The course of knee extensor strength after total knee arthroplasty: a systematic review with meta-analysis and -regression.

PURPOSE: Muscular strength loss and atrophy are postoperative complications. This systematic review with meta-analysis investigated the course of on knee extensor mass and strength from pre-surgery over total knee arthroplasty to rehabilitation and recovery. METHODS: A systematic literature search was conducted in PubMed (Medline), Cochrane Library (CINAHL, Embase) and Web of Science (until 29th of June 2022). Main inclusion criteria were ≥ 1 preoperative and ≥ 1 measurement ≥ 3-months post-operation and ≥ 1 objective assessment of quadriceps strength, muscle mass or neuromuscular activity, measured at both legs. Studies were excluded if they met the following criteria: further impairment of treated extremity or of the contralateral extremity; further muscle affecting disease, or muscle- or rehabilitation-specific intervention. The Robins-I tool for non-randomized studies, and the Cochrane Rob 2 tool for randomized controlled studies were used for risk of bias rating. Pre-surgery, 3 months, 6 months and 1 year after surgery data were pooled using random effects meta-analyses (standardized mean differences, SMD, Hedge's g) in contrast to the pre-injury values. RESULTS: 1417 studies were screened, 21 studies on 647 participants were included. Thereof, 13 were non-randomized controlled trails (moderate overall risk of bias in most studies) and 7 were randomized controlled trials (high risk of bias in at least one domain in most studies). Three (k = 12 studies; SMD = - 0.21 [95% confidence interval = - 0.36 to - 0.05], I2 = 4.75%) and six (k = 9; SMD = - 0.10 [- 0.28 to - 0.08]; I2 = 0%) months after total knee arthroplasty, a deterioration in the strength of the operated leg compared with the strength of the non-operated leg was observed. One year after surgery, the operated leg was stronger in all studies compared to the preoperative values. However, this increase in strength was not significant compared to the non-operated leg (k = 6, SMD = 0.18 [- 0.18 to 0.54], I2 = 77.56%). CONCLUSION: We found moderate certainty evidence that deficits in muscle strength of the knee extensors persist and progress until 3 months post-total knee arthroplasty in patients with end-stage knee osteoarthritis. Very low certainty evidence exists that preoperatively existing imbalance of muscle strength and mass in favor of the leg not undergoing surgery is not recovered within 1 year after surgery.

Comparison of Different Methods of Semiquantitative Assessment and Subjective Scores for Retropatellar Articular Cartilage Evaluation in Advancing Osteoarthritis.

BACKGROUND: cartilage layer thickness, composition of the extracellular matrix (ECM), geometry and configuration of retropatellar cartilage partially differ significantly from those found at other locations and are essential for patellofemoral biomechanics. MATERIAL AND METHODS: 119 serial medial and lateral patella facet samples of patients undergoing implantation of a total knee endoprosthesis of areas showing mild (Group A, macroscopically ICRS Grade 1b) respectively advanced (Group B, macroscopically ICRS Grade 3a/3b) (38 each) osteoarthritis according to the histological-histochemical grading system (HHGS) were compared with 22 healthy biopsies by means of immunohistochemistry and histology investigations. We quantified our results on the gene expression of collagen type I and II and aggrecan with real-time (RT)-PCR rsp using colourimetry for proteoglycan content. The digitized images of histology and immunohistochemistry staining with Safranin O, Alcian blue, PAS, Masson Goldner, immunostaining, e.g. for collagen I and II were also analyzed with Photoshop software. RESULTS: The most significant decrease in staining intensity was revealed for Safranin-O staining in Group B at the lateral patellar facet, and the most relevant increase was for Col I staining at the same site. The lateral patella site in Group B also showed the highest increase in the ratio of expression indices for the genes Col1A1 and the reference gene following the equation 2-ΔCt with a quotient of 29.6. CONCLUSIONS: 1. Comparisons of our retropatellar cartilage analysis with femoral and tibial studies utilizing similar techniques show significant differences. 2. Cartilage layer thickness, ECM composition, geometry and configuration are essential for patellofemoral biomechanics. 3. Consequently, there is a need for diversified approaches towards retropatellar surface during TKA as well as for advanced cartilage restoration techniques.

