A Survey of Proteomic Biomarkers for Heterotopic Ossification in Blood Serum

Background: Heterotopic ossification (HO) is a significant problem for wounded warriors surviving high-energy blast injuries; however, currently, there is no biomarker panel capable of globally characterizing, diagnosing, and monitoring HO progression. The aim of this study was to identify biomarkers for HO using proteomic techniques and blood serum. Methods: Isobaric tags for relative and absolute quantitation (iTRAQ) was used to generate a semi-quantitative global proteomics survey of serum from patients with and without heterotopic ossification. Leveraging the iTRAQ data, a targeted selection reaction monitoring mass spectrometry (SRM-MS) assay was developed for 10 protein candidates: alkaline phosphatase, osteocalcin, alpha-2 type I collagen, collagen alpha-1(V) chain isoform 2 preprotein, bone sialoprotein 2, phosphatidate phosphatase LPIN2, osteomodulin, protein phosphatase 1J, and RRP12-like protein. Results: The proteomic survey of serum from both healthy and disease patients includes 1220 proteins and was enriched for proteins involved in the response to elevated platelet Ca+2, wound healing, and extracellular matrix organization. Proteolytic peptides from three of the ten SRM-MS proteins, osteocalcin preprotein, osteomodulin precursor, and collagen alpha-1(v) chain isoform 2 preprotein from serum, are potential clinical biomarkers for HO. Conclusions: This study is the first reported SRM-MS analysis of serum from individuals with and without heterotopic ossification, and differences in the serum proteomic profile between healthy and diseased subjects were identified. Furthermore, our results indicate that normal wound healing signals can impact the ability to identify biomarkers, and a multi-protein panel assay, including osteocalcin preproprotein, osteomodulin precursor, and collagen alpha-1(v) chain isoform 2 preprotein, may provide a solution for HO detection and monitoring

Revised National Pressure Ulcer Advisory Panel Pressure Injury Staging System: Revised Pressure Injury Staging System

Our understanding of pressure injury etiology and development has grown in recent years through research, clinical expertise, and global interdisciplinary expert collaboration. Therefore, the National Pressure Ulcer Advisory Panel (NPUAP) has revised the definition and stages of pressure injury. The revision was undertaken to incorporate the current understanding of the etiology of pressure injuries, as well as to clarify the anatomical features present or absent in each stage of injury. An NPUAP-appointed Task Force reviewed the literature and created drafts of definitions, which were then reviewed by stakeholders and the public, including clinicians, educators, and researchers around the world. Using a consensus-building methodology, these revised definitions were the focus of a multidisciplinary consensus conference held in April 2016. As a result of stakeholder and public input, along with the consensus conference, important changes were made and incorporated into the new staging definitions. The revised staging system uses the term injury instead of ulcer and denotes stages using Arabic numerals rather than Roman numerals. The revised definition of a pressure injury now describes the injuries as usually occurring over a bony prominence or under a medical or other device. The revised definition of a Stage 2 pressure injury seeks to clarify the difference between moisture-associated skin damage and injury caused by pressure and/or shear. The term suspected has been removed from the Deep Tissue Pressure Injury diagnostic label. Each definition now describes the extent of tissue loss present and the anatomical features that may or may not be present in the stage of injury. These important revisions reflect the methodical and collaborative approach used to examine the available evidence and incorporate current interdisciplinary clinical expertise into better defining the important phenomenon of pressure injury etiology and development

Pressure ulcer tissue histology: An appraisal of current knowledge

Although it is well accepted that pressure ulcers occur as a result of mechanical loading of tissue, their specific etiology of development remains unknown. Knowledge of tissue response to pressure is critical to understanding and elucidating the specific mechanism of pressure ulcer development. A literature review to appraise the histology of pressure ulcer tissue shows that numerous in vitro and in vivo studies examining tissue changes in response to pressure have been conducted. In vitro findings indicate that relatively small loads cause structural changes to the dermal component of tissue. Studies examining tissue from humans with pressure ulcers have shown that changes visible at the surface are often minor compared to the damage seen in deeper tissue layers. In vivo animal studies evaluating the changes in tissue histology following application of various loads support findings related to human pressure ulcer tissue and further elucidate the tissue changes seen in response to load. Studies to evaluate whether the visible changes in human and animal tissue are precursors to ulcer development or remodeling responses to loading are needed to increase understanding of pressure ulcer formation. © 2007 HMP Communications

Granulation tissue of chronic pressure ulcers as a predictive indicator of wound closure.

