An initiative to assess and improve the resources and patient care processes used among Chest Wall Injury Society collaborative centers study (CWIS-CC2).

BACKGROUND: Over the last two decades, the acute management of rib fractures has changed significantly. In 2021, the Chest Wall injury Society (CWIS) began recognizing centers that epitomize their mission as CWIS Collaborative Centers. The primary aim of this study was to determine the resources, surgical expertise, access to care, and institutional support that are present among centers. METHODS: A survey was performed including all CWIS Collaborative Centers evaluating the resources available at their hospital for the treatment of patients with chest wall injury. Data about each chest wall injury center care process, availability of resources, institutional support, research support, and educational offerings were recorded. RESULTS: Data were collected from 20 trauma centers resulting in an 80% response rate. These trauma centers were made up of 5 international and 15 US-based trauma centers. Eighty percent (16 of 20) have dedicated care team members for the evaluation and management of rib fractures. Twenty-five percent (5 of 20) have a dedicated rib fracture service with a separate call schedule. Staffing for chest wall injury clinics consists of a multidisciplinary team: with attending surgeons in all clinics, 80% (8 of 10) with advanced practice providers and 70% (7 of 10) with care coordinators. Forty percent (8 of 20) of centers have dedicated rib fracture research support, and 35% (7 of 20) have surgical stabilization of rib fracture (SSRF)-related grants. Forty percent (8 of 20) of centers have marketing support, and 30% (8 of 20) have a web page support to bring awareness to their center. At these trauma centers, a median of 4 (1-9) surgeons perform SSRFs. In the majority of trauma centers, the trauma surgeons perform SSRF. CONCLUSION: Considerable similarities and differences exist within these CWIS collaborative centers. These differences in resources are hypothesis generating in determining the optimal chest wall injury center. These findings may generate several patient care and team process questions to optimize patient care, patient experience, provider satisfaction, research productivity, education, and outreach. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.

Rib fixation in non-ventilator-dependent chest wall injuries: A prospective randomized trial.

BACKGROUND: The aim of this study was to assess pain and quality of life (QoL) outcomes in patients with multiple painful displaced fractured ribs with and without operative fixation. Rib fractures are common and can lead to significant pain and disability. There is minimal level 1 evidence for rib fixation in non-ventilator-dependent patients with chest wall injuries. We hypothesized that surgical stabilization of rib fractures would reduce pain and improve QoL during 6 months. METHODS: A prospective multicenter randomized controlled trial comparing rib fixation to nonoperative management of nonventilated patients with at least three consecutive rib fractures was conducted. Inclusion criteria were rib fracture displacement and/or ongoing pain. Pain (McGill Pain Questionnaire) and QoL (Short Form 12) at 3 and 6 months postinjury were assessed. Surgeons enrolled patients in whom they felt there was clinical equipoise. Patients who were deemed to need surgical fixation or who were deemed to be too well to be randomized to rib fixation were not enrolled. RESULTS: A total of 124 patients were enrolled at four sites between 2017 and 2020. Sixty-one patients were randomized to operative management and 63 to nonoperative management. No differences were seen in the primary endpoint of Pain Rating Index at 3 months or in the QoL measures. Return-to-work rates improved between 3 and 6 months, favoring the operative group. CONCLUSION: In this study, no improvements in pain or QoL at 3 and 6 months in patients undergoing rib fixation for nonflail, non-ventilator-dependent rib fractures have been demonstrated. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Treatment with a long-acting chimeric CSF1 molecule enhances fracture healing of healthy and osteoporotic bones.

Macrophage-targeted therapies, including macrophage colony-stimulating factor 1 (CSF1), have been shown to have pro-repair impacts post-fracture. Preclinical/clinical applications of CSF1 have been expedited by development of chimeric CSF1-Fc which has extended circulating half-life. Here, we used mouse models to investigate the bone regenerative potential of CSF1-Fc in healthy and osteoporotic fracture. We also explored whether combination of CSF1-Fc with interleukin (IL)-4 provided additional fracture healing benefit in osteopenic bone. Micro-computed tomography, in situ histomorphometry, and bone mechanical parameters were used to assess systemic impacts of CSF1-Fc therapy in naive mice (male and female young, adult and geriatric). An intermittent CSF1-Fc regimen was optimized to mitigate undesirable impacts on bone resorption and hepatosplenomegaly, irrespective of age or gender. The intermittent CSF1-Fc regimen was tested in a mid-diaphyseal femoral fracture model in healthy bones with treatment initiated 1-day post-fracture. Weekly CSF1-Fc did not impact osteoclasts but increased osteal macrophages and improved fracture strength. Importantly, this treatment regimen also improved fracture union and strength in an ovariectomy-model of delayed fracture repair. Combining CSF1-Fc with IL-4 initiated 1-week post-fracture reduced the efficacy of CSF1-Fc. This study describes a novel strategy to specifically achieve bone regenerative actions of CSF1-Fc that has the potential to alleviate fragility fracture morbidity and mortality.

