-
Journal of Orthopaedic Research :... Dec 2017We completed a systematic literature review of in vivo animal models that use arthrotomy-based methods to study particle-induced peri-implant osteolysis. The purpose of...
We completed a systematic literature review of in vivo animal models that use arthrotomy-based methods to study particle-induced peri-implant osteolysis. The purpose of the review was to characterize the models developed to date, to determine the questions addressed, to assess scientific rigor and transparency, and to identify gaps in knowledge. We probed three literature databases (Medline, Embase, and Scopus) and found 77 manuscripts that fit the search parameters. In the most recent 10 years, researchers mainly used rat and mouse models, whereas in the previous 20 years, large animal, canine, and rabbit models were more common. The studies have demonstrated several pathophysiology pathways, including macrophage migration, particle phagocytosis, increased local production of cytokines and lysosomal enzymes, elevated bone resorption, and suppressed bone formation. The effect of variation in particle characteristics and concentration received limited attention with somewhat mixed findings. Particle contamination by endotoxin was shown to exacerbate peri-implant osteolysis. The possibility of early diagnosis was demonstrated through imaging and biomarker approaches. Several studies showed that both local and systemic delivery of bisphosphonates inhibits the development of particle-induced osteolysis. Other methods of inhibiting osteolysis include the use of anabolic agents and altering the implant design. Few studies examined non-surgical rescue of loosened implants, with conflicting results with alendronate. We found that the manuscripts often lacked the methodological detail now advocated by the ARRIVE guidelines, suggesting that improvement in reporting would be useful to maximize rigor and transparency. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2595-2605, 2017.
Topics: Animals; Disease Models, Animal; Osteolysis
PubMed: 28548682
DOI: 10.1002/jor.23619 -
Journal of Neurochemistry Apr 2017We conducted a systematic review and individual participant data meta-analysis to explore the role of C-reactive protein (CRP) in early detection or prediction of... (Meta-Analysis)
Meta-Analysis Review
We conducted a systematic review and individual participant data meta-analysis to explore the role of C-reactive protein (CRP) in early detection or prediction of post-stroke infections. CRP, an acute-phase reactant binds to the phosphocholine expressed on the surface of dead or dying cells and some bacteria, thereby activating complement and promoting phagocytosis by macrophages. We searched PubMed up to May-2015 for studies measuring CRP in stroke and evaluating post-stroke infections. Individual participants' data were merged into a single database. CRP levels were standardized and divided into quartiles. Factors independently associated with post-stroke infections were determined by logistic regression analysis and the additional predictive value of CRP was assessed by comparing areas under receiver operating characteristic curves and integrated discrimination improvement index. Data from seven studies including 699 patients were obtained. Standardized CRP levels were higher in patients with post-stroke infections beyond 24 h. Standardized CRP levels in the fourth quartile were independently associated with infection in two different logistic regression models, model 1 [stroke severity and dysphagia, odds ratio = 9.70 (3.10-30.41)] and model 2 [age, sex, and stroke severity, odds ratio = 3.21 (1.93-5.32)]. Addition of CRP improved discrimination in both models [integrated discrimination improvement = 9.83% (0.89-18.77) and 5.31% (2.83-7.79), respectively], but accuracy was only improved for model 1 (area under the curve 0.806-0.874, p = 0.036). In this study, CRP was independently associated with development of post-stroke infections, with the optimal time-window for measurement at 24-48 h. However, its additional predictive value is moderate over clinical information. Combination with other biomarkers in a panel seems a promising strategy for future studies.
Topics: Biomarkers; C-Reactive Protein; Communicable Diseases; Humans; Statistics as Topic; Stroke
PubMed: 28171699
DOI: 10.1111/jnc.13973 -
The Journal of Clinical Psychiatry Jul 2016To evaluate the epidemiology, pathobiology, and management of benign ethnic neutropenia and determine the extent to which these factors should influence measures... (Review)
Review
OBJECTIVE
To evaluate the epidemiology, pathobiology, and management of benign ethnic neutropenia and determine the extent to which these factors should influence measures designed to avoid clozapine-induced agranulocytosis.
DATA SOURCES
A structured MEDLINE search with no language limitation was performed from database inception until March 31, 2015, using the terms clozapine and benign ethnic neutropenia. Retrieved articles were cross-checked for additional relevant studies.
STUDY SELECTION
Included in the study were articles that reported on the prevalence, etiology, and complications of benign ethnic neutropenia and the hematologic outcome of clozapine treatment in patients with this condition.
