Injective Treatments for Sacroiliac Joint Pain: A Systematic Review and Meta-analysis.

Background: The most effective injective treatment approach for sacroiliac joint (SIJ) pain remains unclear. Aim of this study was to quantify the safety and effectiveness of the available injective strategies to address SIJ pain. Methods: A systematic review and meta-analysis of the literature was conducted on PubMed, Scopus, and Embase databases from inception until January 2023. Inclusion criteria were studies written in English, comparative and non-comparative studies regardless of the minimum follow-up, and case series on SIJ injections. Safety and efficacy of the different injection therapies for the SIJ were quantified. A meta-analysis was conducted on the available data of the documented injective therapies. The "Checklist for Measuring Quality" by Downs and Black was used to assess the risk of bias and the quality of papers. Results: The literature search retrieved 43 papers (2431 patients): 16 retrospective case series, 2 retrospective comparative studies, 17 prospective case series, 3 prospective comparative studies, and 5 randomized controlled trials. Of the selected studies, 63% examined the effect of steroid injections, 16% of PRP injections, while 21% reported other heterogeneous treatments. The failure rate was 26% in steroid injections and 14% in PRP injections. The meta-analysis showed a statistically significant reduction in pain with the VAS score for both steroids and PRP: steroids improvement at mid-term 3.4 points (p < 0.05), at long-term 3.0 (p < 0.05), PRP improvement at mid-term 2.2 (p = 0.007), at long-term 2.3 points of the VAS pain scale (p = 0.02). Conclusions: Steroids are the most documented injective approach, with studies showing an overall safety and effectiveness. Still, the high number of failures underlined by some studies suggest the need for alternative procedures. Early PRP data showed promise, but the limitations of the current literature do not allow to clearly define the most suitable injective approach, and further studies are needed to identify the best injective treatment for SIJ patients.

Exercise training and atrial fibrillation: a systematic review and literature analysis.

OBJECTIVE: There are concerns in maintaining adequate levels of physical activity in patients with atrial fibrillation (AF). This could be related to the type of exercise delivered, different among studies, as the words used to describe it as treatment. We have analysed the state-of-art of the role of the exercise in AF by a mathematical analysis. This analysis documented the connections between topics and updated the available evidence through a systematic review of the current literature. MATERIALS AND METHODS: A literature search was conducted using specific terms for studies published between 2000 and 2019. For the descriptive analysis of the current literature, we used the LExical Network analysed by the Graph THeory (LENGTH) method, while to perform our review we followed the PRISMA statement. Downs and Black Quality Index was also used to assess the quality of studies. The LENGTH approach indicated nonspecific terms as "exercise", "physical" and "activity" as more representative than "rehabilitation" to describe the intervention. RESULTS: The systematic review identified nine studies on 882 patients of moderate (n=4) to good (n=5) quality. Training consisted of a combination of supervised ambulatory and home-based outpatient programs, focused on aerobic elements (endurance and resistance training, walking, treadmill and bicycle ergometer). Significant improvements in 6-minute walking test distance and peak oxygen uptake and in quality of life were obtained, with high adherence to training and no serious/significant adverse events. Only one trial was based on cardiac rehabilitation principles. CONCLUSIONS: Adequate exercise training can get a favourable cardiovascular outcome in patients with AF.

Biosynthetic scaffolds for partial meniscal loss: A systematic review from animal models to clinical practice.

Acute or degenerative meniscus tears are the most common knee lesions. Meniscectomy provides symptomatic relief and functional recovery only in the short- to mid-term follow-up but significantly increases the risk of osteoarthritis. For this reason, preserving the meniscus is key, although it remains a challenge. Allograft transplants present many disadvantages, so during the last 20 years preclinical and clinical research focused on developing and investigating meniscal scaffolds. The aim of this systematic review was to collect and evaluate all the available evidence on biosynthetic scaffolds for meniscus regeneration both in vivo and in clinical studies. Three databases were searched: 46 in vivo preclinical studies and 30 clinical ones were found. Sixteen natural, 15 synthetic, and 15 hybrid scaffolds were studied in vivo. Among them, only 2 were translated into clinic: the Collagen Meniscus Implant, used in 11 studies, and the polyurethane-based scaffold Actifit®, applied in 19 studies. Although positive outcomes were described in the short- to mid-term, the number of concurrent procedures and the lack of randomized trials are the major limitations of the available clinical literature. Few in vivo studies also combined the use of cells or growth factors, but these augmentation strategies have not been applied in the clinical practice yet. Current solutions offer a significant but incomplete clinical improvement, and the regeneration potential is still unsatisfactory. Building upon the overall positive results of these "old" technologies to address partial meniscal loss, further innovation is urgently needed in this field to provide patients better joint sparing treatment options.

