The Orthopaedic Traumatologist and the Peritrochanteric Hip Fracture-Does Experience Matter?

The purpose of this study was to review our protocol of sliding hip screws for stable and cephallomedullary devices for unstable peritrochanteric fractures to evaluate the correctness of the decisions made based on complication rates and on shortening of the fractures as well as financial implications. Over a five-year period, two orthopaedic traumatologists followed a protocol utilizing a sliding hip screw (SHS) for all fractures that were deemed stable and a cephallomedullary nail for unstable fractures. Injury radiographs were then re-reviewed by a blinded observer to classify each fracture pattern as stable or unstable based on the Evans classification. Of 121 patients, 62 were classified as stable and 59 unstable. The tip apex distance averaged 16 mm with 2/61 (3.3%) > 25mm for plates and 22 mm with 6/60 (10%) > 25mm for intermedullary (IM) nails. Two partial cutouts occurred, both in the SHS group. Minimal shortening and deformity were noted for each group. A stability-based protocol utilizing sliding hip screws for stable and IM nails for unstable peritrochanteric hip fractures based on the judgment of experienced surgeons is valid and reasonable, resulting in significant savings compared to using IM nails for all cases ($104,898 in this series). (Journal of Surgical Orthopaedic Advances 30(3):140-143, 2021).

Use of clinical assessment tools in the evaluation of fracture healing.

Fracture healing is an optimized biological process yet the ability to determine when a fracture is healed, or to measure the healing response can present a clinical challenge. This review will focus on the evidence for the implementation of imaging modalities as tools to assist in evaluating fracture union. This is particularly important for common fractures that have a propensity to have delayed union or non-union, where a diagnosis of non-union would alter the treatment. We also present methods, such as biochemical markers and clinical scores that are in development or have the potential to aid in the diagnosis of non-union. Ultimately, clinical exam combined with the available modalities can help the clinician judge the progression of healing with some confidence. There is still a need for continued development of new modalities and tests to improve accuracy of the diagnosis of non-union, as well as predict which fractures are at risk for non-union.

Bone morphogenetic proteins in orthopaedic surgery.

Bone healing is a predictable process that has a high rate of success. For some patients, and in certain clinical settings, this process can be delayed or completely inhibited. This leads to significant morbidity and may also result in time lost from work, costs related to prolonged medical treatment, and continued pain at the site of nonunion or failed spinal fusion. Several growth factors, specifically BMP-2 and BMP-7, have been approved in several countries for specific indications. The use of these products and potential complications of their use are reviewed.

New technologies for the enhancement of skeletal repair.

Although fracture healing is a well-optimized biological process that leads to healing, approximately 10-20% of fractures result in impaired or delayed healing and these fractures may benefit from the use of biotechnologies to enhance skeletal repair. Peptide signaling molecules such as the bone morphogenetic proteins have been shown to stimulate the healing of fresh fractures, nonunions, and spinal fusions and side effects from their use appear to be minimal. Other growth factors currently being studied for local application include growth and differentiation factor-5 (GDF-5), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGFbeta), and platelet-derived growth factor (PDGF). Molecules such as prostaglandin E receptor agonists and the thrombin-related peptide, TP508, have shown promise in animal models of fracture repair. Gene therapy using various growth factors or combinations of factors might also aid in fracture repair, particularly as new methods for delivery that do not require viral vectors are developed. Systemic therapy with agents such as parathyroid hormone (PTH), growth hormone (GH), and the HMG-CoA reductase inhibitors are also under investigation. As these and other technologies are shown to be safe and effective, their use will become a part of the standard of care in managing skeletal injuries.

Platelet-activating factor (PAF) induces activation of matrix metalloproteinase 2 activity and vascular endothelial cell invasion and migration.

