https://www.srcv.ro/en/ghiduri/Preventia%20trombembolismului%20la%20pacientii%20nonortopedici%20-%20Ghidurile%20ACCP%202012.pdf

Prevention of VTE in Nonorthopedic Surgical Patients : Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

Calcium phosphate (CaP) bioceramics are widely used in the field of bone regeneration, both in orthopedics and in dentistry, due to their good biocompatibility, osseointegration and osteoconduction. The aim of this article is to review the history, structure, properties and clinical applications of these materials, whether they are in the form of bone cements, paste, scaffolds, or coatings. Major analytical techniques for characterization of CaPs, in vitro and in vivo tests, and the requirements of the US Food and Drug Administration (FDA) and international standards from CaP coatings on orthopedic and dental endosseous implants, are also summarized, along with the possible effect of sterilization on these materials. CaP coating technologies are summarized, with a focus on electrochemical processes. Theories on the formation of transient precursor phases in biomineralization, the dissolution and reprecipitation as bone of CaPs are discussed. A wide variety of CaPs are presented, from the individual phases to nano-CaP, biphasic and triphasic CaP formulations, composite CaP coatings and cements, functionally graded materials (FGMs), and antibacterial CaPs. We conclude by foreseeing the future of CaPs.

Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications.

Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well-documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast-mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP-2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting.

A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2

Organ and tissue loss through disease and injury motivate the development of therapies that can regenerate tissues and decrease reliance on transplantations. Regenerative medicine, an interdisciplinary field that applies engineering and life science principles to promote regeneration, can potentially restore diseased and injured tissues and whole organs. Since the inception of the field several decades ago, a number of regenerative medicine therapies, including those designed for wound healing and orthopedics applications, have received Food and Drug Administration (FDA) approval and are now commercially available. These therapies and other regenerative medicine approaches currently being studied in preclinical and clinical settings will be covered in this review. Specifically, developments in fabricating sophisticated grafts and tissue mimics and technologies for integrating grafts with host vasculature will be discussed. Enhancing the intrinsic regenerative capacity of the host by altering its environment, whether with cell injections or immune modulation, will be addressed, as well as methods for exploiting recently developed cell sources. Finally, we propose directions for current and future regenerative medicine therapies.

https://www.pnas.org/content/pnas/112/47/14452.full.pdf

Regenerative medicine: Current therapies and future directions.

Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can be used. They can be either derived from biological products such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (like bone morphogenetic protein) or synthetic such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes. All these substitutes are not suitable for every clinical use, and they have to be chosen selectively depending on their purpose. Thus, this review aims to highlight the principal characteristics of the most commonly used bone substitutes and to give some directions concerning their clinical use, as spine fusion, open-wedge tibial osteotomy, long bone fracture, oral and maxillofacial surgery, or periodontal treatments. However, the main limitations to bone substitutes use remain the management of large defects and the lack of vascularization in their central part, which is likely to appear following their utilization. In the field of bone tissue engineering, developing porous synthetic substitutes able to support a faster and a wider vascularization within their structure seems to be a promising way of research.

https://journals.sagepub.com/doi/pdf/10.1177/2041731418776819

Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management

Background: The use of multidisciplinary in-hospital teams limits adverse events (AE), improves outcomes, and adds to patient and employee satisfaction.
 Methods: Acting like "well-oiled machines," multidisciplinary in-hospital teams include "staff" from different levels of the treatment pyramid (e.g. staff including nurses' aids, surgical technicians, nurses, anesthesiologists, attending physicians, and others). Their enhanced teamwork counters the "silo effect" by enhancing communication between the different levels of healthcare workers and thus reduces AE (e.g. morbidity/mortality) while improving patient and healthcare worker satisfaction.
 Results: Multiple articles across diverse disciplines incorporate a variety of concepts of "teamwork" for staff covering emergency rooms (ERs), hospital wards, intensive care units (ICUs), and most critically, operating rooms (ORs). Cohesive teamwork improved communication between different levels of healthcare workers, and limited adverse events, improved outcomes, decreased the length of stay (LOS), and yielded greater patient "staff" satisfaction.
 Conclusion: Within hospitals, delivering the best medical/surgical care is a "team sport." The goals include: Maximizing patient safety (e.g. limiting AE) and satisfaction, decreasing the LOS, and increasing the quality of outcomes. Added benefits include optimizing healthcare workers' performance, reducing hospital costs/complications, and increasing job satisfaction. This review should remind hospital administrators of the critical need to keep multidisciplinary teams together, so that they can continue to operate their "well-oiled machines" enhancing the quality/safety of patient care, while enabling "staff" to optimize their performance and enhance their job satisfaction.