Influence of a Calcium Phosphate Coating (BONIT®) on the Proliferation and Differentiation Potential of Human Mesenchymal Stroma Cells in the Early Phase of Bone Healing.

When implanting osteosynthetic materials or orthopedic implants, the surface condition plays a decisive role for mid- to long-term osseointegration. BONIT®, an electrochemically produced calcium phosphate (CaP) coating, has been used in the surface refinement of implants since 1995. More than 3.5 million coated implants have been successfully placed so far. BONIT® has thus been able to demonstrate clinical success. However, due to its surface properties and solubility, and the resulting difficulty in culturing cells, there are no in vitro studies investigating its influence at the molecular level, particularly on bone metabolism. In a first step, the cells from a total of ten donors were seeded separately on four different surfaces: 1. a pure corundum-blasted titanium surface (CELLTex®, CT), 2. CT with additional BONIT® coating (CT + B), 3. a hydroxyapatite-blasted titanium surface (DUOTex®, DT), 4. DT with additional BONIT® coating (DT + B). In a second step, the cells were grown for 48 h. The proliferation behavior and differentiation potential of hMSCs were investigated at three consecutive time points (12 h, 24 h and 48 h) by quantifying the mRNA expression of ten important differentiation markers using quantitative real-time polymerase chain reaction (qRT-PCR). We were able to show that BONIT® has an influence on the early proliferation and differentiation behavior of hMSCs in patients of all age groups. The additional BONIT® coating on CELLTex® or DUOTex® led to a defined mRNA expression pattern for the investigated factors: a tendency towards a higher expression rate with coating present could be found for bone morphogenetic protein 2 (BMP2), osteopontin (OPN), osteocalcin (OC), receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG). A similar or lower expression rate was detected for runt-related transcription factor 2 (RUNX2), alpha-1 type I collagen (COL1A1), alkaline phosphatase (AP), osteonectin (ON) and insulin-like growth factor I (IGF1). We have developed a new method that allows the cultivation of human mesenchymal stromal cells (hMSCs) on the soluble coating BONIT® for gene expression analysis. BONIT® has a significant influence on the proliferation and differentiation behavior of human mesenchymal stroma cells. This study describes a defined gene expression pattern of bone metabolism that may help to understand the influence of this CaP coating on the early phase of implant osseointegration.

Impact of a Six-Week Prehabilitation With Blood-Flow Restriction Training on Pre- and Postoperative Skeletal Muscle Mass and Strength in Patients Receiving Primary Total Knee Arthroplasty.

