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"Busch, Hans"
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Monocyte subset distribution and surface expression of HLA-DR and CD14 in patients after cardiopulmonary resuscitation
by
Bemtgen, Xavier
,
Fink, Katrin
,
Busch, Hans-Jörg
in
692/420/256/2516
,
692/53/2421
,
692/699/249/2510
2021
Systemic inflammation is a major feature of the post-cardiac arrest syndrome. The three monocyte subpopulations are thought to play an important role in this inflammatory state because they are endowed with numerous pattern recognition receptors, such as CD14, that have been associated with ischemia–reperfusion injury. By contrast, an exaggerated antiinflammatory response has also been described following cardiac arrest, which may be mediated by downregulation of antigen presentation receptor HLA-DR. We report the composition of monocyte subpopulations and the expression of CD14 and HLA-DR following cardiac arrest. Blood specimens were collected from 32 patients at three timepoints in the first 48 h after cardiac arrest. Monocyte subset composition was determined by flow cytometry based on the expression of CD14, CD16, and HLA-DR. Monocyte subset composition and the expression of CD14 and HLA-DR were correlated with patient outcomes. The results were compared to 19 patients with coronary artery disease. Cardiac arrest patients showed a significant decline in the percentage of nonclassical monocytes. Monocyte CD14 expression was upregulated after 24 h and correlated with the time to return of spontaneous circulation. Downregulation of HLA-DR expression was observed mainly among classical monocytes and significantly correlated with the dose of norepinephrine used to treat shock. Downregulation of HLA-DR among nonclassical and intermediate monocytes was significantly associated with disease severity. Our data demonstrate the disturbance of monocyte subset composition with a significant decline in nonclassical monocytes at an early stage following cardiac arrest. Our findings suggest the simultaneous presence of hyperinflammation, as evidenced by upregulation of CD14, and monocyte deactivation, characterized by downregulation of HLA-DR. The extent of monocyte deactivation was significantly correlated with disease severity.
Journal Article
Inflammasome and toll-like receptor signaling in human monocytes after successful cardiopulmonary resuscitation
by
Fink, Katrin
,
Busch, Hans-Jörg
,
Helbing, Thomas
in
Adaptor Proteins, Signal Transducing - analysis
,
Adaptor Proteins, Signal Transducing - blood
,
Aged
2016
Background
Whole body ischemia-reperfusion injury (IRI) after cardiopulmonary resuscitation (CPR) induces a generalized inflammatory response which contributes to the development of post-cardiac arrest syndrome (PCAS). Recently, pattern recognition receptors (PRRs), such as toll-like receptors (TLRs) and inflammasomes, have been shown to mediate the inflammatory response in IRI. In this study we investigated monocyte PRR signaling and function in PCAS.
Methods
Blood samples were drawn in the first 12 hours, and at 24 and 48 hours following return of spontaneous circulation in 51 survivors after cardiac arrest. Monocyte mRNA levels of TLR2, TLR4, interleukin-1 receptor-associated kinase (IRAK)3, IRAK4, NLR family pyrin domain containing (NLRP)1, NLRP3, AIM2, PYCARD, CASP1, and IL1B were determined by real-time quantitative PCR. Ex vivo cytokine production in response to stimulation with TLR ligands Pam
3
CSK
4
and lipopolysaccharide (LPS) was assessed in both whole blood and monocyte culture assays. Ex vivo cytokine production of peripheral blood mononuclear cells (PBMCs) from a healthy volunteer in response to stimulation with patients’ sera with or without LPS was assessed. The results were compared to 19 hemodynamically stable patients with coronary artery disease.
Results
Monocyte TLR2, TLR4, IRAK3, IRAK4, NLRP3, PYCARD and IL1B were initially upregulated in patients following cardiac arrest. The NLRP1 and AIM2 inflammasomes were downregulated in resuscitated patients. There was a significant positive correlation between TLR2, TLR4, IRAK3 and IRAK4 expression and the degree of ischemia as assessed by serum lactate levels and the time until return of spontaneous circulation. Nonsurvivors at 30 days had significantly lower mRNA levels of TLR2, IRAK3, IRAK4, NLRP3 and CASP1 in the late phase following cardiac arrest. We observed reduced proinflammatory cytokine release in response to both TLR2 and TLR4 activation in whole blood and monocyte culture assays in patients after CPR. Sera from resuscitated patients attenuated the inflammatory response in cultured PBMCs after co-stimulation with LPS.
Conclusions
Successful resuscitation from cardiac arrest results in changes in monocyte pattern recognition receptor signaling pathways, which may contribute to the post-cardiac arrest syndrome.
Trial registration
The trial was registered in the German Clinical Trials Register (
DRKS00009684
) on 27/11/2015.