Multidisciplinary in-hospital teams improve patient outcomes: A review.

Increasingly, adverse events (AE) attributed to utilizing BMP/INFUSE (Bone Morphogenetic Protein, Medtronic, Memphis, TN, USA) “off-label” in spine surgery are being reported. In 2008, the Food and Drug Administration (FDA) issued a warning that in anterior cervical spine surgery, the “off-label” use of BMP/INFUSE contributed to marked dysphagia, hematoma, seroma, swelling, and/or the need for intubation/tracheostomy. Subsequent studies have cited the following AE; heterotopic ossification (HO), osteolysis, infection, arachnoiditis, increased neurological deficits, retrograde ejaculation, and cancer. Furthermore, in 2011, Carragee et al. noted that 13 of the original industry-sponsored BMP/INFUSE spinal surgery studies failed to acknowledge multiple AE. Additionally, in 2012, Comer et al. observed that the frequency of retrograde ejaculation reported for BMP/INFUSE used “on-label” to perform Anterior Lumbar Interbody Fusion/Lumbar Tapered Fusion-Cage Device (ALIF/LT-Cage) was also largely “under-reported.” To summarize, there is mounting evidence in the spinal literature that utilizing BMP/INFUSE in spinal fusions contributes to major perioperative and postoperative morbidity.

Complications due to the use of BMP/INFUSE in spine surgery: The evidence continues to mount.

✓ This report describes the first author's surgical experience with a series of 19 consecutive cases of spinal cord astrocytoma treated over the past 2 years, with a follow-up period of 6 to 24 months. The clinical presentation, neurodiagnostic investigation, surgical technique, and results are analyzed. The authors conclude that radical resection (gross total removal of the tumor) is the optimal therapeutic option.

Surgical treatment of spinal cord astrocytomas of childhood. A series of 19 patients.

Background: INFUSE (recombinant human bone morphogenetic protein-2 [rhBMP-2]; Medtronic, Memphis, TN, USA) is approved by the Federal Drug Administration (FDA) only for use with the lumbar tapered fusion device (LT Cage; Medtronic) to perform single-level anterior lumbar interbody fusions (ALIF: L2–S1 levels). INFUSE, however, is widely utilized in an “off-label” capacity for anterior and/or posterior cervical, thoracic, and lumbar surgery. Nevertheless, Medicare and other insurance companies, are now increasingly denying reimbursement (average cost of a “large” INFUSE to the hospital without overhead $5000–6000) to hospitals for INFUSE when utilized “off-label.” Methods: This commentary looks at several representative studies citing the cons associated with utilizing INFUSE in spinal surgery, contraindications, complications, and cost factors. Results: There are multiple cons of utilizing INFUSE in an “off-label” capacity for spinal surgery. Direct contraindications include pregnancy, allergy to titanium, allergy to bovine type I collagen or rhBMP-2, infection, tumor, liver or kidney disease, immunosuppression (e.g., lupus, HIV/AIDS); contraindications are also seen in those receiving radiation, chemotherapy, or steroids. Reported complications include exuberant/ectopic bone formation, paralysis (cord, nerve damage), dural tears, bowel–bladder and sexual dysfunction, respiratory failure, inflammation of adjacent tissues, fetal developmental complications, scar, excessive bleeding, and even death. Complications are so prevalent in the anterior cervical spine, that many surgeons no longer use it in this region. Similarly, INFUSE complications and indications for posterior lumbar interbody fusions (PLIFs) and transforaminal interbody lumbar fusions (TLIFs) should also be reexamined. Conclusions: More surgeons need to question the safety, efficacy, and appropri ate “off-label” use of INFUSE in all spine surgeries.

/pdf/pros-cons-and-costs-of-infuse-in-spinal-surgery-47t8ghp4qz.pdf

Pros, cons, and costs of INFUSE in spinal surgery.

Background:
The impact of early mobilization on perioperative comorbidities and length of stay (LOS) has shown benefits in other medical/surgical subspecialties. However, few spinal series have specifically focused on the “pros” of early mobilization for spinal surgery, other than in acute spinal cord injury. Here we reviewed how early mobilization and other adjunctive measures reduced morbidity and LOS in both medical and/or surgical series, and focused on how their treatment strategies could be applied to spinal patients.

Nancy E. Epstein

Papers

Multidisciplinary in-hospital teams improve patient outcomes: A review.

Complications due to the use of BMP/INFUSE in spine surgery: The evidence continues to mount.

Surgical treatment of spinal cord astrocytomas of childhood. A series of 19 patients.

Pros, cons, and costs of INFUSE in spinal surgery.

A review article on the benefits of early mobilization following spinal surgery and other medical/surgical procedures.