A comparative in vitro and in vivo analysis of the impact of copper substitution on the cytocompatibility, osteogenic, and angiogenic properties of a borosilicate bioactive glass.

The 0106-B1-bioactive glass (BG) composition (in wt %: 37.5 SiO2, 22.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, and 12.5 B2O3) has demonstrated favorable processing properties and promising bone regeneration potential. The present study aimed to evaluate the biological effects of the incorporation of highly pro-angiogenic copper (Cu) in 0106-B1-BG in vitro using human bone marrow-derived mesenchymal stromal cells (BMSCs) as well as its in vivo potential for bone regeneration. CuO was added to 0106-B1-BG in exchange for CaO, resulting in Cu-doped BG compositions containing 1.0, 2.5 and 5.0 wt % CuO (composition in wt %: 37.5 SiO2, 21.6/ 20.1/17.6 CaO, 5.9 Na2O, 4.0 P2O5, 12.0 K2O, 5.5 MgO, 12.5 B2O3, and 1.0/ 2.5/ 5.0 CuO). In vitro, the BGs' impact on the viability, proliferation, and growth patterns of BMSCs was evaluated. Analyses of protein secretion, matrix formation, and gene expression were used for the assessment of the BGs' influence on BMSCs regarding osteogenic differentiation and angiogenic stimulation. The presence of Cu improved cytocompatibility, osteogenic differentiation, and angiogenic response when compared with unmodified 0106-B1-BG in vitro. In vivo, a critical-size femoral defect in rats was filled with scaffolds made from BGs. Bone regeneration was evaluated by micro-computed tomography. Histological analysis was performed to assess bone maturation and angiogenesis. In vivo effects regarding defect closure, presence of osteoclastic cells or vascular structures in the defect were not significantly changed by the addition of Cu compared with undoped 0106-B1-BG scaffolds. Hence, while the in vitro properties of the 0106-B1-BG were significantly improved by the incorporation of Cu, further evaluation of the BG composition is necessary to transfer these effects to an in vivo setting.

Fat embolism syndrome in Duchenne muscular dystrophy: Report on a novel case and systematic literature review.

We report a non-ambulatory 13-year-old boy with Duchenne muscular dystrophy who experienced severe acute respiratory distress syndrome and cerebral fat embolism following elective soft tissue surgery. Post-surgery radiological examination revealed bilateral femoral fractures and marked osteopenia that were believed to have caused disseminated pulmonary and cerebral fat embolism. The patient had never been on glucocorticoid treatment. Five months post-surgery, he remained in a state of minimal consciousness. A literature review was performed and eleven publications included, providing case reports of a total number of 23 patients with Duchenne muscular dystrophy with fat embolism syndrome. The most common causes were falls from the wheelchair that predominantly resulted in femoral fractures. Median age at the event was around 14 years. Seven patients succumbed to complications of fat embolism. No event was described in the context of surgery. We want to raise awareness that spontaneous unnoticed fractures may occur especially in adolescents with DMD from traumatic injury of large bones and also during elective surgery with a high risk of causing fat embolism with severe sequelae.

The Impact of 45S5-Bioactive Glass on Synovial Cells in Knee Osteoarthritis-An In Vitro Study.

Synovial inflammation in osteoarthritis (OA) is characterized by the release of cartilage-degrading enzymes and inflammatory cytokines. 45S5-bioactive glass (45S5-BG) can modulate inflammation processes; however, its influence on OA-associated inflammation has hardly been investigated. In this study, the effects of 45S5-BG on the release of cartilage-degrading metalloproteinases and cytokines from synovial membrane cells (SM) isolated from patients with knee OA was assessed in vitro. SM were cultivated as SM monocultures in the presence or absence of 45S5-BG. On day 1 (d1) and d7 (d7), the concentrations of Matrix Metalloproteinases (MMPs) and cytokines were assessed. In 45S5-BG-treated SM cultures, MMP9 concentration was significantly reduced at d1 and d7, whilst MMP13 was significantly increased at d7. Concentrations of interleukin (IL)-1B and C-C motif chemokine ligand 2 (CCL2) in 45S5-BG-treated SM cultures were significantly increased at both time points, as were interferon gamma (IFNG) and IL-6 at d7. Our data show an effect of 45S5-BG on SM activity, which was not clearly protective, anti-inflammatory, or pro-inflammatory. The influence of 45S5-BG on MMP release was more suggestive of a cartilage protective effect, but 45S5-BG also increased the release of pro-inflammatory cytokines. Further studies are needed to analyze the effect of BGs on OA inflammation, including the anti-inflammatory modification of BG compositions.

