The hidden value of MRI: modifying treatment decisions in C-spine injuries.

BACKGROUND DATA Computed Tomography (CT) is the gold standard for cervical spine (c-spine) evaluation. Magnetic resonance imaging (MRI) emerges due to its increasing availability and the lack of radiation exposure. However, MRI is costly and time-consuming, questioning its role in the emergency department (ED). This study investigates the added the value of an additional MRI for patients presenting with a c-spine injury in the ED. METHODS We conducted a retrospective monocenter cohort study that included all patients with neck trauma presenting in the ED, who received imaging based on the NEXUS criteria. Spine surgeons performed a full-case review to classify each case into "c-spine injured" and "c-spine uninjured". Injuries were classified according to the AO Spine classification. We assessed patients with a c-spine injury detected by CT, who received a subsequent MRI. In this subset, injuries were classified separately in both imaging modalities. We monitored the treatment changes after the additional MRI to evaluate characteristics of this cohort and the impact of the AO Spine Neurology/Modifier modifiers. RESULTS We identified 4496 subjects, 2321 were eligible for inclusion and 186 were diagnosed with c-spine injuries in the retrospective case review. Fifty-six patients with a c-spine injury initially identified through CT received an additional MRI. The additional MRI significantly extended (geometric mean ratio 1.32, p < 0.001) the duration of the patients' stay in the ED. Of this cohort, 25% had a change in treatment strategy and among the patients with neurological symptoms (AON ≥ 1), 45.8% experienced a change in treatment. Patients that were N-positive, had a 12.4 (95% CI 2.7-90.7, p < 0.01) times higher odds of a treatment change after an additional MRI than neurologically intact patients. CONCLUSION AND RELEVANCE Our study suggests that patients with a c-spine injury and neurological symptoms benefit from an additional MRI. In neurologically intact patients, an additional MRI retains value only when carefully evaluated on a case-by-case basis

SETD3 acts as a prognostic marker in breast cancer patients and modulates the viability and invasion of breast cancer cells

In several carcinomas, the SET Domain Containing 3, Actin Histidine Methyltransferase (SETD3) is associated with oncogenesis. However, there is little knowledge about the role of SETD3 in the progression and prognosis of breast cancer. In this study, we first analyzed the prognostic value of SETD3 in breast cancer patients using the database of the public Kaplan-Meier plotter. Moreover, in vitro assays were performed to assess the role of SETD3 in the viability and capacity of invasion of human breast cancer cell lines. We observed that the high expression of SETD3 was associated with better relapse-free survival (RFS) of the whole collective of 3,951 patients, of Estrogen Receptor-positive, and of Luminal A-type breast cancer patients. However, in patients lacking expression of estrogen-, progesterone- and HER2-receptor, and those affected by a p53-mutation, SETD3 was associated with poor RFS. In vitro analysis showed that SETD3 siRNA depletion affects the viability of triple-negative cells as well as the cytoskeletal function and capacity of invasion of highly invasive MDA-MB-231 cells. Interestingly, SETD3 regulates the expression of other genes associated with cancer such as β-actin, FOXM1, FBXW7, Fascin, eNOS, and MMP-2. Our study suggests that SETD3 expression can act as a subtype-specific biomarker for breast cancer progression and prognosis

Incentivizing the Dynamic Workforce: Learning Contracts in the Gig-Economy

In principal-agent models, a principal offers a contract to an agent to perform a certain task. The agent exerts a level of effort that maximizes her utility. The principal is oblivious to the agent's chosen level of effort, and conditions her wage only on possible outcomes. In this work, we consider a model in which the principal is unaware of the agent's utility and action space. She sequentially offers contracts to identical agents, and observes the resulting outcomes. We present an algorithm for learning the optimal contract under mild assumptions. We bound the number of samples needed for the principal obtain a contract that is within $\epsilon$ of her optimal net profit for every $\epsilon>0$

Rigid spine injuries - A comprehensive review on diagnostic and therapeutic challenges.

