Development of antibiotic resistance in periprosthetic joint infection after total knee arthroplasty.

AIMS: The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown. METHODS: A review of all revision TKAs which were undertaken between 2006 and 2018 in a tertiary referral centre was performed, including all those meeting the consensus criteria for PJI, in which organisms were identified. Using a cluster analysis, three chronological time periods were created. We then evaluated the antibiotic resistance of the identified bacteria between these three clusters and the effectiveness of our antibiotic regime. RESULTS: We identified 129 PJIs with 161 culture identified bacteria in 97 patients. Coagulase-negative staphylococci (CNS) were identified in 46.6% cultures, followed by Staphylococcus aureus in 19.8%. The overall resistance to antibiotics did not increase significantly during the study period (p = 0.454). However, CNS resistance to teicoplanin (p < 0.001), fosfomycin (p = 0.016), and tetracycline (p = 0.014) increased significantly. Vancomycin had an 84.4% overall sensitivity and 100% CNS sensitivity and was the most effective agent. CONCLUSION: Although we were unable to show an overall increase in antibiotic resistance in organisms that cause PJI after TKA during the study period, this was not true for CNS. It is concerning that resistance of CNS to new antibiotics, but not vancomycin, has increased in a little more than a decade. Our findings suggest that referral centres should continuously monitor their bacteriological analyses, as these have significant implications for prophylactic treatment in both primary arthroplasty and revision arthroplasty for PJI. Cite this article: Bone Joint J 2021;103-B(6 Supple A):171-176.

Direct incorporation of mesenchymal stem cells into a Nanofiber scaffold - in vitro and in vivo analysis.

Bony defects are a common problem in musculoskeletal surgery. Replacement with autologous bone grafts is limited by availability of transplant material. Sterilized cancellous bone, while being osteoconductive, has limited osteoinductivity. Nanofiber scaffolds are currently used for several purposes due to their capability of imitating the extracellular matrix. Furthermore, they allow modification to provide functional properties. Previously we showed that electrospun nanofiber scaffolds can be used for bone tissue regeneration. While aiming to use the osteoinductive capacities of collagen type-I nanofibers we saw reduced scaffold pore sizes that limited cellular migration and thus colonization of the scaffolds. Aim of the present study was the incorporation of mesenchymal stem cells into the electrospinning process of a nanofiber scaffold to produce cell-seeded nanofiber scaffolds for bone replacement. After construction of a suitable spinning apparatus for simultaneous electrospinning and spraying with independently controllable spinning and spraying devices and extensive optimization of the spinning process, in vitro and in vivo evaluation of the resulting scaffolds was conducted. Stem cells isolated from rat femora were incorporated into PLLA (poly-l-lactide acid) and PLLA-collagen type-I nanofiber scaffolds (PLLA Col I Blend) via simultaneous electrospinning and -spraying. Metabolic activity, proliferation and osteoblastic differentiation were assessed in vitro. For in vivo evaluation scaffolds were implanted into critical size defects of the rat scull. After 4 weeks, animals were sacrificed and bone healing was analyzed using CT-scans, histological, immunhistochemical and fluorescence evaluation. Successful integration of mesenchymal stem cells into the scaffolds was achieved by iteration of spinning and spraying conditions regarding polymer solvent, spinning distance, the use of a liquid counter-electrode, electrode voltage and spinning duration. In vivo formation of bone tissue was achieved. Using a PLLA scaffold, comparable results for the cell-free and cell-seeded scaffolds were found, while the cell-seeded PLLA-collagen scaffolds showed significantly better bone formation when compared to the cell-free PLLA-collagen scaffolds. These results provide support for the future use of cell-seeded nanofiber scaffolds for large bony defects.

Are Serum Metal Ion Levels a Concern at Mid-term Followup of Revision Knee Arthroplasty With a Metal-on-metal Hinge Design?