A new alignment device for standardization of marker placement on the hindfoot.

BACKGROUND: For multi-segment foot models, next to a (dorsal) heel marker, further markers are typically placed medially (MCL) and laterally (LCL) on the calcaneus. However, there is a lack of easily identifiable landmarks on the hindfoot limiting the repeatability of measurements. For a more consistent placement of these markers, an improved Hindfoot Alignment Device (HiAD) was developed. METHODS: With the HiAD, the position of the MCL and LCL can be individually scaled. Flexible bars allow the adaptation to foot deformities. Three rater placed markers with the HiAD four times on ten typical developed subjects (20 feet). Rigid segment residuals of the hindfoot were calculated and compared with the residuals when using the device of Simon et al. (2006) [12]. The variability of the placement of MCL, LCL and the clinical parameter medial arch were determined. For assessing the inter- and intra-rater reliability, intraclass correlation coefficient (ICC) and the standard error of measurement (SEM) were calculated. RESULTS: Rigid segment residuals of the hindfoot could be reduced by 70 % by using the HiAD. Largest inter-rater variability in the MCL and LCL placement was found in z-direction with less than 3.2 ± 2.7 mm and 3.8 ± 2.8 mm, respectively. Correspondingly, largest intra-rater variability was 3.4 ± 2.3 mm for LCL and 2.4 ± 1.9 mm for MCL, respectively. Regarding reliability ICC showed good to excellent results for the medial arch (interrater ICC 0.471-0.811). SIGNIFICANCE: The application of HiAD to place MCL and LCL appear to be a reliable method with robust marker positions and could be implemented in any multi segment foot model. However, further investigation would be helpful to determine the sensitivity of the marker positions in detecting hindfoot deformities.

A comparative in vitro and in vivo analysis of the biological properties of the 45S5-, 1393-, and 0106-B1-bioactive glass compositions using human bone marrow-derived stromal cells and a rodent critical size femoral defect model.

Since the introduction of the 45S5-bioactive glass (BG), numerous new BG compositions have been developed. Compared to the 45S5-BG, 1393-BG shows favorable processing properties due to its low crystallization tendency and the 1393-BG-based borosilicate 0106-B1-BG exhibits improved angiogenic properties due to its boron content. Despite their close (chemical) relationship, the biological properties of the mentioned BG composition have not yet been comparatively examined. In this study, the effects of the BGs on proliferation, viability, osteogenic differentiation, and angiogenic factor production of human bone marrow-derived mesenchymal stromal cells were assessed. Scaffolds made of the BGs were introduced in a critical-sized femur defect model in rats in order to analyze their impact on bone defect regeneration. In vitro, 1393-BG and 0106-B1-BG outperformed 45S5-BG with regard to cell proliferation and viability. 1393-BG enhanced osteogenic differentiation; 0106-B1-BG promoted angiogenic factor production. In vivo, 0106-B1-BG and 45S5-BG outperformed 1393-BG in terms of angiogenic and osteoclastic response resulting in improved bone regeneration. In conclusion, the biological properties of BGs can be significantly modified by tuning their composition. Demonstrating favorable processing properties and an equally strong in vivo bone regeneration potential as 45S5-BG, 0106-B1-BG qualifies as a basis to incorporate other bioactive ions to improve its biological properties.

Functional outcome and athletic level after arthroscopic repair followed by triple pelvic osteotomy in patients with labral tears resulting from acetabular dysplasia.