Journal Article
Development and evaluation of a mechanical chest compression device for standardized rodent cardiopulmonary resuscitation
by
Brixius, Sam Joé
,
Dinkelaker, Johannes
,
Czerny, Martin
in
692/308/1426
,
692/308/2778
,
692/308/575
2025
Small animal models are indispensable in cardiopulmonary resuscitation (CPR) research. High-quality CPR, characterized by consistent chest compression rate, depth, and positioning is crucial for survival. However, achieving standardization in manual high-frequency chest compressions in small animal models remains technically challenging. This study evaluated the reproducibility of manual chest compressions and introduced a novel mechanical chest compression device (MCD) designed to improve consistency in rodent experiments. In an in vitro setup, manual compressions were performed by ten participants at target rates ranging from 100 to 260 bpm, guided by a metronome. Compressions performed on a fluid-filled polymer reservoir were analyzed for the compression rate, variability, and time within a ± 10% target range. A color indicator was used to assess the variability of the compression point. A small animal MCD was designed and tested under the same conditions. In vivo, 5 Sprague-Dawley rats underwent 5 min of electrically induced normothermic cardiac arrest followed by 8 min of external chest compressions using the MCD. Obtained data was compared to the in vitro results. A total of 21,650 manual and 20,098 mechanical compressions were analyzed. At 200 bpm, chest compressions using the MCD were significantly more precise (201 ± 1.2 bpm) than manual compressions (218 ± 21 bpm,
p
< 0.001) with a significant reduced compression point variability (1.7 ± 0.1 cm
2
vs. 10.8 ± 3.1 cm
2
,
p
< 0.001). Manual compressions maintained target rate in 58.8% of time compared to 100% for the MCD. In vivo testing confirmed these findings with chest compressions remaining within the target range 100% of the time and showing minimal rate variability (1.8 ± 1.7 bpm). These results highlight the limitations of manual chest compressions and demonstrate the potential of the MCD to enhance standardization and reproducibility in rodent CPR research.
Journal Article
Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR): consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC
by
Hagl, Christian
,
Hans Martin Hoffmeister
,
Boeken, Udo
in
Algorithms
,
Cardiac arrest
,
Cardiopulmonary resuscitation
2019
Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible aetiology. Currently, there are no randomised, controlled studies on eCPR. Thus, prospective validated predictors of benefit and outcome are lacking. Currently, selection criteria and procedure techniques differ across hospitals and standardised algorithms are lacking. Based on expert opinion, the present consensus statement provides a first standardised treatment algorithm for eCPR.
Journal Article
Prospective evaluation of the quickSOFA score as a screening for sepsis in the emergency department
by
Fink, Katrin
,
Loritz Monika
,
Busch Hans-Jörg
in
Emergency medical care
,
Inflammation
,
Mortality
2020
In 2016, the new bedside tool quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) was presented to identify patients at high risk of developing sepsis or adverse outcome. The aim of this study was to investigate the diagnostic performance of the qSOFA scoring system as a screening in patients presenting at an emergency department (ED) of any cause. Therefore, we compared qSOFA with the systemic inflammatory response syndrome (SIRS) criteria and two modifications of qSOFA score. This is a prospective single-center study including patients presenting to the ED of any non-traumatic cause. Primary outcome was development of sepsis within 48 h, secondary outcomes were 30-day mortality and ICU stay for > 3 days. Data were collected within one hour after arrival to indicate an impression of initial medical contact. Among 1,668 patients, 105 sepsis cases were identified. 8.4% presented with qSOFA ≥ 2, 27.2% with SIRS ≥ 2 within one hour. Sensitivity of qSOFA in predicting sepsis was lower compared to the SIRS criteria. qSOFA showed better prognostic accuracy for 30-day mortality compared to SIRS (p < 0.05), but not for prolonged ICU stay (p = 0.56). Modification of qSOFA in replacing GCS by other scoring systems recording altered mental status did not improve its sensitivity. The qSOFA score has poor sensitivity to identify patients at risk of developing sepsis and can therefore not be considered as an adequate screening for sepsis in patients presenting to the ED. Furthermore, a positive qSOFA at arrival at the ED showed no sufficient reliability in detecting patients with adverse clinical course.
Journal Article
Workplace violence against healthcare workers in the emergency department — a 10-year retrospective single-center cohort study
by
Klöppel, Stefan
,
Röttger, Michael Clemens
,
Hans, Felix P.
in
Adult
,
Aggression
,
Aggressiveness
2024
Background
Medical staff are regularly confronted with workplace violence (WPV), which poses a threat to the safety of both staff and patients. Structured de-escalation training (DET) for Emergency Department (ED) staff has been shown to positively affect the reporting of WPV incidents and possibly reduce its impact. This study aimed to describe the development of incidence rates, causes, means, targets, locations, responses, and the time of WPV events. Additionally, it explored the effect of the staff trained in DET on the objective and subjective severity of the respective WPV events.
