Causes of brain dysfunction in acute coma: a cohort study of 1027 patients in the emergency department

BACKGROUND: Coma of unknown etiology (CUE) is a major challenge in emergency medicine. CUE is caused by a wide variety of pathologies that require immediate and targeted treatment. However, there is little empirical data guiding rational and efficient management of CUE. We present a detailed investigation on the causes of CUE in patients presenting to the ED of a university hospital. METHODS: One thousand twenty-seven consecutive ED patients with CUE were enrolled. Applying a retrospective observational study design, we analyzed all clinical, laboratory and imaging findings resulting from a standardized emergency work-up of each patient. Following a predefined protocol, we identified main and accessory coma-explaining pathologies and related these with (i.a.) GCS and in-hospital mortality. RESULTS: On admission, 854 of the 1027 patients presented with persistent CUE. Their main diagnoses were classified into acute primary brain lesions (39%), primary brain pathologies without acute lesions (25%) and pathologies that affected the brain secondarily (36%). In-hospital mortality associated with persistent CUE amounted to 25%. 33% of patients with persistent CUE presented with more than one coma-explaining pathology. In 173 of the 1027 patients, CUE had already resolved on admission. However, these patients showed a spectrum of main diagnoses similar to persistent CUE and a significant in-hospital mortality of 5%. CONCLUSION: The data from our cohort show that the spectrum of conditions underlying CUE is broad and may include a surprisingly high number of coincidences of multiple coma-explaining pathologies. This finding has not been reported so far. Thus, significant pathologies may be masked by initial findings and only appear at the end of the diagnostic work-up. Furthermore, even transient CUE showed a significant mortality, thus rendering GCS cutoffs for selection of high- and low-risk patients questionable. Taken together, our data advocate for a standardized diagnostic work-up that should be triggered by the emergency symptom CUE and not by any suspected diagnosis. This standardized routine should always be completed - even when initial coma-explaining diagnoses may seem evident