BACKGROUND: Elevated serum levels of chromium and cobalt ions in metal-on-metal (MoM) bearing surfaces is a well-known phenomenon in THA. However, few studies have addressed this issue in complex primary and revision knee arthroplasty using a MoM hinged mechanism, and no study, to our knowledge, has investigated knees with MoM hinges in patients without megaprostheses (tumor prostheses). QUESTIONS/PURPOSES: We analyzed a series of patients who received MoM hinged revision knee prostheses and asked: (1) What are the serum metal ion levels at short-term followup? (2) Is there any correlation between metal ion levels and the Knee Society Score (KSS) at this followup? METHODS: Between 2013 and 2017, we performed 198 revision knee arthroplasties, of which 32 (17.7%) were performed with a latest-generation MoM hinge knee design. In addition, three complex primary TKAs utilizing the same design were included in this study. The device features a metal-on-polyethylene bearing with a MoM hinge. During that period, our general indications for using a hinge were single-stage and two-stage revision surgeries, revisions with large bone defects, and primary TKA with > 20° mechanical malalignment or collateral ligament insufficiency. Of the 35 patients who received this device, 23 patients (65% of the overall group who received this implant; 11 males, 12 females) were available for followup at a median of 28 months (range, 13-61 months), and the remaining 12 (35%) patients were lost to followup. Our rationale for reporting before the more typical 2-year minimum was the finding of elevated serum ion levels with unclear clinical significance. Median age at the time of surgery was 68 years (range, 52-84 years). None of the patients included in the study had other implants with MoM bearings. Serum ion levels of chromium (III) and cobalt were assessed using mass spectrometry. Ion levels > 5 ppb were considered elevated. Clinical outcome was assessed using the original KSS. RESULTS: Median chromium serum level was 6.3 ppb (range, 0.6-31.9 ppb) and median cobalt serum level was 10.5 (range, 1.0-47.5 ppb). Of the 23 patients, 16 had elevated serum ion levels. There was a moderate correlation between KSS and both chromium (p = 0.029, r = 0.445) and cobalt (p = 0.012, r = 0.502) levels. CONCLUSIONS: Elevated metal ion levels and radiolucent lines are common after surgery with this MoM hinge design at short-term followup, and we believe this finding is of great concern. Although no patient has yet been revised, these patients will be closely monitored. We recommend that serum ion analysis become a routine part of followup after any hinge TKA in an attempt to better understand the potential consequences of this phenomenon. LEVEL OF EVIDENCE: Level IV, therapeutic study.

The prevalence of a prominent anterior inferior iliac spine.

INTRODUCTION: Impingement of the prominent anterior inferior iliac spine (AIIS) against the femoral neck has recently been described as another type of impingement. The purpose of this study is to provide a distribution of AIIS types using the classification proposed by Hetsroni and thus report on the prevalence of prominent types. MATERIALS AND METHODS: A total of 400 patients were included in the study with an average age 27.3 ± 6.9 years (range 18-40). All patients received a whole-body polytrauma computer tomography (CT) scan in the emergency room (ER) upon arrival. The classification of AIIS proposed by Hetsroni et al., which describes three morphological types, was used. Type II and III were grouped as prominent types. The measurements were performed in all three planes by two examiners. RESULTS: Male to female ratio was 71:29. Type I was observed in 367 (91.7%) patients. Type II was observed in 31 (7.8%) patients and type III was observed in 2 (0.5%) patients, unilaterally. Prominent types were much more prevalent in men (10.5%) than in women (2.6%). The CT assessment demonstrated excellent intra- and interreliability (overall: 0.926, I/II: 0.906, III: 1.000). CONCLUSION: A young population demonstrates a prevalence of a prominent AIIS of 11.5%. Prominent AIIS is more common in men than in women.

Expression of MMP-9 decreases metastatic potential of Chondrosarcoma: an immunohistochemical study.

BACKGROUND: Chondrosarcoma is the second most common primary malignant bone tumor. Because of their heterogeneity, with differences in invasive and metastatic behavior, it is important to identify biological markers that will allow for a more accurate estimation of prognosis in patients with these tumors. Matrix metalloproteinases (MMP) play a crucial role in tumor progression, invasion and metastasis. The mechanism of tumor progression dependent of MMPs is complex and influences malignant transformation, angiogenesis and tumor growth at the primary and metastatic sites. The purpose of this study was to investigate immunohistochemicaly the influence of MMP-1, MMP-3, MMP-9 and MMP-13 expression on prognostic parameter in chondrosarcoma. METHODS: We investigated tissue samples of 28 patients with chondrosarcoma. Immunohistochemical staining to evaluate the expression of MMP-1, MMP-3, MMP-9 and MMP-13 was performed. Subsequently, the expression level was correlated with metastatic potential, histological grading and overall survival in patients with this neoplasm. RESULTS: In consideration of semi quantitative scoring 64% of chondrosarcoma were scored as positive for MMP-1, 46% for MMP-3, 61% for MMP-9. The specimens had shown no expression of MMP-13. High expression of MMP-9 was associated with better histological differentiation, decreased metastatic potential and favourable overall survival. No correlation was found for expression of MMP-1, MMP-3 or MMP-13. CONCLUSIONS: MMP-1, MMP-3 and MMP-9 are expressed in chondrosarcoma. Our findings suggest that the expression of MMP-9 is associated with clinical outcome parameters in chondrosarcoma.