Introduction: Total Knee Arthroplasty (TKA) is one of the most successful interventions in gonarthrosis, however the operation is leading to muscle atrophy and long-term muscular deficits. To enhance rehabilitation after TKA, exercise programs try to improve muscle function preoperatively, called prehabilitation. Blood-Flow-Restriction Exercises (BFRE) is a training method which is characterized by using tourniquets to reduce arterial and occlude venous blood flow simultaneously during the exercise to increase metabolic stress. The present study aimed to evaluate the effects of a 6-week prehabilitation with BFR on pre- and postoperative muscle mass, strength, and quality of life (QoL). Methods: 30 patients with end-stage gonarthrosis participated in this study. Patients were randomized into one of three groups: 1) Control-Group (CON): Standard clinical approach without prehabilitation. 2) Active-Control-Group (AC): Participation in a prehabilitation with sham-BFR. 3) BFR-Group (BFR): Participation in a prehabilitation with BFR. The prehabilitation protocol consist of a cycling-ergometer-based training performed twice per week over 6 weeks. During exercise, BFR was applied periodically three times per leg with a pressure of 40% of the individual-limb-occlusion-pressure. Measurement time points were six- (baseline), 3-weeks and 5-days before the surgery (Pre-OP), as well as three- and 6-months postoperatively. Outcome measures were muscular strength of the thigh muscles, thigh circumference as well as QoL and functional activity, examined by 6-min walking- and chair rising test. Results: Both training groups indicated significantly improved leg muscle strength following the prehabilitation period with a superior effect for the BFR-group (BFR: ∼170% vs. AC: ∼91%, p < 0.05). No significant changes in leg strength occurred in the CON (∼3%, p = 0.100). Further, patients in BFR-group indicated significantly improved skeletal muscle mass assessed by femoral circumference following prehabilitation period (∼7%, p < 0.05), while no significant changes occurred in the CON (-1.14%, p = 0.131) and AC-group (∼3%, p = 0.078). At 3-months Post-OP, the CON and BFR-group revealed a significant decrease in femoral circumference compared to the Pre-OP (CON: ∼3%, BFR: ∼4%; p < 0.05), but BFR-group remained above the baseline level (∼3%, p < 0.05). No significant change in femoral circumference was found for AC-group (∼2%, p = 0.078). In addition, the prehabilitation with BFR provided notably improved Knee Injury and Osteoarthritis Outcome Scores (KOOS) especially in pain perception with significant higher effect compared to other groups (CON: -2%, AC: 13%, BFR: 41%; p < 0.05). In long-term rehabilitation after 6-months, all groups showed significantly improved KOOS scores in all dimensions (CON: ∼110%, AC: ∼132%, BFR: ∼225%; p < 0.01), and functional examinations (CON: ∼26%, AC: ∼16%, BFR: ∼53%; p < 0.01). Conclusion: The present findings show that BFR-prehabilitation induce significant improvements in muscle function and QoL before TKA surgery. In addition, the supporting effect of prehabilitation on postoperative regeneration and QoL should be highlighted, illustrating prolonged beneficial effects of BFR on muscular and functional performance in a "better in, better out"-manner.

Acute myeloid leukemia-induced functional inhibition of healthy CD34+ hematopoietic stem and progenitor cells.

Acute myeloid leukemia (AML) is characterized by an expansion of leukemic cells and a simultaneous reduction of normal hematopoietic precursors in the bone marrow (BM) resulting in hematopoietic insufficiency, but the underlying mechanisms are poorly understood in humans. Assuming that leukemic cells functionally inhibit healthy CD34+ hematopoietic stem and progenitor cells (HSPC) via humoral factors, we exposed healthy BM-derived CD34+ HSPC to cell-free supernatants derived from AML cell lines as well as from 24 newly diagnosed AML patients. Exposure to AML-derived supernatants significantly inhibited proliferation, cell cycling, colony formation, and differentiation of healthy CD34+ HSPC. RNA sequencing of healthy CD34+ HSPC after exposure to leukemic conditions revealed a specific signature of genes related to proliferation, cell-cycle regulation, and differentiation, thereby reflecting their functional inhibition on a molecular level. Experiments with paired patient samples showed that these inhibitory effects are markedly related to the immunomagnetically enriched CD34+ leukemic cell population. Using PCR, ELISA, and RNA sequencing, we detected overexpression of TGFß1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFß1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFß1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFß receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFß1, suggesting that blockage of this pathway may improve hematopoiesis in AML.

Invasive Assessment of Hemodynamic, Metabolic and Ionic Consequences During Blood Flow Restriction Training.