BACKGROUND: Patients with acetabular dysplasia are at a higher risk of developing symptomatic labral tears. Isolated treatments that address these pathologies are well established. Combined treatment with hip reorientation osteotomy using Bernese periacetabular osteotomy in addition to arthroscopic labral repair show good results. Studies that report the outcome in patients who received both arthroscopic labral repair and a triple pelvic osteotomy (TPO) are lacking. The aim of this study is to investigate the short to midterm functional outcome and activity level in these patients. METHODS: This case series retrospectively included 8 patients (2 male, 6 female) with acetabular dysplasia (lateral center-edge angle [LCEA] ≤ 25°) and a labral tear on magnetic resonance arthrography (MRA). All patients underwent arthroscopic labral repair followed by TPO after an average period of 3 months (range 2-6). Average age at the time of surgery was 25 years (range 15-37). Patients were followed up and the following main parameters were assessed: LCEA, modified Harris hip score (mHSS), Tegner score, UCLA score, patient satisfaction on a scale of 1-4. RESULTS: The mean follow-up was 19 months (range 15-25). The mean LCEA increased from 18° to 37° (p < 0.0001). The mHSS improved from a mean of 79 to 94 on final follow-up (p = 0.00123). The Tegner and UCLA scores had a median of 4 and 5, respectively. The mean LCEA increased from 18° to 37° (p < 0.0001). The mean patient satisfaction was 3.6. CONCLUSION: Patients with evidence of a labral tear resulting from acetabular dysplasia benefit from arthroscopic repair followed by a TPO. The literature still lacks evidence that labral repair and reorientation osteotomy produce superior outcome compared to osteotomy alone. Treatment should consider clinical presentation in addition to radiological findings with emphasis on MRA.

[Solidarity with children and people with disabilities? : An economic analysis of reconstructive hip interventions in pediatric orthopedics]. / Solidarität mit Kindern und Menschen mit Behinderung? : Eine Wirtschaftlichkeitsanalyse hüftrekonstruierender Eingriffe in der Kinderorthopädie.

BACKGROUND: Brain damage in childhood can be caused cerebral palsy (CP) or be due to other diseases. Disturbance of muscle tone results in consecutive development of hip subluxation. Hip reconstructive surgery can significantly improve the mobility and quality of care of children. However, the DRG for surgical care of these conditions has been increasingly devalued. In Germany, this has already led to a reduction of pediatric orthopedics departments, accompanied by an important risk of insufficient treatment options for children and people with disabilities. METHOD: The aim of this retrospective study was an economic analysis of pediatric orthopedic interventions using the example of neurogenic hip decentration. For this purpose, the revenue-cost situation in patients with CP or other causes of brain damage was evaluated at a maximum care hospital in the period of 2019-2021. RESULTS: The entire analysis period showed a deficit. The non-CP-group showed the most important deficit. In CP-patients, however, the plus decreased each year and resulted in a deficit in 2021. CONCLUSION: While the distinction between cerebral palsy and other forms of brain damage in children is usually not relevant for treatment, it is evident that the non-CP group is massively underfinanced. Overall, the negative economic balance of pediatric orthopedics in the field of neurogenic hip reconstruction is clearly revealed. In the current interpretation of the DRG system, children with disabilities cannot be offered cost-effective care at a maximum-care university center.

Quantifying the effects of achilles tendon lengthening surgery: An intraoperative approach.

Achilles tendon lengthening (ATL) is frequently used in the treatment of foot deformities. However, there is currently no objective method to determine the optimal muscle length during surgery. We developed an intraoperative approach to evaluate the passive and active forces of the triceps surae muscle group before and after ATL and aimed to test the following hypotheses: 1) the ankle passive range of motion (ROM) increases, 2) passive muscle forces decrease post-ATL, and 3) forces measured from patients with non-neurological and neurological conditions demonstrate different characteristics. Passive forces at various ankle joint positions were measured in ten patients (11.3 ± 3.0 years old) pre- and post-ATL using a force transducer attached to the Achilles tendon. In six patients, active isometric forces were measured by stimulating the triceps surae supramaximally. Passive forces decreased by 94.3% (p < 0.0001), and ROM increased by 89.4% (p < 0.0001) post-ATL. The pre-ATL passive forces were 70.8% ± 15.1% lower in patients with idiopathic foot deformities than in patients with neurological conditions (p < 0.001). The peak active force of 209.8 ± 114.3 N was achieved at an ankle angle of 38.3° ± 16.0°, where the passive force was 6.3 ± 6.7 N. The inter-individual variability was substantial in both groups. In conclusion, the hypotheses posed were supported. The present findings suggest that muscle passive and active force production as well as the inter-individual variability should be considered when planning further treatment.

