Background and purposeFungal prosthetic joint infections are rare and difficult to treat. This systematic review was conducted to determine outcome and to give treatment recommendations.Patients and methodsAfter an extensive search of the literature, 164 patients treated for fungal hip or knee prosthetic joint infection (PJI) were reviewed. This included 8 patients from our own institutions.ResultsMost patients presented with pain (78%) and swelling (65%). In 68% of the patients, 1 or more risk factors for fungal PJI were found. In 51% of the patients, radiographs showed signs of loosening of the arthroplasty. Candida species were cultured from most patients (88%). In 21% of all patients, fungal culture results were first considered to be contamination. There was co-infection with bacteria in 33% of the patients. For outcome analysis, 119 patients had an adequate follow-up of at least 2 years. Staged revision was the treatment performed most often, with the highest success rate (85%).InterpretationFungal PJI resembles chronic bacterial PJI. For diagnosis, multiple samples and prolonged culturing are essential. Fungal species should be considered to be pathogens. Co-infection with bacteria should be treated with additional antibacterial agents.We found no evidence that 1-stage revision, debridement, antibiotics, irrigation, and retention (DAIR) or antifungal therapy without surgical treatment adequately controls fungal PJI. Thus, staged revision should be the standard treatment for fungal PJI. After resection of the prosthesis, we recommend systemic antifungal treatment for at least 6 weeks—and until there are no clinical signs of infection and blood infection markers have normalized. Then reimplantation can be performed.

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro's and con's should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or coagulase negative). If DAIR treatment is unsuccessful, the following treatment option should be based on the patient health status and his or her expectations. For the best functional outcome, one-or two-stage revision should be performed after DAIR failure. In conclusion, DAIR is the obvious choice for treatment of acute PJI, with good success rates in selected patients. Key words: Arthroplasty; Prosthesis; Infection; Periprosthetic joint infection; Retention; Debridement antibiotics and implant retention; Debridement; Acute Core tip: Acute periprosthetic joint infection (PJI) is a major complication after total joint arthroplasty, and occurs either postoperatively or via hematogenous spreading. Debridement, antibiotics and implant retention (DAIR), the primary treatment for acute PJI, should be performed as soon as possible after the development of symptoms, and has success rates around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. Sys- REVIEW

Controlled biomaterial-based corticosteroid release might circumvent multiple injections and the accompanying risks, such as hormone imbalance and muscle weakness, in osteoarthritic (OA) patients. For this purpose, microspheres were prepared from an amino acid-based polyester amide (PEA) platform and loaded with triamcinolone acetonide (TAA). TAA loaded microspheres were shown to release TAA for over 60days in PBS. Furthermore, the bioactivity lasted at least 28days, demonstrated by a 80-95% inhibition of PGE production using TNFα-stimulated chondrocyte culture, indicating inhibition of inflammation. Microspheres loaded with the near infrared marker NIR780-iodide injected in healthy rat joints or joints with mild collagenase-induced OA showed retention of the microspheres up till 70days after injection. After intra-articular injection of TAA-loaded microspheres, TAA was detectable in the serum until day seven. Synovial inflammation was significantly lower in OA joints injected with TAA-loaded microspheres based on histological Krenn scores. Injection of TAA-loaded nor empty microspheres had no effect on cartilage integrity as determined by Mankin scoring. In conclusion, the PEA platform shows safety and efficacy upon intra-articular injection, and its extended degradation and release profiles compared to the currently used PLGA platforms may render it a good alternative. Even though further in vivo studies may need to address dosing and readout parameters such as pain, no effect on cartilage pathology was found and inflammation was effectively lowered in OA joints.

In the future it will be important to determine the exact mechanism of action of placebo as this may give us an idea of how to treat osteoarthritis more efficiently. Due to the limitations of this review (follow-up of just 3 months and large heterogeneity of the included studies), it is also important to compare the different HA products to determine which product(s), or which molecular weight range, concentration, or volume of HA is the best option to treat osteoarthritis. Our recommendation is to start large (multicenter) RCTs to give us more evidence about the efficacy of the different HA products.

BackgroundAlthough intra-articular hyaluronic acid is well established as a treatment for osteoarthritis of the knee, its use in hip osteoarthritis is not based on large randomized controlled trials. There is a need for more rigorously designed studies on hip osteoarthritis treatment as this subject is still very much under debate.Methods/DesignRandomized, controlled trial with a three-armed, parallel-group design. Approximately 315 patients complying with the inclusion and exclusion criteria will be randomized into one of the following treatment groups: infiltration of the hip joint with hyaluronic acid, with a corticosteroid or with 0.125% bupivacaine.The following outcome measure instruments will be assessed at baseline, i.e. before the intra-articular injection of one of the study products, and then again at six weeks, 3 and 6 months after the initial injection: Pain (100 mm VAS), Harris Hip Score and HOOS, patient assessment of their clinical status (worse, stable or better then at the time of enrollment) and intake of pain rescue medication (number per week). In addition patients will be asked if they have complications/adverse events. The six-month follow-up period for all patients will begin on the date the first injection is administered.DiscussionThis randomized, controlled, three-arm study will hopefully provide robust information on two of the intra-articular treatments used in hip osteoarthritis, in comparison to bupivacaine.Trial registrationNCT01079455