Purpose: Medically recommended training often faces the dilemma that necessary mechanical intensities for muscle adaptations exceed patients' physical capacity. In this regard, blood flow restriction (BFR) training is becoming increasingly popular because it enables gains in muscle mass and strength despite using low-mechanical loads combined with external venous occlusion. Since the underlying mechanisms are still unknown, we applied invasive measurements during exercise with and without BFR to promote physiological understanding and safety of this popular training technique. Methods: In a randomized cross-over design, ten healthy men (28.1 ± 6.5 years) underwent two trials of unilateral biceps curls either with (BFR) and without BFR (CON). For analysis of changes in intravascular pressures, blood gases, oximetry and electrolytes, an arterial and a venous catheter were placed at the exercising arm before exercise. Arterial and venous blood gases and intravascular pressures were analyzed before, during and 5 min after exercise. Results: Intravascular pressures in the arterial and venous system were more increased during exercise with BFR compared to CON (p < 0.001). Furthermore, arterial and venous blood gas analyses revealed a BFR-induced metabolic acidosis (p < 0.05) with increased lactate production (p < 0.05) and associated elevations in [K+], [Ca2+] and [Na+] (p < 0.001). Conclusion: The present study describes for the first time the local physiological changes during BFR training. While BFR causes greater hypertension in the arterial and venous system of the exercising extremity, observed electrolyte shifts corroborate a local metabolic acidosis with concurrent rises in [K+] and [Na+]. Although BFR could be a promising new training concept for medical application, its execution is associated with comprehensive physiological challenges.

Automatic Cartilage Segmentation for Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Hip Joint Cartilage: A Feasibility Study.

OBJECTIVE: Automatic segmentation for biochemical cartilage evaluation holds promise for an efficient and reader-independent analysis. This pilot study aims to investigate the feasibility and to compare delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) hip joint assessment with manual segmentation of acetabular and femoral head cartilage and dGEMRIC hip joint assessment using automatic surface and volume processing software at 3 Tesla. DESIGN: Three-dimensional (3D) dGEMRIC data sets of 6 patients with hip-related pathology were assessed (1) manually including multiplanar image reformatting and regions of interest (ROI) analysis and (2) automated by using a combined surface and volume processing software. For both techniques, T1Gd values were obtained in acetabular and femoral head cartilage at 7 regions (anterior, anterior-superior, superior-anterior, superior, superior-posterior, posterior-superior, and posterior) in central and peripheral portions. Correlation between both techniques was calculated utilizing Spearman's rank correlation coefficient. RESULTS: A high correlation between both techniques was observed for acetabular (ρ = 0.897; P < 0.001) and femoral head (ρ = 0.894; P < 0.001) cartilage in all analyzed regions of the hip joint (ρ between 0.755 and 0.955; P < 0.001). CONCLUSIONS: Automatic cartilage segmentation with dGEMRIC assessment for hip joint cartilage evaluation seems feasible providing high to excellent correlation with manually performed ROI analysis. This technique is feasible for an objective, reader-independant and reliable assessment of biochemical cartilage status.

Influence of leg length inequalities on pelvis and spine in patients with total hip arthroplasty.

BACKGROUND: Leg length inequalities (LLIs) are a common finding in patients with a total hip arthroplasty (THA). Therefore, we compared the effects of simulated LLIs in patients with total hip arthroplasty (THA) with a matched control group. RESEARCH QUESTION: Do LLIs lead to different effects on the musculoskeletal apparatus of patients with a THA then in a control group? METHODS: In 99 patients with a THA the effects of simulated LLIs were compared to a matched control group of 101 subjects without a hip arthroplasty. First, we compared methods for LLI quantification (tape measurements, pelvic x- ray and rasterstereography). Second, the effects of simulated LLIs on the spine and pelvis were evaluated in both groups using surface topography. LLIs of 5, 10, 15, 20 and 30 mm were simulated on both sides with a simulation platform. The changes of pelvic position (pelvic obliquity & pelvic torsion) and the effects on spinal posture (surface rotation & lateral deviation) were measured and analysed using a surface topography system. RESULTS: Mean LLI measured with a tape was 0.9 mm (SD +/- 14.8). Mean pelvic obliquity measured on x-rays was 1.2 mm (SD +/- 11.6) and with surface topography 0.9 mm (SD +/- 7.9). Simulated LLIs resulted in significant changes of pelvic position and spinal posture in the patient and control group. Interestingly, our study showed that simulated LLIs lead to greater changes in pelvic position (p<0.05) in patients with a THA. SIGNIFICANCE: This is the first study to demonstrate that LLIs might have a greater impact on the pelvic position of THA patients than in native hips, which could indicate that LLIs do need to be compensated differently in patients with THA than in patients without a THA.