Internal femoral component malrotation in TKA significantly alters tibiofemoral kinematics.

PURPOSE: Femoral component malrotation in total knee arthroplasty (TKA) is clinically proven to cause dissatisfaction and impaired function. This study is an attempt to characterize the tibiofemoral kinematics following femoral malrotation in posterior stabilized (PS) TKA. It was hypothesized that internal malrotation would introduce the most pronounced changes. METHODS: Six fresh-frozen cadaver specimens were mounted in a kinematic rig. Three motion patterns were applied with the native knee and following PS TKA (passive motion, open chain extension, and squatting) while infrared cameras recorded the trajectories of markers attached to femur and tibia. Three different femoral implants were tested: a conventional posterior stabilized component, and adapted components of the same implant with 5° of intrinsic external and internal rotation, respectively. RESULTS: The implantation of the PS TKA resulted in less tibial internal rotation (squat 33-70°, p < 0.05) and the medial femoral condyle shifted posteriorly especially in deep flexion (squat 84-111°, p < 0.05). Internal component malrotation caused internal rotation and abduction of the tibia in flexion (squat 33-111°, p < 0.05), an elevated (squat 43-111°, p < 0.05) and more anterior (passive 61-126°, p < 0.05) located medial femoral condyle and a lateral femoral condyle located more posterior and inferior (squat 73-111°, p < 0.05) than in the neutrally aligned TKA. External component malrotation caused only little changes under passive motion. Under a squat there was less internal rotation and more adduction to the tibia (33-111°, p < 0.05). The medial femoral condyle was moved more posterior (squat 59-97°, p < 0.05), the lateral femoral condyle more superior (squat 54-105°, p < 0.05) than in the neutrally aligned TKA. CONCLUSION: The greatest differences to the native tibiofemoral kinematics were introduced by internal rotation of the femoral component. Also neutrally and externally rotated femoral components introduce kinematic changes, but to a lesser extent. With respect to the alterations introduced to kinematics internal malrotation should be avoided when performing PS TKA.

Kinematics of mobile-bearing unicompartmental knee arthroplasty compared to native: results from an in vitro study.

INTRODUCTION: Fixed-bearing unicompartmental knee arthroplasty (UKA) closely replicates native knee kinematics. As few studies have assessed kinematics following mobile-bearing (MB) UKA, the current study aimed to investigate whether MB UKA preserves natural knee kinematics. MATERIALS AND METHODS: Seven fresh-frozen full-leg cadaver specimens were prepared and mounted in a kinematic rig that allowed all degrees of freedom at the knee. Three motion patterns, passive flexion-extension (0°-110° flexion), open-chain extension (5°-70° flexion) and squatting (30°-100° flexion), were performed pre- and post-implantation of a medial MB UKA and compared in terms of rotational and translational knee joint kinematics in the different anatomical planes, respectively. RESULTS: In terms of frontal plane rotational kinematics, MB UKA specimens were in a more valgus orientation for all motion patterns. In the axial plane, internal rotation of the tibia before and after UKA was consistent, regardless of motion task, with no significant differences. In terms of frontal plane, i.e., inferior-superior, translations, the FMCC was significantly higher in UKA knees in all flexion angles and motor tasks, except in early flexion during passive motion. In terms of axial plane, i.e., anteroposterior (AP), translations, during open-chain activities, the femoral medial condyle center (FMCC) tended to be more posterior following UKA relative to the native knee in mid-flexion and above. AP excursions of the FMCC were small in all tested motions, however. There was substantial AP translation of the femoral lateral condyle center during passive motion before and after UKA, which was significantly different for flexion angles > 38°. CONCLUSIONS: Our study data demonstrate that the kinematics of the unloaded knee following MB UKA closely resemble those of the native knee while relative medial overstuffing with UKA will result in the joint being more valgus. However, replacing the conforming and rigidly fixed medial meniscus with a mobile inlay may successfully prevent aberrant posterior translation of the medial femoral compartment during passive motion and squatting motion.