3D Computer graphical anatomy study of the femur: a basis for a new nail design.

BACKGROUND: Current intramedullary nails with a radius of curvature (ROC) of 1500-2000 mm sometimes cause distal anterior cortical encroachment. Furthermore, clinical data indicate that the proximal nail end is too long for some Asian patients. The objective of our study was to develop a comprehensive 3D measurement protocol that measures both the anatomy of the canal and the proximal region. The protocol was used to obtain measurements from Caucasian and Asian (Japanese and Thai) specimens. MATERIALS AND METHODS: A total of 90 3D bone models representative of hip fracture patients were reconstructed from CT data. RapidForm 2006 was used to generate the reference geometries required for determining radius and angulation of shaft antecurvature as well as measurements of the proximal anatomy. Multiple linear regression analyses were used to determine the relative contribution of height, age, ethnicity, gender, and body side on the total variance. RESULTS: The mean ROC in the natural 3D antecurvature plane was 885 mm overall, 974 mm in Caucasians and 787 mm in Asians. Height, age, ethnicity, gender, and body side significantly predicted ROC (R = 0.53, p = 0.000). The mean values of anteversion measurements for Asians (Japanese: 22.1°; Thai: 22.7°) were significantly larger than those of the Caucasians (14.5°; p = 0.001). There was virtually no difference (p = 0.186) between the measurements pertaining to the length of the proximal nail end between Caucasian and Asian samples. There was no significant difference between the mean neck-to-shaft angles (Caucasian: 126°; Japanese: 128.2°; Thai: 125.7°; p = 0.198 for Asians vs Caucasians). CONCLUSIONS: The developed comprehensive anatomical 3D measurement protocol could serve as standardised approach for anthropometric studies in the future. Our data suggest that the ROC of current nail designs should be reduced from between 1500 and 2000 to 1000 mm to achieve an improved fit for the investigated population.

Endometrial decidualization: a rare cause of acute appendicitis during pregnancy.

Appendicular endometriosis is a rare and poorly understood pathology that affects women in their reproductive years. In the gravid woman, ectopic endometrial tissue undergoes decidualization. This physiological process can result in acute appendicitis in exceptional cases. Here we describe a patient in her second trimester of pregnancy who presented with right iliac fossa pain and clinical, laboratory and imaging findings consistent with acute appendicitis. A laparoscopic appendectomy was performed with intraoperative findings suspicious for malignancy. Histological analysis made the surprising diagnosis of decidualized endometriosis causing luminal constriction resulting in acute appendicitis. We also detail the challenging diagnostic and management issues faced by clinicians in such cases.

Fracture healing via periosteal callus formation requires macrophages for both initiation and progression of early endochondral ossification.

The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80(+)Mac-2(+)) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80(+)Mac-2(neg)), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.

Influence of internal fixator flexibility on murine fracture healing as characterized by mechanical testing and microCT imaging.

Mechanically well-defined stabilization systems have only recently become available, providing standardized conditions for studying the role of the mechanical environment on mouse bone fracture healing. The aim of this study was to characterize the time course of strength recovery and callus development of mouse femoral osteotomies stabilized with either low or high flexibility (in bending and torsion) internal fixation plates. Animals were euthanized and femora excised at 14, 21, and 28 days post-osteotomy for microCT analysis and torsional strength testing. While a larger mineralized callus was observed in osteotomies under more flexible conditions at all time points, the earlier bridging of the mineralized callus under less flexible conditions by 1 week resulted in an earlier recovery of torsional strength in mice stabilized with low flexibility fixation. Ultimate torque values for these bones were significantly higher at 14 and 21 days post-osteotomy compared to bones with the more flexible stabilization. Our study confirms the high reproducibility of the results that are achieved with this new implant system, therefore making it ideal for studying the influence of the mechanical environment on murine fracture healing under highly standardized conditions.