Methods
In a retrospective, single-center cohort study, we analyzed ten years of WPV events using the data of Staff Observation Aggression Scale-Revised (SOAS-R) score (ranging from 0 to 22) in a tertiary ED from 2014 to 2023. The events were documented by ED staff and stored in the electronic health record (EHR).
Results
Between 2014 and 2023, 160 staff members recorded 859 incidents, noting an average perceived severity of 5.78 (SD = 2.65) and SOAS-R score of 11.18 (SD = 4.21). Trends showed a non-significant rise in incident rates per 10,000 patients over time. The WPV events were most frequently reported by nursing staff, and the cause of the aggression was most often not discernible (
n
= 353, 54.56%). In total,
n
= 273 (31.78%) of the WPV events were categorized as severe, and the most frequent target of the aggressive behavior was the staff. WPV events occurred most frequently in the traumatology section and the detoxification rooms. While the majority of events could be addressed with verbal interventions, more forceful interventions were performed significantly more often for higher severity WPV events. More WPV events occurred during off-hours and were of a significantly higher objective and subjective severity. Overall, the presence of staff with completed DET led to significantly higher SOAS-R scores and higher perceived severity.
Conclusion
The findings underline the relevance of WPV events in the high-risk environment of an ED. The analyzed data suggest that DET significantly fostered the awareness of WPV. While most events can be addressed with verbal interventions, WPV remains a concern that needs to be addressed through organizational measures and further research.
Journal Article
Provider perception of presentations with nonspecific back pain in the emergency department and primary care practices: a semi-structured interview study
2024
Background
Increasing numbers of patients treated in the emergency departments pose challenges to delivering timely and high-quality care. Particularly, the presentation of patients with low-urgency complaints consumes resources needed for patients with higher urgency. In this context, patients with non-specific back pain (NSBP) often present to emergency departments instead of primary care providers. While patient perspectives are well understood, this study aims to add a provider perspective on the diagnostic and therapeutic approach for NSBP in emergency and primary care settings.
Methods
In a qualitative content analysis, we interviewed seven Emergency Physicians (EP) and nine General Practitioners (GP) using a semi-structured interview to assess the diagnostic and therapeutic approach to patients with NSBP in emergency departments and primary care practices. A hypothetical case of NSBP was presented to the interviewees, followed by questions on their diagnostic and therapeutic approaches. Recruitment was stopped after reaching saturation of the qualitative content analysis. Reporting this work follows the consolidated criteria for reporting qualitative research (COREQ) checklist.
Results
EPs applied two different strategies for the workup of NSBP. A subset pursued a guideline-compliant diagnostic approach, ruling out critical conditions and managing pain without extensive diagnostics. Another group of EPs applied a more extensive approach, including extensive diagnostic resources and specialist consultations. GPs emphasized physical examinations and stepwise treatment, including scheduled follow-ups and a better knowledge of the patient history to guide diagnostics and therapy. Both groups attribute ED visits for NSBP to patient related and healthcare system related factors: lack of understanding of healthcare structures, convenience, demand for immediate diagnostics, and fear of serious conditions. Furthermore, both groups reported an ill-suited healthcare infrastructure with insufficiently available primary care services as a contributing factor.
Conclusions
The study highlights a need for improving guideline adherence in younger EPs and better patient education on the healthcare infrastructure. Furthermore, improving access and availability of primary care services could reduce ED visits of patients with NSBP.
Trial registration
No trial registration needed.
Journal Article
Selenium prevents microparticle-induced endothelial inflammation in patients after cardiopulmonary resuscitation
by
Fink, Katrin
,
Vetter, Caroline
,
Moebes, Monica
in
Antioxidants - therapeutic use
,
Blood platelets
,
Cardiopulmonary Resuscitation
2015
Introduction
Microparticles are elevated in patients after successful cardiopulmonary resuscitation (CPR) and may play a role in the development of endothelial dysfunction seen in post-cardiac arrest syndrome (PCAS), a life threatening disease with high mortality. To identify mechanisms of endothelial activation and to develop novel approaches in the therapy of PCAS, the impact of selenium, a trace element with antioxidative properties, was characterized in endothelial dysfunction induced by microparticles of resuscitated patients. Additionally, course of plasma selenium levels was characterized in the first 72 hours post-CPR.
Methods
Endothelial cells were exposed to microparticles isolated of the peripheral blood of resuscitated patients, and leukocyte-endothelial interaction was measured by dynamic adhesion assay. Expression of adhesion molecules was assessed by immunoblotting and flow chamber. Blood samples were drawn 24, 48 and 72 hours after CPR for determination of plasma selenium levels in 77 resuscitated patients; these were compared to 50 healthy subjects and 50 patients with stable cardiac disease and correlated with severity of illness and outcome.