Patient-specific meniscus prototype based on 3D bioprinting of human cell-laden scaffold.

OBJECTIVES: Meniscal injuries are often associated with an active lifestyle. The damage of meniscal tissue puts young patients at higher risk of undergoing meniscal surgery and, therefore, at higher risk of osteoarthritis. In this study, we undertook proof-of-concept research to develop a cellularized human meniscus by using 3D bioprinting technology. METHODS: A 3D model of bioengineered medial meniscus tissue was created, based on MRI scans of a human volunteer. The Digital Imaging and Communications in Medicine (DICOM) data from these MRI scans were processed using dedicated software, in order to obtain an STL model of the structure. The chosen 3D Discovery printing tool was a microvalve-based inkjet printhead. Primary mesenchymal stem cells (MSCs) were isolated from bone marrow and embedded in a collagen-based bio-ink before printing. LIVE/DEAD assay was performed on realized cell-laden constructs carrying MSCs in order to evaluate cell distribution and viability. RESULTS: This study involved the realization of a human cell-laden collagen meniscus using 3D bioprinting. The meniscus prototype showed the biological potential of this technology to provide an anatomically shaped, patient-specific construct with viable cells on a biocompatible material. CONCLUSION: This paper reports the preliminary findings of the production of a custom-made, cell-laden, collagen-based human meniscus. The prototype described could act as the starting point for future developments of this collagen-based, tissue-engineered structure, which could aid the optimization of implants designed to replace damaged menisci.Cite this article: G. Filardo, M. Petretta, C. Cavallo, L. Roseti, S. Durante, U. Albisinni, B. Grigolo. Patient-specific meniscus prototype based on 3D bioprinting of human cell-laden scaffold. Bone Joint Res 2019;8:101-106. DOI: 10.1302/2046-3758.82.BJR-2018-0134.R1.

Low rate of return to pre-injury sport level in athletes after cartilage surgery: a 10-year follow-up study.

PURPOSE: Although articular surface is frequently damaged in athletes, results in terms of return to sport and level of activity after cartilage surgery remain rather unpredictable and poorly documented. The aim of this study is to evaluate the clinical outcome in terms of rate and level of return to sport in a group of competitive athletes who underwent matrix-assisted autologous chondrocyte transplantation (MACT), as well as the impact on their athletic career. METHODS: Thirty-one male patients (mean age 22.6 ± 6.3 years) p racticing sport at competitive level, affected by focal chondral/osteochondral lesions of the distal femur, were enrolled and treated with arthroscopic hyaluronan-based MACT. Patients were evaluated prospectively at 1-year intervals with the IKDC subjective, Tegner, and EuroQol VAS scores during their pre-operative visit and subsequent follow-ups for up to 10 years. Return to sport in terms of level, time and maintenance of the activity level was documented, together with surgical or clinical failures. RESULTS: A marked improvement in all scores was found: IKDC increased from 40.3 ± 13.4 to 81.7 ± 14.4 (p < 0.0005) at 12 months; a further improvement was observed at 2 years (89.5 ± 11.3; p = 0.008), then results were stable for up to 10 years (87.3 ± 13.6). The analysis of return to sport documented that 64.5% of patients were able to return at a competitive level, and 58.1% performed at the same pre-injury level, with activity rates decreasing over time. The rate of patients returning to competitive level was 84% in those without previous surgery (vs. 33% who had undergone previous surgery), 87% for those with traumatic lesions (vs. 33% and 50% for degenerative and OCD lesions, respectively), and 92.3% in younger patients (age < 20 years). Among these factors, multivariate analysis demonstrated that previous surgery was the single most influencing factor for returning to the same sport level (p = 0.010). CONCLUSIONS: These long-term results showed that chondrocyte-based regenerative approach has some limitations in terms of sport-related outcomes. The level of high functional knee restoration needed for such high-demanding activity level can be challenging to achieve, especially in patients with a more compromised joint homeostasis. Return to sport rate varies significantly according to specific patient and lesion characteristics and best results are obtained in young patients with traumatic lesions without previous surgery, which should be considered when treating athletes affected by cartilage lesions. LEVEL OF EVIDENCE: IV.

