Mid-term clinical results of chronic cavitary long bone osteomyelitis treatment using S53P4 bioactive glass: a multi-center study

Introduction: Chronic osteomyelitis is a challenging condition in the orthopedic practice and traditionally treated using local and systemic antibiotics in a two-stage surgical procedure. With the introduction of the antimicrobial biomaterial S53P4 bioactive glass (Bonalive®), chronic osteomyelitis can be treated in a one-stage procedure. This study evaluated the mid-term clinical results of patients treated with S53P4 bioactive glass for long bone chronic osteomyelitis. Methods: In this prospective multi-center study, patients from two different university medical centers in the Netherlands were included. One-stage treatment consisted of debridement surgery, implantation of S53P4 bioactive glass, and treatment with culture-based systemic antibiotics. If required, wound closure by a plastic surgeon was performed. The primary outcome was the eradication of infection, and a secondary statistical analysis was performed on probable risk factors for treatment failure. Results: In total, 78 patients with chronic cavitary long bone osteomyelitis were included. Follow-up was at least 12 months (mean 46; standard deviation, SD, 20), and 69 patients were treated in a one-stage procedure. Overall infection eradication was 85 %, and 1-year infection-free survival was 89 %. Primary closure versus local/muscular flap coverage is the only risk factor for treatment failure. Conclusion: With 85 % eradication of infection, S53P4 bioactive glass is an effective biomaterial in the treatment of chronic osteomyelitis in a one-stage procedure. A major risk factor for treatment failure is the necessity for local/free muscle flap coverage. These results confirm earlier published data, and together with the fundamentally different antimicrobial pathways without antibiotic resistance, S53P4 bioactive glass is a recommendable biomaterial for chronic osteomyelitis treatment and might be beneficial over other biomaterials.

Does the Implementation of the PRO-IMPLANT Foundation Treatment Algorithm Improve the Outcome of Chronic Periprosthetic Knee Infections? Mid-Term Results of a Prospective Study

Background Several treatment options for chronic periprosthetic joint infections have been published in the current literature, with an on-going discussion to determine effective management algorithms. Objectives To compare outcomes of the two-stage exchange procedure in revision TKA prior to and after implementation of the PRO-IMPLANT Foundation treatment algorithm. The primary endpoints were defined as (i) revisions during the interval time, (ii) duration of the interval time and (iii) successful PJI eradication. Material and Methods Between 02/2013 and 09/2016, 122 patients were included in a single-centre cohort analysis. 55 patients were treated according to the previously used algorithm (K1) and 67 according to the PRO-IMPLANT Foundation algorithm (K2). A minimum follow-up period of 3 years was set as the inclusion criterion. Successful eradication of infection was defined in accordance with the consensus criteria by Diaz-Ledezma et al. Results Successful eradication was achieved in 42 (67%) patients in K1 and 47 (85.5%) in K2 (p ≤ 0.005). The mean interval time was 88 days (range 51 – 353) in K1 and 52 days (range 42 – 126) in K2 (p ≤ 0.005). In K1, a mean of 0.8 (range 0 – 6) revisions were necessary during the interval period compared with 0.5 (range 0 – 4) in K2 (p = 0.066). Conclusion Implementation of the PRO-IMPLANT treatment algorithm led to significant improvement in the outcome of periprosthetic joint infections. During mid-term follow-up, infection eradication was highly successful, with decreases in the interval time as well as the number of revisions.

The alpha defensin lateral flow test is effective in predicting eradication of periprosthetic joint infection after surgical debridement

The primary aim of this study was to assess the utility of the alpha defensin lateral flow (ADLF) test for predicting the eradication of PJI after surgical debridement. The secondary aim was to describe the reliability of ADLF test in diagnosis of PJI intra- operatively. A prospective observational study was conducted in three independent orthopaedic centres. Twenty-two patients undergoing revision surgery (debridement, antibiotics and implant retention (DAIR), single or two-stage revision) for PJI were recruited, 13 female and 9 male with an average age of 64 years. Samples were collected intra-operatively at the start of the first surgical procedure and then at the completion of debridement or prior to reimplantation depending on the operation performed. These samples were tested using ADLF and then sent for microbiological analysis. The ADLF result was then compared to the corresponding culture result in order to determine the diagnostic predictive accuracy. The reliability of ADLF test to predict eradication of infection after debridement of PJI was excellent for specificity and positive predictive value (PPV) of which both where 100%, but had a poor sensitivity (14.3%) and negative predictive value (NPV) (62.5%). The reliability of ADLF test to predict PJI was poor with only a 50% sensitivity and specificity. The ADLF test has a high specificity and PPV for diagnosing eradication of infection after debridement. In contrast the ADLF testing appears to have poor diagnostic accuracy for PJI when used on intra-operative samples, prior to surgical intervention. No benefits or funds were received in suppo

