Corey O. Montgomery

Concurrent septic arthritis and osteomyelitis in children.

Introduction: Septic arthritis and osteomyelitis can both independently cause substantial morbidity. With concomitant septic arthritis and osteomyelitis, the septic arthritis may be treated without knowledge of the adjacent osteomyelitis resulting in delayed treatment. This study aims to identify factors that may help to diagnosis concurrent infections (CI) earlier. Methods: A retrospective chart review of 200 patients with septic arthritis was performed. Patients with CI were compared with patients with septic arthritis alone using tests determined by the nature of the variable being analyzed (the &khgr;2 test, the Fisher exact test, the Cochran-Armitage trend test, and the Kruskal-Wallis test.). Results: Two hundred patients were eligible and analyzed, of which 43 (21.5%) had CI. On the basis of age, CI were most common in newborns and adolescents (P<0.0001). On the basis of location, 72% of shoulder infections (P<0.0001) were concurrent, whereas <50% of elbows, hips, knees, and ankle were CI. The most common infective organism was methicillin-sensitive Staphylococcus aureus (P<0.0001). CI were significantly associated with increased median (6) days of clinical symptoms before presentation (P<0.0001), increased duration of median (6) days of hospital stay (P<0.0001), increased number of operative procedures (P=0.005), and increased need for ICU admission (P=0.024). Conclusions: Utilizing advanced imaging (CT scan, bone scan, and/or MRI) in patients with septic arthritis who are younger than 4 months of age, between ages 13 and 20 years, with septic arthritis involving the shoulder, and with symptoms for more than 6 days may shorten hospital stays, decrease the number of operative procedures required, and possibly limit infection-related sequelae by identifying CI earlier. Level of Evidence: III.

Increased risk of Blount disease in obese children and adolescents with vitamin D deficiency.

Background Poor dietary habits and decreased outdoor activity has led to an epidemic of obese children and vitamin D deficiency. The lack of vitamin D alters bone development and mineralization by diminishing physiological levels of calcium and phosphorus. Given vitamin Ds role in bone and growth plate mineralization and regulation, we hypothesized that vitamin D deficiency would lead to higher rates of fractures, slipped capital femoral epiphysis (SCFE), and Blount disease in obese youth. Methods A retrospective review was performed at the obesity clinic using the obesity database (890 patients). Data obtained included body mass index (BMI), vitamin D levels (25-vitamin D), history of fractures, Blount disease, and/or SCFE. The chart review identified 2 populations of obese patients, those with vitamin D deficiency, <16 ng/mL (198 patients) and those not vitamin D deficient >16 ng/mL (692 patients). Fisher exact, &khgr;2, and 2-sample t tests along with logistic regression were used for statistical analysis. A P value ⩽0.05 was considered statistically significant. Results Blount disease was found to have a statistically significant (P<0.05) positive association with patients sex, BMI, and vitamin D level. Specifically, males were 8.16 times more likely than females to be observed with Blount disease (P=0.01). Patients with very low vitamin D levels were 7.33 times more likely to have Blount disease than patients with higher levels (P=0.002). Each whole number increase in BMI increases the likelihood of Blount disease by 3% (P=0.01). There was no association between increased number of fractures or SCFE with vitamin D deficiency in these obese patients. Conclusion As our findings indicate, BMI and vitamin D levels have a strong association with Blount disease, which may be especially important among males. Ours is the first study to show a relationship between vitamin D deficiency and Blount disease, but further prospective studies are needed with larger numbers to confirm this independent association of vitamin D deficiency with Blount disease. Level of Evidence Level III retrospective study.

The promise of bone cancer proteomics.

