleeding control. While less blood loss can result in less end-organ damage, including myocardial injury, TXA also exhibits prothrombotic effects with potentially adverse myocardial effects. The aim of this study was to investigate the association between the administration of TXA and myocardial injury in patients with severe trauma. We conducted a monocentric cohort study including severely injured patients ≥ 18 years [defined by Injury severity score (ISS) ≥ 16], who were admitted to a tertiary care hospital between 2016 and 2019. Primary outcome measure was myocardial injury according to the fourth Universal Definition (= high sensitive troponin T ≥ 14 ng/l). Secondary endpoints were in-hospital major adverse cardiovascular events (MACE) and mortality. Main exposure was defined as administration of TXA during prehospital period. We conducted multivariate logistic regression models including predefined covariables. A total of 368 patients were screened. Among the 297 included patients (72% male, age. 55?21 years), 119 (40%) presented myocardial injury at hospital arrival. TXA was administered to 20/297 (7%) patients in the prehospital setting, and in 96/297 (32%) patients during pre-or in-hospital period. MACE incidence was 9% (26/297) and in-hospital mortality was 26% (76/297). The adjusted odds ratios (OR) for prehospital TXA and myocardial injury, MACE and mortality were 0.75 [95% confidence interval (CI): 0.25-2.23], 0.51 [95%CI: 0.06-4.30] and 0.84 [0.21-3.33], respectively. In the present cohort of patients suffering from severe trauma, prehospital TXA did not affect the incidence of myocardial injury., (© 2023. The Author(s).)

Objectives: In patients undergoing heart transplantation (HTX), preoperative liver impairment and consecutive hypoalbuminaemia are associated with increased mortality. The role of early postoperative hypoalbuminaemia after HTX is unclear. This study investigated the association between early postoperative hypoalbuminaemia and 1-year mortality as well as 'days alive and out of hospital' (DAOH) after HTX., Methods: This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany, between 2010 and 2022. The main exposure was serum albumin concentration at intensive care unit (ICU) arrival. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis was performed and logistic and quantile regression models with adjustment for 13 a priori defined clinical risk factors were conducted., Results: Out of 241 patients screened, 229 were included in the analysis (mean age 55 ± 11 years, 73% male). ROC analysis showed moderate discrimination for 1-year mortality by postoperative serum albumin after HTX [AUC = 0.74; 95% confidence interval (CI): 0.66-0.83]. The cutoff for serum albumin at ICU arrival was 3.0 g/dl. According to multivariate logistic and quantile regression, there were independent associations between hypoalbuminaemia and mortality/DAOH [odds ratio of 4.76 (95% CI: 1.94-11.67) and regression coefficient of -46.97 (95% CI: -83.81 to -10.13)]., Conclusions: Postoperative hypoalbuminaemia <3.0 g/dl is associated with 1-year mortality and reduced DAOH after HTX and therefore might be used for early postoperative risk re-assessment in clinical practice., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Health-care professionals are confronted with patients who wish to end their lives through voluntarily stopping eating and drinking (VSED). During VSED, symptoms such as agitation, thirst or psychological distress may arise, thus making close medical accompaniment necessary. Dealing with these symptoms can put a high burden on palliative care teams. Furthermore, divergent perceptions of the ethical classification of VSED may lead to moral distress. The aim of this study was to assess the influence of experience gained over time on the burden of palliative care professionals while accompanying patients during VSED and to assess the perceptions of coping strategies., Methods: This is a prospective single-centre study conducted at the Interdisciplinary Centre for Palliative Care at University Hospital Duesseldorf, Germany. At two points in time (T1, T2) one year apart, team members of all professions who were actively involved in the accompaniment were eligible to complete a pretested questionnaire., Results: Team members perceived the symptom complex of psychological distress, anxiety, and agitation to be the most burdensome symptoms for the patients (T1: 28/49, 57.1%; T2: 33/59, 55.9%). Thirst was the second most observed symptom (T1: 17/49, 34.7%, T2: 19/59, 32.2%). These were also the most burdensome symptoms for individual team members. Most team members found there were no general moral concerns. There was a decrease in the perceived importance of support strategies such as ethical counselling (85.7% versus 63.6%)., Conclusions: Accompanying patients during VSED is a challenge for health-care professionals. When comparing T2 to T1, less emphasis lies on the importance of ethical counselling or psychiatric assessment to build a foundation for the accompaniment. Moral and ethical concerns seem to play a minor role. More in-depth studies covering a bigger sample size as well as qualitative studies are needed., (© 2023. The Author(s).)