An algorithm to avoid missed open-book pelvic fractures.

OBJECTIVE: In polytrauma patients, to limit the pelvic space favouring internal bleeding, the use of pelvic binders is now a standard practice. In case of external pelvic binder placement with anatomic reduction of the symphyseal and sacroiliac joints, delayed diagnosis and missed injuries could occur. The aim of this study is to document the risk of missed diagnosis, as well as to identify a possible algorithm for optimal management of traumatized patients with pelvic binders, in order to reach an early diagnosis of pelvic fractures without additional risks. CASE REPORT: We report three cases of open-book pelvic fractures that were initially missed. The external pelvic binders applied had adequately reduced the fractures. The computed tomography on arrival excluded a diastasis of the symphysis pubis. On removal of the pelvic binder and repetition of the radiological imaging, the fractures were evidenced. CONCLUSIONS: We have accordingly created an algorithm for polytrauma patients to determine when the pelvic binder should be released before radiological imaging and when repeated radiological imaging should be done. The use of this algorithm in trauma centers will help to reduce the number of missed injuries, and the number of late diagnoses as well as will increase the patient survival rates.

Cultures of a human synovial cell line to evaluate platelet-rich plasma and hyaluronic acid effects.

Synovial inflammation plays an important role in osteoarthritis (OA) pathogenesis. Different biological compounds have been tested mainly on chondrocytes, to treat early stages of OA. However, because OA has been recently defined as "an organ" pathology, investigation on synoviocytes is also needed. Therefore, the aim of the present study was to validate a human fibroblast-like synoviocytes cell line (K4IM) to test the effects of platelet-rich plasma (PRP) and hyaluronan (HA) on anabolic and catabolic gene expression and on HA secretion from cell cultures. In order to determine the effect of PRP and HA, K4IM cells were maintained in culture with or without TNF-α stimulation. In the presence of PRP, unstimulated K4IM cells presented the same expression of IL1B, IL6, CXCL8, VEGF, TIMP1, and hyaluronic synthase isoform HAS3 as primary human synoviocytes, while HA addition did not change their expression pattern, which was similar to control cells. Stimulated cells expressed significantly higher values of IL1B, CXCL8, and VEGF compared with unstimulated ones. PRP did not show any modification, except for VEGF, while HA addition modulated IL1B expression. PRP did not modulate HA release of both stimulated and unstimulated cells. Our study showed the possibility to use K4IM synoviocytes as an in vitro model to test biological compounds useful for the treatment of early OA. Primary cells reflect the phenotype of cells in vivo, but limited recovery from biopsies and restricted lifespan makes experimental manipulation challenging. Therefore, despite cell lines present some limitations, they could be used as an alternative for preliminary experiments.

No evidence for combining cartilage treatment and knee osteotomy in osteoarthritic joints: a systematic literature review.

PURPOSE: To assess whether the combination of HTO and cartilage treatment produced an additional clinical benefit compared to HTO alone. The secondary aim was to identify if there was any difference among different cartilage procedures in terms of healing potential and clinical outcome. METHODS: A systematic review of the literature was performed on PubMed database by three independent observers according to the following inclusion criteria: clinical reports of any level of evidence, written in the English language, with no time limitation, about HTO associated with cartilage surgical and injective treatment, including surveys reporting clinical, radiological, or second-look outcomes at any follow-up time. RESULTS: The database search identified 1956 records: 21 studies were included for the final analysis, for a total of 1068 patients; 10 case series and 11 comparative studies. While overall good results were reported in the case series, the analysis of the comparative studies showed less uniform results. Among the eight studies investigating HTO with cartilage surgical procedures, improved tissue regeneration was found in 5/8 studies, whereas a clinical improvement was reported only in two studies. Three studies on HTO combination with injective treatment showed better tissue regeneration and clinical benefit. CONCLUSIONS: Literature presents low-quality studies, with only few heterogeneous comparative papers. While surgical treatments targeting only the cartilage layer did not achieve clinical improvements, injective treatments targeting the overall joint environment showed promising findings. This prompts further research towards the development of treatments able to improve knee osteotomies outcomes. However, until new evidence will prove otherwise, there is no indication for a combined cartilage treatment in routine clinical practice. LEVEL OF EVIDENCE: Level IV.

