Trauma is danger

<p>Abstract</p> <p>Background</p> <p>Trauma is one of the leading causes of death in young adult patients. Many pre-clinical and clinical studies attempt to investigate the immunological pathways involved, however the true mediators remain to be elucidated. Herein, we attempt to describe the immunologic response to systemic trauma in the context of the Danger model.</p> <p>Data Sources</p> <p>A literature search using PubMed was used to identify pertinent articles describing the Danger model in relation to trauma.</p> <p>Conclusions</p> <p>Our knowledge of Danger signals in relation to traumatic injury is still limited. Danger/alarmin signals are the most proximal molecules in the immune response that have many possibilities for effector function in the innate and acquired immune systems. Having a full understanding of these molecules and their pathways would give us the ability to intervene at such an early stage and may prove to be more effective in blunting the post-injury inflammatory response unlike previously failed cytokine experiments.</p

Wound trauma mediated inflammatory signaling attenuates a tissue regenerative response in MRL/MpJ mice

<p>Abstract</p> <p>Background</p> <p>Severe trauma can induce pathophysiological responses that have marked inflammatory components. The development of systemic inflammation following severe thermal injury has been implicated in immune dysfunction, delayed wound healing, multi-system organ failure and increased mortality.</p> <p>Methods</p> <p>In this study, we examined the impact of thermal injury-induced systemic inflammation on the healing response of a secondary wound in the MRL/MpJ mouse model, which was anatomically remote from the primary site of trauma, a wound that typically undergoes scarless healing in this specific strain. Ear-hole wounds in MRL/MpJ mice have previously displayed accelerated healing and tissue regeneration in the absence of a secondary insult.</p> <p>Results</p> <p>Severe thermal injury in addition to distal ear-hole wounds induced marked local and systemic inflammatory responses in the lungs and significantly augmented the expression of inflammatory mediators in the ear tissue. By day 14, 61% of the ear-hole wounds from thermally injured mice demonstrated extensive inflammation with marked inflammatory cell infiltration, extensive ulceration, and various level of necrosis to the point where a large percentage (38%) had to be euthanized early during the study due to extensive necrosis, inflammation and ear deformation. By day 35, ear-hole wounds in mice not subjected to thermal injury were completely closed, while the ear-hole wounds in thermally injured mice exhibited less inflammation and necrosis and only closed partially (62%). Thermal injury resulted in marked increases in serum levels of IL-6, TNFα, KC (CXCL1), and MIP-2α (CXCL2). Interestingly, attenuated early ear wound healing in the thermally injured mouse resulted in incomplete tissue regeneration in addition to a marked inflammatory response, as evidenced by the histological appearance of the wound and increased transcription of potent inflammatory mediators.</p> <p>Conclusion</p> <p>These findings suggest that the observed systemic inflammatory response of a severe thermal injury undoubtedly has an adverse effect on wound healing and tissue regeneration.</p

Non-invasive monitoring of tissue oxygenation during laparoscopic donor nephrectomy

<p>Abstract</p> <p>Background</p> <p>Standard methods for assessment of organ viability during surgery are typically limited to visual cues and tactile feedback in open surgery. However, during laparoscopic surgery, these processes are impaired. This is of particular relevance during laparoscopic renal donation, where the condition of the kidney must be optimized despite considerable manipulation. However, there is no <it>in vivo </it>methodology to monitor renal parenchymal oxygenation during laparoscopic surgery.</p> <p>Methods</p> <p>We have developed a method for the real time, <it>in vivo</it>, whole organ assessment of tissue oxygenation during laparoscopic nephrectomy to convey meaningful biological data to the surgeon during laparoscopic surgery. We apply the 3-CCD (charge coupled device) camera to monitor qualitatively renal parenchymal oxygenation with potential real-time video capability.</p> <p>Results</p> <p>We have validated this methodology in a porcine model across a range of hypoxic conditions, and have then applied the method during clinical laparoscopic donor nephrectomies during clinically relevant pneumoperitoneum. 3-CCD image enhancement produces mean region of interest (ROI) intensity values that can be directly correlated with blood oxygen saturation measurements (R²> 0.96). The calculated mean ROI intensity values obtained at the beginning of the laparoscopic nephrectomy do not differ significantly from mean ROI intensity values calculated immediately before kidney removal (<it>p </it>> 0.05).</p> <p>Conclusion</p> <p>Here, using the 3-CCD camera, we qualitatively monitor tissue oxygenation. This means of assessing intraoperative tissue oxygenation may be a useful method to avoid unintended ischemic injury during laparoscopic surgery. Preliminary results indicate that no significant changes in renal oxygenation occur as a result of pneumoperitoneum.</p