Kinematics of a bicruciate-retaining total knee arthroplasty.

PURPOSE: The recently reintroduced bicruciate-retaining Total Knee Arthroplasty (BCR TKA) is an interesting approach in the quest for close replication of knee joint biomechanics and kinematics closer to the native knee. Therefore, this study aimed at providing a detailed biomechanical view on the functional resemblance of BCR TKA to the native knee joint. METHODS: Seven fresh-frozen full leg cadaver specimens (76 ± 10 year) were mounted in a 6 degrees-of-freedom kinematic rig that applied a dynamic squatting motion knee flexion. Two motion patterns were performed pre- and post-implantation of a fixed bearing BCR TKA: passive flexion-extension and squatting while an infrared camera system tracked the location of reflective markers attached to the tibia and femur. Additionally, specimen laxity was assessed using Lachman tests and varus/valgus stress tests in triplicate. RESULTS: Overall, differences in tibiofemoral kinematics between native knee and BCR TKA were small. Some minor differences appeared under the load of a squat: less internal tibial rotation and some minor paradoxical anterior translation of the medial femoral condyle during mid-flexion. BCR TKA may slightly elevate the joint line. Knee laxity as measured by the Lachman and varus/valgus tests was not significantly influenced by BCR TKA implantation. CONCLUSION: As both cruciate ligaments are preserved with BCR TKA the unloaded knee closely resembles native knee kinematics including preserving the rollback mechanism. The loss of the conforming anatomy of menisci and tibial cartilage and replacement via a relatively flat polyethylene inlay may account for the loss of tibial internal rotation and the slight paradoxical AP motion of the medial femoral condyle with BCR TKA. This phenomenon reproduces findings made earlier with fixed bearing unicondylar knee arthroplasty.

Balancing mobile-bearing unicondylar knee arthroplasty in vitro.

PURPOSE: Balancing mobile-bearing (MB) unicondylar knee arthroplasty (UKA) is challenging. If performed improperly, potential complications include pain, implant loosening, or progression of osteoarthritis in the preserved compartment. The purpose of this study was to document effects of improper balancing on knee kinematics and joint contact stress. It was hypothesized that over-stuffing would lead to more valgus and higher lateral contact force. METHODS: Seven fresh-frozen cadaver legs were mounted in a kinematic rig that applied three motion patterns to the specimens: passive flexion-extension, open chain extension, and squatting. During testing, an infrared camera system recorded the trajectories of markers rigidly attached to femur and tibia, while a pressure sensor measured contact pressure in the lateral compartment. Prior computer tomography scans allowed identification of coordinate frames of the bones and calculations of anatomical rotations and translations. Collateral ligament strains were calculated, and quadriceps forces recorded. Following testing on the native knee, a medial MB UKA was implanted in each specimen and all motion trials were repeated. Three inlay thicknesses were tested to simulate optimal balancing as well as under- (1 mm thinner) and over-stuffing (1 mm thicker) of the medial compartment relative to the optimal thickness. RESULTS: Under-stuffing of the medial compartment leads to kinematics closest to the native knee. Subjectively balanced and over-stuffed MB UKA knees were in more valgus. Lateral peak contact stress was higher from mid- to deep flexion following UKA in all three tested states; however, these results were not significant. Peak strain in the superficial medial collateral ligament (sMCL) was significantly higher in MB UKA, regardless of the inlay thickness mainly in mid-flexion. Inlay thickness had no significant impact on measured quadriceps force during squatting. CONCLUSION: The results underline the importance of optimal balancing. Over-stuffing should be avoided as it results in the largest kinematic changes relative to the native condition and induces higher strains in the sMCL. Based on the kinematic findings, it is advisable to use thinner inlays, as long as this is not compromising stability or risking inlay luxation.

Fixation techniques and stem dimensions in hinged total knee arthroplasty: a finite element study.