Implant strategy affects scaffold stability and integrity in cartilage treatment.

PURPOSE: To identify the most appropriate implantation strategy for a novel chondral scaffold in a model simulating the early post-operative phase, in order to optimize the implant procedure and reduce the risk of early failure. METHODS: Eight human cadaveric limbs were strapped to a continuous passive motion device and exposed to extension-flexion cycles (0°-90°). Chondral lesions (1.8 cm diameter) were prepared on condyles, patella and trochlea for the implant of a bi-layer collagen-hydroxyapatite scaffold. The first set-up compared four fixation techniques: press-fit (PF) vs. fibrin glue (FG) vs. pins vs. sutures; the second compared circular and square implants; the third investigated stability in a weight-bearing simulation. The scaffolds were evaluated using semi-quantitative Drobnic and modified Bekkers scores. RESULTS: FG presented higher total Drobnic and Bekkers scores compared to PF (both p = 0.002), pins (p = 0.013 and 0.001) and sutures (p = 0.001 and < 0.0005). Pins offered better total Drobnic and Bekkers scores than PF in the anterior femoral condyles (p = 0.007 and 0.065), similar to FG. The comparison of round and square implants applied by FG showed worst results for square lesions (Drobnic score p = 0.049, Bekkers score p = 0.037). Finally, load caused worst overall results (Drobnic p = 0.018). CONCLUSIONS: FG improves the fixation of this collagen-HA scaffold regardless of lesion location, improving implant stability while preserving its integrity. Pins represent a suitable option only for lesions of the anterior condyles. Square scaffolds present weak corners, therefore, round implants should be preferred. Finally, partial weight-bearing simulation significantly affected the scaffold. These findings may be useful to improve surgical technique and post-operative management of patients, to optimize the outcome of chondral scaffold implantation.

Glycogen Synthase Kinase-3ß Inhibition Links Mitochondrial Dysfunction, Extracellular Matrix Remodelling and Terminal Differentiation in Chondrocytes.

Following inflammatory stimuli, GSK3 inhibition functions as a hub with pleiotropic effects leading to cartilage degradation. However, little is known about the effects triggered by its direct inhibition as well as the effects on mitochondrial pathology, that contributes to osteoarthritis pathogenesis. To this aim we assessed the molecular mechanisms triggered by GSK3ß inactivating stimuli on 3-D (micromass) cultures of human articular chondrocytes. Stimuli were delivered either at micromass seeding (long term) or after maturation (short term) to explore "late" effects on terminal differentiation or "early" mitochondrial effects, respectively. GSK3ß inhibition significantly enhanced mitochondrial oxidative stress and damage and endochondral ossification based on increased nuclear translocation of Runx-2 and ß-catenin, calcium deposition, cell death and enhanced remodelling of the extracellular matrix as demonstrated by the increased collagenolytic activity of supernatants, despite unmodified (MMP-1) or even reduced (MMP-13) collagenase gene/protein expression. Molecular dissection of the underlying mechanisms showed that GSK3ß inhibition achieved with pharmacological/silencing strategies impacted on the control of collagenolytic activity, via both decreased inhibition (reduced TIMP-3) and increased activation (increased MMP-10 and MMP-14). To conclude, the inhibition of GSK3ß enhances terminal differentiation via concerted effects on ECM and therefore its activity represents a tool to keep articular cartilage homeostasis.

Adipose stromal cells mediated switching of the pro-inflammatory profile of M1-like macrophages is facilitated by PGE2: in vitro evaluation.