Injuries to the rigid spine have a distinguished position in the broad spectrum of spinal injuries due to altered biomechanical properties. The rigid spine is more prone to fractures. Two ossification bone disorders that are of particular interest are Ankylosing Spondylitis (AS) and Diffuse Idiopathic Skeletal Hyperostosis (DISH). DISH is a non-inflammatory condition that leads to an anterolateral ossification of the spine. AS on the other hand is a chronic inflammatory disease that leads to cortical bone erosions and spinal ossifications. Both diseases gradually induce stiffening of the spine. The prevalence of DISH is age-related and is therefore higher in the older population. Although the prevalence of AS is not age-related the occurrence of spinal ossification is higher with increasing age. This association with age and the aging demographics in industrialized nations illustrate the need for medical professionals to be adequately informed and prepared. The aim of this narrating review is to give an overview on the diagnostic and therapeutic measures of the ankylosed spine. Because of highly unstable fracture configurations, injuries to the rigid spine are highly susceptible to neurological deficits. Diagnosing a fracture of the ankylosed spine on plain radiographs can be challenging. Moreover, since 8% of patients with ankylosing spine disorders (ASD) have multiple non-contagious fractures, a CT scan of the entire spine is highly recommended as the primary diagnostic tool. There are no consensus-based guidelines for the treatment of spinal fractures in ASD. The presence of neurological deficit or unstable fractures are absolute indications for surgical intervention. If conservative therapy is chosen, patients should be monitored closely to ensure that secondary neurologic deterioration does not occur. For the fractures that have to be treated surgically, stabilization of at least three segments above and below the fracture zone is recommended. These fractures mostly are treated via the posterior approach. Patients with AS or DISH share a significant risk for complications after a traumatic spine injury. The most frequent complications for patients with thoracolumbar burst fractures are respiratory failure, pseudoarthrosis, pneumonia, and implant failure

Impact of different surgical and non-surgical interventions on health-related quality of life after thoracolumbar burst fractures without neurological deficit: protocol for a comprehensive systematic review with network meta-analysis

Introduction There is no international consensus on how to treat thoracolumbar burst fractures (TLBFs) without neurological deficits. The planned systematic review with network meta-analyses (NMA) aims to compare the effects on treatment outcomes, focusing on midterm health-related quality of life (HRQoL).Methods and analysis We will conduct a comprehensive and systematic literature search, identifying studies comparing two or more treatment modalities. We will search MEDLINE, EMBASE, Google Scholar, Scopus and Web of Science from January 2000 until July 2023 for publications. We will include (randomised and non-randomised) controlled clinical trials assessing surgical and non-surgical treatment methods for adults with TLBF. Screening of references, data extraction and risk of bias (RoB) assessment will be done independently by two reviewers. We will extract relevant studies, participants and intervention characteristics. The RoB will be assessed using the revised Cochrane RoB V.2.0 tool for randomised trials and the Newcastle-Ottawa Scale for controlled trials. The OR for dichotomous data and standardised mean differences for continuous data will be presented with their respective 95% CIs. We will conduct a random-effects NMA to assess the treatments and determine the superiority of the therapeutic approaches. Our primary outcomes will be midterm (6 months to 2 years after injury) overall HRQoL and pain. Secondary outcomes will include radiological or clinical findings. We will present network graphs, forest plots and relative rankings on plotted rankograms corresponding to the treatment rank probabilities. The ranking results will be represented by the area under the cumulative ranking curve. Analyses will be performed in Stata V.16.1 and R. The quality of the evidence will be evaluated according to the Grading of Recommendations, Assessment, Development and Evaluations framework.Ethics and dissemination Ethical approval is not required. The research will be published in a peer-reviewed journal

Cervical spine trauma - Evaluating the diagnostic power of CT, MRI, X-Ray and LODOX.

BACKGROUND Traumatic cervical spine (c-spine) injuries account for 10% of all spinal injuries. The c-spine is prone to injury by blunt acceleration/deceleration traumas. The Canadian C-Spine rule and NEXUS criteria guide clinical decision-making but lack consensus on imaging modality when necessary. This study aims to evaluate the sensitivity and specificity of CT, MRI, X-Ray, and, for the first time, LODOX-Statscan in identifying c-spine injuries in patients with blunt trauma and neck pain. METHODS We conducted a retrospective monocenter cohort study using patient data from the emergency department at Inselspital, Bern, Switzerland's largest level one trauma center. We identified patients presenting with trauma and neck pain during the recruitment period from 01.01.2012 to 31.12.2017. We included all patients that required a radiographic c-spine evaluation according to the NEXUS criteria. Certified spine surgeons reviewed each case, analyzed patient demographics, injury classification, trauma mechanism, and emergency management. The retrospective full case review was established as gold standard to decide whether the c-spine was injured. Sensitivity and specificity were calculated for CT, MRI, LODOX, and X-Ray imaging methods. RESULTS We identified 4996 patients, of which 2321 met the inclusion criteria. 91.3% (n = 2120) patients received a CT scan, 8.9% (n = 206) a MRI, 9.3% (n = 215) an X-ray, and 21.5% (n = 498) a LODOX scan. By retrospective case review, 186 participants were classified as injured. The sensitivity of CT was 88.6% (specificity 99%), and 89.8% (specificity 99.2%) with orthopedic surgeon consultation. MRI had a sensitivity of 88.5% (specificity of 96.9%); highlighting 14 cases correctly diagnosed as injured by MRI and misdiagnosed by CT. Projection radiography (36.4% sensitivity, 95.1% specificity) and LODOX (5.3% sensitivity, 100% specificity) were unsuitable for ruling out spinal injury. CONCLUSION While CT offers high sensitivity for detecting traumatic c-spine injury, MRI holds clinical significance in revealing injuries not recognized by CT in symptomatic patients. LODOX and projection radiography are insufficient for accurately ruling out c-spine injury. For patients with neurological symptoms, we recommend extended MRI use when CT scans are negative