Secretome analysis of human bone marrow derived mesenchymal stromal cells.

As an essential cellular component of the bone marrow (BM) microenvironment mesenchymal stromal cells (MSC) play a pivotal role for the physiological regulation of hematopoiesis, in particular through the secretion of cytokines and chemokines. Mass spectrometry (MS) facilitates the identification and quantification of a large amount of secreted proteins (secretome), but can be hampered by the false-positive identification of contaminating proteins released from dead cells or derived from cell medium. To reduce the likelihood of contaminations we applied an approach combining secretome and proteome analysis to characterize the physiological secretome of BM derived human MSC. Our analysis revealed a secretome consisting of 315 proteins. Pathway analyses of these proteins revealed a high abundance of proteins related to cell growth and/or maintenance, signal transduction and cell communication thereby representing key biological functions of BM derived MSC on protein level. Within the MSC secretome we identified several cytokines and growth factors such as VEGFC, TGF-ß1, TGF-ß2 and GDF6 which are known to be involved in the physiological regulation of hematopoiesis. By comparing the peptide patterns of secretomes and cell lysates 17 proteins were identified as candidates for proteolytic processing. Taken together, our combined MS work-flow reduced the likelihood of contaminations and enabled us to carve out a specific overview about the composition of the secretome from human BM derived MSC. This methodological approach and the specific secretome signature of BM derived MSC may serve as basis for future comparative analyses of the interplay of MSC and HSPC in patients with hematological malignancies.

Biomechanical Stability and Osteogenesis in a Tibial Bone Defect Treated by Autologous Ovine Cord Blood Cells-A Pilot Study.

The aim of this study was to elucidate the impact of autologous umbilical cord blood cells (USSC) on bone regeneration and biomechanical stability in an ovine tibial bone defect. Ovine USSC were harvested and characterized. After 12 months, full-size 2.0 cm mid-diaphyseal bone defects were created and stabilized by an external fixateur containing a rigidity measuring device. Defects were filled with (i) autologous USSC on hydroxyapatite (HA) scaffold (test group), (ii) HA scaffold without cells (HA group), or (iii) left empty (control group). Biomechanical measures, standardized X-rays, and systemic response controls were performed regularly. After six months, bone regeneration was evaluated histomorphometrically and labeled USSC were tracked. In all groups, the torsion distance decreased over time, and radiographies showed comparable bone regeneration. The area of newly formed bone was 82.5 ± 5.5% in the control compared to 59.2 ± 13.0% in the test and 48.6 ± 2.9% in the HA group. Labeled cells could be detected in lymph nodes, liver and pancreas without any signs of tumor formation. Although biomechanical stability was reached earliest in the test group with autologous USSC on HA scaffold, the density of newly formed bone was superior in the control group without any bovine HA.

Tensiomyography parameters and serum biomarkers after eccentric exercise of the elbow flexors.

PURPOSE: The tensiomyography (TMG) technique is increasingly used to determine muscle contractile properties in exercise and injury management. The present study investigated the informative value of TMG parameters in correlation with commonly used (creatine kinase, CK; myoglobin, Mb) and novel candidate biomarkers of muscle damage (heart-type fatty acid-binding protein, h-FABP; high-mobility group box 1, HMGB1). METHODS: Ten untrained men performed 6 × 10 eccentric contractions of the elbow flexors at 110% of the concentric one repetition maximum. CK, Mb, h-FABP, HMGB1, arm circumference, pain and TMG data, including maximal displacement (Dm) and temporal outcomes as the contraction time (Tc), sustained time (Ts), delay time (Td), and relaxation time (Tr), were assessed pre-exercise, post-exercise, 20 min, 2 h and on the consecutive 3 days post-exercise. RESULTS: CK and h-FABP significantly increased beginning at 24 h, Mb already increased at 2 h (p < 0.05). HMGB1 was only increased immediately post-exercise (p = 0.02). Tc and Td remained unchanged, whereas Ts and Tr were significantly slower beginning at 24 h (p < 0.05). Dm was decreased within the first 24 h and after 72 h (p < 0.01). The % change from pre-exercise correlated for Dm with CK, Mb, and h-FABP the highest at 48 h (r = - 0.95, - 0.87 and - 0.79; p < 0.01) and for h-FABP with CK and Mb the highest at 24 h (r = 0.96 and 0.94, for all p < 0.001). CONCLUSION: This study supports the correlation of TMG parameters with muscle damage markers after eccentric exercise. Therefore, TMG could represent a non-invasive and cost effective alternative to quantify the degree of muscle damage after exercise interventions.