OBJECTIVE: To define if adipose mesenchymal stromal cell (ASC) treatment mediated switching of the pro-inflammatory profile of M1-like macrophages as a means to develop a tailored in vitro efficacy/potency test. DESIGN: We firstly performed immunohistochemical analysis of CD68, CD80 (M1-like) and CD206 (M2-like) macrophages in osteoarthritic (OA) synovial tissue. ASC were co-cultured in contact and in transwell with activated (GM-CSF + IFNγ)-M1 macrophages. We analyzed IL1ß, TNFα, IL6, MIP1α/CCL3, S100A8, S100A9, IL10, CD163 and CD206 by qRT-PCR or immunoassays. Prostaglandin E2 (PGE2) blocking experiments were performed using PGE2 receptor antagonist. RESULTS: In moderate grade OA synovium we did not always find a higher percentage of CD80 with respect to CD206. M1-like-activated macrophage factors IL1ß, TNFα, IL6, MIP1α/CCL3, S100A8 and S100A9 were down-modulated both in contact and in transwell by ASC. However, in both systems ASC induced the typical M2-like macrophage markers IL10, CD163 and CD206. Activated-M1-like macrophages pre-treated with PGE2 receptor antagonist failed to decrease secretion of TNFα, IL6 and to increase that of IL10, CD163 and CD206 when co-cultured with ASC confirming a PGE2 specific role. CONCLUSIONS: We demonstrated that ASC are responsible for the switching of activated-M1-like inflammatory macrophages to a M2-like phenotype, mainly through PGE2. This evidenced that activated-M1-like macrophages may represent a relevant cell model to test the efficacy/potency of ASC and suggests a specific role of ASC as important determinants in therapeutic dampening of synovial inflammation in OA.

Patients control preferences and results in knee arthroplasty.

PURPOSE: Patient engagement in a patient-physician decision-making process has been correlated with satisfaction and clinical outcomes. Aim of this study is to evaluate if patient control preference may also influence TKA results. METHODS: One hundred and seventy-six patients (120w-56m, age 66 ± 9 years, BMI 28 ± 4) underwent TKA and were prospectively evaluated, before surgery and at 6 and 12 months. The preoperative assessment included the Control Preference Scale (CPS) and other scales measuring psychological aspects (STAI, BDI, TSK), as well as SF12 (physical and mental subscales) and the assessment of pain and function. Pain, function, and SF12 subscales were then used to evaluate the improvement at 6- and 12-month follow-up. RESULTS: Pain, function, and SF12 scores improved at 6 and 12 months. CPS correlated with the outcome: pain and functional improvement at 6 months (p = 0.014; p = 0.003, respectively), patient function at 6 months (p = 0.022), improvement of SF12 physical subscale at 6 and 12 months (p = 0.027; p = 0.037, respectively), and satisfaction at 6 months (p = 0.033). Moreover, the multivariate analysis confirmed the importance of CPS regardless of other demographic, physical or psychological characteristics. CONCLUSION: In contrast with previous literature findings, this study shows that patients with more propensity for control presented lower improvements of pain and function than those more prone to rely on the physician making the decision. Physicians should be aware that the patient control preference may influence the treatment outcome and undertake measurements to optimize patient participation in the shared process to optimize the chances of TKA success. LEVEL OF EVIDENCE: IV.

Kinesiophobia and depression affect total knee arthroplasty outcome in a multivariate analysis of psychological and physical factors on 200 patients.

PURPOSE: To evaluate the effects of kinesiophobia on the outcomes of total knee arthroplasty (TKA), and to investigate whether kinesiophobia represents an independent factor influencing the surgery success or whether the observed effects are driven by other physical or psychological aspects such as anxiety and depression. METHODS: Two hundred patients were evaluated prospectively (mean age 65.7 ± 9.1 years, 134 women and 66 men) at 12 months after TKA. Kinesiophobia was assessed with the Tampa Scale for kinesiophobia (TSK: Activity Avoidance-TSK1 and Harm-TSK2 subscales); anxiety and depression were assessed with STAI and BDI, respectively, and preoperative pain and function, sex, age, BMI, education level, number of painful joints and years of symptoms' duration before surgery were documented as well. Results were evaluated with pain and function on 0-10 numeric rating scales, while the overall clinical outcome was documented with WOMAC and SF-12 (Physical and Mental subscales) scores. RESULTS: TSK1 was correlated with WOMAC results at 12 months (p = 0.005, ρ = 0.197). STAI (p = 0.002, ρ = 0.222), BDI (p < 0.0005, ρ = 0.307), and sex (p = 0.004) also influenced the outcome after TKA, while other parameters, such as age, BMI, education level, and number of painful joints and years of symptoms' duration before surgery, did not correlate with the clinical outcome. The multivariate analysis confirmed the role of BDI (p = 0.006, partial η 2 = 0.038), TSK1 (p = 0.011, partial η 2 = 0.033), and sex (p = 0.048, partial η 2 = 0.020), and a synergic interaction of BDI and TSK1, which together presented an even stronger correlation (p < 0.0005, partial η 2 = 0.111) with WOMAC at 12-month follow-up. CONCLUSIONS: Kinesiophobia is a factor influencing the outcome after TKA independently from other psychological and physical variables. This risk factor may affect TKA results, especially in women, and shows a further synergic interaction with depression in terms of lower surgical outcome. These findings are of clinical relevance because they show the impact of psychological factors such as kinesiophobia, and suggest the possibility of adopting co-interventions to overcome the fear of physical activity, and in the end improve patient recovery and final outcome after TKA. LEVEL OF EVIDENCE: IV.