Mass spectrometric analysis of the low‐molecular‐weight (LMW) range of the serum/plasma proteome is revealing the existence of large numbers of previously unknown peptides and protein fragments, predicted to be derived from circulating low‐abundance proteins. While genomics and proteomics are the primary discovery research tool, recent innovations in high‐throughput proteomics are now standard practice for biomarker and target discovery. Surface‐enhanced laser desorption/ionization time‐of‐flight (SELDI‐TOF) mass spectrometry (MS) is the current mainstay for serum or plasma analysis, although other methods are emerging as alternative high‐throughput approaches. From a proteomics perspective, the bone cancers, such as myeloma, breast and prostate cancer bony metastases, and osteosarcoma, are likely among the least studied. As recent advances in proteomic technology have thrust the bone cancer field into the era of proteomics, a review of the current status of the proteome as it relates to the skeletal consequences of malignancy seems reasonable.

Circulating interleukin-8 levels explain breast cancer osteolysis in mice and humans.

Skeletal metastases of breast cancer and subsequent osteolysis connote a dramatic change in the prognosis for the patient and significantly increase the morbidity associated with disease. The cytokine interleukin 8 (IL-8/CXCL8) is able to directly stimulate osteoclastogenesis and bone resorption in mouse models of breast cancer bone metastasis. In this study, we determined whether circulating levels of IL-8 were associated with increased bone resorption and breast cancer bone metastasis in patients and investigated IL-8 action in vitro and in vivo in mice. Using breast cancer patient plasma (36 patients), we identified significantly elevated IL-8 levels in bone metastasis patients compared with patients lacking bone metastasis (p<0.05), as well as a correlation between plasma IL-8 and increased bone resorption (p<0.05), as measured by NTx levels. In a total of 22 ER+ and 15 ER- primary invasive ductal carcinomas, all cases examined stained positive for IL-8 expression. In vitro, human MDA-MB-231 and MDA-MET breast cancer cell lines secrete two distinct IL-8 isoforms, both of which were found to stimulate osteoclastogenesis. However, the more osteolytic MDA-MET-derived full length IL-8(1-77) had significantly higher potency than the non-osteolytic MDA-MB-231-derived IL-8(6-77), via the CXCR1 receptor. MDA-MET breast cancer cells were injected into the tibia of nude mice and 7days later treated daily with a neutralizing IL-8 monoclonal antibody. All tumor-injected mice receiving no antibody developed large osteolytic bone tumors, whereas 83% of the IL-8 antibody-treated mice had no evidence of tumor at the end of 28days and had significantly increased survival. The pro-osteoclastogenic activity of IL-8 in vivo was confirmed when transgenic mice expressing human IL-8 were examined and found to have a profound osteopenic phenotype, with elevated bone resorption and inherently low bone mass. Collectively, these data suggest that IL-8 plays an important role in breast cancer osteolysis and that anti-IL-8 therapy may be useful in the treatment of the skeletal related events associated with breast cancer.

Cisplatin Inhibits Bone Healing During Distraction Osteogenesis

Osteosarcoma (OS) is the most common malignant bone tumor affecting children and adolescents. Many patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. Surgical reconstructions after tumor resection include structural allografts, non‐cemented endoprostheses, and distraction osteogenesis (DO), which require direct bone formation. Although cisplatin (CDP) is extensively used for OS chemotherapy, the effects on bone regeneration are not well studied. The effects of CDP on direct bone formation in DO were compared using two dosing regimens and both C57BL/6 (B6) and tumor necrosis factor receptor 1 knockout (TNFR1KO) mice, as CDP toxicity is associated with elevated TNF levels. Detailed evaluation of the five‐dose CDP regimen (2 mg/kg/day), demonstrated significant decreases in new bone formation in the DO gaps of CDP treated versus vehicle treated mice (p < 0.001). Further, no significant inhibitory effects from the five‐dose CDP regimen were observed in TNFR1KO mice. The two‐dose regimen significantly inhibited new bone formation in B6 mice. These results demonstrate that CDP has profound short term negative effects on the process of bone repair in DO. These data provide the mechanistic basis for modeling peri‐operative chemotherapy doses and schedules and may provide new opportunities to identify molecules that spare normal cells from the inhibitory effects of CDP.

Arthroscopic reduction and internal fixation of a medial femoral condylar fracture after anterior cruciate ligament reconstruction. A case report.