Elite Rowers Demonstrate Consistent Patterns of Hip Cartilage Damage Compared With Matched Controls: A T2* Mapping Study.

BACKGROUND: Rowing exposes the femoral head and acetabulum to high levels of repetitive abutment motion and axial loading that may put elite athletes at an increased risk for developing early hip osteoarthritis. QUESTIONS/PURPOSES: Do elite rowers demonstrate characteristic hip cartilage lesions on T2 MRI sequences compared with asymptomatic individuals who do not row? METHODS: This study included 20 asymptomatic rowers (mean age, 23 ± 3 years; nine females, 11 males) who had a minimum of 5 years of intensive (≥ 12 hours/week) training. The recruiting of the rowers took place from the central German federal rowing base, which has inherent intense training and selection requirements to declare these athletes as "elite rowers." We investigated one hip per study participant. MRI was performed on a 3-T scanner. The protocol included standard sequences, a double-echo steady-state sequence, and a multiecho data image combination sequence with inline T2 calculation (= the decay of transverse magnetization arising from molecular interactions [T2] and inhomogeneities in the magnetic field resulting from tissue susceptibility-induced field distortions and variations in the magnet itself), which detects changes in water content and the disruption of collagen structure. Although extrinsic and intrinsic influences on the T2 values including diurnal effects, MR technic-derived variations, and anatomic-related regional disparities need to be taken into account, low T2 values well below 20 ms indicate cartilage degeneration. Cartilage was morphologically analyzed in the anterior, anterosuperior, superoanterior, superior, superoposterior, posterosuperior, and posterior regions of the hip and graded as follows: Grade 0 = normal; Grade 1 = signal changes; Grade 2 = cartilage abrasion; Grade 3 = cartilage loss. Labrum was classified as follows: Grade 0 = normal; Grade 1 = partial tear; Grade 2 = full-thickness tear; Grade 3 = labrum degeneration. The T2 measurement was done through a region of interest analysis. For reliability assessment, morphologic evaluation and T2 measurement were performed by two observers while one observer repeated his analysis with a time interval > 2 weeks. Intra- and interobserver reliability was determined using κ analysis and intraclass correlation coefficients. Control T2 data were derived from a previous study on 15 hips in 15 asymptomatic volunteers of similar ages (seven males and eight females) who were not competitive rowers with similar MR hardware and imaging sequences. RESULTS: Compared with the control group of asymptomatic volunteers who were not competitive rowers, we noted a high level of labrum and cartilage degeneration in the cohort of elite rowers. In the group of elite rowers, cartilage degeneration was noted in all hips. Regarding the acetabular cartilage, 271 zones could be evaluated. Of those, 44% (120 of 271) were graded normal, 6% (15 of 271) revealed signal alteration, 45% (122 of 271) demonstrated cartilage abrasion, and 5% (14 of 271) were noted to have full-thickness cartilage loss. Morphologic cartilage degeneration in the femoral head was less frequent. T2 values were lower than the control hips in all zones except for the posterior central acetabular zone (global T2 acetabular: 20 ± 6 ms, range, 9-36 ms, 95% confidence interval [CI], 19-21 ms versus 25 ± 5 ms, range, 14-44 ms, 95% CI, 24-25 ms, p < 0.001; global T2 femoral: 23 ± 7 ms, range, 9-38 ms, 95% CI, 22-24 ms versus 27 ± 5 ms, range, 17-45 ms, 95% CI, 26-28 ms, p < 0.001). The difference in T2 between the two study groups was superior in the peripheral zone of the anterosuperior region (16 ± 3 ms; range, 10-22 ms, 95% CI, 15-18 ms versus 26 ms ± 5 ms, range, 18-38 ms, 95% CI, 24-29 ms, p < 0.001). CONCLUSIONS: We found signs of hip cartilage degeneration to a much greater degree in elite rowers than in asymptomatic controls. Although causation cannot be inferred, this is concerning, and future investigations including controlled longitudinal studies both on elite and nonelite athletes with sufficient cohort size are warranted to clarify our findings. LEVEL OF EVIDENCE: Level III, therapeutic study.