Transversal Malalignment and Proximal Involvement Play a Relevant Role in Unilateral Cerebral Palsy Regardless the Subtype.

Classification of gait disorders in cerebral palsy (CP) remains challenging. The Winters, Gage, and Hicks (WGH) is a commonly used classification system for unilateral CP regarding the gait patterns (lower limb kinematics) solely in the sagittal plane. Due to the high number of unclassified patients, this classification system might fail to depict all gait disorders accurately. As the information on trunk/pelvic movements, frontal and transverse planes, and kinetics are disregarded in WGH, 3D instrumented gait analysis (IGA) for further characterization is necessary. The objective of this study was a detailed analysis of patients with unilateral CP using IGA taking all planes/degrees of freedom into account including pelvic and trunk movements. A total of 89 individuals with unilateral CP matched the inclusion criteria and were classified by WGH. Subtype-specific differences were analyzed. The most remarkable findings, in addition to the established WGH subtype-specific deviations, were pelvic obliquity and pelvic retraction in all WGH types. Furthermore, the unclassified individuals showed altered hip rotation moments and pelvic retraction almost throughout the whole gait cycle. Transversal malalignment and proximal involvement are relevant in all individuals with unilateral CP. Further studies should focus on WGH type-specific rotational malalignment assessment (static vs. dynamic, femoral vs. tibial) including therapeutic effects and potential subtype-specific compensation mechanisms and/or tertiary deviations of the sound limb.

Estimation of a midfoot joint center in typically developed adults using functional calibration methods.

BACKGROUND: There are detailed findings on hip and knee joint parameters determined via functional calibration methods for use in instrumented 3D-gait analysis but these methods have not yet been addressed to the foot. RESEARCH QUESTION: Are functional calibration methods feasible for determining foot joint parameters and may they help for clinical interpretation of foot deformities? METHODS: Rigid segments were formed by markers on forefoot and hindfoot via a least square method. The position of the midfoot joint articulating both foot segments was then determined via a functional calibration motion. This two-stage procedure was applied on a cohort of 17 typically developed adults and one subject with severe planovalgus foot deformity for determining the location of the midfoot joint and kinematics of hindfoot and forefoot. RESULTS: The position of the midfoot joint center could be estimated in the typically developed cohort and also in the demonstration case with planovalgus foot deformity. Depending on the choice of marker set for hindfoot and forefoot, the position of the joint center varied in the anatomic midfoot region with most robust results when addressing the marker on the navicular to the hindfoot. CONCLUSION: The presented method for joint center determination within the foot and the characteristic results of the foot joint angles appear promising for typically developed feet. However, further validation of the method is needed for application in clinical context.

Outcome Prognostic Factors in MRI during Spica Cast Therapy Treating Developmental Hip Dysplasia with Midterm Follow-Up.

Closed reduction followed by spica casting is a conservative treatment for developmental dysplasia of the hip (DDH). Magnetic resonance imaging (MRI) can verify proper closed reduction of the dysplastic hip. Our aim was to find prognostic factors in the first MRI to predict the possible outcome of the initial treatment success by means of ultrasound monitoring according to Graf and the further development of the hip dysplasia or risk of recurrence in the radiological follow-up examinations. A total of 48 patients (96 hips) with DDH on at least one side, and who were treated with closed reduction and spica cast were included in this retrospective cohort study. Treatment began at a mean age of 9.9 weeks. The children were followed for 47.4 months on average. We performed closed reduction and spica casting under general balanced anaesthesia. This was directly followed by MRI to control the position/reduction of the femoral head without anaesthesia. The following parameters were measured in the MRI: hip abduction angle, coronal, anterior and posterior bony axial acetabular angles and pelvic width. A Graf alpha angle of at least 60° was considered successful. In the radiological follow-up controls, we evaluated for residual dysplasia or recurrence. In our cohort, we only found the abduction angle to be an influencing factor for improvement of the DDH. No other prognostic factors in MRI measurements, such as gender, age at time of the first spica cast, or treatment involving overhead extension were found to be predictive of mid-term outcomes. This may, however, be due to the relatively small number of treatment failures.