Influence of internal fixator stiffness on murine fracture healing: two types of fracture healing lead to two distinct cellular events and FGF-2 expressions.

This study aimed to clarify the relationship between the mechanical environment at the fracture site and endogenous fibroblast growth factor-2 (FGF-2). We compared two types of fracture healing with different callus formations and cellular events using MouseFix(TM) plate fixation systems for murine fracture models. Left femoral fractures were induced in 72 ten-week-old mice and then fixed with a flexible (Group F) or rigid (Group R) Mouse Fix(TM) plate. Mice were sacrificed on days 3, 5, 7, 10, 14, and 21. The callus volumes were measured by 3D micro-CT and tissues were histologically stained with hematoxylin & eosin or safranin-O. Sections from days 3, 5, and 7 were immunostained for FGF-2 and Proliferating Cell Nuclear Antigen (PCNA). The callus in Group F was significantly larger than that in Group R. The rigid plate allowed bone union without a marked external callus or chondrogenesis. The flexible plate formed a large external callus as a result of endochondral ossification. Fibroblastic cells in the granulation tissue on days 5 and 7 in Group F showed marked FGF-2 expression compared with Group R. Fibroblastic cells showed ongoing proliferation in granulation tissue in group F, as indicated by PCNA expression, which explained the relative granulation tissue increase in group F. There were major differences in early phase endogenous FGF-2 expression between these two fracture healing processes, due to different mechanical environments.

Fit optimisation of a distal medial tibia plate.

An iterative method for the fit optimisation of a pre-contoured fracture fixation plate for a given bone data set is presented. Both plate shape optimisation and plate fit quantification are conducted in a virtual environment utilising computer graphical methods and 3D bone and plate models. Two optimised shapes of the undersurface of an existing distal medial tibia plate were generated based on a dataset of 45 3D bone models reconstructed from computed tomography image data of Japanese tibiae. The existing plate shape achieved an anatomical fit on 13% of tibiae from the dataset. Modified plate 1 achieved an anatomical fit for 42% and modified plate 2 a fit for 67% of the bones. If either modified plate 1 or plate 2 is used, then the anatomical fit can be increased to 82% for the same dataset. Issues pertaining to any further improvement in plate fit/shape are discussed.

Custom-made composite scaffolds for segmental defect repair in long bones.

Current approaches for segmental bone defect reconstruction are restricted to autografts and allografts which possess osteoconductive, osteoinductive and osteogenic properties, but face significant disadvantages. The objective of this study was to compare the regenerative potential of scaffolds with different material composition but similar mechanical properties to autologous bone graft from the iliac crest in an ovine segmental defect model. After 12 weeks, in vivo specimens were analysed by X-ray imaging, torsion testing, micro-computed tomography and histology to assess amount, strength and structure of the newly formed bone. The highest amounts of bone neoformation with highest torsional moment values were observed in the autograft group and the lowest in the medical grade polycaprolactone and tricalcium phosphate composite group. The study results suggest that scaffolds based on aliphatic polyesters and ceramics, which are considered biologically inactive materials, induce only limited new bone formation but could be an equivalent alternative to autologous bone when combined with a biologically active stimulus such as bone morphogenetic proteins.

A comparison of severely injured trauma patients admitted to level 1 trauma centres in Queensland and Germany.

BACKGROUND: The allocation of a trauma network in Queensland is still in the developmental phase. In a search for indicators to improve trauma care both locally as state-wide, a study was carried out comparing trauma patients in Queensland to trauma patients in Germany, a country with 82.4 million inhabitants and a well-established trauma system. METHODS: Trauma patients > or =15 years of age, with an Injury Severity Score (ISS) > or = 16 admitted to the Princess Alexandra Hospital (PAH) and to the 59 German hospitals participating in the Trauma Registry of the German Society for Trauma Surgery (DGU-G) during the year 2005 were retrospectively identified and analysed. RESULTS: Both cohorts are comparable when it comes to demographics and injury mechanism, but differ significantly in other important aspects. Striking is the low number of primary admitted patients in the PAH cohort: 58% versus 83% in the DGU-G cohort. PAH patients were less physiologically deranged and less severely injured: ISS 25.2 +/- 9.9 versus 29.9 +/- 13.1 (P < 0.001). Subsequently, they less often needed surgery (61% versus 79%), ICU admission (49% versus 92%) and had a lower mortality: 9.8% versus 17.9% of the DGU-G cohort. CONCLUSIONS: Relevant differences were the low number of primary admissions, the lesser severity of injuries, and the low mortality of the patients treated at the PAH. These differences are likely to be interrelated and Queensland's size and suboptimal organization of trauma care may have played an important role.