[Degenerative changes in the hand and wrist in elite MMA fighting - an MRI study in comparison to boxing]. / Degenerative Veränderungen an Hand und Handgelenk bei MMA-Kämpfern ­ Eine MRT Studie im Vergleich zu Boxern.

OBJECTIVE: Mixed martial arts (MMA) is a combination of multiple combat sports. Acute injuries in MMA are well known and have been broadly described. However, there is little knowledge about degenerative changes in the musculoskeletal system. The aim of this study was to investigate the impact of techniques used in MMA on the occurrence of degenerative changes in the hand and wrist in comparison to classical boxing. METHODS: 11 MMA fighters and 10 boxers with chronic wrist pain were clinically examined. Age, weight, years of training, number of fights, level of competition and weekly hours of training were recorded. To determine degenerative changes, an MRI of the symptomatic hand was assessed. RESULTS: Years of training, level of competition and number of fights did not show a significant difference between MMA and boxing fighters (p > 0.05), but MMA fighters showed significantly more hours of training per week (p < 0.001). The MMA fighters had more often and more severe degenerative changes of all examined structures (bone, fibrocartilage, ligaments and tendons), with the category "bone" reaching significance (p = 0.002). CONCLUSION: MMA athletes show significantly greater incidence and degree of degeneration in hand and wrist joints. The exact reasons are still unknown and further research is needed to determine the influence of MMA techniques on the severity of degenerative changes in the hand and wrist.

The role of oxidative and nitrosative stress in the pathology of osteoarthritis: Novel candidate biomarkers for quantification of degenerative changes in the knee joint.

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.

Transforming growth factor ß1-mediated functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia.

Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia and found a specific molecular signature of genes commonly deregulated in these disorders. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines, thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level. Further analysis identified transforming growth factor ß1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to transforming growth factor ß1, healthy mesenchymal stromal cells developed functional deficits and adopted a phenotype reminiscent of that observed in patient-derived stromal cells. These suppressive effects of transforming growth factor ß1 on stromal cell functionality were abrogated by SD-208, an established inhibitor of transforming growth factor ß receptor signaling. Blockade of transforming growth factor ß signaling by SD-208 also restored the osteogenic differentiation capacity of patient-derived stromal cells, thus confirming the role of transforming growth factor ß1 in the bone marrow microenvironment of patients with myelodysplastic syndromes and acute myeloid leukemia. Our findings establish transforming growth factor ß1 as a relevant trigger causing functional inhibition of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia and identify SD-208 as a candidate to revert these effects.

Partial Hemiresurfacing of Osteochondral Defects of the Talus? Surgical Technique and Preliminary Report from Four Patients.

BACKGROUND: Osteochondral lesions of the medial talus (OLT) frequently lead to chronic ankle pain and osteoarthritis. Arthroscopic debridement, subchondral bone stimulation by drilling, and microfracturing are options for primary therapy in small lesions. In larger lesions, restoration of the talar dome contour seems to be a mandatory course of action. METHODS: In a case series, we followed up four patients being treated with a focal resurfacing prosthetic due to large osteochondral talar lesions. In contrast to other studies, we can report on an off-label application to restore defects of the lateral talar dome with two patients for the first time. At follow-up, three patients reported a remarkable reduction in pain and were able to return to sports activities. One patient developed pseudarthrosis of the medial malleolar osteosynthesis. CONCLUSIONS: With selected patients, focal resurfacing appears to be an option for large osteochondral defects of the talus.

