The importance of plasmin for the healing of the anterior cruciate ligament.

AIMS: The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily. Plasmin has been identified as a major component in the synovial fluid that varies among patients. The aim of this study was to test whether plasmin, a component of synovial fluid, could be a main factor responsible for the poor wound healing capacity of the ACL. METHODS: The effects of increasing concentrations of plasmin (0, 0.1, 1, 10, and 50 µg/ml) onto the wound closing speed (WCS) of primary ACL-derived ligamentocytes (ACL-LCs) were tested using wound scratch assay and time-lapse phase-contrast microscopy. Additionally, relative expression changes (quantitative PCR (qPCR)) of major LC-relevant genes and catabolic genes were investigated. The positive controls were 10% fetal calf serum (FCS) and platelet-derived growth factor (PDGF). RESULTS: WCS did not differ significantly among no plasmin versus each of the tested concentrations (six donors). The positive controls with PDGF and with FCS differed significantly from the negative controls. However, we found a trend demonstrating that higher plasmin concentrations up-regulate the expression of matrix metalloproteinase 13 (MMP13), 3 (MMP3), and tenomodulin (TNMD). CONCLUSION: The clinical relevance of this study is the possibility that it is not solely the plasmin, but also additional factors in the synovial fluid of the knee, that may be responsible for the poor healing capacity of the ACL.Cite this article: Bone Joint Res 2020;9(9):543-553.

Periprosthetic Infection: Major Cause of Early Failure of Primary and Revision Total Knee Arthroplasty.

Revision total knee arthroplasty (RTKA) represents an effective treatment for failed TKA, but with less favorable outcomes. Considering the technical complexity and economic burden of RTKA procedures, it is mandatory to investigate current mechanisms and predictors for RTKA failure. The objective of this study is to evaluate the survivorship and determine the predominant causes of failure of RTKA. A total of 146 patients undergoing RTKA between 2003 and 2013 were identified from the institutional database. Revision was defined as surgery in which the whole prostheses (inlay and both femoral and tibial components) required exchange. Median follow-up was 6.3 ± 2.7 years (range: 2.2-10). Patient demographics, year of primary implantation, reasons for revision surgery, implant type, pain, knee mobility, systemic or local postoperative complications, and treatment of the complications were recorded and evaluated. Infection was a major cause of failure followed by aseptic loosening, instability, pain, malalignment, and inlay wear. Following RTKA, Knee Society Score (KSS) (knee score and functional score) demonstrated a significant improvement (p < 0.05). No significant difference in flexion, extension deficit, and KSS was detected between aseptic and septic primary TKAs preoperatively and following first RTKA. Reinfection rate of the septic primary TKAs was 5%. Infection was the major cause of a second revision, reaching as high as 50% in all cases. The results of this study support that septic failure of a primary TKA is likely to occur within the first 2 years following implantation. Septic failure of primary TKA does not influence survival of the revision prosthesis.

The cement prosthesis-like spacer: an intermediate halt on the road to healing.

BACKGROUND: Periprosthetic infections remain a devastating problem in the field of joint arthroplasty. In the following study, the results of a two-stage treatment protocol for chronic periprosthetic infections using an intraoperatively molded cement prosthesis-like spacer (CPLS) are presented. METHODS: Seventy-five patients with chronically infected knee prosthesis received a two-stage revision procedure with the newly developed CPLS between June 2006 and June 2011. Based on the microorganism involved, patients were grouped into either easy to treat (ETT) or difficult to treat (DTT) and treated accordingly. Range of motion (ROM) and the knee society score (KSS) were utilized for functional assessment. RESULTS: Mean duration of the CPLS implant in the DTT group was 3.6 months (range 3-5 months) and in the ETT group 1.3 months (range 0.7-2.5 months). Reinfection rates of the final prosthesis were 9.6% in the ETT and 8.3% in the DTT group with no significant difference between both groups regarding ROM or KSS (P = 0.87, 0.64, resp.). CONCLUSION: The results show that ETT patients do not necessitate the same treatment protocol as DTT patients to achieve the same goal, emphasizing the need to differentiate between therapeutic regimes. We also highlight the feasibility of CLPS in two-stage protocols.

Absence of paraneoplastic antineuronal antibodies in sera of 145 patients with motor neuron disease.

BACKGROUND: Well characterised antineuronal antibodies (ANAbs) have been shown to be highly specific markers of neurological syndromes with a paraneoplastic aetiology. Previous reports indicate that pure motor neuron disease (MND) is rarely of paraneoplastic origin. OBJECTIVE: To screen systematically for the prevalence of well characterised paraneoplastic ANAbs in a large collective of patients with pure MND. METHODS: In a cohort of 145 patients with MND, the frequency of ANAbs was estimated by ELISA, employing recombinant antigens (HuD, Yo, Ri, CV2/CRMP5, Ma2 and amphiphysin). RESULTS: None of the sera revealed high antineuronal antigen reactivity. Very low reactivity was detected in only five sera, in all probability representing background activity. CONCLUSION: According to these data, routine analysis for ANAbs in patients with isolated MND is not mandatory.

Specific antibody index in cerebrospinal fluid from patients with central and peripheral paraneoplastic neurological syndromes.

We evaluated the concentration of antineuronal antibodies in paired cerebrospinal fluid (CSF) and serum samples from 19 patients with central and peripheral paraneoplastic neurological syndromes (PNS), using an enzyme linked immunosorbent assay (ELISA) employing recombinant antineuronal antigens (HuD, Yo, Ri, CV2/CRMP5, amphiphysin, PNMA2/Ma2). The specific antibody index (AI) [Qspec/QIgG] was calculated to estimate specific intrathecal antibody synthesis. An AI>1.3 was considered as evidence of intrathecal specific antibody synthesis. 14 (88%) of 16 patients with exclusive or predominant paraneoplastic involvement of the central nervous system (CNS) showed an AI>1.3, indicating a specific intrathecal antibody synthesis, while all three patients with isolated involvement of the peripheral nervous system showed an AI<0.8. All together, in 17 of 19 patients (89%) we found a significant association (p<0.05) between central or peripheral neurological manifestations on the one hand and presence or absence of specific intrathecal synthesis respectively on the other hand. These data support the hypothesis that autoimmunity is involved in the pathogenesis of PNS.