Pediatric patient with a bilateral Salter-Harris II fracture and slipped capital femoral epiphysis secondary to autosomal recessive osteopetrosis.

Treatment of femoral neck fractures secondary to osteopetrosis is an uncertain and puzzled decision. Experience in the treatment, especially in the pediatric population, is scarcely reported. The duration of conservative treatment is prolonged and poses the risks of non-union and development of coxa vara deformity. The recommended treatment is closed reduction and internal fixation; however, surgery on osteopetrotic bone is challenging due to defective bone marrow function, delayed consolidation and higher risk of intraoperative fractures. Slipped capital femoral epiphysis secondary to osteopetrosis is very rarely reported. This article presents the case of a 5-year-old female patient with rapidly deteriorating physical function due to bilateral proximal femoral Salter-Harris type II fractures with associated slippage of the growth plates secondary to confirmed autosomal recessive osteopetrosis. Operative treatment was performed in a tertiary level orthopedic center with closed reduction and internal fixation with cannulated screws. A loss of fixation with coxa vara deformity was seen on the left side 7 months postoperatively with increasing pain. A revision surgery with reosteosynthesis and a valgus osteotomy was thus performed which showed good subjective and objective results 1 year postoperatively with complete bony union.

GMFCS Level-Specific Differences in Kinematics and Joint Moments of the Involved Side in Unilateral Cerebral Palsy.

A variety of gait pathologies is seen in cerebral palsy. Movement patterns between different levels of functional impairment may differ. The objective of this work was the evaluation of Gross Motor Function Classification System (GMFCS) level-specific movement disorders. A total of 89 individuals with unilateral cerebral palsy and no history of prior treatment were included and classified according to their functional impairment. GMFCS level-specific differences, kinematics and joint moments, exclusively of the involved side, were analyzed for all planes for all lower limb joints, including pelvic and trunk movements. GMFCS level I and level II individuals most relevantly showed equinus/reduced dorsiflexion moments, knee flexion/reduced knee extension moments, reduced hip extension moments with pronounced flexion, internal hip rotation and reduced hip abduction. Anterior pelvic tilt, obliquity and retraction were found. Individuals with GMFCS level II were characterized by an additional pronounced reduction in all extensor moments, pronounced rotational malalignment and reduced hip abduction. The most striking characteristics of GMFCS level II were excessive anterior pelvic/trunk tilt and excessive trunk obliquity. Pronounced reduction in extensor moments and excessive trunk lean are distinguishing features of GMFCS level II. These patients would benefit particularly from surgical treatment restoring pelvic symmetry and improving hip abductor leverage. Future studies exploring GMFCS level-specific compensation of the sound limb and GMFCS level-specific malalignment are of interest.

The Ali Krogius procedure for treatment of patellofemoral instability should be regarded as obsolete even in skeletally immature patients.

BACKGROUND: Several interventions are established for treating patellofemoral instability in adults. Fewer exist for pediatric patients without damaging the epiphysis. The Ali Krogius (AK) method is currently still being used. Most studies are not current and report varying results in small patient population. The aim of this study is to determine the long-term results of the AK method. METHODS: In this monocentric, retrospective study design, 33 knees in 33 patients who received the AK procedure for recurrent patellar dislocation were assessed. The average age was 20.8 years (range 6-40). The following functional scores were assessed: Kujala Score, Lysholm Score and Tegner Score. Subgroup analysis was done for patients ≤16 years of age. Available preoperative imaging was assessed for known risk factors. RESULTS: After an average follow-up of 7.8 years (Range 59-145 months), a total of 8 (24%) knees suffered a redislocation postoperatively. Seven of the eight dislocations occurred in patients ≤ 16 years of age. One knee (3%) was revised due to persistent pain. The median score was 86 points for the Kujala score and 90 for the Lysholm score. The median in the Tegner score was level 6. Clinically, the patellar glide was lateralized in 7 knees (21%) and an apprehension sign was triggered in 8 knees (24%). CONCLUSIONS: Including the present study, the existing literature indicates a redislocation rate between 24 and 41% following AK. It should thus be regarded as obsolete even though it protects the epiphysis. Surgical interventions such as medial patellofemoral ligament reconstruction with femoral drilling distal to the epiphysis should be preferred. TRIAL REGISTRATION: Retrospectively registered: S-302/2016. LEVEL OF EVIDENCE: III.