INTRODUCTION: No evidence-based guidelines are available to determine the appropriate stem length, and whether or not to cement stems in revision total knee arthroplasty (TKA). Therefore, the objective of this study was to compare stresses and relative movement of cemented and uncemented stems of different lengths using a finite element analysis. MATERIALS AND METHODS: A finite element model was created for a synthetic tibia. Two stem lengths (95 and 160 mm) and two types of fixation (cemented or press fit) of a hinged TKA were examined. The average compressive stress distribution in different regions of interest, as well as implant micromotions, was determined and compared during lunge and squat motor tasks. RESULTS: Both long and short stems in revision TKA lead to high stresses, primarily in the region around the stem tip. The presence of cement reduces the stresses in the bone in every region along the stem. Short stem configurations are less affected by the presence of cement than the long stem configuration. Press-fit stems showed higher micromotions compared to cemented stems. CONCLUSIONS: Lowest stresses and micromotion were found for long cemented stems. Cementless stems showed more micromotion and increased stress levels especially at the level of the stem tip, which may explain the clinical phenomenon of stem-end pain following revision knee arthroplasty. These findings will help the surgeon with optimal individual implant choice.

Systemic antibiotic therapy does not significantly improve outcome in a rat model of implant-associated osteomyelitis induced by Methicillin susceptible Staphylococcus aureus.

INTRODUCTION: Treatment of implant-associated osteomyelitis regularly involves the use of systemic antibiotics in addition to surgical intervention. However, it remains unclear if perioperative systemic application of bactericide substances can improve overall outcome in models of severe intramedullary infection. The present study investigated the use of systemic gentamicin in addition to a controlled local release from a highly lipophilic gentamicinpalmitate compound while the previous study showed efficacy of sole antibiotic implant-coating. METHODS: Forty male Sprague-Dawley rats were divided into two groups receiving an intramedullary femoral injection of 10(2) CFU of a common methicillin susceptible Staphylococcus aureus strain (MSSA Rosenbach). Group I received an uncoated implant whereas group II received a coated implant. All animals received a single shot intraperitoneal application of gentamicinsulfate directly after wound closure while the historical control group III (n = 20) had no antibiotic treatment at all. Animals were observed for 28 and 42 days. Serum haptoglobin and relative weight gain were assessed as well as roll over cultures of explanted femur nails and histological scores of periprosthetic infection in dissected femora. RESULTS: Systemic application of gentamicin combined with antibiotic-coated implant did not further reduce bacterial growth significantly compared with systemic or local antibiotic application alone. Combined local and systemic therapy reduced serum haptoglobin significantly after day 7, 28 and 42 whereas systemic application alone did not compare to controls. CONCLUSIONS: Systemic perioperative and implant-associated application of antibiotics were both comparably effective to treat implant-associated infections whereas the combined antibiotic therapy further reduced systemic signs of infection time dependent.

Balancing UKA: overstuffing leads to high medial collateral ligament strains.

PURPOSE: Balancing unicondylar knee arthroplasty (UKA) is challenging. If not performed properly, it may lead to implant loosening or progression of osteoarthritis in the preserved compartment. This study was aimed to document the biomechanical effects of improper balancing. We hypothesised that overstuffing would lead to more valgus, higher strain in the medial collateral ligament (sMCL), and higher lateral contact force. METHODS: Six fresh-frozen cadaver specimens were mounted in a kinematic rig. Three motion patterns were applied with the native knee and following medial UKA (passive motion, open-chain extension, and squatting), while infrared cameras recorded the trajectories of markers attached to femur and tibia. Three inlay thicknesses were tested (8, 9, 10 mm). RESULTS: Overstuffed knees were in more valgus and showed less tibial rotation and higher strains in the sMCL (p < 0.05). Lateral contact forces were higher in some specimens and lower in others. Stiffening of the medial compartment by UKA, even well balanced, already leads to a knee more in valgus with a more stressed sMCL. Overstuffing increases these effects. Knees with a tight sMCL may even see lower lateral contact force. Biomechanics were closest to the native knee with understuffing. CONCLUSION: The first two hypotheses were confirmed, but not the latter. This underlines the importance of optimal balancing. Overstuffing should certainly be avoided. Although kinematics is only slightly affected, contact forces and ligament strains are considerably changed and this might be of more clinical importance. It is advisable to use thinner inlays, if stability is not compromised.

Juvenile osteochondritis dissecans of the talus: predictors of conservative treatment failure.