More than 100,000 anterior cruciate ligament reconstruction operations are performed annually in the United States1. Autogenous bone-patellar tendon-bone graft is the most frequent graft option used. The reported prevalence of complications varies widely, and serious complications include infection, stiffness, graft failure, deep venous thrombosis, tendon rupture, osteonecrosis, and periarticular fracture2-6. Periarticular fractures associated with anterior cruciate ligament reconstruction have been reported and include patellar, tibial plateau, tibial tubercle, and lateral femoral condylar and supracondylar femoral fracture patterns. Patellar fracture has been the most commonly documented postoperative fracture complication and occurs in conjunction with the harvesting of autogenous bone-patellar tendon-bone graft7,8. Additionally, eight tibial fractures9-16 and eight lateral condylar or supracondylar femoral fractures associated with anterior cruciate ligament reconstruction have been reported17-24. These fractures occurred through iatrogenic stress-risers25,26 created at the time of reconstruction, and the reported treatment had been arthrotomy with open reduction and internal fixation. To our knowledge, the case of our patient represents the first published report of medial femoral condylar fracture occurring after arthroscopic anterior cruciate ligament reconstruction and the first report of the use of arthroscopically assisted medial femoral condylar reduction and percutaneous internal fixation. Arthroscopically assisted reduction with internal fixation of a displaced lateral condylar fracture has been reported rarely27-29; however, to our knowledge, a similar approach to a medial condylar fracture has not been reported. In the case of our patient, the mechanism of injury causing the medial femoral condylar fracture appeared to be the direct impact onto the medial femoral condyle of a flexed knee during a fall. Similar to the other reported femoral fracture patterns, this fracture occurred through the femoral tunnel stress-riser that had been created during …

Diabetic Myonecrosis: Likely an Underrecognized Entity

Diabetic myonecrosis is a rare complication of long-standing diabetes mellitus that presents as acute onset of swelling and pain of the affected muscles. The differential diagnosis includes cellulitis/pyomyositis, necrotizing fasciitis, neoplasm, and deep venous thrombosis (DVT). Missed diagnoses can lead to unnecessary invasive diagnostic procedures and inappropriate treatment. The diagnosis is established by the clinical presentation and findings on magnetic resonance imaging (MRI) scan. A 30-year-old African-American man presented with a painful mass affecting the medial aspect of the right thigh for several months. Initial laboratory studies showed white blood cell count of 8800 cells/mm(3), D-dimer value of 0.55 µg/mL, HgBA1c level of 15.1%, glucose level of 352 mg/dL, erythrocyte sedimentation rate of 22 mm/h, and C-reactive protein level of 222 mg/L. An MRI scan was obtained, and diabetic myonecrosis was diagnosed and treated. One year later, the patient had similar symptoms of pain in the contralateral thigh. Repeat workup and MRI scan were obtained. The MRI abnormalities originally seen in the right thigh 1 year earlier were present in the left thigh, with complete resolution of the abnormalities seen in the right thigh. Treatment with bed rest and analgesics resulted in symptom resolution. Patients with diabetic myonecrosis typically have no fever, normal white blood cell count, mildly increased erythrocyte sedimentation rate, and elevated C-reactive protein level in 50% of cases. They lack the radiologic signs of fascial enhancement or well-defined, rim-enhancing collections that are seen in necrotizing fasciitis and pyomyositis/abscess. The onset of severe pain and the lack of mass effect on imaging differentiate diabetic myonecrosis from tumor-like conditions such as vascular malformations or soft tissue tumors. Normal D-dimer levels and ultrasound Doppler examination of the extremity help to rule out DVT. The typical MRI scan findings and clinical presentation can lead to the diagnosis of diabetic myonecrosis, allowing the physician to avoid invasive tests, such as muscle biopsy, and to reassure patients that this condition is self-limiting with appropriate treatment.