Tumor-induced angiogenic responses lead to complex phenotypic changes in vascular endothelial cells, which must coordinate the expression of both proteases and protease inhibitors prior to the proliferation and invasion of surrounding stroma. Matrix metalloproteinase 2 (MMP2), which degrades Type IV collagen, is produced as proMMP2. proMMP2 is activated in part through its interactions with membrane Type 1 MMP (MT1-MMP) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2). In this study, we demonstrate that platelet-activating factor (PAF) is a potent inducer of human umbilical vein endothelial cell (HUVEC) migration and invasion, which is attenuated by PAF receptor antagonists, and that PAF receptor antagonists inhibit the migration and invasion of HUVEC mediated by medium conditioned by a prostatic carcinoma cell line. We confirm that PAF receptor antagonists inhibit proliferation of HUVEC grown in rich growth medium. We show that PAF increases mRNA levels for MT1-MMP and TIMP2, followed by increased temporal conversion of latent proMMP2 to MMP2. Finally, we demonstrate that the ratio of MT1-MMP to TIMP2 in membrane preparations from PAF-stimulated HUVEC is 1.6:1, approximating the hypothesized ideal ratio of 2:1 necessary for the conversion of proMMP2 to MMP2. Our data support the involvement of PAF in vascular endothelial cell migration and invasion.

Differences in KRAS mutation spectrum in lung cancer cases between African Americans and Caucasians after occupational or environmental exposure to known carcinogens.

Elevated mortality rates of lung cancer in the Mississippi River corridor in Louisiana have been clearly documented for the past half-century and rank among the highest in the nation. A population-based case-control study of lung cancer termed Lower Mississippi River Interagency Cancer Study was conducted in southern Louisiana. Lung tumor specimens were collected, isolated by laser capture microdissection, subjected to PCR to amplify KRAS, and sequenced to confirm mutation status and specificity. Of the 116 lung tumors analyzed to date, 32 (27.6%) contained mutations in either codon 12 or 13 of KRAS. This frequency is comparable to that reported in the literature; however, the mutation spectrum was strikingly different. Of the 32 mutations observed, 21 (65.6%) resulted in the inappropriate insertion of cysteine, 6 (18.8%) resulted in the insertion of serine, 3 (9.4%) resulted in the insertion of valine, and 1 (3.1%) each resulted in the insertion of aspartate and alanine. These data indicate that an abnormally high proportion of cysteine (P = 0.010) and serine (P = 0.002) mutations was observed in our sample group versus lung cancers reported in the literature. KRAS mutations were more common in African Americans with an odds ratio of 2.4 (P = 0.048), as were serine mutations, although the latter did not reach statistical significance (odds ratio, 2.6; P = 0.373). No association was found between the observed mutation spectrum and known lung cancer risk factors.

Phosphorylation of STAT-3 in response to basic fibroblast growth factor occurs through a mechanism involving platelet-activating factor, JAK-2, and Src in human umbilical vein endothelial cells. Evidence for a dual kinase mechanism.

Platelet-activating factor (PAF) is a potent proinflammatory phospholipid with multiple pathological and physiological effects. We have shown that basic fibroblast growth factor (bFGF) supplementation induces rapid proliferation of human umbilical vein endothelial cells (HUVEC), which is reduced upon removal of bFGF or by bFGF immunoneutralization. The PAF receptor antagonist LAU-8080 inhibited bFGF-stimulated HUVEC proliferation, indicating the involvement of PAF in the bFGF-mediated signaling of HUVEC. Although FGF receptor phosphorylation was not affected by LAU-8080, the bFGF-mediated prolonged phosphorylation, and activation of Erk-1 and -2 were attenuated. Phosphorylation of STAT-3 was observed in the presence of PAF or bFGF, which was attenuated by PAFR antagonists. PAF-induced STAT-3 phosphorylation observed in HUVEC pretreated with either Src inhibitor PP1 or JAK-2 inhibitor AG-490 indicated (i) immediate (1 min) phosphorylation of STAT-3 is dependent on Src, (ii) JAK-2-dependent STAT-3 phosphorylation occurs after the delayed (30 min) PAF exposure, and (iii) prolonged (60 min) STAT-3 phosphorylation may be either through Src and/or JAK-2. Attenuation of the STAT-3 phosphorylation by the PAFR antagonists indicated signaling through the PAF receptor. Taken together, these findings suggest the production of PAF is important for bFGF-mediated signaling and that a dual kinase mechanism is involved in the PAF-mediated signal transduction cascade.