BACKGROUND: The ideal treatment for juvenile osteochondritis dissecans of the talus (ODT) is still unclear. To determine predictors of failure of conservative treatment, children admitted for ODT were retrospectively analyzed. METHODS: Patient files were analyzed to search for children treated for an ODT between 2000 and 2011. X-rays and MRI at baseline were evaluated for grading of lesions and the patient history was obtained. Final follow-up evaluation was performed via questionnaire and complementary telephone interview. Outcome was measured using the AOFAS and the Olerud/Molander scores. Conservative treatment consisted of out of sports and modification of activity under full weight-bearing. In case of persisting pain, full load removal on crutches was initiated. For further analysis, two groups were formed: (1) successful conservative treatment; (2) converted to surgical therapy. A logistic regression was used to determine potential predictors of conservative treatment failure. RESULTS: Seventy-seven lesions in 67 children with a mean age of 11.4 years (range 4-15 years) at the time of diagnosis were identified. Every patient received conservative treatment as a first-line treatment after diagnosis of ODT except for one single patient with a grade IV lesion at time of diagnosis who received operative treatment directly after diagnosis. Sixty-one percent of the lesions failed conservative treatment. A higher age as well as a grade III lesion at time of diagnosis was predictive for failure of the conservative treatment (p = 0.03 and p = 0.02, respectively). Regarding the functional outcome, a higher grade lesion in general was predictive for an inferior outcome as measured by clinical score. CONCLUSION: Grade III ODT especially in older children leads significantly more often to treatment failure when treated non-surgically. No other predictors for treatment failure could be identified. LEVEL OF EVIDENCE: Level III (retrospective comparative study).

Bleeding in TKA: posterior stabilized vs. cruciate retaining.

INTRODUCTION: Posterior-stabilized (PS) and cruciate-retaining (CR) total knee arthroplasties (TKA) are both successfully used for treatment of end-stage osteoarthritis. The choice of constraint depends on knee deformity and stability as well as most importantly surgeon preference. The aim of this study was to compare the amount of blood loss and required transfusions following TKA with the two different designs. MATERIALS AND METHODS: In a retrospective approach, 473 patients undergoing TKA were included (240 CR and 233 PS from a single manufacturer). Demographics at base line were comparable between both groups. Blood loss [red blood cell (RBC) loss] was calculated after documentation of pre- and postoperative hematocrit levels at discharge. Transfusion requirements were recorded. Statistical analysis was done using Mann-Whitney U test. RESULTS: The calculated blood loss (RBC loss) at discharge was 548 ± 216 ml in the PS group compared with 502 ± 186 ml in the CR group (p = 0.032). There were no differences in the transfusion requirements between both groups (PS 0.41 vs. CR 0.37, p = 0.39). DISCUSSION: The blood loss was significantly higher in the PS group. This may be due to the box preparation that exposes more cancellous femoral bone, which may add to postoperative bleeding. The differences remain, however, small, as they did not lead to a significantly higher transfusion rate with PS TKA.

Immunosuppressive capabilities of mesenchymal stromal cells are maintained under hypoxic growth conditions and after gamma irradiation.

BACKGROUND AIMS: The discovery of regenerative and immunosuppressive capacities of mesenchymal stromal cells (MSCs) raises hope for patients with tissue-damaging or severe, treatment-refractory autoimmune disorders. We previously presented a method to expand human MSCs in a bioreactor under standardized Good Manufacturing Practice conditions. Now we characterized the impact of critical treatment conditions on MSCs with respect to immunosuppressive capabilities and proliferation. METHODS: MSC proliferation and survival after γ irradiation were determined by 5-carboxyfluorescein diacetate N-succinimidyl ester and annexinV/4',6-diamidino-2-phenylindole (DAPI) staining, respectively. T-cell proliferation assays were used to assess the effect of γ irradiation, passaging, cryopreservation, post-thaw equilibration time and hypoxia on T-cell suppressive capacities of MSCs. Quantitative polymerase chain reaction and ß-galactosidase staining served as tools to investigate differences between immunosuppressive and non-immunosuppressive MSCs. RESULTS: γ irradiation of MSCs abrogated their proliferation while vitality and T-cell inhibitory capacity were preserved. Passaging and long cryopreservation time decreased the T-cell suppressive function of MSCs, and postthaw equilibration time of 5 days restored this capability. Hypoxic culture markedly increased MSC proliferation without affecting their T-cell-suppressive capacity and phenotype. Furthermore, T-cell suppressive MSCs showed higher CXCL12 expression and less ß-galactosidase staining than non-suppressive MSCs. DISCUSSION: We demonstrate that γ irradiation is an effective strategy to abrogate MSC proliferation without impairing the cells' immunosuppressive function. Hypoxia significantly enhanced MSC expansion, allowing for transplantation of MSCs with low passage number. In summary, our optimized MSC expansion protocol successfully addressed the issues of safety and preservation of immunosuppressive MSC function after ex vivo expansion for therapeutic purposes.