Preclinical Testing of New Hydrogel Materials for Cartilage Repair: Overcoming Fixation Issues in a Large Animal Model.

Reinforced hydrogels represent a promising strategy for tissue engineering of articular cartilage. They can recreate mechanical and biological characteristics of native articular cartilage and promote cartilage regeneration in combination with mesenchymal stromal cells. One of the limitations of in vivo models for testing the outcome of tissue engineering approaches is implant fixation. The high mechanical stress within the knee joint, as well as the concave and convex cartilage surfaces, makes fixation of reinforced hydrogel challenging. Methods. Different fixation methods for full-thickness chondral defects in minipigs such as fibrin glue, BioGlue®, covering, and direct suturing of nonenforced and enforced constructs were compared. Because of insufficient fixation in chondral defects, superficial osteochondral defects in the femoral trochlea, as well as the femoral condyle, were examined using press-fit fixation. Two different hydrogels (starPEG and PAGE) were compared by 3D-micro-CT (µCT) analysis as well as histological analysis. Results. Our results showed fixation of below 50% for all methods in chondral defects. A superficial osteochondral defect of 1 mm depth was necessary for long-term fixation of a polycaprolactone (PCL)-reinforced hydrogel construct. Press-fit fixation seems to be adapted for a reliable fixation of 95% without confounding effects of glue or suture material. Despite the good integration of our constructs, especially in the starPEG group, visible bone lysis was detected in micro-CT analysis. There was no significant difference between the two hydrogels (starPEG and PAGE) and empty control defects regarding regeneration tissue and cell integration. However, in the starPEG group, more cell-containing hydrogel fragments were found within the defect area. Conclusion. Press-fit fixation in a superficial osteochondral defect in the medial trochlear groove of adult minipigs is a promising fixation method for reinforced hydrogels. To avoid bone lysis, future approaches should focus on multilayered constructs recreating the zonal cartilage as well as the calcified cartilage and the subchondral bone plate.

Gait Indices for Characterization of Patients with Unilateral Cerebral Palsy.

As cerebral palsy (CP) is a complex disorder, classification of gait pathologies is difficult. It is assumed that unclassified patients show less functional impairment and less gait deviation. The aim of this study was to assess the different subgroups and the unclassified patients with unilateral CP using different gait indices. The Gillette Gait Index (GGI), Gait Deviation Index (GDI), Gait Profile Score (GPS) and spatiotemporal parameters derived from instrumented 3D-Gait Analysis (IGA) were assessed. Subgroups were defined using morphological and functional classification systems. Regarding the different gait indices, a ranking of the different gait patterns is evident. Significant differences were found between GMFCS level I and II, Winters et al. (Winters, Gage, Hicks; WGH) type IV and type I and the WGH-unclassified. Concerning the spatiotemporal parameters significant differences were found between GMFCS level I and II concerning velocity. The unclassified patients showed mean values for the different gait indices that were comparable to those of established subgroups. Established gait patterns cause different degrees of gait deviation and functional impairment. The unclassified patients do not differ from established gait patterns but from the unimpaired gait. Further evaluation using 3D-IGA is necessary to identify the underlying gait pathologies of the unclassified patients.

[Hip joint contractures, leg length discrepancies, and spinopelvic alignment: impact on the development of osteoarthritis of the hip?] / Hüftgelenkskontrakturen, Beinlängendifferenzen und spinopelvines Alignement ­ Einfluss auf die Arthroseentwicklung der Hüfte?

Hip joint problems are common in every-day orthopedic practice. At the age of 60, approximately 5% of the German population suffer from symptomatic osteoarthritis of the hip. One of the main trigger is the morphological abnormality of the joint. Causes may also be overloading of the joint, developmental dysplasia of the hip with reduced coverage, as well as femoral or acetabular malpositioning, for example. The impact of hip joint contractures, leg length discrepancies, and the spinopelvic alignment and their prophylactic treatment in childhood, adolescence and early adulthood are discussed here.

Peripheral Blood Lymphocyte Subpopulations in Patients Following Small Diameter Metal-On-Metal Total Hip Replacement at Long-Term Follow-Up.