Sonication fluid culture of antibiotic-loaded bone cement spacer has high accuracy to confirm eradication of infection before reimplantation of new prostheses

Background Sonication fluid culture of antibiotic-loaded bone cement spacer has been used to predict reinfection of two-stage revision, but its value remains disputable. This study aims to evaluate the association between the culture result of the sonicated spacer and the status of patients with periprosthetic joint infection receiving two-stage revision. Materials and methods A comprehensive electronic literature search was performed through four databases including PubMed, Embase/Ovid, and EBSCO, and the Cochrane Library to retrieve studies in which sonication fluid culture of the antibiotic spacer was conducted before reimplantation. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the association between the culture result of sonicated spacer and prognosis of the two-stage revision. Results Eleven eligible studies comprising 603 artificial joints with PJI (134 suffering a clinical failure of two-stage revision) were included in the quantitative analysis. The pooled incidences of positive culture of sonicated spacer and intraoperative tissue were 0.14 (95% confidence interval [CI] 0.08–0.21) and 0.14 (95% CI 0.08–0.20), respectively. A positive culture of sonicated antibiotic-loaded bone cement spacer illustrated moderate sensitivity (0.31, 95% CI 0.13–0.58) but high specificity (0.94, 95% CI 0.86–0.98) for the diagnosis of therapeutic failure of two-stage revision; the pooled DOR was 7.67 (95% CI, 3.63–16.22). Meanwhile, the pooled sensitivity, specificity, and DOR of intraoperative tissue culture during the two-stage revision to predict therapeutic failure were 0.32 (95% CI, 0.20–0.47), 0.96 (95% CI, 0.92–0.98), and 10.62 (95% CI, 4.90–23.01), respectively. Conclusions Sonication fluid culture of antibiotic-loaded bone cement spacer revealed high accuracy for confirming eradication of infection before reimplantation of new prostheses and therefore could be used as a supplement for assessing therapeutic effect for PJI. However, both sonication fluid culture and intraoperative tissue culture from antibiotic-loaded bone cement spacer showed restricted yield for the prediction of a septic failure after the two-stage revision of PJI. Large-scale, prospective studies are still needed to testify current findings.

Kinetic aspects of virus targeting by nanoparticles in vivo

One of the suggested ways of the use of nanoparticles in virology implies their association with and subsequent deactivation of virions. The conditions determining the efficiency of this approach in vivo are now not clear. Herein, I propose the first kinetic model describing the corresponding processes and clarifying these conditions. My analysis indicates that nanoparticles can decrease concentration of infected cells by a factor of one order of magnitude, but this decrease itself (without feedback of the immune system) is insufficient for full eradication of infection. It can, however, induce delay in the progress of infection, and this delay can help to form sufficient feedback of the immune system.

Phylogenetic and Molecular Analyses of More Prevalent HCV1b Subtype in the Calabria Region, Southern Italy

Hepatitis C virus subtype 1b (HCV1b) is still the most prevalent subtype worldwide, with massive expansion due to poor health care standards, such as blood transfusion and iatrogenic procedures. Despite safe and effective new direct antiviral agents (DAA), treatment success can depend on resistance-associated substitutions (RASs) carried in target genomic regions. Herein we investigated transmission clusters and RASs among isolates from HCV1b positive subjects in the Calabria Region. Forty-one NS5B and twenty-two NS5A sequences were obtained by Sanger sequencing. Phylogenetic analysis was performed using the maximum likelihood method and resistance substitutions were analyzed with the Geno2pheno tool. Phylogenetic analysis showed sixteen statistically supported clusters, with twelve containing Italian sequences mixed with foreign HCV1b isolates and four monophyletic clusters including only sequences from Calabria. Interestingly, HCV1b spread has been maintained by sporadic infections in geographically limited areas and by dental treatment or surgical intervention in the metropolitan area. The L159F NS5B RAS was found in 15 isolates and in particular 8/15 also showed the C316N substitution. The Y93H and L31M NS5A RASs were detected in three and one isolates, respectively. The A92T NS5A RAS was found in one isolate. Overall, frequencies of detected NS5B and NS5A RASs were 36.6% and 22.7%, respectively. For the eradication of infection, improved screening policies should be considered and the prevalence of natural RASs carried on viral strains.

