A 72-h sedated porcine model of traumatic spinal cord injury.

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

PDP type brain tumor in association with multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by inactivating pathogenic variants in the tumor suppressor gene menin 1 on chromosome 11q13 (Falchetti et al., 2009). The syndrome is characterized by neoplasia in two or more endocrine glands and has a high degree of penetrance. Pathogenic germline multiple neoplasia type 1 variants primarily result in neoplasia affecting the parathyroid glands, the pancreatic islet cells, and the anterior pituitary in combination. Primary hyperparathyroidism is the most common pathological manifestation of the syndrome, followed by pancreatic neuroendocrine tumors. Important genetic confirmation has been provided showing that ependymoma should be considered as a neoplasm that can occur in patients with MEN1 (Kato et al., 1996; Cuevas-Ocampo et al., 2017). The biphasic histopathological tumor entity shown in the present case we name Pleomorphic Xanthoastocytoma grade 3 differential pathology (PDP) in association with Multiple Endocrine Neoplasia type 1. This MEN1 associated tumor subtype is an extension of the findings on MEN1 associated ependymoma, where we show that the clinical phenotype itself may potentially be triggered by a frameshift germline pathogenic variant for the MEN1 gene, in combination with cyclin-dependent kinase inhibitor 1B gene germline variant and cyclin dependent kinase inhibitor 2A somatic deletion downstream of menin.

Spontaneous Extradural Hematoma in a Sickle Cell Anemia Patient with Hyperinflammation and Thrombotic Microangiopathy successfully treated with Eculizumab: A case report and review of the literature.

Background The event of extradural hematoma in the absence of head trauma is a rare central nervous system complication of sickle cell disease. We report here a case of spontaneous extradural hematoma in a patient being treated for sickle cell vaso-occlusive crisis complicated by hyperinflammation and thrombotic microangiopathy. The significance of inflammation as an integral component of the pathomechanism of vaso-occlusive crisis in patients with sickle cell disease and the role of heme in activating the complement system's alternative pathway are highlighted in this case report. Case Presentation A teenage patient with sickle cell disease developed a spontaneous right parietal extradural hematoma while receiving treatment for sickle cell vaso-occlusive crisis. The concurrent events of hyperinflammation, disseminated intravascular coagulation, hyperhemolysis syndrome, thrombotic microangiopathy and refractory post-operative bleeding complicated this patient's clinical course after surgical evacuation of extradural hematoma. This patient was subsequently treated with eculizumab and improved in the days following. Conclusion Treatment with the anti-C5 monoclonal antibody eculizumab which targets and inhibits terminal complement system activation reversed the deleterious cascade of events in this patient with sickle cell disease.

Intraoperative neuromonitoring during intradural spinal neurosurgery.

Intraoperative neuromonitoring (IONM) allows for a perioperative evaluation of the functional integrity of the spinal cord and nerve roots during intradural neurosurgery. This review examines established techniques as somatosensory evoked potentials and motor evoked potentials, as well as electromyography which all provide real-time feedback for the surgical team. IONM represents a valuable tool which can identify emerging neurological complications, and thus can be utilised to reduce the incidence of postoperative neurological deficits by timely interventions.

Hydroflex: Use of Patient Reported Outcomes in a Clinical Setting Among Patients with Hydrocephalus.

OBJECTIVE/BACKGROUND: A patient-reported outcome (PRO) measure is defined as "any report of the status of a patient's health condition that comes directly from the patient without interpretation of the patient's response by a clinician or anyone else". PRO data are increasingly being used in health care to facilitate monitoring of symptoms, facilitate communication between patients and clinicians, facilitate early identification of problems, and reduce unnecessary outpatient appointments for stable patients. METHODS: We have designed a PRO system specifically for hydrocephalus, a program named Hydroflex. The aim of Hydroflex is to use PRO measures to decide the need for clinical attention and let the patients report their need regarding a physical consultation. Patients receive questionnaires at home instead of having prescheduled appointments at the outpatient clinic. Based on an automated algorithm, the patients' PRO measures are ranked to help clinical decision-making. RESULTS: In this paper, we describe the implementation and early experience of Hydroflex at our institution. CONCLUSIONS: It is our belief that Hydroflex provides more continuity in the treatment of patients with hydrocephalus. Also, it provides for a more standardized follow-up scheme, and we postulate this will lead to improved patient satisfaction and involvement and fewer outpatient appointments. Also, Hydroflex is useful for quality control and prospective research.

Comparison of outcomes and complications between one- and two-level anterior cervical discectomy and fusion: a population-based study of 410 patients.

