Severe trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution. The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013. The guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome. A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

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The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition

Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace damaged or diseased organs and tissues. Fibrin is a critical blood component responsible for hemostasis, which has been used extensively as a biopolymer scaffold in tissue engineering. In this review we summarize the latest developments in organ and tissue regeneration using fibrin as the scaffold material. Commercially available fibrinogen and thrombin are combined to form a fibrin hydrogel. The incorporation of bioactive peptides and growth factors via a heparin-binding delivery system improves the functionality of fibrin as a scaffold. New technologies such as inkjet printing and magnetically influenced self-assembly can alter the geometry of the fibrin structure into appropriate and predictable forms. Fibrin can be prepared from autologous plasma, and is available as glue or as engineered microbeads. Fibrin alone or in combination with other materials has been used as a biological scaffold for s...

Fibrin: a versatile scaffold for tissue engineering applications.

/pdf/the-present-and-future-of-nanotechnology-in-human-health-fqafmk7ns9.pdf

The present and future of nanotechnology in human health care

Adult stem cells provide replacement and repair descendants for normal turnover or injured tissues. These cells have been isolated and expanded in culture, and their use for therapeutic strategies requires technologies not yet perfected. In the 1970s, the embryonic chick limb bud mesenchymal cell culture system provided data on the differentiation of cartilage, bone, and muscle. In the 1980s, we used this limb bud cell system as an assay for the purification of inductive factors in bone. In the 1990s, we used the expertise gained with embryonic mesenchymal progenitor cells in culture to develop the technology for isolating, expanding, and preserving the stem cell capacity of adult bone marrow-derived mesenchymal stem cells (MSCs). The 1990s brought us into the new field of tissue engineering, where we used MSCs with site-specific delivery vehicles to repair cartilage, bone, tendon, marrow stroma, muscle, and other connective tissues. In the beginning of the 21st century, we have made substantial advances: the most important is the development of a cell-coating technology, called painting, that allows us to introduce informational proteins to the outer surface of cells. These paints can serve as targeting addresses to specifically dock MSCs or other reparative cells to unique tissue addresses. The scientific and clinical challenge remains: to perfect cell-based tissue-engineering protocols to utilize the body's own rejuvenation capabilities by managing surgical implantations of scaffolds, bioactive factors, and reparative cells to regenerate damaged or diseased skeletal tissues.

Review: mesenchymal stem cells: cellbased reconstructive therapy in orthopedics

Physicians, policymakers, and researchers are increasingly focused on finding ways to decrease opioid use and overdose in the United States both of which have sharply increased over the past decade. While many efforts are focused on the management of chronic pain, the use of opioids in surgical patients presents a particularly challenging problem requiring clinicians to balance 2 competing interests: managing acute pain in the immediate postoperative period and minimizing the risks of persistent opioid use after the surgery. Finding ways to minimize this risk is particularly salient in light of a growing literature suggesting that postsurgical patients are at increased risk for chronic opioid use. The perioperative care team, including surgeons and anesthesiologists, is poised to develop clinical- and systems-based interventions aimed at providing pain relief in the immediate postoperative period while also reducing the risks of opioid use longer term. In this paper, we discuss the consequences of chronic opioid use after surgery and present an analysis of the extent to which surgery has been associated with chronic opioid use. We follow with a discussion of the risk factors that are associated with chronic opioid use after surgery and proceed with an analysis of the extent to which opioid-sparing perioperative interventions (eg, nerve blockade) have been shown to reduce the risk of chronic opioid use after surgery. We then conclude with a discussion of future research directions.

Chronic Opioid Use After Surgery: Implications for Perioperative Management in the Face of the Opioid Epidemic.

Background:Opioid use is endemic in the U.S. and is associated with morbidity and mortality. The impact of long-term opioid use on joint-replacement outcomes remains unknown. We tested the hypothesis that use of opioids is associated with adverse outcomes after total knee arthroplasty (TKA).Methods:

Preoperative Opioid Use Is Associated with Early Revision After Total Knee Arthroplasty: A Study of Male Patients Treated in the Veterans Affairs System.