Evidence-based Surgical Competency Outcomes from the Clinical Readiness Program

Objectives: 1) Evaluate the value and strength of a competency framework for identifying and measuring performance requirements for expeditionary surgeons; 2) Verify psychometric integrity of assessment instrumentation for measuring domain knowledge and skills; 3) Identify gaps in knowledge and skills capabilities using assessment strategies; 4) Examine shared variance between knowledge and skills outcomes, and the volume and diversity of routine surgical practice. Background: Expeditionary military surgeons provide care for patients with injuries that extend beyond the care requirements of their routine surgical practice. The readiness of these surgeons to independently provide accurate care in expeditionary contexts is important for casualty care in military and civilian situations. Identifying and closing performance gap areas are essential for assuring readiness. Methods: We implemented evidence-based processes for identifying and measuring the essential performance competencies for expeditionary surgeons. All assessment instrumentation was rigorously examined for psychometric integrity. Performance outcomes were directly measured for expeditionary surgical knowledge and skills and gap areas were identified. Knowledge and skills assessment outcomes were compared, and also compared to the volume and diversity of routine surgical practice to determine shared variance. Results: Outcomes confirmed the integrity of assessment instrumentation and identified significant performance gaps for knowledge and skills in the domain. Conclusions: Identification of domain competencies and performance benchmarks, combined with best-practices in assessment instrumentation, provided a rigorous and defensible framework for quantifying domain competencies. By identifying and implementing strategies for closing performance gap areas, we provide a positive process for assuring surgical competency and clinical readiness

Method to compute the stress-energy tensor for the massless spin 1/2 field in a general static spherically symmetric spacetime

A method for computing the stress-energy tensor for the quantized, massless, spin 1/2 field in a general static spherically symmetric spacetime is presented. The field can be in a zero temperature state or a non-zero temperature thermal state. An expression for the full renormalized stress-energy tensor is derived. It consists of a sum of two tensors both of which are conserved. One tensor is written in terms of the modes of the quantized field and has zero trace. In most cases it must be computed numerically. The other tensor does not explicitly depend on the modes and has a trace equal to the trace anomaly. It can be used as an analytic approximation for the stress-energy tensor and is equivalent to other approximations that have been made for the stress-energy tensor of the massless spin 1/2 field in static spherically symmetric spacetimes.Comment: 34 pages, no figure

Development of a clinical decision model for thyroid nodules

<p>Abstract</p> <p>Background</p> <p>Thyroid nodules represent a common problem brought to medical attention. Four to seven percent of the United States adult population (10–18 million people) has a palpable thyroid nodule, however the majority (>95%) of thyroid nodules are benign. While, fine needle aspiration remains the most cost effective and accurate diagnostic tool for thyroid nodules in current practice, over 20% of patients undergoing FNA of a thyroid nodule have indeterminate cytology (follicular neoplasm) with associated malignancy risk prevalence of 20–30%. These patients require thyroid lobectomy/isthmusectomy purely for the purpose of attaining a definitive diagnosis. Given that the majority (70–80%) of these patients have benign surgical pathology, thyroidectomy in these patients is conducted principally with diagnostic intent. Clinical models predictive of malignancy risk are needed to support treatment decisions in patients with thyroid nodules in order to reduce morbidity associated with unnecessary diagnostic surgery.</p> <p>Methods</p> <p>Data were analyzed from a completed prospective cohort trial conducted over a 4-year period involving 216 patients with thyroid nodules undergoing ultrasound (US), electrical impedance scanning (EIS) and fine needle aspiration cytology (FNA) prior to thyroidectomy. A Bayesian model was designed to predict malignancy in thyroid nodules based on multivariate dependence relationships between independent covariates. Ten-fold cross-validation was performed to estimate classifier error wherein the data set was randomized into ten separate and unique train and test sets consisting of a training set (90% of records) and a test set (10% of records). A receiver-operating-characteristics (ROC) curve of these predictions and area under the curve (AUC) were calculated to determine model robustness for predicting malignancy in thyroid nodules.</p> <p>Results</p> <p>Thyroid nodule size, FNA cytology, US and EIS characteristics were highly predictive of malignancy. Cross validation of the model created with Bayesian Network Analysis effectively predicted malignancy [AUC = 0.88 (95%CI: 0.82–0.94)] in thyroid nodules. The positive and negative predictive values of the model are 83% (95%CI: 76%–91%) and 79% (95%CI: 72%–86%), respectively.</p> <p>Conclusion</p> <p>An integrated predictive decision model using Bayesian inference incorporating readily obtainable thyroid nodule measures is clinically relevant, as it effectively predicts malignancy in thyroid nodules. This model warrants further validation testing in prospective clinical trials.</p