Results
Microparticles of resuscitated patients enhance monocyte-endothelial interaction by up-regulation of ICAM-1 and VCAM-1. Selenium administration diminished ICAM-1 and VCAM-1-mediated monocyte adhesion induced by microparticles of resuscitated patients, suggesting that selenium has anti-inflammatory effects after CPR. Lowered selenium plasma levels were observed in resuscitated patients compared to controls and selenium levels immediately and 24 hours after CPR, inversely correlated with clinical course and outcome after resuscitation.
Conclusions
Endothelial dysfunction is a pivotal feature of PCAS and is partly driven by microparticles of resuscitated patients. Administration of selenium exerted anti-inflammatory effects and prevented microparticle-mediated endothelial dysfunction. Decline of selenium was observed in plasma of patients after CPR and is a novel predictive marker of ICU mortality, suggesting selenium consumption promotes inflammation in PCAS.
Journal Article
Major medical events in patients with acute coronary syndrome during helicopter emergency medical service operations
by
Ganter, Julian
,
Braun, Jörg
,
Busch, Hans-Jörg
in
Acute Coronary Syndrome - complications
,
Acute Coronary Syndrome - epidemiology
,
Acute Coronary Syndrome - therapy
2025
Background
Acute coronary syndromes (ACS) are a leading cause of helicopter emergency medical services (HEMS) operations in Germany. Complications that arise during HEMS operations are challenging due to limited resources. However, the National Advisory Committee for Aeronautics (NACA) score and National Early Warning Score (NEWS) provide potential for risk stratification. Nevertheless, there is an absence of data concerning the incidence and risk of medical events (e.g. malignant arrhythmia, cardiac arrest, cardiogenic shock) in ACS patients during HEMS operations. The objective of this study is to evaluate the incidence of medical events and to assess risk stratification using scoring systems.
Methods
This retrospective observational cohort study analyzed prehospital records from 38,473 HEMS operations with “ACS” coding conducted between 2012 and 2024 in Germany. Routine data were systematically recorded using a standardized digital form that captured patient demographics, clinical presentation, and medical interventions. Major medical events (MME) were defined using surrogate markers, including defibrillation, resuscitation, airway management, ventilation, and new ST-elevation myocardial infarction (STEMI) findings. Scores (NACA, NEWS, and a combined MME-score) were calculated, with the MME-score integrating NACA and NEWS. Ethical approval was obtained from the Albert-Ludwigs-University Freiburg Ethics Committee (No: 24-1082-S1, 25 April 2024).
Results
MME occurred in 8.8% of the 38,473 HEMS operations. They occurred more frequently during secondary missions (interfacility transports) (11.8%) than primary missions (6.7%), and at night (15.3%) than during the day (8.2%) (both
p
< 0.001). The NACA, NEWS, and MME-scores were significantly higher in cases with medical events (
p
< 0.001). The risk stratification exhibited areas under the curve in the receiver operating characteristics (ROC) curve, with values of 0.831 for NACA, 0.866 for NEWS, and 0.895 for the MME-score.
Conclusion
The incidence of MMEs is subject to variation depending on the operational context. Established scoring systems such as the NACA and NEWS are available for the purpose of risk stratification of medical events in patients with ACS during air rescue operations. The combination of these scores may indicate potential for improved risk stratification.
Journal Article
A simulation-based pilot study of crisis checklists in the emergency department
by
Lienkamp, Soeren Sten
,
Busch Hans-Jörg
,
Knoche, Beatrice Billur
in
Cardiopulmonary resuscitation
,
Check lists
,
Clinical outcomes
2021
Checklists can improve adherence to standardized procedures and minimize human error. We aimed to test if implementation of a checklist was feasible and effective in enhancing patient care in an emergency department handling internal medicine cases. We developed four critical event checklists and confronted volunteer teams with a series of four simulated emergency scenarios. In two scenarios, the teams were provided access to the crisis checklists in a randomized cross-over design. Simulated patient outcome plus statement of the underlying diagnosis defined the primary endpoint and adherence to key processes such as time to commence CPR represented the secondary endpoints. A questionnaire was used to capture participants’ perception of clinical relevance and manageability of the checklists. Six teams of four volunteers completed a total of 24 crisis sequences. The primary endpoint was reached in 8 out of 12 sequences with and in 2 out of 12 sequences without a checklist (Odds ratio, 10; CI 1.11, 123.43; p = 0.03607, Fisher’s exact test). Adherence to critical steps was significantly higher in all scenarios for which a checklist was available (performance score of 56.3% without checklist, 81.9% with checklist, p = 0.00284, linear regression model). All participants rated the checklist as useful and 22 of 24 participants would use the checklist in real life. Checklist use had no influence on CPR quality. The use of context-specific checklists showed a statistically significant influence on team performance and simulated patient outcome and contributed to adherence to standard clinical practices in emergency situations.
Journal Article