We describe an ultrasound-guided technique of continuous bilateral paravertebral block using an intercostal approach in 12 patients undergoing elective abdominal surgery. Postoperatively, each of the patient's paravertebral catheters was bolused with 10 mL lidocaine (15 mg/mL), and each of the patient's catheters was infused with 0.2% ropivacaine at 10 mL/h. Using a pinprick test, the median number of dermatomes blocked after the initial bolus was 5 (interquartile range, 4-6), and 23 of 24 catheters produced a local anesthetic block. The median verbal pain score on postoperative day 1 was 5.5 (interquartile range, 3.5-6), and median dose of IV hydromorphone consumed during the first 24 h after surgery was 1.9 mg (interquartile range, 0.7-5.05). All catheters were removed within 72 h after surgery.

Ultrasound-guided paravertebral block using an intercostal approach.

Protein and peptide delivery has been a challenge due to their limited stability during preparation of formulation, storage and in vitro and in vivo release. These biopolymers have traditionally been administered via intramuscular or subcutaneous routes. Recent efforts have been made to develop formulations for non-invasive routes of administration, including oral, intranasal, transdermal and transmucosal delivery. Despite these efforts, invasive delivery remains the main method of administering peptide and protein drugs. This review focuses on recent developments in injectable, polymeric controlled-release formulations, with an emphasis on hydrogels and particulate systems.

Protein and peptide parenteral controlled delivery.

In this report, we describe the feasibility of locating the sacral plexus nerve using a parasacral approach and an ultrasound-guided technique. The parasacral region using a curved probe (2-5 MHz) was scanned in 17 patients in search of the medial border of the ischial bone and the lateral border of the sacrum, which represent the limit of the greater sciatic foramen. In addition, attempts were made to identify the piriformis muscles and the gluteal arteries. The sacral plexus was identified at the level of the sciatic foramen as a round hyperechoic structure. The gluteal arteries were identified in 10 of 17 patients, but we failed to positively identify the piriformis muscle in any patient. To confirm localization of the sacral plexus, an insulated needle attached to a nerve stimulator was advanced and, in each case, a sacral plexus motor response was elicited (plantar flexion-12, dorsal flexion-1, hamstring muscle stimulation-3, gastrocnemius muscle stimulation-1-not recorded) at a current between 0.2 and 0.5 mA. No complications were observed. This report confirms the feasibility of using ultrasound to locate the sacral plexus using a parasacral approach.

Ultrasound localization of the sacral plexus using a parasacral approach.

Fibrin microbeads (FMBs) made using thermal treatment of fibrin drops in oil can efficiently isolate mesenchymal stem cells (MSCs) from bone marrow (BM) and other similar sources and culture them continuously in suspension culture. The pure mesenchymal profile of MSCs isolated using FMBs and their differentiation potency to different mesenchymal lineages were previously described in detail. In the current study, MSCs were isolated from the BM of (GFP+) C57/bl mice using FMBs. Addition of pro-osteogenic medium with 10 mM of ss-glycerolphosphate, 50 microg/mL of ascorbic acid, and 10(-8) M of dexamethasone for 1 month resulted in ossified bone-like solid cellular structures, as seen using fluorescence and scanning electron microscopy (SEM). Such spontaneously formed structures were implanted in full-depth approximately 5-mm-diameter drilled defects in the skulls of wild-type c57/bl mice. Two months later, the excised upper parts of the skulls with the defects were viewed using fluorescence microscopy for green fluorescence protein of the cells in the defect and using SEM. They were also scanned using micro-computed tomography to visualize the formation of new hard tissue. Then the samples were processed and sectioned for hematoxylin and eosin staining and immunohistochemistry. Implanted FMBs loaded with (GFP+) MSCs formed partially mature, dense bone-like tissue using a residual moderate inflammatory process containing remnants of FMBs and neo-angiogenesis. The filled defect with bone-like tissue had a Ca/P ratio similar to that of native bone. Limited merging of the implant with the skull indicated that the induced bone regeneration derived from the MSCs that were delivered with the implant. No repair was seen in the control animals without implants or where the defect was filled with FMBs only. Repair scoring (on a 0-5 scale) was found to be 3.38+/-0.35 in the experimental arm, relative to 0 in the controls (p < 0.001).

Alon Ben-Ari

Papers

Preoperative Opioid Use Is Associated with Early Revision After Total Knee Arthroplasty: A Study of Male Patients Treated in the Veterans Affairs System.

Ultrasound-guided paravertebral block using an intercostal approach.

Protein and peptide parenteral controlled delivery.

Ultrasound localization of the sacral plexus using a parasacral approach.

Isolation and implantation of bone marrow-derived mesenchymal stem cells with fibrin micro beads to repair a critical-size bone defect in mice.