Risk Factors Associated With Complications After Operative Treatment of Multiligament Knee Injury.

BACKGROUND: Many factors can affect clinical outcomes and complications after a complex multiligament knee injury (MLKI). Certain aspects of the treatment algorithm for MLKI, such as the timing of surgery, remain controversial. PURPOSE: To determine the risk factors for common complications after MLKI reconstruction. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: A retrospective review was conducted on 134 patients with MLKI who underwent reconstruction between 2011 and 2018 at a single academic center. Patients included in the review had a planned surgical reconstruction of >1 ligament based on clinical examination and magnetic resonance imaging. Complications were categorized as (1) wound infection requiring irrigation and debridement, (2) arthrofibrosis requiring manipulation under anesthesia and/or lysis of adhesions, (3) deep venous thrombosis, (4) need for removal of hardware, and (5) revision ligament surgery. The potential risk factors for complications included patient characteristics, injury pattern categorized according to Schenck classification (knee dislocation [KD] I-KD IV), and timing of surgery. Significant risk factors for complications were analyzed by t test, chi-square test, and Fisher exact test. RESULTS: A total of 108 patients met the inclusion criteria; of these, 29.6% experienced at least 1 complication. Smoking (odds ratio [OR], 3.20 [95% CI, 1.28-8.02]; P = .01) and planned staged surgery (OR, 2.71 [95% CI, 1.04-7.04]; P = .04) significantly increased the overall risk of complication, while increased time from injury to surgery (OR, 0.99 [95% CI, 0.98-0.998]; P < .01) significantly decreased the risk. Increasing time from injury to surgery (OR, 0.99 [95% CI, 0.97-0.998]; P = .02) also led to a slightly but significantly decreased risk for arthrofibrosis. CONCLUSION: The study findings suggest that smoking, decreased time from injury to initial surgery, and planned staged procedures may increase the rate of complications. Further studies are needed to determine which changes in the treatment algorithm are most effective to reduce the complication rate in patients.

Obesity Is Associated with Significant Morbidity after Multiligament Knee Surgery.

The objective was to report the effect of obesity, utilizing a body mass index (BMI) threshold of 35 kg/m2, on outcomes and complications of multiple ligament knee injury (MLKI). It was hypothesized that obese patients would have longer intraoperative times and hospital length of stay, greater estimated blood loss, and higher rates of wound infection requiring irrigation and debridement (I&D) and revision ligament surgery. A retrospective review was performed on 143 individuals who underwent surgery for an MLKI between 2011 and 2018 at a single academic center. Patients were included if there was a plan for potential surgical repair/reconstruction of two or more ligaments. Patients with prior surgery to the affected knee or intra-articular fracture requiring reduction and fixation were excluded. Comparisons between obese and nonobese patients were made using two-sample t-test and either chi-square or Fisher's exact test for continuous and categorical variables, respectively. Significance was set at p < 0.05. Of 108 patients meeting inclusion criteria, 83 had BMI < 35 kg/m2 and 25 had BMI ≥ 35 kg/m2. Obese patients sustained higher rates of MLKI due to ultralow velocity mechanisms (28.0 vs. 1.2%; p = 0.0001) and higher rates of concomitant lateral meniscus injury (48.0 vs. 25.3%; p = 0.04). Among patients undergoing single-staged surgery, obese patients had significantly longer duration of surgery (219.8 vs. 178.6 minutes; p = 0.02) and more wound infections requiring I&D (20.0 vs. 4.8%; p = 0.03). In contrast, nonobese patients had higher rates of arthrofibrosis requiring manipulation under anesthesia and/or arthrolysis (25.3 vs. 0%; p = 0.003). Obese patients undergoing surgery of an MLKI have longer operative times, greater rates of wound infection requiring I&D, and lower rates of arthrofibrosis. Surgeons may consider these results when counseling patients on their postoperative course and risk for complications. Future research might focus on strategies to reduce complication rates in obese patients with MLKI. This is a Level III, retrospective comparative study.

Intercondylar Notch Measurement During Arthroscopy and on Preoperative Magnetic Resonance Imaging.

Small intercondylar notch size is associated with increased risk of anterior cruciate ligament (ACL) injuries and increased difficulty of ACL reconstruction. When encountering a small notch during surgery, some surgeons may resort to a notchplasty, which has been shown to have associated morbidity. The ability to predict notch size on preoperative imaging could allow the orthopaedic surgeon to anticipate surgical difficulty such as an oversized graft and graft impingement and possibly avoid a notchplasty. Many methods have been proposed for measuring intercondylar notch size, but they do not correlate with intraoperative measurements or they utilize computed tomography scanning, which is not readily obtained before ACL reconstruction. The purpose of this study was to develop a method of notch measurement on preoperative radiography and magnetic resonance imaging that match intraoperative arthroscopic measurements. The method presented here can be used to identify narrow intercondylar notches, prepare for potential intraoperative challenges, and formulate surgical plans such as for graft choice in individualized ACL reconstruction.

Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model.

Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 µg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro-computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 ± 0.50) and OVX groups (1.83 ± 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats.

Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents.

Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.

Dioxin Exposure Impairs BMP-2-Mediated Spinal Fusion in a Rat Arthrodesis Model.

BACKGROUND: Cigarette smoking inhibits bone-healing and leads to increased rates of pseudarthrosis. However, the mechanisms behind these effects are controversial. Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin)--a cigarette smoke constituent and potent activator of the aryl hydrocarbon receptor (Ahr)--negatively impacts bone quality and osteoblast differentiation. We hypothesized that activation of the Ahr by dioxin would inhibit bone morphogenetic protein (BMP)-2-mediated spinal fusion in a rat arthrodesis model. METHODS: Female Long-Evans rats were pretreated with dioxin or vehicle in six weekly doses, followed by bilateral posterior lumbar spinal fusion across the L4-L5 transverse processes using recombinant human BMP (rhBMP)-2. Treatments continued until sacrifice at four weeks postoperatively. A third group was treated with dioxin for six weeks, followed by a recovery period of four elimination half-lives to assess the reversible effects of dioxin exposure on spinal fusion capacity. Bone formation and fusion capacity were evaluated using fusion scoring, radiography, micro-computed tomography, and histologic analysis. RESULTS: Fusion scores for dioxin-treated and dioxin-recovery rats were significantly lower than those for controls. Although fusion rates were also significantly reduced in dioxin-treated animals relative to controls (50% versus 100%, respectively), rates were not significantly reduced in dioxin-recovery animals (80%). CONCLUSIONS: Dioxin treatment significantly inhibited spinal fusion in a rat arthrodesis model, and a prolonged cessation of dioxin exposure facilitated only a partial recovery of bone-healing capacity. This finding indicates that, although the effects of dioxin are persistent, an extended recovery from exposure could potentially restore bone regeneration in vivo. CLINICAL RELEVANCE: Development of a pharmacologic agent that reduces the adverse effects of cigarette smoke on bone-healing could prove useful to orthopaedic surgeons. Since dioxin and other similar cigarette smoke toxins exert their effects through Ahr pathway activation, the receptor represents a potential therapeutic target to improve spinal fusion rates in patients who smoke.

Gel scaffolds of BMP-2-binding peptide amphiphile nanofibers for spinal arthrodesis.

Peptide amphiphile (PA) nanofibers formed by self-assembly can be customized for specific applications in regenerative medicine through the use of molecules that display bioactive signals on their surfaces. Here, the use of PA nanofibers with binding affinity for the bone promoting growth factor BMP-2 to create a gel scaffold for osteogenesis is reported. With the objective of reducing the amount of BMP-2 used clinically for successful arthrodesis in the spine, amounts of growth factor incorporated in the scaffolds that are 10 to 100 times lower than that those used clinically in collagen scaffolds are used. The efficacy of the bioactive PA system to promote BMP-2-induced osteogenesis in vivo is investigated in a rat posterolateral lumbar intertransverse spinal fusion model. PA nanofiber gels displaying BMP-2-binding segments exhibit superior spinal fusion rates relative to controls, effectively decreasing the required therapeutic dose of BMP-2 by 10-fold. Interestingly, a 42% fusion rate is observed for gels containing the bioactive nanofibers without the use of exogenous BMP-2, suggesting the ability of the nanofiber to recruit endogenous growth factor. Results obtained here demonstrate that bioactive biomaterials with capacity to bind specific growth factors by design are great targets for regenerative medicine.

Ectonucleotide triphosphate diphosphohydrolase-1 (CD39) mediates resistance to occlusive arterial thrombus formation after vascular injury in mice.

Modulation of purinergic signaling, which is critical for vascular homeostasis and the response to vascular injury, is regulated by hydrolysis of proinflammatory ATP and/or ADP by ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD-1; CD39) to AMP, which then is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine. We report here that compared with littermate controls (wild type), transgenic mice expressing human ENTPDase-1 were resistant to the formation of an occlusive thrombus after FeCl(3)-induced carotid artery injury. Treatment of mice with the nonhydrolyzable ADP analog, adenosine-5'-0-(2-thiodiphosphate) trilithium salt, Ado-5'-PP[S], negated the protection from thrombosis, consistent with a role for ADP in platelet recruitment and thrombus formation. ENTPD-1 expression decreased whole-blood aggregation after stimulation by ADP, an effect negated by adenosine-5'-0-(2-thiodiphosphate) trilithium salt, Ado-5'-PP[S] stimulation, and limited the ability to maintain the platelet fibrinogen receptor, glycoprotein α(IIb)/ß(3), in a fully activated state, which is critical for thrombus formation. In vivo treatment with a CD73 antagonist, a nonselective adenosine-receptor antagonist, or a selective A(2A) or A(2B) adenosine-receptor antagonist, negated the resistance to thrombosis in transgenic mice expressing human ENTPD-1, suggesting a role for adenosine generation and engagement of adenosine receptors in conferring in vivo resistance to occlusive thrombosis in this model. In summary, our findings identify ENTPDase-1 modulation of purinergic signaling as a key determinant of the formation of an occlusive thrombus after vascular injury.