The New Frontier of Host-Directed Therapies for Mycobacterium avium Complex

Mycobacterium avium complex (MAC) is an increasingly important cause of morbidity and mortality, and is responsible for pulmonary infection in patients with underlying lung disease and disseminated disease in patients with AIDS. MAC has evolved various virulence strategies to subvert immune responses and persist in the infected host. Current treatment for MAC is challenging, requiring a combination of multiple antibiotics given over a long time period (for at least 12 months after negative sputum culture conversion). Moreover, even after eradication of infection, many patients are left with residual lung dysfunction. In order to address similar challenges facing the management of patients with tuberculosis, recent attention has focused on the development of novel adjunctive, host-directed therapies (HDTs), with the goal of accelerating the clearance of mycobacteria by immune defenses and reducing or reversing mycobacterial-induced lung damage. In this review, we will summarize the evidence supporting specific adjunctive, HDTs for MAC, with a focus on the repurposing of existing immune-modulatory agents targeting a variety of different cellular pathways. We also highlight areas meriting further investigation.

5 Osteomyelitis

Osteomyelitis is a fascinating condition that can affect all parts of the human skeleton. It presents in several distinct ways, but all have varying degrees of inflammation, systemic ill health, bone death, and soft-tissue compromise. Understanding the components of the disease and the interplay between bacteria, biofilm formation, and the host response is critical to successful treatment. Recent advances in diagnostic methods, imaging, local delivery of antimicrobials, and bone reconstruction have greatly improved the outcome for many patients. Surgery remains central to the effective treatment of chronic osteomyelitis and many acute cases. Eradication of infection is largely dependent on the skill of the surgeon in identifying the areas of dead bone and removing them during surgery. Osteomyelitis is challenging and rewarding to treat, and most patients should enjoy prolonged disease-free periods or cure. Holistic care of the patient requires close collaborative working in a multidisciplinary team including physicians, surgeons, nurses, and therapists to achieve the best outcomes.

The Role of Yersinia enterocolitica O:3 Lipopolysaccharide in Collagen-Induced Arthritis

Yersinia enterocolitica O:3 is mentioned among the most common arthritogenic pathogens. Bacterial components (including lipopolysaccharide (LPS)) may persist in the joint after eradication of infection. Having an adjuvant activity, LPS may enhance production of anticollagen antibodies, involved in the pathogenesis of rheumatoid arthritis. Furthermore, its ability to activate complement contributes to the inflammation. The aim of this work was to investigate whether Yersinia LPS (coinjected with collagen) is associated with arthritis progression or other pathological effects and to elucidate the mechanism of this association. It was demonstrated that murine mannose-binding lectin C (MBL-C) recognizes the inner core heptoses of the Rd1 chemotype LPS of Yersinia. In addition, the Rd1 LPS activates the MBL-associated serine protease 1 (MASP-1) stronger than the S and Ra chemotype LPS and comparable to Klebsiella pneumoniae O:3 LPS. However, in contrast to the latter, Yersinia Rd1 LPS was associated neither with the adjuvancity nor with the enhancement of pathological changes in animal paws/impairment of motility. On the other hand, it seemed to be more hepatotoxic when compared with the other tested endotoxins, while the enlargement of inguinal lymph nodes and drop in hepatic MBL-C expression (at the mRNA level) were independent of LPS chemotype. Our data did not suggest no greater impact Y. enterocolitica O:3 on the development or severity of arthropathy related to anticollagen antibody-induced arthritis in mice, although its interaction with MBL-C and subsequent complement activation may contribute to some adverse effects.