: To describe the temporal relationship between the quantity of granulation tissue in a chronic pressure ulcer (PrU) and its clinical outcome. : Study participants were seen on days 0, 1, 2, 3, 4, 7, 8, 9, 10, 11, 14, 21, 28, 35, and 42. On each visit, the wounds were digitally photographed with a 3-cm calibration target. Images were analyzed using VeV MD (version 1.1.14; VERG Inc, Winnipeg, Manitoba, Canada) and Adobe Photoshop CS3 Extended (version 10.0.1; Adobe Systems Inc, San Jose, California). Granulation tissue was selected from calibrated digital images by 1 of 2 methods: manual selection and automated selection. Granulation tissue area was expressed as a percentage of total wound area. : Academic research laboratory. : Thirty-one chronic PrUs were observed in 27 subjects. : Quantitative measure of granulation tissue area. : There was no relationship between the amount of granulation tissue expressed as a percentage of the total PrU area and wound outcome. : This study is the first to both quantitatively measure the amount of granulation tissue in a chronic PrU and attempt to correlate it to wound outcome. Although counterintuitive, the amount of granulation tissue was not predictive of outcome, and no temporal trends could be described

Mechanical characteristics of human skin subjected to static versus cyclic normal pressures

Several hypotheses exist for the etiology of decubitus ulcers, with external pressures exceeding internal capillary pressures over bony prominences claimed to be the major factor. This investigation evaluated the mechanical changes that occurred in human skin as a result of its exposure to static versus cyclic normal pressures of the magnitudes earlier recorded for the heels of human subjects on various support surfaces. The skin was characterized through uniaxial tensile testing. Static pressure alone altered the tissue\u27s mechanical properties more than dynamic pressure cycles. Tissue subjected to pressure prior to uniaxial tensile testing always was less stiff than control tissue. Damage to the initially randomly oriented tissue collagen fiber bundles in the fibrous matrix, which may occur as a result of sustained compression, may be the cause of a decrease in stiffness of tissue subjected to prior pressure loading. This is the first report of compressive- pre-load-induced strain softening (Mullins effect) of a biological material

Longitudinal study of stage III and stage IV pressure ulcer area and perimeter as healing parameters to predict wound closure

Documentation of healing progress is central to the plan of care for patients with a pressure ulcer. Several studies have shown that a reduction in wound area is a predictor of chronic wound healing, but data about pressure ulcers are limited. Furthermore, consensus is lacking as to which wound characteristics such as volume, area, and perimeter should be measured and what methods or tools to use when collecting measurements. This hampers comparisons among research studies and their eventual translation into clinical practice. The purpose of this longitudinal, repeated measurements study was to calculate healing parameters using wound area and perimeter measurements and evaluate their potential to predict closure. Twenty-seven (27) patients with 31 Stage III and Stage IV pressure ulcers participated in the 42-day study. Wound length, width, and perimeter were measured at 15 time points or until healing, and the following healing parameters were calculated: absolute area, percent area reduction, mean percent area reduction, trajectory, and three variations of the linear healing parameter. Ulcer size at day 0 was a significant predictor of time to heal (P = 0.0231). Smaller wounds required less time, but initial size did not influence wound outcome (P = 0.3537). Among ulcers that closed 81% or more of their original area, the initial linear healing rate (4 weeks) was 0.16 ± 0.02 cm/week and mean percent area reduction was 35.37% + 4.83, compared to 0.021 + 0.02 cm/week and - 4.66% + 6.24, respectively, for ulcers that closed 40% or less of their original area. Percent area reduction and linear healing parameters all were predictive of wound outcomes. Percent area measurements are easiest to determine but sensitive to initial wound size. The linear healing parameter requires calculation of both wound area and perimeter, but it is independent of initial wound size and yields rates directly comparable among wounds. These findings confirm that change in wound size after 4 weeks of care is a predictor of healing Stage III and Stage IV pressure ulcers. Future research studies should include other wound characteristics and patient comorbidities to further refine acceptable rates of wound closure

Maxillary sinus elevation for implant placement using calcium sulfate with and without DFDBA: Six cases

Maxillary sinus lift is a surgical procedure performed to increase the volume of bone mass so that dental implants can be placed in the maxillary arch. Several materials have been suggested to be used for this procedure. The purpose of this study was to present the clinical and histologic results of using calcium sulfate with and without demineralized freeze-dried bone allograft (DFDBA) in sinus lift. Medical-grade sterile calcium sulfate was used alone or in combination with DFDBA in 6 patients undergoing sinus lift surgery for implant placement. Bone biopsies were taken at different times ranging from 6 to 24 months. All samples examined showed bone growth with some possible remnants of the grafted DFDBA. Implants were inserted either at the time of the lift or 6 months later. All of them were secure with primary stability. The cases reported indicate that calcium sulfate can be successfully used alone or in combination with DFDBA for sinus lift procedures and that possible residues of DFDBA can be found within newly generated bone

Microstructural and mechanical characterization of human tissue at and adjacent to pressure ulcers

This investigation evaluated the microstructural and mechanical properties of human skin at and adjacent to pressure ulcers (PUs). Healthy breast and leg tissue served as control tissue. The tissue was characterized through uniaxial tensile testing and histomorphometric analysis. The PU tissue had significantly fewer straight and wavy fibers, but the fibers present were significantly wider and longer than those found in the healthy control tissue. PU ulcer tissue tested in tension had significantly lower strains at peak stress, versus the control breast tissue. Tissue at and adjacent to PUs has undergone significant adaptation or remodeling, as a result of the pressure sustained by the tissue