Use of a Fibular Strut Allograft in an Osteoporotic Distal Humerus Fracture

Hildebrand, Gregory; Wright, David M.; Marston, Scott B.; Switzer, Julie A.

doi:10.1177/2151458513477108

Cited by 6 publications

(4 citation statements)

References 16 publications

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“…We also noted a robust effect of iNOS inhibition or knockdown on in vitro colony formation by human melanoma cells, suggesting that even in vitro iNOS may be required for optimum clonogenicity of founder cells. We also found that exogenously-supplied NO reverses mTOR pathway inhibition seen after Vemurafenib treatment, suggesting that NO can act downstream of BRAF to bypass BRAF inhibition, and thus is a potential mechanism of escape (44, 45)…”

Section: Discussionmentioning

confidence: 68%

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

et al. 2014

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Melanoma is one of the cancers of fastest-rising incidence in the world. iNOS is overexpressed in melanoma and other cancers, and previous data suggest that iNOS and nitric oxide (NO) drive survival and proliferation of human melanoma cells. However, specific mechanisms through which this occurs are poorly defined. One candidate is the PI3K/AKT/mTOR pathway, which plays a major role in proliferation, angiogenesis, and metastasis of melanoma and other cancers. We used the chick embryo chorioallantoic membrane (CAM) assay to test the hypothesis that melanoma growth is regulated by iNOS-dependent mTOR pathway activation. Both pharmacologic inhibition and siRNA-mediated gene silencing of iNOS suppressed melanoma proliferation and in vivo growth on the CAM in human melanoma models. This was associated with strong downregulation of mTOR pathway activation by Western blot analysis of p-mTOR, p-P70S6K, p-S6RP, and p-4EBP1. iNOS expression and NO were associated with reversible nitrosylation of TSC2, and inhibited dimerization of TSC2 with its inhibitory partner TSC1, enhancing GTPase activity of its target Rheb, a critical activator of mTOR signaling. Immunohistochemical analysis of tumor specimens from stage III melanoma patients showed a significant correlation between iNOS expression levels and expression of mTOR pathway members. Exogenously-supplied NO was also sufficient to reverse mTOR pathway inhibition by the B-Raf inhibitor Vemurafenib. In summary, covalent modification of TSC2 by iNOS-derived NO is associated with impaired TSC2/TSC1 dimerization, mTOR pathway activation, and proliferation of human melanoma. This model is consistent with the known association of iNOS overexpression and poor prognosis in melanoma and other cancers.

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Section: Discussionmentioning

confidence: 68%

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

et al. 2014

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“…Fibular strut allografting has been reported to provide immediate and long-term stability in the treatment of comminuted fractures of different long bones such as the humerus [7,15]. We have been using fibular strut grafts to treat UBCs in patients with a closed physis for several years.…”

Section: Introductionmentioning

confidence: 99%

Are Fibular Allograft Struts Useful for Unicameral Bone Cysts of the Proximal Humerus in Skeletally Mature Patients?

Jamshidi

Bahradadi

Bahrabadi

et al. 2021

Clin Orthop Relat Res

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Background Although most unicameral bone cysts (UBCs) are either successfully treated or have healed by the time of skeletal maturity, a small proportion of patients will have persistent UBCs beyond the age of skeletal maturity. More reliable methods are needed to treat persistent UBCs in the humerus because these cysts are associated with a high risk of fracture due to thinning of the humeral cortex. In this study, we evaluated whether inserting a fibular strut allograft into the humerus would be associated with healing of the cyst and union of associated pathologic fractures in skeletally mature patients with a UBC of the proximal humerus. Questions/purposes (1) How effective is inserting a fibular strut allograft in the healing of proximal humerus UBCs in skeletally mature patients with bone cysts and associated fractures? (2) What are the functional results of this procedure? (3) What complications are associated with this procedure? Methods Between 2005 and 2018, we surgically treated 23 skeletally mature patients with persistent humeral UBCs and any of the following indications: a progressive cyst that was not responsive to aspiration and 2 to 3 steroid injections, a cyst with a pathologic fracture, and a cyst at high risk of fracture. Of those, patients with a cyst located in the proximal humerus and a defect length more than 6 cm (n = 18) were considered eligible to be treated with insertion of a fibular strut allograft through a hole created in the greater tuberosity. A further two patients were excluded because they were treated by other surgical methods. From the remaining 16 patients, two patients were lost to follow-up before 2 years and could not be analyzed in this study. Another two patients had incomplete datasets, leaving 12 for analyses in this retrospective study. Three patients presented with a pathologic fracture. Complete filling of the cysts with bone within 24 months was regarded as healing, and after 24 months it was classified as delayed healing. Cyst consolidation with small residual areas of osteolysis was considered healed with residual radiographic appearance. Fracture union was determined by the clear observation of at least three of four cortical views bridged by bone in the radiographic follow-up 3 months after the operation. Fractures in which the cortices were not bridged by bone after 3 months were regarded as a delayed union. The functional outcome of the patients Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request.

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“…A fibular strut allograft was then used to compensate for this fracture. The results of this operation showed that the patient was able to work without pain after three months, and after 6 months, the fracture completely healed through radiographic diagnosis 18 .…”

Section: Discussionmentioning

confidence: 91%

Massive bone defects due to infection at the surgical site associated with a distal humeral fracture that was treated using fibula autograft: a case report

Fouladpour

Asadi

Aris

et al. 2023

Annals of Medicine &Amp; Surgery

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Introduction and importance: Distal humerus fractures comprise between 2 and 5% of all fractures, and approximately one-third of all humerus fractures are of this type. In the present report, the authors described the massive bone defects due to infection at the surgical site associated with a distal humeral fracture that was treated using fibula autograft. Case presentation: A 28-year-old female patient experienced a fall from a height of 4 m and was referred to Poursina Educational and Medical Center. Clinical examinations and radiological imaging showed an open fracture of the right distal humerus. In the postoperative 50-day follow-up, the complication of infection at the surgical site causes bone loss of up to 8 cm. The posterior triceps-split approach (Campbell) to the distal humerus was used in this surgery. To evaluate the quality of surgery, standard radiographs of anteroposterior and lateral of the elbow joint and humeral shaft were performed after surgery. Clinical discussion: At 5 months postoperatively, the patient’s initial results are good, and the range of motion of the elbow joint is ~10–120°. Conclusion: Based on the results of the present study, fibular transplantation in distal humerus fractures is considered one of the bone treatment options for repair.

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Use of a Fibular Strut Allograft in an Osteoporotic Distal Humerus Fracture

Cited by 6 publications

References 16 publications

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

Inducible Nitric Oxide Synthase Drives mTOR Pathway Activation and Proliferation of Human Melanoma by Reversible Nitrosylation of TSC2

Are Fibular Allograft Struts Useful for Unicameral Bone Cysts of the Proximal Humerus in Skeletally Mature Patients?

Massive bone defects due to infection at the surgical site associated with a distal humeral fracture that was treated using fibula autograft: a case report

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