In addition to advance care instruments, such as advance directives and healthcare powers of attorney, adapted directives for emergency situations might be beneficial. These could avoid problems occurring with advance directives (e.g., lack of availability in acute emergencies, insufficient applicability to specific situations) when patients are no longer capable of making decisions but prompt decisions are required. Patients at the end of life are particularly relevant in this context, as they can refuse invasive procedures. Emergency advance directives should provide legally certain, quickly accessible and easily interpretable information about patient wishes regarding procedures such as resuscitation, intubation, and hospital admission. This narrative review provides a compact overview in the form of a needs and current status survey on emergency advance directives in Germany, presenting clinical and research projects. Overall, the current situation is one of inconsistent and insufficient implementation, with a concurrent increase in the proportion of palliative care patients in emergency services.An acute need for action to strengthen the cooperation between palliative medicine, emergency medicine and rescue services emerges. Training on palliative knowledge and care of patients at the end of life is also useful for prehospital care., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Microcirculatory and mitochondrial dysfunction are considered the main mechanisms of septic shock. Studies suggest that statins modulate inflammatory response, microcirculation, and mitochondrial function, possibly through their action on peroxisome proliferator-activated receptor alpha (PPAR-α). The aim of this study was to examine the effects of pravastatin on microcirculation and mitochondrial function in the liver and colon and the role of PPAR-α under septic conditions. This study was performed with the approval of the local animal care and use committee. Forty Wistar rats were randomly divided into 4 groups: sepsis (colon ascendens stent peritonitis, CASP) without treatment as control, sepsis + pravastatin, sepsis + PPAR-α-blocker GW6471, and sepsis + pravastatin + GW6471. Pravastatin (200 µg/kg s.c.) and GW6471 (1 mg/kg) were applied 18 h before CASP-operation. 24 h after initial surgery, a relaparotomy was performed, followed by a 90 min observation period for assessment of microcirculatory oxygenation (μHbO 2 ) of the liver and colon. At the end of the experiments, animals were euthanized, and the colon and liver were harvested. Mitochondrial function was measured in tissue homogenates using oximetry. The ADP/O ratio and respiratory control index (RCI) for complexes I and II were calculated. Reactive oxygen species (ROS) production was assessed using the malondialdehyde (MDA)-Assay. Statistics: two-way analysis of variance (ANOVA) + Tukey's/Dunnett's post hoc test for microcirculatory data, Kruskal-Wallis test + Dunn's post hoc test for all other data. In control septic animals µHbO 2 in liver and colon deteriorated over time (µHbO 2 : -9.8 ± 7.5%* and -7.6 ± 3.3%* vs. baseline, respectively), whereas after pravastatin and pravastatin + GW6471 treatment μHbO 2 remained constant (liver: µHbO 2 pravastatin: -4.21 ± 11.7%, pravastatin + GW6471: -0.08 ± 10.3%; colon: µHbO 2 pravastatin: -0.13 ± 7.6%, pravastatin + GW6471: -3.00 ± 11.24%). In both organs, RCI and ADP/O were similar across all groups. The MDA concentration remained unchanged in all groups. Therefore, we conclude that under septic conditions pravastatin improves microcirculation in the colon and liver, and this seems independent of PPAR-α and without affecting mitochondrial function.

Background: Orthotopic heart transplantation (HTX) is the gold standard to treat end-stage heart failure. Numerous risk stratification tools have been developed in the past years. However, their clinical utility is limited by their poor discriminative ability. High sensitivity troponin T (hsTnT) is the most specific biomarker to detect myocardial cell injury. However, its prognostic relevance after HTX is not fully elucidated. Thus, this study evaluated the predictive value of postoperative hsTnT for 1-year survival and days alive and out of hospital (DAOH) after HTX., Methods: This retrospective cohort study included patients who underwent HTX at the University Hospital Duesseldorf, Germany between 2011 and 2021. The main exposure was hsTnT concentration at 48 h after HTX. The primary endpoints were mortality and DAOH within 1 year after surgery. Receiver operating characteristic (ROC) curve analysis, logistic regression model and linear regression with adjustment for risk index for mortality prediction after cardiac transplantation (IMPACT) were performed., Results: Out of 231 patients screened, 212 were included into analysis (mean age 55 ± 11 years, 73% male). One-year mortality was 19.7% (40 patients) and median DAOH was 298 days (229-322). ROC analysis revealed strongest discrimination for mortality by hsTnT at 48 h after HTX [AUC = 0.79 95% CI 0.71-0.87]. According to Youden Index, the cutoff for hsTnT at 48 h and mortality was 1640 ng/l. After adjustment for IMPACT score multivariate logistic and linear regression showed independent associations between hsTnT and mortality/DAOH with odds ratio of 8.10 [95%CI 2.99-21.89] and unstandardized regression coefficient of -1.54 [95%CI -2.02 to -1.06], respectively., Conclusion: Postoperative hsTnT might be suitable as an early prognostic marker after HTX and is independently associated with 1-year mortality and poor DAOH., (© 2023. The Author(s).)