Establishment of a preclinical ovine model for tibial segmental bone defect repair by applying bone tissue engineering strategies.

Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties; however, they are limited in access and availability and associated with donor-site morbidity, hemorrhage, risk of infection, insufficient transplant integration, graft devitalization, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench-to-bedside translations are still infrequent as the process toward approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence, commercialization, is referred to as the "Valley of Death" and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes and scalable designs and to apply these in preclinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopedic bone engineering from bench to bedside by establishing a preclinical ovine critical-sized tibial segmental bone defect model, and we discuss our preliminary data relating to this decisive step.

Transplanted abdominal granulation tissue induced bone formation--an in vivo study in sheep.

Many wounds to both soft and hard tissues heal via the formation of a granulation tissue bed. This bed is supportive of neoangiogenesis and releases proangiogenic, migratory, and proliferative growth factors and cytokines. In this study granulation tissue was grown on an intraperitoneal implant (4 mm diameter, 20 mm length) in a sheep. After 2 weeks, this implant was removed and transplanted into a femoral bone defect (4 mm diameter, 20 mm length). The sheep were sacrificed after 3 months, and the implant site examined using micro-CT and histology. A bone plaque formed adjacent to the implant, only in the presence of the peritoneal granulation tissue. This suggests that the formation of granulation tissue is a relatively conserved response at various locations in the body and its transplantation from one location to another can be used to induce tissue healing. This technique may prove useful as a method of improving physiological response to biomaterials.

The challenge of establishing preclinical models for segmental bone defect research.

A considerable number of international research groups as well as commercial entities work on the development of new bone grafting materials, carriers, growth factors and specifically tissue-engineered constructs for bone regeneration. They are strongly interested in evaluating their concepts in highly reproducible large segmental defects in preclinical and large animal models. To allow comparison between different studies and their outcomes, it is essential that animal models, fixation devices, surgical procedures and methods of taking measurements are well standardized to produce reliable data pools and act as a base for further directions to orthopaedic and tissue engineering developments, specifically translation into the clinic. In this leading opinion paper, we aim to review and critically discuss the different large animal bone defect models reported in the literature. We conclude that most publications provide only rudimentary information on how to establish relevant preclinical segmental bone defects in large animals. Hence, we express our opinion on methodologies to establish preclinical critically sized, segmental bone defect models used in past research with reference to surgical techniques, fixation methods and postoperative management focusing on tibial fracture and segmental defect models.

Fit assessment of anatomic plates for the distal medial tibia.

OBJECTIVES: With the development and popularization of minimally invasive surgical methods and implants for fracture fixation, it is increasingly important that the available implants are precontoured to the specific anatomic location for which they are designed. The objective of this study was to develop a noninvasive method and criteria for quantifying the fit of a distal periarticular medial tibia plate and to test the method on a small set of tibia models. METHODS: The undersurface of the plate was extracted from a digital model of the plate. The surface of the plate was fitted to 21 computer tomography (CT)-based 3-dimensional (3-D) models of human tibiae. Four criteria were defined that constitute an anatomic plate fit and subsequently were applied for the quantitative fit assessment. The fitting of the plate undersurface to the bone was entirely conducted in a virtual environment. RESULTS: An anatomic fit of the plate was achieved for 4 of the models (19%). The individual categories generated fits of 62% (n = 13) for the proximal end; 43% (n = 9) for the proximal angle; 57% (n = 12) for the middle distance; and 57% (n = 12) for a distal fit. CONCLUSIONS: Although for the 4 individual criteria plate fits of 43%-62% were achieved, a global/anatomic fit only occurred for 19% of the bone models. This outcome is likely a result of bone morphology variations, which exist in a random population sample combined with the effects of a nonoptimized plate shape. Recommendations for optimizing the fit of the plate are discussed.