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Osteoarthritis (OA) of the hip and knee joint is a common disease worldwide and is associated with chronic disability and progressive pain. Currently, themost suitable treatment method in end-stage OA is surgical restoration by total joint replacement (TJR). In this regard, patients suffering from end-stage OA and waiting forTJR intervention are also affected by extensively impaired skeletal muscle health. This is characterized by progressive muscle atrophy, strength decline and associated deficits in neuromuscular activation. Unfortunately the importance of skeletal muscle health, as a predictor for a successful muscular and functional recovery, is clinically underrepresented in medical indication and preoperative diagnostics. Therefore, this review aims to describe patients pre, peri and postoperative muscle health during the whole process of aTJR intervention. Additionally, underlying mechanisms and potential perioperative stressors, which may be responsible for impaired muscular physiology after TJR, will be described. As a second purpose, this review illustrates the potential impact of preoperative exercise interventions by challenging the better in, better out approach in TJR therapy. KEY WORDS: Muscle Atrophy, Total Knee Arthroplasty, Total Hip Arthroplasty, Preoperative Intervention, Arthrogenic Muscle Inhibition

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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.

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], I 2  = 4.75%) and six (k = 9; SMD = - 0.10 [- 0.28 to - 0.08]; I 2  = 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], I 2  = 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., (© 2023. The Author(s).)

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.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Franz, Ji, Bittersohl, Zilkens and Behringer.)

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 TGFβ1 in leukemic cells on the transcriptional and protein level and, correspondingly, a molecular signature related to TGFβ1 signaling in healthy CD34+ HSPC. This inhibitory effect of TGFβ1 on healthy hematopoiesis was functionally corrobated and could be pharmacologically reverted by SD208, an inhibitor of TGFβ receptor 1 signaling. Overall, these data indicate that leukemic cells induce functional inhibition of healthy CD34+ HSPC, at least in part, through TGFβ1, suggesting that blockage of this pathway may improve hematopoiesis in AML., (© 2021 The Authors. STEM CELLS published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

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 + ], [Ca 2+ ] 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Franz, Berndt, Raabe, Harmsen, Zilkens and Behringer.)

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, T1 Gd 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.

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., Competing Interests: The authors have declared that no competing interests exist.

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.