A defect-in-continuity in the canine femur: and in-vivo experimental model for the study of bone graft incorporation.

The in-vivo study of bone graft incorporation has traditionally used a segmental diaphyseal bone defect. This model reliably produces a nonunion, but is complicated by graft instability and altered limb loading stresses. The authors discuss the advantages of a defect-in-continuity canine femur model which produces a more consistent union with fewer mechanical complications despite the absence of fixation. This proposed model permits analysis of radiographic, histologic and biomechanical data which are more applicable to the usual clinical setting in which bone graft is required

Cellular biology of fracture healing

The biology of bone healing is a rapidly developing science. Advances in transgenic and gene‐targeted mice have enabled tissue and cell‐specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing—coupled with the heterogeneity of animal models—renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop ResAdvances in transgenic and gene‐targeted mice have enabled tissue and cell‐specific investigation of skeletal regeneration. While genetically modified animals offer incredible insights into the temporal and spatial importance of various molecules, the complexity and rapidity of healing renders studies of regenerative biology challenging. Herein, cells and extracellular mediators that play a key role in bone healing are reviewed. We will focus on recent studies that explore the origins and fates of various cells in the fracture environment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148261/1/jor24170_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148261/2/jor24170-sup-0002-SuppTab-S2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148261/3/jor24170-sup-0001-SuppTab-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148261/4/jor24170.pd

Current Status of Musculoskeletal Trauma Care Systems Worldwide

BACKGROUND AND RATIONALE Although general trauma care systems and their effects on mortality reduction have been studied, little is known of the current state of musculoskeletal trauma delivery globally, particularly in low-income (LI) and low middle-income (LMI) countries. The goal of this study is to assess and describe the development and availability of musculoskeletal trauma care delivery worldwide. MATERIALS & METHODS A questionnaire was developed to evaluate different characteristics of general and musculoskeletal trauma care systems, including general aspects of systems, education, access to care and pre- and posthospital care. Surgical leaders involved with musculoskeletal trauma care were contacted to participate in the survey. RESULTS Of the 170 surveys sent, 95 were returned for use for the study. Nearly 30 percent of surgeons reported a formalized and coordinated trauma system in their countries. Estimates for the number of surgeons providing musculoskeletal trauma per one million inhabitants varied from 2.6 in LI countries to 58.8 in high-income countries. Worldwide, 15% of those caring for musculoskeletal trauma are fellowship trained. The survey results indicate a lack of implemented musculoskeletal trauma care guidelines across countries, with even high-income countries reporting less than 50% availability in most categories. Seventy-nine percent of the populations from LI countries were estimated to have no form of health care insurance. Formalized emergency medical services were reportedly available in only 33% and 50% of LI and LMI countries, respectively. Surgeons from LI and LMI countries responded that improvements in the availability of equipment (100%), number and locations of trauma-designated hospitals (90%), and physician training programs (88%) were necessary in their countries. The survey also revealed a general lack of resources for postoperative and rehabilitation care, irrespective of the country's income level. CONCLUSION This study addresses the current state of musculoskeletal trauma care delivery worldwide. These results indicate a greater need for trauma system development and support, from prehospital through posthospital care. Optimization of these systems can lead to better outcomes for patients after trauma. This study represents a critical first step toward better understanding the state of musculoskeletal trauma care in countries with different levels of resources, developing strategies to address deficiencies, and forming regional and international collaborations to develop musculoskeletal trauma care guidelines

