Arthroplasty for Treating Proximal Femur Metastatic Lesions May Be Associated with Lower Mortality Rates Compared to Intramedullary Nailing within the VA Healthcare System.

Metastatic bony disease is a significant health issue, with approximately 700,000 new cases annually that tend to metastasize to bones. The proximal femur in the appendicular skeleton is commonly affected. Our study aimed to investigate mortality rates and hospital stay duration in patients with pathologic proximal femur fractures treated with either intramedullary nailing or arthroplasty within the Veterans Health Administration system. In total, 679 patients (265 arthroplasty, 414 intramedullary nails) were identified through ICD-9 and CPT codes from 30 September 2010 to 1 October 2015. Hospital stays were similar for both groups (arthroplasty: 10.5 days, intramedullary nails: 11 days, p = 0.1). Mortality was associated with increased age and Gagne comorbidity scores (p < 0.001). Arthroplasty showed a survival benefit in the log-rank test (p = 0.018), and this difference persisted in the multivariate analysis after adjusting for age and comorbidities, with a hazard ratio of 1.3. Our study reported evidence that arthroplasty is associated with increased patient survival even when accounting for age and comorbidities in treating metastatic disease of the proximal femur.

Mirels Scores in Patients Undergoing Prophylactic Stabilization for Femoral Metastatic Bone Disease in the Veterans Administration Healthcare System.

INTRODUCTION: A retrospective review was performed for patients in the Veterans Administration Healthcare System who underwent prophylactic stabilization of the femur for metastatic disease. The goal was to evaluate indications for prophylactic stabilization through Mirels criteria. METHODS: All veterans who underwent inpatient prophylactic femoral stabilization between October 2010 and September 2015 were identified. Procedure and demographic variables were collected by using chart review. Provider notes and radiographs were reviewed to calculate Mirels scores. RESULTS: Ninety-two patients underwent confirmed prophylactic stabilization for metastatic bone disease. Lung cancer and multiple myeloma accounted for most lesions. The mean Mirels score was 10.3 (range 7 to 12). 3.2% of patients had a score of 7, and 6.5% had a score of 8. Most lesions were peritrochanteric (66%) and lytic (85%). There was more variability in size (mean 2.3), with 15% being under one third of bony width and 38% between one and two-thirds. The mean pain score was 2.5; 73% reported functional pain. Of lytic and peritrochanteric lesions (53% of all cases), 55% were less than two-thirds the cortical width and 31% lacked functional pain. CONCLUSION: This retrospective study of prophylactically stabilized metastatic lesions revealed that more than 90% of patients had Mirels scores greater than 8, suggesting a substantial risk of pathologic fracture. Over half of all stabilized lesions were peritrochanteric and lytic. These criteria alone achieve a minimum Mirels score of 8; however, one-third of these lacked functional pain. Notably, Mirels' original paper found location and type criteria to be the least predictive of impending fracture. Contrariwise, functional pain was the most accurate predictor. Multiple studies have found poor specificity of the Mirels criteria. The high scores achievable by the location and type criteria may represent an overrepresentation of their contribution to fracture risk. Reconsideration of the relative weights of each criterion warrants further examination.

Treatment Modalities for Pathologic Fractures of the Proximal Femur Pertrochanteric Region: A Systematic Review and Meta-Analysis of Reoperation Rates.

BACKGROUND: The proximal femur represents the most common site of metastatic bone disease in the appendicular skeleton, and associated pathologic pertrochanteric femur fractures contribute to cancer-related morbidity and mortality. Controversy exists as to whether these injuries are best managed with intramedullary nailing (IMN) or with arthroplasty. METHODS: A systematic review of the literature was performed using a PubMed search following PRISMA guidelines to identify studies performed within the last 20 years regarding treatment of proximal femur metastatic lesions with either nailing or arthroplasty with a reported reoperation rate. Sixteen studies were selected for inclusion containing 1414 patients. Pooled estimates and 95% confidence intervals (CIs) for reoperation rates associated with IMN and endoprosthetic reconstruction (EPR) were separately calculated. RESULTS: The pooled estimate for reoperation for IMN was a median of 9% (95% CI, 5%-14%) and the pooled estimate for reoperation for EPR was a median of 7% (95% CI, 5%-11%). Significant heterogeneity was present in studies reporting on both treatment modalities: for IMN, I2 = 55%, and for EPR, I2 = 51%. CONCLUSION: This systematic literature review identified 16 eligible, nonrandomized, retrospective studies that reported on the results of surgical treatment for proximal femur metastatic disease. The pooled estimate of reoperation was similar between patients treated with IMN and EPR. Inconsistencies among follow-up and the study designs used limited evidence-based conclusions. As the oncologic care of patients with metastatic disease continues to evolve and improve, patient-specific needs must be carefully considered when selecting an optimal treatment strategy. LEVEL OF EVIDENCE: Level III.

Identification of Elaiophylin Skeletal Variants from the Indonesian Streptomyces sp. ICBB 9297.

Four new elaiophylin macrolides (1-4), together with five known elaiophylins (5-9), have been isolated from cultures of the Indonesian soil bacterium Streptomyces sp. ICBB 9297. The new compounds have macrocyclic skeletons distinct from those of the known dimeric elaiophylins in that one or both of the polyketide chains contain(s) an additional pendant methyl group. Further investigations revealed that 1 and 2 were derived from 3 and 4, respectively, during isolation processes. Compounds 1-3 showed comparable antibacterial activity to elaiophylin against Staphylococcus aureus. However, interestingly, only compounds 1 and 3, which contain a pendant methyl group at C-2, showed activity against Mycobacterium smegmatis, whereas compound 2, which has two pendant methyl groups at C-2 and C-2', and the known elaiophylin analogues (5-7), which lack pendant methyl groups at C-2 and/or C-2', showed no activity. The production of 3 and 4 in strain ICBB 9297 indicates that one of the acyltransferase (AT) domains in the elaiophylin polyketide synthases (PKSs) can recruit both malonyl-CoA and methylmalonyl-CoA as substrates. Bioinformatic analysis of the AT domains of the elaiophylin PKSs revealed that the ela_AT7 domain contains atypical active site amino acid residues, distinct from those conserved in malonyl-CoA- or methylmalonyl-CoA-specific ATs.