DATA EXTRACTION
Study results that documented the epidemiology, pathobiology, and clozapine utilization in persons of African, Arabian, and Mediterranean descent with a neutrophil count in the 1,000-1,800/mm³ range.
RESULTS
The search identified 342 publications. Forty-two articles described the epidemiology, pathobiology, and management of benign ethnic neutropenia. Of these, 12 articles described patients with benign ethnic neutropenia whose neutrophil count decreased during treatment with clozapine. Persons with benign ethnic neutropenia do not have signs of impaired phagocytosis, and the frequency, severity, and outcome of their infections are similar to those observed in the general population. These features suggest that a neutrophil count > 1,000/mm³ is safe for initiating and/or resuming clozapine therapy.
CONCLUSIONS
The presence of benign ethnic neutropenia should not prevent treatment with clozapine. Patients with benign ethnic neutropenia who develop a clozapine-induced decrease in the neutrophil count, but have no evidence of infection or impaired phagocytosis, may resume clozapine as soon as they have > 1,000 neutrophils/mm³.
Topics: Agranulocytosis; Clozapine; Contraindications; Ethnicity; Humans; Leukocyte Count; Neutropenia; Neutrophils
PubMed: 27464332
DOI: 10.4088/JCP.15r10085 -
Clinical Orthopaedics and Related... Nov 2016Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range... (Review)
Review
BACKGROUND
Polyetheretherketone (PEEK) and its composites are polymers resistant to fatigue strain, radiologically transparent, and have mechanical properties suitable for a range of orthopaedic applications. In bulk form, PEEK composites are generally accepted as biocompatible. In particulate form, however, the biologic response relevant to joint replacement devices remains unclear. The biologic response to wear particles affects the longevity of total joint arthroplasties. Particles in the phagocytozable size range of 0.1 µm to 10 µm are considered the most biologically reactive, particularly particles with a mean size of < 1 µm. This systematic review aimed to identify the current evidence for the biologic response to PEEK-based wear debris from total joint arthroplasties.
QUESTIONS/PURPOSES
(1) What are the quantitative characteristics of PEEK-based wear particles produced by total joint arthroplasties? (2) Do PEEK wear particles cause an adverse biologic response when compared with UHMWPE or a similar negative control biomaterial? (3) Is the biologic response affected by particle characteristics?
METHODS
Embase and Ovid Medline databases were searched for studies that quantified PEEK-based particle characteristics and/or investigated the biologic response to PEEK-based particles relevant to total joint arthroplasties. The keyword search included brands of PEEK (eg, MITCH, MOTIS) or variations of PEEK types and nomenclature (eg, PAEK, CFR-PEEK) in combination with types of joint (eg, hip, knee) and synonyms for wear debris or immunologic response (eg, particles, cytotoxicity). Peer-reviewed studies, published in English, investigating total joint arthroplasty devices and cytotoxic effects of PEEK particulates were included. Studies investigating devices without articulating bearings (eg, spinal instrumentation devices) and bulk material or contact cytotoxicity were excluded. Of 129 studies, 15 were selected for analysis and interpretation. No studies were found that isolated and characterized PEEK wear particles from retrieved periprosthetic human tissue samples.
RESULTS
In the four studies that quantified PEEK-based particles produced using hip, knee, and spinal joint replacement simulators, the mean particle size was 0.23 µm to 2.0 µm. The absolute range reported was approximately 0.01 µm to 50 µm. Rod-like carbon particulates and granular-shaped PEEK particles were identified in human tissue by histologic analysis. Ten studies, including six animal models (rat, mouse, and rabbit), three cell line experiments, and two human tissue retreival studies, investigated the biologic response to PEEK-based particles. Qualitative histologic assessments showed immunologic cell infiltration to be similar for PEEK particles when compared with UHMWPE particles in all six of the animal studies identified. However, increased inflammatory cytokine release (such as tumor necrosis factor-α) was identified in only one in vitro study, but without substantial suppression in macrophage viability. Only one study tested the effects of particle size on cytotoxicity and found the largest unfilled PEEK particles (approximately 13 µm) to have a toxic effect; UHMWPE particles in the same size range showed a similar cytotoxic effect.
CONCLUSIONS
Wear particles produced by PEEK-based bearings were, in almost all cases, in the phagocytozable size range (0.1-10 µm). The studies that evaluated the biologic response to PEEK-based particles generally found cytotoxicity to be within acceptable limits relative to the UHMWPE control, but inconsistent when inflammatory cytokine release was considered.