Realitäts-Check auf regionaler Ebene: Implikationen der CBD-COP15 für Sachsen

Um die Ziele des Kunming-Montreal Global Biodiversity Frameworks zu erreichen, ist Engagement auf allen politischen Ebenen und in allen Sektoren nötig. Auch der Freistaat Sachsen muss seinen Beitrag leisten. Sachsen hat großes Potenzial, steht aber auch vor besonderen Herausforderungen. Fast die Hälfte der Landfläche wird landwirtschaftlich genutzt, hauptsächlich für Ackerbau. Doch nur etwa acht Prozent der Fläche wird ökologisch bewirtschaftet. Intensivierung und Monotonisierung der Landwirtschaft, sowie der Einsatz von Pestiziden und Düngemitteln, tragen erheblich zum Verlust der biologischen Vielfalt bei. Die Landwirtschaft spielt eine entscheidende Rolle als Lebensraum für Biodiversität. Es gilt, biodiversitätsfreundliche Nutzung zu fördern, den Anteil der Fläche mit ökologischem Landbau zu erhöhen und entsprechende Praktiken in der konventionellen Landwirtschaft zu etablieren. Sachsen ist auch als Erzeuger fossiler Energien, speziell durch das Lausitzer und das Mitteldeutsche Braunkohlerevier, stark von der Energiewende betroffen. Der Ausbau erneuerbarer Energien muss naturverträglich und im Einklang mit dem Biodiversitätsschutz erfolgen. Konzepte der multifunktionalen Landnutzung können hierbei unterstützen. Prof. Dr. Edeltraud Günther, Direktorin des UNU-FLORES, betont ebenfalls die Notwendigkeit, Biodiversität im Ressourcen-Nexus zu berücksichtigen. Sachsen hat gute Voraussetzungen, um diese Herausforderungen zu meistern. Mit dem Programm Sachsens Biologische Vielfalt 2030 verfügt es über eine Biodiversitätsstrategie, um die globalen Ziele zu erreichen. Darüber hinaus beherbergt Sachsen starke Forschungsinstitutionen, die sich intensiv dem Thema Biodiversität widmen. Forschung, Bildung und Wissenschaftskommunikation spielen hierbei eine zentrale Rolle. Prof. Tshilidzi Marwala, Rektor der UNU und Under-Secretary-General der UN, betonte in seiner Eröffnungsansprache der DNCi 2023 die Schlüsselrolle von Bildung: 'Bildung ist der Schlüssel, um unser Potenzial zu entfalten. Sie befähigt uns, Verwalter unserer Umwelt zu werden, indem sie uns eine tiefe Wertschätzung für die biologische Vielfalt vermittelt und zu nachhaltigen Praktiken in jedem Aspekt unseres Lebens inspiriert. Durch die Integration von transformierender Bildung auf internationaler, nationaler und lokaler Ebene können wir einen tiefgreifenden Wandel von Einstellungen, Wissen und Verhaltensweisen bewirken.“ Die Bedeutung von Bildung und Wissenschaftskommunikation zum Thema Biodiversität konnten die Teilnehmenden der DNCi 2023 dank einer Führung durch den Botanischen Garten praktisch erleben. Herzlichen Dank an Prof. Dr. Christoph Neinhuis, Direktor des Botanischen Gartens, und Dr. Barbara Dietsch, Wissenschaftliche Leitung des Botanischen Gartens, für diese wertvollen Einblicke. Im Rahmen der gemeinsam durch UNU-FLORES, dem IÖR und der TU Dresden organisierten DNCi 2023 ist es uns gelungen, unterschiedliche Akteure aus Wissenschaft, Regierung, Zivilgesellschaft und Privatwirtschaft zusammenzubringen und eine dynamische Plattform für Austausch und Zusammenarbeit zum Thema Biodiversität zu schaffen. Herzlicher Dank gilt allen Teilnehmenden für ihr Engagement im Rahmen der Veranstaltung und darüber hinaus dem Sächsischen Staatsministerium für Energie, Klimaschutz, Umwelt und Landwirtschaft für die Unterstützung der Veranstaltung im Rahmen seiner Kooperation mit UNU-FLORES.:VORWORT 5 Vorwort 6 Vorwort der Veranstalter:innen 8 EINLEITUNG 12 POLITIK IN SACHSEN 14 Handlungsempfehlungen für die Politik in Sachsen 16 WIRTSCHAFT IN SACHSEN 21 Handlungsempfehlungen für die Wirtschaft in Sachsen 22 LANDWIRTSCHAFT IN SACHSEN 26 Handlungsempfehlungen für die Landwirtschaft in Sachsen 28 BILDUNG IN SACHSEN 31 Handlungsempfehlungen für die Bildung in Sachsen 32 FAZIT 35 TEILNEHMENDE DER DNCi 2023 36 Thema Biodiversität in der Politik 38 Thema Biodiversität in der Landwirtschaft 39 Thema Biodiversität in der lokalen Wirtschaft 40 Thema Biodiversität in der Bildung für Nachhaltige Entwicklung 41Reaching the goals of the Kunming-Montreal Global Biodiversity Framework requires commitment at all political levels and in all sectors. The State of Saxony also has to contribute its share. Saxony has a great potential, but also faces particular challenges. Almost half of the land area is used for agriculture, mainly for arable farming. However, only around eight percent of the land is farmed ecologically. Intensification and monotonization of agriculture, as well as the use of pesticides and fertilizers, significantly contribute to the loss of biodiversity. Agriculture plays a crucial role as a habitat for biodiversity. It is indispensable to promote biodiversity-friendly use, increase the proportion of land under organic farming, and establish corresponding methods in conventional agriculture. As a producer of fossil fuels, especially by the Lusatian and Central German lignite mining regions, Saxony is also strongly affected by the energy transition. The expansion of renewable energies needs to be nature-compatible and in harmony with the protection of biodiversity. Approaches to multifunctional landuse may provide support in this regard. Prof. Dr. Edeltraud Günther, Director of UNU-FLORES, emphasizes the need to consider biodiversity in the resource nexus. Saxony has good prerequisites to meet these challenges. With its Saxony Biodiversity 2030 Program, it has a revised biodiversity strategy to meet the global targets. In addition, Saxony is home to major research institutions that intensively focus on biodiversity. Research, education, and science communication play a central role in this context. Prof. Tshilidzi Marwala, Rector of UNU and Under-Secretary-General of the UN, emphasized the key role of education in his opening address of the DNCi 2023: 'Education is the key to unlock our potential. It empowers us to become stewards of our environment by providing us with a deep appreciation for biodiversity and inspiring sustainable practices in every aspect of our lives. By integrating transformative education at the international, national, and local levels, we can create profound change in attitudes, knowledge, and behaviors.' The DNCi 2023 participants had a hands-on experience of the importance of education and science communication on biodiversity thanks to a guided tour of the Botanical Garden. Many thanks to Prof. Dr. Christoph Neinhuis, Director of the Botanical Garden, and Dr. Barbara Dietsch, Scientific Director of the Botanical Garden, for these valuable insights. As part of the DNCi 2023, co-organized by UNU-FLORES, the IOER, and TU Dresden, we succeeded in bringing together different stakeholders from science, government, civil society, and the private sector to create a dynamic platform for exchange and collaboration on the topic of biodiversity. We would like to express our sincere gratitude to all participants for their commitment during the event and beyond, and to the Saxon State Ministry of Energy, Climate Protection, Environment and Agriculture for supporting the event within the framework of its cooperation with UNU-FLORES.:VORWORT 5 Vorwort 6 Vorwort der Veranstalter:innen 8 EINLEITUNG 12 POLITIK IN SACHSEN 14 Handlungsempfehlungen für die Politik in Sachsen 16 WIRTSCHAFT IN SACHSEN 21 Handlungsempfehlungen für die Wirtschaft in Sachsen 22 LANDWIRTSCHAFT IN SACHSEN 26 Handlungsempfehlungen für die Landwirtschaft in Sachsen 28 BILDUNG IN SACHSEN 31 Handlungsempfehlungen für die Bildung in Sachsen 32 FAZIT 35 TEILNEHMENDE DER DNCi 2023 36 Thema Biodiversität in der Politik 38 Thema Biodiversität in der Landwirtschaft 39 Thema Biodiversität in der lokalen Wirtschaft 40 Thema Biodiversität in der Bildung für Nachhaltige Entwicklung 4