Improvement in outcomes after implantation of a novel polyurethane meniscal scaffold for the treatment of medial meniscus deficiency.

PURPOSE: Meniscal injury resulting in segmental loss of meniscal tissue is a major risk factor for the development of osteoarthritis. Tissue engineering strategies have provided scaffolds for meniscal regeneration in order to establish a treatment option for patients with limited opportunities for meniscal reconstruction. The purpose of this study was to assess the clinical and magnetic resonance imaging (MRI) results 2 years after implantation of a polyurethane scaffold for chronic segmental medial meniscus deficiency following partial medial meniscectomy. METHODS: Eighteen patients were treated with arthroscopic implantation of an ActiFit(®) (Orteq Sports Medicine) polyurethane meniscal scaffold for meniscus deficiency of the medial meniscus. Patients were followed up at 6, 12, and 24 months. Clinical outcome was assessed using patient-reported outcome scores (KOOS, KSS, UCLA activity scale, VAS for pain). Radiological outcome was assessed using MRI at 6, 12, and 24 months by evaluating scaffold morphology, scaffold integration, and additional joint injury, as well as joint inflammation. RESULTS: Eighteen patients with a median age of 32.5 years (range 17-49) were enrolled. Statistically significant improvements were present in all patients, but one at 2 years compared to baseline in all categories. Complete resorption of the scaffold occurred in one patient representing a failure to treatment. MRI showed abnormal signal intensity of the scaffold when compared to residual meniscal tissue but without synovitis or joint inflammation. Extrusion of the scaffold was present in four patients. No correlation between scaffold extrusion and clinical outcome was observed. CONCLUSION: Arthroscopic implantation of a polyurethane meniscal scaffold in patients with chronic segmental medial meniscus deficiency is not only a safe procedure but leads to good clinical results at a 2-year follow-up. Scaffold extrusion did not appear to affect clinical outcome. LEVEL OF EVIDENCE: IV.

Clubfoot associated with preaxial polydactyly.

We report on three children with bilateral, congenital clubfoot. Four of the six clubfeet were associated with preaxial polydactyly. Five of the six clubfeet were treated without extensive surgery. A plantigrade foot was achieved, even in the three clubfeet with polydactyly, using serial casting and percutaneous Achilles tenotomy. Casting was adapted according to the existing polydactyly. One case with tibial hemimelia and a complex clubfoot deformity with preaxial tarsal polydactyly required more comprehensive surgery. A foot with good weight-bearing function was also achieved in this case following resection of the accessory medial ray, including resection of the accessory tarsal bones and posterior release. Remaining limitations in mobility were ascribed to hindfoot pathologies.

Chondrosarcoma of the tibial head during pregnancy: a challenging diagnosis.

Chondrosarcoma is one of the most common malignant bone tumours in adults. However, it rarely occurs during pregnancy. Therefore, reports on surgical and medical management of this entity are hard to find. Different studies suggest a possible growth-enhancing effect of altered hormone levels on various bone tumours. The effect of pregnancy on growth characteristics of chondrosarcomas however remains unclear. We report a case of a 32-year-old pregnant woman with a newly occurred chondrosarcoma of the tibial head. Intense clinical monitoring and repeated MRI scans showed a tumour progression during pregnancy followed by the need of above-knee amputation after 30 weeks gestation. Spontaneous vaginal delivery after 38 weeks gestation was complicated by an amniotic infection syndrome and finally stopped, necessitating a caesarean section. Despite this there were no further complications to be mentioned. No local tumour recurrence or metastases could be detected in the staging CT scans following pregnancy.