Background: Severe trauma potentially results in end-organ damage such as myocardial injury. Data suggest that myocardial injury is associated with increased mortality in this cohort, but the association with the incidence of in-hospital major adverse cardiac events (MACE) remains undetermined., Methods: Retrospective cohort study including adult patients with severe trauma treated at the University Hospital Duesseldorf between January 2016 and December 2019. The main exposure was myocardial injury at presentation. Endpoints were in-hospital incidence of MACE and incidence of acute kidney injury (AKI) within 72 h. Discrimination of hsTnT for MACE and AKI was examined by the receiver operating characteristic curve (ROC) and the area under the curve (AUC). We conducted multivariate logistic regression analysis., Results: We included 353 patients in our final analysis (72.5% male (256/353), age: 55 ± 21 years). The AUC for hsTnT and MACE was 0.68 [95% confidence interval (CI): 0.59-0.78]. The AUC for hsTnT and AKI was 0.64 [95% (CI): 0.55-0.72]. The adjusted odds ratio (OR) for myocardial injury and MACE was 2.97 [95% (CI): 1.31-6.72], and it was 2.14 [95% (CI): 1.03-4.46] for myocardial injury and AKI., Conclusion: Myocardial injury at presentation in patients with severe trauma is independently associated with the incidence of in-hospital MACE and AKI.

The two main surgical options to treat end-stage heart failure are heart transplantation (HTx) or left ventricular assist device (LVAD) implantation. In hemodynamically stable patients, the decision for HTx listing with or without LVADs is challenging. We analyzed the impact of both options on days alive and out of hospital (DAOH) and survival. This retrospective study screened all patients with HTx or LVAD implantation between 2010 and 2020. The main inclusion criterion was hemodynamic stability defined as independence of intravenous inotropic/vasoactive support at decision. Propensity score matching (PSM) was performed. The primary endpoint was DAOH within one year after the decision. Secondary endpoints included survival, duration until HTx, and hospitalizations. In total, 187 patients received HTx and 227 patients underwent LVAD implantation. There were 21 bridge-to-transplant (BTT)-LVAD patients (implantation less than a month after HTx listing or listing after implantation) and 44 HTx-waiting patients included. PSM identified 17 matched pairs. Median DAOH at one year was not significantly different between the groups (BTT-LVAD: median 281, IQR 89; HTx waiting: median 329, IQR 74; p = 0.448). Secondary endpoints did not differ significantly. Our data suggest that BTT-LVAD implantation may not be favorable in terms of DAOH within one year for hemodynamically stable patients compared to waiting for HTx. Further investigations on quality of life and long-term outcomes are warranted.

COVID-19 patients who may require invasive therapeutic procedures such as extracorporeal membrane oxygenation (ECMO) have high symptom burden and in-hospital mortality. In addition, awake patients on ECMO are new in the intensive care unit (ICU) setting. Inpatient specialist palliative care (sPC) provides support such as symptom control on a physical, psychosocial and spiritual level. The field of sPC in COVID-19 patients is still new and important to investigate. We aim to analyze sPC of COVID-19 patients in the ICU with regard to patient characteristics and symptoms from a palliative care perspective. We conducted a retrospective analysis (03/2020-04/2021) and identified 51 ICU patients receiving sPC. The statistical analysis included descriptive statistics and comparisons of symptoms. The first sPC contact of patients (mean age 69.5 years, 62.7% male) was around 14 days after COVID-19 confirmation, and 43% were treated with ECMO therapy. The baseline symptom burden was high with a focus on weakness (100%), tiredness (98%), dyspnea (96%) and family burden (92%). The symptom intensity significantly decreased during the time period of sPC and COVID-19 treatment (t(99) = 3.119, p = 0.003, d = 0.437). These results help intensivists and sPC clinicians to identify symptoms and the need for sPC in COVID-19 patients. However, studies with prospective and controlled designs need to follow.