Polyurethane-based cell-free scaffold for the treatment of painful partial meniscus loss.

PURPOSE: The aim of this study was to document, at mid-term follow-up, the clinical and MRI outcome of a polyurethane-based cell-free scaffold implanted to treat painful partial meniscus loss. METHODS: Eighteen consecutive patients were enrolled and treated with arthroscopic polyurethane meniscal scaffold implantation and, in case of other comorbidities, with concurrent surgical procedures: 16 patients (9 men and 7 women, mean age 45 ± 13 years, mean BMI 25 ± 3, 12 medial and 4 lateral implants) were prospectively evaluated with the subjective and objective IKDC and the Tegner scores at 24, 36, 48, 60, and 72 months of follow-up. Eleven patients were also evaluated by 1.5-T MRI at the final follow-up. RESULTS: The IKDC subjective score showed a significant improvement from baseline to 24 months (45.6 ± 17.5 and 75.3 ± 14.8, respectively; p = 0.02) and subsequent stable results over time for up to 72 months (final score 75.0 ± 16.8). The Tegner score improvement between pre-operative status and final follow-up was also significant (p = 0.039). Nevertheless, the final score remained significantly lower than the pre-injury sports activity level (p = 0.027). High-resolution MRIs documented the presence of abnormal findings in terms of morphology, signal intensity, and interface between the implant and the native meniscus. Implant extrusion and bone oedema at the treated compartment were also observed in most of the cases, even though no correlation was found between imaging findings and clinical outcome. CONCLUSIONS: The present study reports satisfactory clinical outcomes at mid-term follow-up after polyurethane-based meniscal cell-free scaffold implantation. The treatment was effective both in cases of isolated partial meniscal lesions and in complex cases requiring the combination with other surgical procedures. On the other hand, a high rate of altered MRI aspects was documented. However, no correlation was found between the altered imaging parameters and the overall positive clinical findings, thus supporting the use of this procedure to treat painful partial meniscus loss. LEVEL OF EVIDENCE: Case series, Level IV.

ACL rupture and joint laxity progression: a quantitative in vivo analysis.

PURPOSE: Benefits of an early reconstruction and the optimal time lapse between injury and surgery to reduce the effects of altered kinematics in ACL-deficient knees are still controversial. AIM: The aim of this study was to clarify, through a quantitative in vivo evaluation, the effects of the time lapse between ACL injury and surgery in terms of changes in the pre-operative knee laxity. METHODS: An in vivo study was performed on 99 patients who underwent ACL surgery. Just before the graft fixation, six laxity tests were performed for all the subjects at manual-maximum load: anterior-posterior displacement and internal-external rotation at 30° and 90° of knee flexion (AP30, AP90, IE30, IE90) as well as varus-valgus rotation (VV0, VV30) at 0° and 30° of flexion. Kinematics data were acquired by a navigation system. The Spearman rank correlation was used to assess correlation between rank and continuous data. Significance was set at P = 0.05. RESULTS: The analysis highlighted a significant influence of the injury-to-surgery time lapse on VV0 and AP90 compared with pre-operative laxity levels. Meniscus status also significantly affected the pre-operative laxity in the VV0 (Spearman's ρ = 0.203, P = 0.038; GLM with meniscal correction partial Î· = 0.27, P = 0.007) and AP90 (Spearman's ρ = 0.329, P = 0.001; GLM with meniscal correction partial Î· = 0.318, P = 0.017) tests. CONCLUSION: The main finding of this study is that patients with ACL rupture and a higher injury-to-surgery time present higher values of knee laxity involving AP90 displacement and VV30 rotation. Clinical relevance of the study is that ACL-deficient joint laxity, involving anterior-posterior displacement at 90° of knee flexion and varus-valgus rotation at 0° of flexion, is significantly affected by the lapse of injury-to-surgery time. This highlights the importance of considering the effects of delaying surgery when managing patients with such deficiency.

