Mechanically stable rifampin antibiotic cement inhibits Pseudomonas aeruginosa biofilm surface growth.

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. The null hypothesis tests if rifampin use in polymethyl methacrylate (PMMA) cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0, 30, 50, 100, 150, or 200 mg of rifampin into a standard 40 g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipopolysaccharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30 and 50 mg, showed no statistically different mechanical characteristics from control PMMA (p > 0.05). The 100-mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to the control at 12 and 24 h. The ability of PMMA with 100 mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 h makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100 mg of rifampin shows promise in the treatment and prevention of periprosthetic joint infection for total knee and total hip arthroplasty.

Graft Choice for Anterior Cruciate Ligament Reconstruction in Women Aged 25 Years and Younger: A Systematic Review.

CONTEXT: Although anterior cruciate ligament (ACL) tears are relatively common in athletic populations, few studies have systematically reviewed graft choice in young women. OBJECTIVE: To quantitatively and qualitatively examine reported outcomes for graft choice in women aged 25 years and younger undergoing primary ACL reconstruction. DATA SOURCE: A systematic review was performed using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. An electronic search in the PubMed (includes MEDLINE) and EMBASE databases was completed using a combination of key terms. STUDY SELECTION: Studies were included if they reported graft choice outcomes in women aged 25 years and younger. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 4. DATA EXTRACTION: The following information was extracted: title, author, year of publication, number of female patients and age, graft type, follow-up, and patient-reported outcome measures. The following outcome scores were identified as being reported or not reported by each study: graft failure, contralateral ACL (CACL) rupture, IKDC (International Knee Documentation Committee), graft survival (Kaplan-Meier), Lysholm, Tegner, KT-1000, kneeling pain, return to sport, and Lachman. RESULTS: Of 1170 identified articles, 16 met inclusion criteria, reporting on 1385 female patients aged 25 years and younger. Comparison of 655 bone-patellar tendon-bone (BPTB) versus 525 hamstring tendon (HT) autografts showed significant differences in mean failure rate between BPTB autografts (6.13% ± 2.58%) and HT autografts (17.35% ± 8.19%), P = 0.001. No statistically significant differences in CACL failure rates were found between BPTB autografts and HT autografts (P = 0.25). Pooled results for IKDC were possible in 3 of the HT autograft studies, showing a mean score of 88.31 (95% CI 83.53-93.08). Pooled Lysholm score results were possible in 2 of the HT autograft studies, showing a mean score of 93.46 (95% CI 91.90-95.01). CONCLUSION: In female patients aged 25 years and younger, BPTB autografts showed significantly less graft failure compared with HT autografts. However, BPTB autografts had comparable patient-reported outcomes compared with HT autografts with the available data. The overall state of evidence for graft choice in female patients aged 25 years and younger is low. Future studies should report statistics by age and sex to allow for further analysis of graft choice for this specific population that is known to be more vulnerable to ACL injury.

Surgeon and Facility Volumes Are Associated With Social Disparities and Post-Operative Complications After Total Hip Arthroplasty.

BACKGROUND: The purpose of this study is to further characterize the volume dependence of facilities and surgeons on morbidity and mortality after total hip arthroplasty (THA). METHODS: Adults who underwent THA from 2009 to 2014 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification and Procedural codes in the New York Statewide Planning and Research Cooperative System database. Complication rates were compared across surgeon and facility volumes using multivariable Cox proportional hazards regression controlling for factors such as the Social Deprivation Index. Surgeon and facility volumes were compared between the low and high volume using cutoffs established by prior research. RESULTS: In total, 99,832 patients were included. Low volume facilities had higher rates of readmission, urinary tract infection (UTI), acute renal failure, pneumonia, surgical site infection (SSI), cellulitis, wound complications, deep vein thrombosis (DVT), in-hospital mortality, and revision. Low volume surgeons had higher rates of readmission, UTI, acute renal failure, pneumonia, SSI, acute respiratory failure, pulmonary embolism, cellulitis, wound complications, in-hospital mortality, cardiorespiratory arrest, DVT, and revision. African Americans, Hispanics, and those with federal insurance had increased rates of readmission. Those with ≥1 Charlson comorbidities or from areas of higher social deprivation had increased incidence of treatment by low volume surgeons and facilities. CONCLUSION: Both low volume facilities and surgeons performing primary THA have higher rates of readmission, UTI, acute renal failure, pneumonia, SSI, cellulitis, wound complications, DVT, in-hospital mortality, and revision. Demographic disparities exist between who is treated at low vs high volume surgeons and facilities placing those groups at higher risks for complications.

GLTSCR2/PICT1 links mitochondrial stress and Myc signaling.

Mitochondrial defects underlie a multitude of human diseases. Genetic manipulation of mitochondrial regulatory pathways represents a potential therapeutic approach. We have carried out a high-throughput overexpression screen for genes that affect mitochondrial abundance or activity using flow-cytometry-based enrichment of a cell population expressing a high-complexity, concentration-normalized pool of human ORFs. The screen identified 94 candidate mitochondrial regulators including the nuclear protein GLTSCR2, also known as PICT1. GLTSCR2 enhances mitochondrial function and is required for the maintenance of oxygen consumption, consistent with a pivotal role in the control of cellular respiration. RNAi inactivation of the Caenorhabditis elegans ortholog of GLTSCR2 reduces respiration in worms, indicating functional conservation across species. GLTSCR2 controls cellular proliferation and metabolism via the transcription factor Myc, and is induced by mitochondrial stress, suggesting it may constitute a significant component of the mitochondrial signaling pathway.