During the COVID-19 pandemic, the care of critically ill and dying patients in isolation wards, intensive care units (ICUs), and regular wards was severely impaired. In order to support physicians in communicative and palliative care skills, an e-learning tool was developed as part of the joint project "Palliative Care in Pandemic Times" (PallPan). This study investigates the feasibility of this e-learning tool. Secondly, we aim to analyze changes in knowledge and attitude upon completion of the e-learning tool. A 38-item questionnaire-based evaluation study with assessment of global and specific outcomes including ICU and non-ICU physicians was performed. In total, 24 questionnaires were included in the anonymous analysis. Feasibility was confirmed by a very high rate of overall satisfaction (94% approval), with relevance reaching 99% approval. Overall, we detected high gains in knowledge and noticeably lower gains on the attitude plane, with the highest gain in naming reasons for incorporating palliative care. The lowest learning gain on the attitude plane was observed when the participants were confronted with their own mortality. This study shows that e-learning is a feasible tool for gaining knowledge and even changing the attitudes of physicians caring for critically ill and dying patients in a self-assessment evaluation.

Background: The number of patients waiting for heart transplantation (HTX) is increasing. Optimizing the use of all available donor hearts is crucial. While mortality seems not to be affected by donor cardiopulmonary resuscitation (CPR), the impact of donor CPR on days alive and out of hospital (DAOH) is unclear., Methods: This retrospective study included adults who underwent HTX at the University Hospital Duesseldorf, Germany from 2010-2020. Main exposure was donor-CPR. Secondary exposure was the length of CPR. The primary endpoint was DAOH at one year., Results: A total of 187 patients were screened and 171 patients remained for statistical analysis. One-year mortality was 18.7%. The median DAOH at one year was 295 days (interquartile range 206-322 days). Forty-two patients (24.6%) received donor-CPR hearts. The median length of CPR was 15 (9-21) minutes. There was no significant difference in DAOH between patients with donor-CPR hearts versus patients with no-CPR hearts (CPR: 291 days (211-318 days) vs. no-CPR: 295 days (215-324 days); p = 0.619). Multivariate linear regression revealed that there was no association between length of CPR and DAOH (unstandardized coefficients B: -0.06, standard error: 0.81, 95% CI -1.65-1.53, p = 0.943)., Conclusions: Donor CPR status and length of CPR are not associated with reduced DAOH at one year after HTX.

Background: Repeat hospitalizations, complications, and psychosocial burdens are common in patients with left ventricular assist devices (LVAD). Specialist palliative care (sPC) involvement supports patients during decision-making until end-of-life. In the United States, guidelines recommend early specialist palliative care (esPC) involvement prior to implantation. Yet, data about sPC and esPC involvement in Europe are scarce., Materials and Methods: This is a retrospective descriptive study of deceased LVAD patients who had received sPC during their LVAD-related admissions to two university hospitals in Duesseldorf, Germany and Basel, Switzerland from 2010 to 2021. The main objectives were to assess: To which extent have LVAD patients received sPC, how early is sPC involved? What are the characteristics of those, how did sPC take place and what are key challenges in end-of-life care?, Results: In total, 288 patients were implanted with a LVAD, including 31 who received sPC (11%). Twenty-two deceased LVAD patients (19 male) with sPC were included. Mean patient age at the time of implantation was 67 (range 49-79) years. Thirteen patients (59%) received LVAD as destination therapy, eight patients (36%) were implanted as bridge to transplantation (BTT), and one as an emergency LVAD after cardiogenic shock (5%). None of the eight BTT patients received a heart transplantation before dying. Most ( n = 13) patients lived with their family and mean Eastern Cooperative Oncology Group (ECOG) performance status was three. Mean time between LVAD implantation and first sPC contact was 1.71 years, with a range of first sPC contact from 49 days prior to implantation to more than 6 years after. Two patients received esPC before implantation. In Duesseldorf, mean time between first sPC contact and in-hospital death was 10.2 (1-42) days. In Basel, patients died 16 (0.7-44) months after first sPC contact, only one died on the external sPC unit. Based on thorough examination of two case reports, we describe key challenges of sPC in LVAD patients including the necessity for sPC expertise, ethical and communicative issues as well as the available resources in this setting., Conclusion: Despite unequivocal recommendations for sPC in LVAD patients, the integration of sPC for these patients is yet not well established., Competing Interests: DSa received speaker honoraria and educational grants from Abott and Medtronic as well as speaker honoraria from Abiomed and Nycomed. PA received speaker honoraria from Medtronic, Abbott, Edwards, Cryolife/Jotec, and Abiomed and has received research grants from Abbott and Edwards outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tenge, Santer, Schlieper, Schallenburger, Schwartz, Meier, Akhyari, Pfister, Walter, Eckstein, Eckstein, Siegemund, Gaertner and Neukirchen.)