(1) Background: The objective of the present study was to investigate peripheral blood lymphocyte subpopulations in patients with small diameter metal-on-metal total hip arthroplasty (MoM THA) and elevated blood metal ion concentrations at long-term follow-up. The hypothesis was that increased blood metal ion levels or the presence of adverse local tissue reactions (ALTR) would be associated with changes in the peripheral expression of lymphocyte subpopulations, which could potentially serve as early diagnostic markers for metal wear related complications. (2) Methods: Peripheral blood samples were analyzed for leucocyte subgroups (CD3+, CD4+, CD8+, CD14+, CD16+/CD56+, CD25+/CD127-, CD19+, IFN-γ+, IL-4+ and IL-17A+ cells) in 34 patients with elevated blood metal ion levels (combined cobalt and chromium levels >2 µg/L) following small head MoM THA at a mean follow-up of 15.6 years. Fifteen patients with small head MoM THA and blood metal ion levels within the normal range and 15 patients with conventional ceramic-on-polyethylene THA served as control groups. In addition, blood metal ion levels and leucocyte subpopulations were compared between patients with and without adverse local tissue reactions (ALTR), which was investigated by MRI in 27 patients of the study cohort. (3) Results: There was a significant decrease in the levels of IFN-γ+ Type-1 T helper cells (Th1) in patients with MoM THA compared to the ceramic-on-polyethylene control group (p < 0.001). No statistically significant differences in the cell counts of other lymphocyte subpopulations were found between the three groups. Cobalt ion levels were significantly higher in patients with ALTR (p < 0.001) compared to the non-ALTR group, but no differences in the levels of lymphocyte subsets were found between the two groups. (4) Conclusions: No adverse systemic effects with respect to peripheral blood leucocyte subpopulations could be detected in the present study in patients following THA with a small diameter MoM articulation at long-term follow-up. We found a significant decrease of IFN-γ+ Th1 cells in patients with MoM THA compared to the control group, but no differences in the peripheral expression of leucocyte subpopulations were seen between patients with and without ALTR. Future studies with larger patient cohorts and additional histopathological investigations could help to better understand the role of Th1 cells and other cell lines of the adaptive immune system in the development of metal wear related complications after total joint replacement.

T Helper Cell Infiltration in Osteoarthritis-Related Knee Pain and Disability.

Despite the growing body of literature demonstrating a crucial role of T helper cell (Th) responses in the pathogenesis of osteoarthritis (OA), only few clinical studies have assessed interactions between Th cells and OA-related symptoms. Yet, the inclusion of clinical data in the interpretation of cellular analyses of Th cell infiltration is essential to reveal the mechanisms underlying the complex pathophysiology of OA pain and disability. Thus, the aim of the study was to analyze the infiltration pattern of Th cells in systemic (peripheral blood) and joint-derived (synovial membrane and fluid) samples from patients with knee OA in relation to OA-induced pain and disability. Therefore, radiographic OA severity, knee pain and function of 47 OA patients undergoing knee arthroplasty were evaluated prior to surgery. In parallel, samples of peripheral blood (PB), synovial membrane (SM) and synovial fluid (SF) were harvested and analyzed for different Th subsets using flow cytometry. According to surface marker expression Th cells (CD3+ CD4+ CD8-) were assigned to the Th subsets Th1 (CXCR3+, CCR5+), Th2 (CCR3+, CCR4+) and Th17 (CD161+, CCR6+). Interestingly, infiltration of the SM with all Th subtypes (Th1, Th2, Th17) significantly correlated with OA-induced disability. Most importantly, synovial CCR5+ and CCR3+ Th cell infiltration was associated with OA-related knee pain and disability. Furthermore, higher percentage rates of CXCR3+ Th cells in all tissue samples (PB, SM, SF) showed significant associations with OA severity. In contrast, increasing percentage rates of CD161+ Th cells in SM samples corresponded to a better functional outcome. In conclusion, the current study provides an extensive profile of the Th cell infiltration pattern in PB, SF and SM from patients with clinically relevant knee OA. Th cell infiltration of the SM might play a crucial role not only in the pathogenesis of OA but also in the development of OA-related knee pain and disability.