OBJECTIVE: The objective of this study was to compare outcomes and patient satisfaction, and secondly to compare complication rates between one- and two-level anterior cervical discectomy and fusion (ACDF) for cervical radiculopathy. METHODS: Data from patients receiving one- or two-level ACDF for cervical radiculopathy at two institutions were prospectively collected and retrospectively analysed. Patients were separated into one-level ACDF and two-level ACDF. Comparison analyses of patient-reported outcome measures (PROMs) comprising Visual Analogue Scale for neck pain (VAS-NP) and arm pain (VAS-AP), Neck Disability Index (NDI), and EQ-5D 3-level version (EQ-5D-3L) were performed between baseline and 1-year follow-up and between groups as well as achievement of minimal clinically important differences (MCID) in PROMs and satisfaction. Additionally, complications were compared between groups. RESULTS: A total of 410 patients (270 one-level and 140 two-level) were included. PROMs improved significantly from baseline to 1-year follow-up (p < 0.001) in both groups. When comparing PROMs between one- and two-level ACDF, a trend towards greater improvement was observed in patients undergoing one-level ACDF, notably in EQ-5D-3L (p = 0.073). Significantly more patients in the one-level group achieved MCID in VAS-NP compared to patients in the two-level group (56% vs 44%, p = 0.025). Two hundred and ninety-six (67%) patients reported to be satisfied, but the one-level group trended to be more satisfied (70% vs. 62%). One-level ACDF further demonstrated a trend of more favourable complication profiles; however, complication rates were low in both groups. The risk of intraoperative complications was 2.4%, postoperative complications in-hospital were 1.2%, and patient-reported postoperative events post-discharge 42%. CONCLUSIONS: One- and two-level ACDF are effective procedures for degenerative cervical nerve root compression. Yet, significantly more patients in the one-level group achieved MCID in neck pain compared to patients in the two-level group.

[Intraoperative neuromonitoring during brain surgery].

Intraoperative neuromonitoring is a perioperative method, supplementary to stealth navigation and fluorescence microscopic imaging in brain surgery. It allows cortical and subcortical mapping, hence real time identification of eloquent brain areas through electrical stimulation of the cerebral cortex and subcortical areas. The method allows for functional guidance during both awake and asleep neurosurgery and aids in optimizing the extent of resection of the relevant pathology while preserving neurological function as summarised in this review.

Predictors of patient satisfaction following anterior cervical discectomy and fusion for cervical radiculopathy.

OBJECTIVE: To evaluate whether preoperative patient-reported outcome measures (PROMs) and immediate postoperative arm pain improvement can predict patient satisfaction following anterior cervical spine surgery. METHODS: A retrospective analysis of prospectively collected data from 193 patients with cervical radiculopathy undergoing surgery at Aarhus University Hospital was performed. Standardized questionnaires were used to assess demographics, clinical outcomes and complications preoperatively, postoperatively and at 1-year follow-up. PROMs covered Visual Analogue Scale for arm pain (VAS-AP) and neck pain (VAS-NP), Neck Disability Index (NDI), EQ-5D 3-level version (EQ-5D-3L), and satisfaction. Immediate upper extremity pain status was assembled from medical records. RESULTS: PROMs significantly improved (p < 0.001) and most patients (66%) were satisfied with the surgical result at follow-up. Complications and complaints occurred in 3.6% intraoperatively, 1.5% postoperatively in-hospital, and 43% postoperatively post-discharge. Patients with a symptom duration exceeding 24 months had significantly decreased odds of being satisfied compared to patients with a symptom duration less than 3 months (OR: 0.32, 95% CI: 0.10-0.98, p = 0.046). Neither baseline PROMs nor immediate pain improvement significantly predicted patient satisfaction. Despite being non-significant, patients experiencing immediate pain improvement had increased odds of being satisfied compared to patients not experiencing immediate improvement (OR: 1.62, 95% CI: 0.65-4.05). CONCLUSIONS: Prolonged symptom duration and immediate pain improvement may have an impact on patient satisfaction.

[Visna of Egill Skallagrimsson].