The Bone Morphogenetic Protein L51P Enhances Spinal Fusion in Combination with BMP2 - An In Vivo Rat Spinal Fusion Model of the Elderly

Non-union and pseudoarthrosis remain major complications after spinal fusion surgery, resulting in unsatisfactory outcomes and high socio-economic costs. Several biomaterials and osteo-biologics have been used to improve spinal fusion, including bone morphogenetic protein (BMP) 2. However, its necessary high dose application often leads to adverse effects. L51P, a BMP-2 analogue and inhibitor of BMP antagonists, has been shown to augment BMP-induced bone formation and lower the required doses. The current study therefore aimed to demonstrate the effects of L51P and BMP-2 on spinal fusion in vivo. 46 elderly Wistar rats (~12 months, 52% female, 423±78g) underwent a two-step spinal fusion surgery [1]. Firstly, a custom external fixator was applied in the proximal tail. Secondly, discectomy and disc replacement with a β tri-calcium-phosphate (β-TCP) carrier were conducted. Carriers were loaded with the study compounds based on random and blinded allocation into seven groups: Phosphate-buffered-saline (PBS) as material control, 1µg and 10µg BMP-2, 10µg L51P, 1µg BMP-2 + 1/5/10µg L51P. Digital X-rays were performed on day zero, at six weeks, and twelve weeks postoperatively. After twelve weeks, high-resolution µCT scans and histology were obtained. Results. At twelve weeks, 10µg BMP-2, 1µg BMP-2 + 5µg L51P and 1µg BMP-2 + 10µg L51P showed significantly higher fusion rates compared to the PBS control in X-ray analysis. µCT analysis showed significantly higher fusion rates for all groups compared to the control group. 1µg BMP-2 + 1µg L51P demonstrated significantly higher fusion rates than 1µg BMP2 alone and equivalent ossification compared to 10µg BMP-2; higher doses of L51P did not lead to a better fusion outcome. Histological analysis confirmed the radiographical results. Combining low doses of L51P and BMP-2 enhances spinal fusion equivalent to high-dose BMP-2 and may reduce BMP-2 doses and side effects at similar to higher efficacy in clinical application

Diabetes With Multiple Autoimmune and Inflammatory Conditions Linked to an Activating SKAP2 Mutation.

ObjectiveMultiple genome-wide association studies have identified a strong genetic linkage between the SKAP2 locus and type 1 diabetes (T1D), but how this leads to disease remains obscure. Here, we characterized the functional consequence of a novel SKAP2 coding mutation in a patient with T1D to gain further insight into how this impacts immune tolerance.Research design and methodsWe identified a 24-year-old individual with T1D and other autoimmune and inflammatory conditions. The proband and first-degree relatives were recruited for whole-exome sequencing. Functional studies of the protein variant were performed using a cell line and primary myeloid immune cells collected from family members.ResultsSequencing identified a de novo SKAP2 variant (c.457G&gt;A, p.Gly153Arg) in the proband. Assays using monocyte-derived macrophages from the individual revealed enhanced activity of integrin pathways and a migratory phenotype in the absence of chemokine stimulation, consistent with SKAP2 p.Gly153Arg being constitutively active. The p.Gly153Arg variant, located in the well-conserved lipid-binding loop, induced similar phenotypes when expressed in a human macrophage cell line. SKAP2 p.Gly153Arg is a gain-of-function, pathogenic mutation that disrupts myeloid immune cell function, likely resulting in a break in immune tolerance and T1D.ConclusionsSKAP2 plays a key role in myeloid cell activation and migration. This particular mutation in a patient with T1D and multiple autoimmune conditions implicates a role for activating SKAP2 variants in autoimmune T1D