Sport and early osteoarthritis: the role of sport in aetiology, progression and treatment of knee osteoarthritis.

Sports activities are considered favourable for general health; nevertheless, a possible influence of sports practice on the development of early osteoarthritis (OA) is a cause for concern. A higher incidence of OA in knees and ankles of former high-impact sports players than in those of the normal population has been shown and it is still debatable whether the cause is either to be recognized generically in the higher number of injuries or in a joint overload. The possibility to address knee OA in its early phases may be strictly connected to the modification of specific extrinsic or intrinsic factors, related to the patient in order to save the joint from further disease progression; these include sport practice, equipment and load. Non-surgical therapies such as continuative muscles reinforce and training play a strong role in the care of athletes with early OA, particularly if professional. There is an overall agreement on the need of an early restoring of a proper meniscal, ligament and cartilage integrity in order to protect the knee and resume sports safely, whereas alignment is a point still strongly debatable especially for professional athletes. Remaining questions still to be answered are the risks of different sports in relation to one another, although an actual protective effect of low-impact sports, such as walking, swimming or cycling, has been recognized on the appearance or worsening of OA, the effect of continuing or ceasing to practice a sport on the natural history of early OA, and even following appropriate treatment is still unknown.

Regenerative approaches for the treatment of early OA.

The diagnosis and the prompt treatment of early osteoarthritis (OA) represent vital steps for delaying the onset and progression of fully blown OA, which is the most common form of arthritis, involving more than 10 % of the world's population older than 60 years of age. Nonsurgical treatments such as physiotherapy, anti-inflammatory medications, and other disease-modifying drugs all have modest and short-lasting effect. In this context, the biological approaches have recently gained more and more attention. Growth factors, blood derivatives, such as platelet concentrates, and mesenchymal adult stem cells, either expanded or freshly isolated, are advocated amongst the most promising tool for the treatment of OA, especially in the early phases. Primarily targeted towards focal cartilage defects, these biological agents have indeed recently showed promising results to relieve pain and reduce inflammation in patients with more advanced OA as well, with the final aim to halt the progression of the disease and the need for joint replacement. However, despite of a number of satisfactory in vitro and pre-clinical studies, the evidences are still limited to support their clinical efficacy in OA setting.

Patient kinesiophobia affects both recovery time and final outcome after total knee arthroplasty.

PURPOSE: To evaluate the effects of kinesiophobia on both phases immediately after surgery and the final results after total knee arthroplasty (TKA). METHODS: This study evaluated prospectively 101 patients (mean age 66 ± 8.0 years, 70 women and 31 men), 5 days after surgery, at 1, 6, 12 months, and at a mean final follow-up of 3.2 ± 0.7 years (2.0-4.2 years). Kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK: Activity Avoidance-TSK1 and Harm-TSK2 subscales), and results were evaluated with range of motion, pain and function on 0-10 numeric rating scales, WOMAC and SF-12 (Physical and Mental subscales) scores. RESULTS: TSK1 was correlated with the acute postoperative pain measured at 5 days (p = 0.031), pain measured at 12 months (p = 0.018), patient perceived function at 12 months (p = 0.025), SF-12P at 6 months (p < 0.001), SF-12P and SF-12M at 12 months (p = 0.001 and p = 0.005, respectively), and WOMAC at both 6 and 12 months of follow-up (p = 0.005 and p = 0.001). The effect of TSK 1 on the final WOMAC score was significant when corrected by age and sex (p = 0.049, η 2 = 0.041): the youngest female patients were affected even by moderate kinesiophobia levels. CONCLUSIONS: Fear of pain and even more avoidance of movement are strongly correlated both with the acute postoperative pain perception and recovery after surgery up to 1 year, thus presenting a relevant clinical impact on the outcome after TKA. Moreover, this study showed that even though at longer follow-up its impact decreases, patients with higher levels of kinesiophobia may present a poorer final outcome, especially women. LEVEL OF EVIDENCE: IV.