implementation of an in-house management routine

Background Coma of unknown origin is an emergency caused by a variety of possibly life-threatening pathologies. Although lethality is high, there are currently no generally accepted management guidelines. Methods We implemented a new interdisciplinary standard operating procedure (SOP) for patients presenting with non-traumatic coma of unknown origin. It includes a new in- house triage process, a new alert call, a new composition of the clinical response team and a new management algorithm (altogether termed “coma alarm”). It is triggered by two simple criteria to be checked with out-of-hospital emergency response teams before the patient arrives. A neurologist in collaboration with an internal specialist leads the in-hospital team. Collaboration with anaesthesiology, trauma surgery and neurosurgery is organised along structured pathways that include standardised laboratory tests and imaging. Patients were prospectively enrolled. We calculated response times as well as sensitivity and false positive rates, thus proportions of over- and undertriaged patients, as quality measures for the implementation in the SOP. Results During 24 months after implementation, we identified 325 eligible patients. Sensitivity was 60 % initially (months 1–4), then fluctuated between 84 and 94 % (months 5–24). Overtriage never exceeded 15 % and undertriage could be kept low at a maximum of 11 % after a learning period. We achieved a median door-to-CT time of 20 minutes. 85 % of patients needed subsequent ICU treatment, 40 % of which required specialised neuro- ICUs. Discussion Our results indicate that our new simple in-house triage criteria may be sufficient to identify eligible patients before arrival. We aimed at ensuring the fastest possible proceedings given high portions of underlying time-sensitive neurological and medical pathologies while using all available resources as purposefully as possible. Conclusions Our SOP may provide an appropriate tool for efficient management of patients with non- traumatic coma. Our results justify the assignment of the initial diagnostic workup to neurologists and internal specialists in collaboration with anaesthesiologists

The accuracy of initial diagnoses in coma: an observational study in 835 patients with non-traumatic disorder of consciousness

Background: Management of patients with coma of unknown etiology (CUE) is a major challenge in most emergency departments (EDs). CUE is associated with a high mortality and a wide variety of pathologies that require differential therapies. A suspected diagnosis issued by pre-hospital emergency care providers often drives the first approach to these patients. We aim to determine the accuracy and value of the initial diagnostic hypothesis in patients with CUE. Methods: Consecutive ED patients presenting with CUE were prospectively enrolled. We obtained the suspected diagnoses or working hypotheses from standardized reports given by prehospital emergency care providers, both paramedics and emergency physicians. Suspected and final diagnoses were classified into I) acute primary brain lesions, II) primary brain pathologies without acute lesions and III) pathologies that affected the brain secondarily. We compared suspected and final diagnosis with percent agreement and Cohen's Kappa including sub-group analyses for paramedics and physicians. Furthermore, we tested the value of suspected and final diagnoses as predictors for mortality with binary logistic regression models. Results: Overall, suspected and final diagnoses matched in 62% of 835 enrolled patients. Cohen's Kappa showed a value of kappa = .415 (95% CI .361-.469, p < .005). There was no relevant difference in diagnostic accuracy between paramedics and physicians. Suspected diagnoses did not significantly interact with in-hospital mortality (e.g., suspected class I: OR .982, 95% CI .518-1.836) while final diagnoses interacted strongly (e.g., final class I: OR 5.425, 95% CI 3.409-8.633). Conclusion: In cases of CUE, the suspected diagnosis is unreliable, regardless of different pre-hospital care providers' qualifications. It is not an appropriate decision-making tool as it neither sufficiently predicts the final diagnosis nor detects the especially critical comatose patient. To avoid the risk of mistriage and unnecessarily delayed therapy, we advocate for a standardized diagnostic work-up for all CUE patients that should be triggered by the emergency symptom alone and not by any suspected diagnosis