CLINICAL RELEVANCE
To translate new and advanced materials into clinical use more quickly, the clinical relevance and validity of preclinical tests need to be improved. To achieve this for PEEK-based devices, human tissue retrieval studies including subsequent particle isolation and characterization analyses are required. In vitro cell studies using isolated wear particles from tissue or validated joint replacement simulators, instead of manufactured particles, are also required.
Topics: Animals; Arthroplasty, Replacement; Benzophenones; Cytokines; Foreign-Body Reaction; Humans; Inflammation Mediators; Joint Prosthesis; Ketones; Particle Size; Phagocytosis; Polyethylene Glycols; Polyethylenes; Polymers; Prosthesis Design; Prosthesis Failure; Risk Factors; Stress, Mechanical; Treatment Outcome
PubMed: 27432420
DOI: 10.1007/s11999-016-4976-z -
Annals of Global Health 2015Household air pollution (HAP)-associated acute lower respiratory infections cause 455,000 deaths and a loss of 39.1 million disability-adjusted life years annually. The... (Review)
Review
BACKGROUND
Household air pollution (HAP)-associated acute lower respiratory infections cause 455,000 deaths and a loss of 39.1 million disability-adjusted life years annually. The immunomodulatory mechanisms of HAP are poorly understood.
OBJECTIVES
The aim of this study was to conduct a systematic review of all studies examining the mechanisms underlying the relationship between HAP secondary to solid fuel exposure and acute lower respiratory tract infection to evaluate current available evidence, identify gaps in knowledge, and propose future research priorities.
METHODS
We conducted and report on studies in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. In all, 133 articles were fully reviewed and main characteristics were detailed, namely study design and outcome, including in vivo versus in vitro and pollutants analyzed. Thirty-six studies were included in a nonexhaustive review of the innate immune system effects of ambient air pollution, traffic-related air pollution, or wood smoke exposure of developed country origin. Seventeen studies investigated the effects of HAP-associated solid fuel (biomass or coal smoke) exposure on airway inflammation and innate immune system function.
RESULTS
Particulate matter may modulate the innate immune system and increase susceptibility to infection through a) alveolar macrophage-driven inflammation, recruitment of neutrophils, and disruption of barrier defenses; b) alterations in alveolar macrophage phagocytosis and intracellular killing; and c) increased susceptibility to infection via upregulation of receptors involved in pathogen invasion.
CONCLUSIONS
HAP secondary to the burning of biomass fuels alters innate immunity, predisposing children to acute lower respiratory tract infections. Data from biomass exposure in developing countries are scarce. Further study is needed to define the inflammatory response, alterations in phagocytic function, and upregulation of receptors important in bacterial and viral binding. These studies have important public health implications and may lead to the design of interventions to improve the health of billions of people daily.
Topics: Air Pollution; Air Pollution, Indoor; Biomass; Carbon Monoxide; Coal; Environmental Exposure; Family Characteristics; Humans; Immunity, Innate; Macrophages, Alveolar; Neutrophil Infiltration; Particulate Matter; Phagocytosis; Respiratory Tract Infections; Smoke; Transportation; Vehicle Emissions; Wood
PubMed: 26615071
DOI: 10.1016/j.aogh.2015.08.006 -
Molecular Neurobiology Feb 2015Continuous renewal of neurons throughout life in the olfactory system is often thought to be partially attributable to specialized glial cells called olfactory... (Review)
Review
Continuous renewal of neurons throughout life in the olfactory system is often thought to be partially attributable to specialized glial cells called olfactory ensheathing cells (OECs). Hitherto, several studies have demonstrated that transplantation of OECs is one of the most promising strategies available to augment axonal regeneration and functional recovery following damage to the nervous system, including spinal cord injury (SCI). Based on these studies, a number of pre-clinical studies worldwide have been initiated using autologous transplantation of OECs into damaged central and peripheral nervous systems. Although OECs play a major role in promotion of neuron regeneration of the injured central nervous system (CNS), especially to SCI, limited valuable information is available regarding the beneficial characteristics of OECs in facilitating neural regeneration. Moreover, an increasing number of controversial issues related to the biology of OECs and their transplantation must be addressed. This step is important to better understand the cellular and molecular mechanisms modulated by transplanted OECs. To start shedding light into these controversial issues, this paper provides a systematic review regarding OECs' beneficial roles in neural regeneration, and the unique properties of these cells that may exert a potential advantage over other cellular transplants.
Topics: Animals; Cell Adhesion Molecules; Cell Movement; Humans; Nerve Growth Factors; Nerve Regeneration; Olfactory Bulb; Phagocytosis
PubMed: 24615159
DOI: 10.1007/s12035-014-8664-2