Clinical Presentation and Causes of Non-traumatic Spinal Cord Injury: An Observational Study in Emergency Patients

Introduction: Diagnosing non-traumatic spinal cord injury (NTSCI) is often challenging. However, clear discrimination from non-spinal pathologies, e.g., "myelopathy-mimics" (MMs), is critical in preventing long-term disability and death. In this retrospective study we (1) investigated causes of NTSCI, (2) identified clinical markers associated with NTSCI and (3) discuss implications for NTSCI management. Methods: Our sample consisted of 5.913 consecutive neurological and neurosurgical patients who were treated in our emergency department during a one-year period. Patients with a new or worsened bilateral sensorimotor deficit were defined as possible NTSCI. We then compared clinical and imaging findings and allocated patients into NTSCIs and MMs. Results: Of ninety-three included cases, thirty-six (38.7%) were diagnosed with NTSCI. Fifty-two patients (55.9%) were classified as MMs. In five patients (5.4%) the underlying pathology remained unclear. Predominant causes of NTSCI were spinal metastases (33.3%), inflammatory disorders (22.2%) and degenerative pathologies (19.4%). 58.6% of NTSCI patients required emergency treatment. Presence of a sensory level (p = <0.001) and sphincter dysfunction (p = 0.02) were the only significant discriminators between NTSCI and MMs. Conclusion: In our study, one-third of patients presenting with a new bilateral sensorimotor deficit had NTSCI. Of these, the majority required emergency treatment. Since there is a significant clinical overlap with non-spinal disorders, a standardized diagnostic work-up including routine spinal MRI is recommended for NTSCI management, rather than an approach that is mainly based on clinical findings

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

The diagnostic value of the neurological examination in coma of unknown etiology

Background: Identifying the cause of non-traumatic coma in the emergency department is challenging. The clinical neurological examination is the most readily available tool to detect focal neurological deficits as indicators for cerebral causes of coma. Previously proposed clinical pathways have granted the interpretation of clinical findings a pivotal role in the diagnostic work-up. We aimed to identify the actual diagnostic reliability of the neurological examination with regard to identifying acute brain damage. Methods: Eight hundred and fifty-three patients with coma of unknown etiology (CUE) were examined neurologically in the emergency department following a predefined routine. Coma-explaining pathologies were identified retrospectively and grouped into primary brain pathology with proof of acute brain damage and other causes without proof of acute structural pathology. Sensitivity, specificity and percentage of correct predictions of different examination protocols were calculated using contingency tables and binary logistic regression models. Results: The full neurological examination was 74% sensitive and 60% specific to detect acute structural brain damage underlying CUE. Sensitivity and specificity were higher in non-sedated patients (87/61%) compared to sedated patients (64%/59%). A shortened four-item examination protocol focusing on pupils, gaze and pyramidal tract signs was only slightly less sensitive (67%) and more specific (65%). Conclusions: Due to limited diagnostic reliability of the physical examination, the absence of focal neurological signs in acutely comatose patients should not defer from a complete work-up including brain imaging. In an emergency, a concise neurological examination should thus serve as one part of a multimodal diagnostic approach to CUE

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

Computational analysis of heat shock proteins and ferroptosis-associated lncRNAs to predict prognosis in acute myeloid leukemia patients

Owing to their functional diversity in many cancers, long noncoding RNAs (lncRNAs) are receiving special attention. LncRNAs not only function as oncogenes or tumor suppressors by participating in various signaling pathways but also serve as predictive markers for various types of cancer, including acute myeloid leukemia (AML). Considering this, we investigated lncRNAs that may act as a mediator between two processes, i.e., heat shock proteins and ferroptosis, which appear to be closely related in tumorigenesis. Using a comprehensive bioinformatics approach, we identified four lncRNAs (AL138716.1, AC000120.1, AC004947.1, and LINC01547) with prognostic value in AML patients. Of interest, two of them (AC000120.1 and LINC01547) have already been reported to be AML-related, and AC004947.1 is considered to have oncogenic potential. In particular, the signature obtained showed a lower survival probability with high-risk patients, and vice versa. To our knowledge, this is the first predictive model of lncRNA that may correlate with the processes of heat shock proteins and ferroptosis in AML. Nevertheless, validation using patient samples is warranted

Two-dimensional hole precession in an all-semiconductor spin field effect transistor

We present a theoretical study of a spin field-effect transistor realized in a quantum well formed in a p--doped ferromagnetic-semiconductor- nonmagnetic-semiconductor-ferromagnetic-semiconductor hybrid structure. Based on an envelope-function approach for the hole bands in the various regions of the transistor, we derive the complete theory of coherent transport through the device, which includes both heavy- and light-hole subbands, proper modeling of the mode matching at interfaces, integration over injection angles, Rashba spin precession, interference effects due to multiple reflections, and gate-voltage dependences. Numerical results for the device current as a function of externally tunable parameters are in excellent agreement with approximate analytical formulae.Comment: 9 pages, 11 figure

Isolated central nervous system relapse of systemic lymphoma (SCNSL): clinical features and outcome of a retrospective analysis

We analyzed clinical outcome of patients with an isolated central nervous system lymphoma (CNSL) relapse after systemic non-Hodgkin’s lymphoma (NHL). All 23 patients with an isolated secondary CNSL (SCNSL) treated at two institutions from 04/2003–12/2007 were included into this analysis. At cerebral relapse, 15/23 patients were treated with a regimen consisting of high-dose methotrexate (Bonn protocol). After a median follow-up of 6.5 months (range 1–68), 15/23 (65%) patients with SCNSL had relapsed or progressed. HD (high-dose)- methotrexate (MTX) chemotherapy according to the Bonn protocol is effective concerning response rates; however, overall survival of patients with SCNSL seems to be impaired in comparison to relapses in primary CNSL (PCNSL)