Non-acute myocardial infarction-related causes of elevated high-sensitive troponin T in the emergency room: a cross-sectional analysis

To systematically investigate putative causes of non-coronary high-sensitive troponin elevations in patients presenting to a tertiary care emergency department. In this cross-sectional analysis, patients who received serial measurements of high-sensitive troponin T between 1 August 2010 and 31 October 2012 at the Department of Emergency Medicine were included. The following putative causes were considered to be associated with non-acute coronary syndrome-related increases in high-sensitive troponin T: acute pulmonary embolism, renal insufficiency, aortic dissection, heart failure, peri-/myocarditis, strenuous exercise, rhabdomyolysis, cardiotoxic chemotherapy, high-frequency ablation therapy, defibrillator shocks, cardiac infiltrative disorders (e.g., amyloidosis), chest trauma, sepsis, shock, exacerbation of chronic obstructive pulmonary disease, and diabetic ketoacidosis. During the study period a total of 1,573 patients received serial measurements of high-sensitive troponin T. Of these, 175 patients were found to have acute coronary syndrome leaving 1,398 patients for inclusion in the study. In 222 (30%) of patients, no putative cause described in the literature could be attributed to the elevation in high-sensitive troponin T observed. The most commonly encountered mechanism underlying the troponin T elevation was renal insufficiency that was present in 286 patients (57%), followed by cerebral ischemia in 95 patients (19%), trauma in 75 patients (15%) and heart failure in 41 patients (8%). Non-acute coronary syndrome-associated elevation of high-sensitive troponin T levels is commonly observed in the emergency department. Renal insufficiency and acute cerebral events are the most common conditions associated with high-sensitive troponin T elevation

Stokes' Drift of linear Defects

A linear defect, viz. an elastic string, diffusing on a planar substrate traversed by a travelling wave experiences a drag known as Stokes' drift. In the limit of an infinitely long string, such a mechanism is shown to be characterized by a sharp threshold that depends on the wave parameters, the string damping constant and the substrate temperature. Moreover, the onset of the Stokes' drift is signaled by an excess diffusion of the string center of mass, while the dispersion of the drifting string around its center of mass may grow anomalous.Comment: 14 pages, no figures, to be published in Phys.Rev.

Diffusion and Current of Brownian Particles in Tilted Piecewise Linear Potentials: Amplification and Coherence

Overdamped motion of Brownian particles in tilted piecewise linear periodic potentials is considered. Explicit algebraic expressions for the diffusion coefficient, current, and coherence level of Brownian transport are derived. Their dependencies on temperature, tilting force, and the shape of the potential are analyzed. The necessary and sufficient conditions for the non-monotonic behavior of the diffusion coefficient as a function of temperature are determined. The diffusion coefficient and coherence level are found to be extremely sensitive to the asymmetry of the potential. It is established that at the values of the external force, for which the enhancement of diffusion is most rapid, the level of coherence has a wide plateau at low temperatures with the value of the Peclet factor 2. An interpretation of the amplification of diffusion in comparison with free thermal diffusion in terms of probability distribution is proposed.Comment: To appear in PR

Wave nucleation rate in excitable systems in the low noise limit

Motivated by recent experiments on intracellular calcium dynamics, we study the general issue of fluctuation-induced nucleation of waves in excitable media. We utilize a stochastic Fitzhugh-Nagumo model for this study, a spatially-extended non-potential pair of equations driven by thermal (i.e. white) noise. The nucleation rate is determined by finding the most probable escape path via minimization of an action related to the deviation of the fields from their deterministic trajectories. Our results pave the way both for studies of more realistic models of calcium dynamics as well as of nucleation phenomena in other non-equilibrium pattern-forming processes