A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R 2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.human disease | translational medicine | inflammation | immune response | injury M urine models have been extensively used in recent decades to identify and test drug candidates for subsequent human trials (1-3). However, few of these human trials have shown success (4-7). The success rate is even worse for those trials in the field of inflammation, a condition present in many human diseases. To date, there have been nearly 150 clinical trials testing candidate agents intended to block the inflammatory response in critically ill patients, and every one of these trials failed (8-11). Despite commentaries that question the merit of an overreliance of animal systems to model human immunology (3,12,13), in the absence of systematic evidence, investigators and public regulators assume that results from animal research reflect human disease. To date, there have been no studies to systematically evaluate, on a molecular basis, how well the murine clinical models mimic human inflammatory diseases in patients.The Inflammation and Host Response to Injury, Large Scale Collaborative Research Program has completed multiple studies on the genomic responses to systemic inflammation in patients and human volunteers as well as murine models (14-18). These datasets include genome-wide expression analysis on white blood cells obtained from serial blood draws in 167 patients up to 28 d after severe blunt trauma (15), 244 patients up to 1 y after burn injury, and 4 healthy humans for 24 h after administration of low-dose bacterial endotoxin (14) and expression analysis on analogous samples from well-established mouse models of trauma, burns, and endotoxemia (16 treated and 16 controls per model) (16-18). In humans, severe inflammatory stress produces a genomic storm affecting all major cellular functions and pathways (15) and therefore, provided sufficient perturbations to allow comparisons between the genes in the human conditions and their orthologs in the murine models.In this article, we report on a systematic comparison of the genomic respo...

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes.

Background and aims: Acute appendicitis (AA) is among the most common causes of acute abdominal pain. Diagnosis of AA is still challenging and some controversies on its management are still present among different settings and practice patterns worldwide. In July 2015, the World Society of Emergency Surgery (WSES) organized in Jerusalem the first consensus conference on the diagnosis and treatment of AA in adult patients with the intention of producing evidence-based guidelines. An updated consensus conference took place in Nijemegen in June 2019 and the guidelines have now been updated in order to provide evidence-based statements and recommendations in keeping with varying clinical practice: use of clinical scores and imaging in diagnosing AA, indications and timing for surgery, use of nonoperative management and antibiotics, laparoscopy and surgical techniques, intra-operative scoring, and perioperative antibiotic therapy.

Intra-abdominal infections (IAIs) are common surgical emergencies and have been reported as major contributors to non-trauma deaths in the emergency departments worldwide.The cornerstones of effective treatment of IAIs are early recognition, adequate source control, and appropriate antimicrobial therapy. Prompt resuscitation of patients with ongoing sepsis is of utmost important.In hospitals worldwide, non-acceptance of, or lack of access to, accessible evidence-based practices and guidelines result in overall poorer outcome of patients suffering IAIs.The aim of this paper is to promote global standards of care in IAIs and update the 2013 WSES guidelines for management of intra-abdominal infections.

Acute appendicitis (AA) is among the most common cause of acute abdominal pain. Diagnosis of AA is challenging; a variable combination of clinical signs and symptoms has been used together with laboratory findings in several scoring systems proposed for suggesting the probability of AA and the possible subsequent management pathway. The role of imaging in the diagnosis of AA is still debated, with variable use of US, CT and MRI in different settings worldwide. Up to date, comprehensive clinical guidelines for diagnosis and management of AA have never been issued. In July 2015, during the 3rd World Congress of the WSES, held in Jerusalem (Israel), a panel of experts including an Organizational Committee and Scientific Committee and Scientific Secretariat, participated to a Consensus Conference where eight panelists presented a number of statements developed for each of the eight main questions about diagnosis and management of AA. The statements were then voted, eventually modified and finally approved by the participants to The Consensus Conference and lately by the board of co-authors. The current paper is reporting the definitive Guidelines Statements on each of the following topics: 1) Diagnostic efficiency of clinical scoring systems, 2) Role of Imaging, 3) Non-operative treatment for uncomplicated appendicitis, 4) Timing of appendectomy and in-hospital delay, 5) Surgical treatment 6) Scoring systems for intra-operative grading of appendicitis and their clinical usefulness 7) Non-surgical treatment for complicated appendicitis: abscess or phlegmon 8) Pre-operative and post-operative antibiotics.

Our results indicate that a strong association exists between trauma center volume and outcomes, with significant improvements in mortality and LOS when volume exceeds 650 cases per year. These benefits are only evident in patients at high risk for adverse outcomes.

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Preventable deaths will occur even in mature trauma systems. This review has identified error patterns that are likely common in all trauma systems, and for which policy interventions can be effectively targeted.