No abstract

Bone healing is a complicated process of tissue regeneration that is influenced by multiple biological and biomechanical processes. In a minority of cases, these physiological processes are complicated by issues such as nonunion and/or fracture-related infection (FRI). Based on a select few in vivo experimental animal studies, construct stability is considered an important factor influencing both prevention and treatment of FRI. Stephan Perren played a pivotal role in the evolution of our current understanding of the critical relationship between biomechanics, fracture healing and infection. Furthermore, his concept of strain theory and the process of fracture healing is familiar to several generations of surgeons and has influenced implant development and design for the past 50 years. In this review we describe the role of biomechanical stability on fracture healing, and provide a detailed analysis of the preclinical studies addressing this in the context of FRI. Furthermore, we demonstrate how Perren's concepts of stability are still applied to current surgical techniques to aid in the prevention and treatment of FRI. Finally, we highlight the key knowledge gaps in the underlying basic research literature that need to be addressed as we continue to optimize patient care.

Introduction: Acetabular dysplasia is a multifactorial condition characterized by a shallow hip socket with predisposition to osteoarthritis of the hip. The Bernese periacetabular osteotomy (PAO), developed by Reinhold Ganz in 1984, reorients the dysplastic hip joint to provide more uniform coverage of the femoral head and to extend the longevity of the native hip. Since 1987, the senior author performed the Bernese PAO on more than 430 patients. We performed a cross-sectional retrospective study on this cohort of patients to determine the 10- and 20-year survivorship after PAO in addition to assessing functional outcomes and radiographic parameters. Methods: Four hundred thirty-four patients were treated for acetabular dysplasia with PAO by the senior surgeon from 1987 to 2014. Data were obtained for 302 hips in 258 patients in a retrospective fashion from medical records and/or mail-in/phone questionnaires. Functional outcome data consisted of postoperative Hip Osteoarthritis Outcome Score and University of California-Los Angeles Activity Score. Pre- and postoperative radiographs were used to determine lateral center-edge angle, anterior center-edge angle, Tönnis angle/grade, and head-to-ilioischial line distance. Survivorship of the native hip was determined by Kaplan-Meier analysis. Results: Of the 302 hips analyzed, 248 were still surviving native hips and 54 had gone on to a total hip arthroplasty (THA) at the time of data acquisition. The average age of patients in the entire cohort at PAO was 32.7 years (range, 13 to 63 years). Of the 258 patients, 215 were female patients (83.3%) and 43 male patients (16.8%). The average age of patients in the surviving group at PAO was 32.3 years, and the average age of patients in the THA group was 36.6 years (P < 0.01). At the time of data acquisition, follow-up ranged from 2 to 27 years (average, 11.2 years). Hip Osteoarthritis Outcome Score and University of California-Los Angeles Activity Score are reported for the surviving native hips after PAO. Radiographic analyses for surviving and failed hips are described, with pre- and postoperative Tönnis grade being statistically significant predictors for conversion to THA (P < 0.01). Survivorship of the native hip was 86% at 10 years and 60% at 20 years in the surviving cohort. Survivorship stratified by age at the time of PAO demonstrated a 10-year survivorship of 93.3%, 90.1%, 81.6%, and 63.2% at ages 20, 30, 40, and 50 years, respectively. No notable difference exists in survivorship between male and female patients; however, male patients had a trend toward lower survivorship compared with female patients at 15 years. Conclusion: The 10- and 20-year survivorship of the native hip after PAO is approximately 86% and 60%, respectively, in our cohort of 302 hips. Older age at the time of PAO and higher Tönnis grade are negative prognostic factors for joint survival after PAO. Surviving hips after PAO have good functional outcomes even up to 20 years after surgery. This survivorship analysis represents one of the largest and longest survival studies of patients after PAO, and our results are consistent with other published studies. Level of Evidence: Level III

Implantable orthopedic devices have had an enormously positive impact on human health; however, despite best practice, patients are prone develop orthopedic device-related infections (ODRI) that have high treatment failure rates. One barrier to the development of improved treatment options is the lack of an animal model that may serve as a robust preclinical assessment of efficacy. We present a clinically relevant large animal model of chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI that persists despite current clinical practice in medical and surgical treatment at rates equivalent to clinical observations. Furthermore, we showed that an injectable, thermo-responsive hyaluronic acid-based hydrogel loaded with gentamicin and vancomycin outperforms current clinical practice treatment in this model, eliminating bacteria from all animals. These results confirm that local antibiotic delivery with an injectable hydrogel can dramatically increase treatment success rates beyond current clinical practice, with efficacy proven in a robust animal model.

HCV was shed into the semen of one-third of HIV-infected MSM with recent or chronic HCV infection. Levels were plausibly sufficient to transmit HCV during unprotected anal intercourse, therefore condoms should be worn to prevent transmission.

This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM.

The success of this short-duration IFN-free treatment in early HCV infection is proof in principle that enhanced treatment responsiveness is an inherent characteristic of early HCV infection and not a function of IFN treatment itself. Future studies should now be done with more potent regimens to try to further shorten therapy. In the mean time, in clinical practice early HCV infection should be treated immediately after detection to take advantage of short-duration treatments, as well as to decrease further HCV transmission among HIV-infected MSM.

Local antimicrobial therapy is an integral aspect of treating orthopedic devicerelated infection (ODRI), which is conventionally administered via polymethylmethacrylate (PMMA) bone cement. PMMA, however, is limited by a suboptimal antibiotic release profile and a lack of biodegradability. In this study, we compare the efficacy of PMMA versus an antibiotic-loaded hydrogel in a single-stage revision for chronic methicillin-resistant Staphylococcus aureus (MRSA) ODRI in sheep. Antibiofilm activity of the antibiotic combination (gentamicin and vancomycin) was determined in vitro. Swiss alpine sheep underwent a single-stage revision of a tibial intramedullary nail with MRSA infection. Local gentamicin and vancomycin therapy was delivered via hydrogel or PMMA (n = 5 per group), in conjunction with systemic antibiotic therapy. In vivo observations included: local antibiotic tissue concentration, renal and liver function tests, and quantitative microbiology on tissues and hardware post-mortem. There was a nonsignificant reduction in biofilm with an increasing antibiotic concentration in vitro (p = 0.12), confirming the antibiotic tolerance of the MRSA biofilm. In the in vivo study, four out of five sheep from each treatment group were culture-negative. Antibiotic delivery via hydrogel resulted in 10-100 times greater local concentrations for the first 2-3 days compared with PMMA and were comparable thereafter. Systemic concentrations of gentamicin were minimal or undetectable in both groups, while renal and liver function tests were within normal limits. This study shows that a single-stage revision with hydrogel or PMMA is equally effective, although the hydrogel offers certain practical benefits over PMMA, which make it an attractive proposition for clinical use.