Treatment of Extra — Abdominal Desmoid Tumors with Chemotherapy

Fibromatosis, or extra-abdominal desmoid tumor, is a benign disease which often has an aggressive clinical course that can be difficult to treat. We performed a retrospective review of 16 patients (12 females and four males) with a mean age of 34.2 years treated with methotrexate and vinblastine for newly diagnosed or recurrent extra-abdominal desmoid tumor. The mean age of our patient cohort was 34.2 years (range 11–70), and the mean tumor size was 11.5 cm (range 2.5–21.2 cm). The mean duration of therapy was 12 months with an average follow-up of 43 months (range 1–149 months). Fourteen of 16 patients demonstrated a clinical response to treatment. Eight of 14 patients demonstrated a radiologic decrease in tumor size. Only one patient progressed on therapy. Six patients developed recurrent symptoms after discontinuation of treatment. Chemotherapy-related symptoms including neutropenia, nausea, and vomiting were common and observed in most patients, however these side effects were mild and transient. Five patients developed peripheral neuropathy that prompted a change from vinblastine to vinorelbine during treatment. One potentially life-threatening complication (pneumocystis pneumonia) occurred which was diagnosed early and successfully treated. The use of methotrexate and vinblastine/vinorelbine in the management of fibromatosis appears to be an effective treatment with minimal treatment-related side effects.

Pediatric Traumatic Amputations in the United States: A 5-Year Review.

Background: Pediatric traumatic amputations are devastating injuries capable of causing permanent physical and psychological sequelae. Few epidemiologic reports exist for guidance of prevention strategies. The objective of this study is to review the recent trends in pediatric traumatic amputations using a national databank. Methods: A review of all pediatric (age, 0 to 17 y) amputee patients was performed using the National Trauma Data Bank from 2007 to 2011. Data including demographics, location of amputation, and mechanism of injury were analyzed. Results: In the analysis 2238 patients were identified. The majority of amputations occurred in the youngest (0 to 5 y) and oldest (15 to 17 y) age groups with a 3:1 male to female ratio. The most common amputation locations were finger (54%) and toe (20%). A caught between mechanism (16.3%) was most common overall followed by machinery, powered lawn mowers, motor vehicle collisions, firearms, and off-road vehicles. Males were statistically more likely to have an amputation and lawnmower injuries were statistically associated with lower extremity amputations in children 5 years old and below. Motor vehicle injuries were the most common cause of adolescent amputations. Firearm-related amputations occurred predominantly in adolescents, whereas off-road vehicle amputations occurred in all ages. Conclusions: Common trends in pediatric amputations are relatively unchanged over the last decade. Young children sustain more finger amputations from a caught between objects mechanism, whereas adolescents sustain serious amputations from higher energy mechanisms such as firearms-related and motor vehicle–related injuries. Lawnmower-related amputations continue to most significantly affect younger children despite increased public awareness. Improved prevention strategies targeting age and mechanism-related trends are necessary to prevent these costly and debilitating injuries. Level of Evidence: Level IV.

Nutlin-3 treatment spares cisplatin-induced inhibition of bone healing while maintaining osteosarcoma toxicity

The majority of Osteosarcoma (OS) patients are treated with a combination of chemotherapy, resection, and limb salvage protocols. These protocols include distraction osteogenesis (DO), which is characterized by direct new bone formation. Cisplatin (CDP) is extensively used for OS chemotherapy and recent studies, using a mouse DO model, have demonstrated that CDP has profound negative effects on bone repair. Recent oncological therapeutic strategies are based on the use of standard cytotoxic drugs plus an assortment of biologic agents. Here we demonstrate that the previously reported CDP‐associated inhibition of bone repair can be modulated by the administration of a small molecule p53 inducer (nutlin‐3). The effects of nutlin‐3 on CDP osteotoxicity were studied using both pre‐ and post‐operative treatment models. In both cases the addition of nutlin‐3, bracketing CDP exposure, demonstrated robust and significant bone sparing activity (p < 0.01–0.001). In addition the combination of nutlin‐3 and CDP induced equivalent OS tumor killing in a xenograft model. Collectively, these results demonstrate that the induction of p53 peri‐operatively protects bone healing from the toxic effects of CDP, while maintaining OS toxicity.