Considering the changes in moral principles, human behavior and behavioral values through the ages, in Egill Skallagrimsson's Saga, Egill presents us with altered mental status. This is in terms of what at present is considered symptoms of an anti-social personality, and bipolar affective disorder. Egill Skallagrimsson is considered one of the most famous Vikings in the Icelandic Sagas. Archaeological findings mentioned in Egill's Saga indicate disfigurement of his skull, which has led many authors to suggest that Egill suffered from skeletal dysplasia. The primary assumption in the literature is that Egill Skallagrimsson was affected by Paget's disease of bone. This consideration is additionally based on the scholar's interpretation of the Saga text. The unique storytelling style in the Saga of Egill Skallagrimsson is evident; however, the question of the story's truthfulness remains open. In this article, we investigate Egill Skallagrimsson's assumed Paget's disease of bone, based on the physical and mental symptoms disclosed in the Saga of Egill Skallagrimsson. Associated with the assumption, the author's hermeneutics of Egill's Saga in the context of modern-day knowledge of Paget's disease of bone, brings forward the probability estimate to the range of permille. In Scandinavian folklore and mythology, a tale by Saxo Grammaticus of a notorious shield-maiden named Visna, reminds of Egill, as noted by Snorri Sturluson. Hence, in reference to Egill Skallagrimsson's mental status and physical appearance as listed in Egill's Saga, the authors recommend the name for his condition to be "Visna of Egill Skallagrimsson".

Spontaneous generation of functional osteoclasts from synovial fluid mononuclear cells as a model of inflammatory osteoclastogenesis.

In osteoimmunology, osteoclastogenesis is understood in the context of the immune system. Today, the in vitro model for osteoclastogenesis necessitates the addition of recombinant human receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). The peripheral joints of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) are characterized by an immune-mediated inflammation that can lead to bone destruction. Here, we evaluate spontaneous in vitro osteoclastogenesis in cultures of synovial fluid mononuclear cells (SFMCs) activated only in vivo. SFMCs were isolated and cultured for 21 days at 0.5-1.0 × 10(6) cells/mL in culture medium. SFMCs and healthy control peripheral blood monocytes were cultured with RANKL and M-CSF as controls. Tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells were found in the SFMC cultures after 21 days. These cells expressed the osteoclast genes calcitonin receptor, cathepsin K, and integrin ß3, formed lacunae on dentin plates and secreted matrix metalloproteinase 9 (MMP9) and TRAP. Adding RANKL and M-CSF potentiated this secretion. In conclusion, we show that SFMCs from inflamed peripheral joints can spontaneously develop into functionally active osteoclasts ex vivo. Our study provides a simple in vitro model for studying inflammatory osteoclastogenesis.

Properties and prospects of adjuvants in influenza vaccination - messy precipitates or blessed opportunities?

Influenza is a major challenge to healthcare systems world-wide. While prophylactic vaccination is largely efficient, long-lasting immunity has not been achieved in immunized populations, at least in part due to the challenges arising from the antigen variation between strains of influenza A virus as a consequence of genetic drift and shift. From progress in our understanding of the immune system, the mode-of-action of vaccines can be divided into the stimulation of the adaptive system through inclusion of appropriate vaccine antigens and of the innate immune system by the addition of adjuvant to the vaccine formulation. A shared property of many vaccine adjuvants is found in their nature of water-insoluble precipitates, for instance the particulate material made from aluminum salts. Previously, it was thought that embedding of vaccine antigens in these materials provided a "depot" of antigens enabling a long exposure of the immune system to the antigen. However, more recent work points to a role of particulate adjuvants in stimulating cellular parts of the innate immune system. Here, we briefly outline the infectious medicine and immune biology of influenza virus infection and procedures to provide sufficient and stably available amounts of vaccine antigen. This is followed by presentation of the many roles of adjuvants, which involve humoral factors of innate immunity, notably complement. In a perspective of the ultrastructural properties of these humoral factors, it becomes possible to rationalize why these insoluble precipitates or emulsions are such a provocation of the immune system. We propose that the biophysics of particulate material may hold opportunities that could aid the development of more efficient influenza vaccines.

Glatiramer acetate in treatment of multiple sclerosis: a toolbox of random co-polymers for targeting inflammatory mechanisms of both the innate and adaptive immune system?

Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA) is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin α(M)ß(2) (also called Mac-1, complement receptor 3, or CD11b/CD18) and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

[Pseudomembranous upper respiratory tract infection caused by herpes simplex virus in an adult]. / Pseudomembranøs øvre luftvejsinfektion fremkaldt af herpes simplex-virus hos voksen.

We report a case of viral laryngitis due to HSV in an adult. The patient was a 61-year-old female alcoholic. She presented with fever and stridor and developed sepsis and multiorgan failure. She was treated with antibiotics to no effect and died 14 days after hospitalisation. Post mortem histology of the larynx showed an acute pseudomembranous inflammation with the classical morphology of HSV infection. An immunohistochemical reaction for HSV was positive.