Wear Kinetics of Highly Cross-Linked and Conventional Polyethylene Are Similar at Medium-term Follow-Up After Primary Total Hip Arthroplasty.

BACKGROUND: Wear debris is a major factor in aseptic loosening of total hip arthroplasty. Ultra high molecular weight polyethylene inlays are known for significant wear, and the following generation, highly cross-linked polyethylene (HCLPE), has shown promising in vitro and short-term in vivo results. This study aimed to investigate wear debris of HCLPE liners with ceramic heads after 9 years to reveal the in vivo wear kinetics of this common bearing combination. METHODS: Fifty-seven patients (72 hips; 46.5 ± 15.5 years; range 16-76 years) who underwent hip arthroplasty with an HCLPE liner (28- or 32-mm Biolox forte ceramic head) were followed up (mean 9.1 ± 2.4 years; range 3.9-13.8 years). Conventional anteroposterior X-rays were analyzed using Hip Analysis Suite software. RESULTS: Volumetric wear had a mean of 38.67 ± 22.09 mm3/year, 333.08 ± 183.93 mm3 overall, and linear wear was 0.063 ± 0.03 mm/year and 0.546 ± 0.27 mm overall. Male patients had a significantly higher wear rate (46.42 ± 27.68 mm3/year) and total wear (400.71 ± 235.21 mm3). Larger femoral heads had a significantly higher wear rate (43.10 ± 23.93 mm3/year) and total wear (364.23 ± 203.68 mm3). Regression analysis showed a significant cubic relationship (R2 = 0.307) with increasing yearly wear after approximately 108 months postoperatively. CONCLUSIONS: HCLPE liners show significant in vivo wear after 9 years. While the total wear compared to ultra high molecular weight polyethylene liners was decreased, the wear kinetics show a comparable course. The increase in wear rate after only 108 months postoperatively is especially alarming. Longer term follow-up is needed to distinguish the long-term superiority of HCLPE liners in polyethylene-ceramic paired hip arthroplasty.

Blood flow restriction training as a prehabilitation concept in total knee arthroplasty: A narrative review about current preoperative interventions and the potential impact of BFR.

Osteoarthritis of the knee is one of the most commonly diagnosed joint ailments and responsible for increased rates of total knee arthroplasty surgeries worldwide. Whereas the surgical approach is able to diminish the perceived knee pain of concerned patients', the postoperative recovery is often accompanied by persistent skeletal muscle dysfunctions and atrophy, which is responsible for functional deficits for up to several years. Recent findings indicate that surgery induced adverse effects on skeletal muscles are largely associated with the use of pneumatic tourniquets, wherefore several studies try to reduce tourniquet use in orthopedic surgery. However, due to comparable incidence of muscle impairment and increased surgical challenge, the most frequently applied surgical technique in TKA is still associated with the use of tourniquets. When attenuating TKA induced adverse effects, the preoperative preparation of patients by specific exercises (called prehabilitation) was able to enhance preoperative overall fitness through associated accelerated recovery. Based on patients' limited functional activity, prehabilitation techniques have to be particularly designed to allow regular adherence. The present paper is based on a narrative review of current literature, and provides a novel hypothesis by which blood flow restriction exercises (BFR) are able to improve patients' compliance to prehabilitation. BFR training is characterized by the application of low-resistance exercise with similar intensities as daily living tasks in association with a suppression of venous blood flow in an extremity, achieving significant morphological and neuromuscular adaptations in skeletal muscles. In addition, preoperative enhancements in muscle health with corresponding benefits in overall fitness, BFR induced molecular alterations could also be able to interfere with TKA induced pathological signaling. Therefore, based on the known major impact of BFR on skeletal muscle physiology, the present paper aims to illustrate the potential beneficial impact of BFR training as a prehabilitation concept to promote patients regular adherence to preoperative exercises and thus achieve an accelerated recovery and increases in patients' satisfaction.