Risk of surgical site infection in patients undergoing orthopedic surgery

This study aimed to identify risk factors associated with surgical site infections in orthopedic surgical patients at a public hospital in Minas Gerais, Brazil, between 2005 and 2007. A historical cohort of 3,543 patients submitted to orthopedic surgical procedures. A descriptive analysis was conducted and surgical site infection incidence rates were estimated. To verify the association between infection and risk factors, the Chi-square Test was used. The strength of association of the event with the independent variables was estimated using Relative Risk, with a 95% confidence interval and pEstudio para identificar factores de riesgo asociados a infecciones de sitio quirúrgico en pacientes quirúrgicos ortopédicos de un hospital público de Minas Gerais, Brasil, entre 2005 y 2007. Cohorte histórica de 3.543 pacientes sometidos a cirugías ortopédicas. Un análisis descriptivo fue realizado y la tasa de incidencia de infección fue estimada. Para verificar la asociación entre la infección y los factores de riesgo se usó el test chi-cuadrado. La fuerza de la asociación del evento con las variables independientes fue estimada por el Riesgo Relativo, con un intervalo de confianza de 95% y p Objetivou-se, neste estudo, identificar fatores de risco associados às infecções de sítio cirúrgico, em pacientes cirúrgicos ortopédicos, de um hospital público de Minas Gerais, Brasil, entre 2005 e 2007. Como método usou-se coorte histórica em 3.543 pacientes submetidos a cirurgias ortopédicas. Análise descritiva e taxa de incidência de infecção foram estimadas. Para verificar a associação entre a infecção e os fatores de risco usou-se o teste qui-quadrado. A força da associação do evento com as variáveis independentes foi estimada pelo risco relativo, intervalo de confiança de 95% e p<0,05. A incidência de infecção de sítio cirúrgico foi de 1,8%. Potencial de contaminação da ferida cirúrgica, condições clínicas do paciente, tempo cirúrgico e tipo de procedimento ortopédico foram estatisticamente associados à infecção. A identificação de associação de infecção de sítio cirúrgico aos fatores de risco mencionados é importante e contribui para a prática clínica do enfermeiro

Post-Fasciotomy Classification System for Acute Compartment Syndrome of the Leg

Objective: Acute compartment syndrome (ACS) is a true emergency. Even with urgent fasciotomy there is often muscle damage and need for further surgery. Although ACS is not uncommon, no validated classification system exists to aid in efficient and clear communication. The aim of this study was to establish and validate a classification system for the consequences of ACS treated with fasciotomy. Methods: Using a modified Delphi method, an international panel of ACS experts was assembled to both establish a grading scheme for the disease and then validate the classification system. The goal was to articulate discrete grades of ACS related to fasciotomy findings and associated costs. A pilot analysis was used to determine questions that were clear to the respondents. Discussion of this analysis resulted in another round of cases used for 24 other raters. The twenty-four individuals implemented the classification system two separate times to compare outcomes for 32 clinical cases. The accuracy and reproducibility of the classification system were subsequently calculated based on the providers' responses. Results: The Fleiss’ Kappa of all raters was at 0.711 showing a strong agreement between the 24 raters. Secondary validation was performed for paired 276 raters and correlation was tested using the Kendall coefficient. The median correlation coefficient was 0.855. All 276 pairs had statistically significant correlation. Correlation coefficient between the first and second rating sessions was strong with the median pair scoring at 0.867. All surgeons had statistically significant internal consistency. Conclusion: This new ACS classification system may be applied to better understand the impact of ACS on patient outcomes and economic costs for leg ACS. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved

Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

Etoposide (VP-16) is a topoisomerase II (topo II) inhibitor chemotherapeutic agent. Studies indicate that VP-16 enhances proinflammatory cytokines secretion from tumour cells, including IL-8, a chemokine associated with proangiogenic effects. Fluoroquinolones inhibit topo II activity in eukaryotic cells by a mechanism different from that of VP-16. The fluoroquinolone moxifloxacin (MXF) has pronounced anti-inflammatory effects in vitro and in vivo. We studied the effects of MXF and VP-16 on purified human topo II activity and further analysed their combined activity on proliferation, apoptosis and caspase-3 activity in THP-1 and Jurkat cells. Moxifloxacin alone slightly inhibited the activity of human topo II; however, in combination with VP-16 it led to a 73% reduction in enzyme activity. VP-16 inhibited cell proliferation in a time and dose-dependent manner. The addition of moxifloxacin for 72 h to low-dose VP-16 doubled its cytotoxic effect in THP-1 and Jurkat cells (1.8- and 2.6-fold decrease in cell proliferation, respectively) (P<0.004). Moxifloxacin given alone did not induce apoptosis but enhanced VP-16-induced apoptosis in THP-1 and Jurkat cells (1.8- and two-fold increase in annexin V positive cells and caspase-3 activity, respectively) (P<0.04). VP-16 induced the release of IL-8 in a time and dose-dependent manner from THP-1 cells. Moxifloxacin completely blocked the enhanced release of IL-8 induced by 0.5 and 1 μg ml−1 VP-16, and decreased IL-8 release from cells incubated for 72 h with 3 μg ml−1 VP-16 (P<0.001). VP-16 enhanced the release of IL-1β and TNF-α from THP-1 cells, whereas the addition of MXF prevented the enhanced cytokine secretion (P<0.001). We conclude that MXF significantly enhances VP-16 cytotoxicity in tumour-derived cells while preventing VP-16-induced proinflammatory cytokine release. This unique combination may have clinical benefits and cytotoxic drug ‘sparing effect' and should be further studied in vivo

Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells

Efficacy of chemotherapy in advanced stages of colorectal tumours is limited. The quinolone antibiotic ciprofloxacin was recently shown to inhibit growth and to induce apoptosis in human bladder carcinomas cells. We investigated the effect of ciprofloxacin on colon carcinoma lines in vitro. CC-531, SW-403 and HT-29 colon carcinoma and HepG2 hepatoma cells (control cells) were exposed to ciprofloxacin. Proliferation was assessed by bromodeoxyuridine-incorporation into DNA and apoptosis was measured by flow cytometry after propidium iodide or JC-1 staining. Expression of anti-apoptotic Bcl-2 and pro-apoptotic Bax was analyzed by semiquantitative Western blot analysis and activity of caspases 3, 8 and 9 by substrate-cleavage assays. Ciprofloxacin suppressed DNA synthesis of all colon carcinoma cells time- and dose-dependently, whereas the hepatoma cells remained unaffected. Apoptosis reached its maximum between 200 and 500 μg ml−1. This was accompanied by an upregulation of Bax and of the activity of caspases 3, 8 and 9, and paralleled by a decrease of the mitochondrial membrane potential. Ciprofloxacin decreases proliferation and induces apoptosis of colon carcinoma cells, possibly in part by blocking mitochondrial DNA synthesis. Therefore, qualification of ciprofloxacin as adjunctive agent for colorectal cancer should be evaluated

Role of Matrix Metalloproteinase 13 in Both Endochondral and Intramembranous Ossification during Skeletal Regeneration

Extracellular matrix (ECM) remodeling is important during bone development and repair. Because matrix metalloproteinase 13 (MMP13, collagenase-3) plays a role in long bone development, we have examined its role during adult skeletal repair. In this study we find that MMP13 is expressed by hypertrophic chondrocytes and osteoblasts in the fracture callus. We demonstrate that MMP13 is required for proper resorption of hypertrophic cartilage and for normal bone remodeling during non-stabilized fracture healing, which occurs via endochondral ossification. However, no difference in callus strength was detected in the absence of MMP13. Transplant of wild-type bone marrow, which reconstitutes cells only of the hematopoietic lineage, did not rescue the endochondral repair defect, indicating that impaired healing in Mmp13−/− mice is intrinsic to cartilage and bone. Mmp13−/− mice also exhibited altered bone remodeling during healing of stabilized fractures and cortical defects via intramembranous ossification. This indicates that the bone phenotype occurs independently from the cartilage phenotype. Taken together, our findings demonstrate that MMP13 is involved in normal remodeling of bone and cartilage during adult skeletal repair, and that MMP13 may act directly in the initial stages of ECM degradation in these tissues prior to invasion of blood vessels and osteoclasts