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.

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.

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.

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.

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.

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.

3D double-echo steady-state sequence assessment of hip joint cartilage and labrum at 3 Tesla: comparative analysis of magnetic resonance imaging and intraoperative data.

OBJECTIVES: To assess the diagnostic accuracy of a high-resolution, three-dimensional (3D) double-echo steady-state (DESS) sequence with radial imaging at 3 Tesla (T) for evaluating cartilage and labral alterations in the hip. METHODS: Magnetic resonance imaging (MRI) data obtained at 3 T, including radially reformatted DESS images and intraoperative data of 45 patients (mean age 42 ± 13.7 years) who underwent hip arthroscopy, were compared. The acetabular cartilage and labrum of the upper hemisphere of the acetabulum and the central femoral head cartilage were evaluated. Sensitivity, specificity, accuracy, and negative and positive predictive values were determined. RESULTS: Sensitivity, specificity and accuracy of the DESS technique were 96.7%, 75% and 93.7% for detecting cartilage lesions and 98%, 76.2% and 95.9% for detecting labral lesions. The positive and negative predictive values for detecting or ruling out cartilage lesions were 96% and 78.9%. For labral lesions, the positive and negative predictive values were 97.5% and 80%. CONCLUSION: A high-resolution, 3D DESS technique with radial imaging at 3 T demonstrated high accuracy for detecting hip cartilage and labral lesions with excellent interobserver agreement and moderate correlation between MRI and intraoperative assessment. KEY POINTS: • High-resolution, 3D DESS with radial imaging allows accurate cartilage and labrum evaluation. • DESS demonstrated high sensitivity, specificity, accuracy for detecting cartilage and labral lesions. • Highly accurate sequence may influence treatment decisions in patients with hip pain.

Glycosaminoglycan chemical exchange saturation transfer at 3T MRI in asymptomatic knee joints.

BACKGROUND: Biochemical alterations such as glycosaminoglycan (GAG) depletion occur early in the course of osteoarthritis, but cannot be detected with standard magnetic resonance techniques. With glycosaminoglycan chemical exchange saturation transfer (gagCEST), a biochemical imaging technique, it is feasible to detect biochemical components in knee joint cartilage. PURPOSE: To establish baseline values for gagCEST magnetic resonance imaging (MRI) in knee joint cartilage at 3 Tesla (T). MATERIAL AND METHODS: Twenty volunteers (8 women, 12 men; mean age, 24.55 ± 2.35 years;age range, 21-29 years) with no history or clinical findings indicative of knee joint pathologies underwent MRI at 3T. The imaging protocol included three-dimensional (3D) double-echo steady-state sequence for morphological cartilage assessment and a prototype 3D CEST pulse sequence to evaluate the CEST effects in six cartilage regions of the knee joint: (i) lateral femoral condyle; (ii) medial femoral condyle; (iii) lateral tibial plateau; (iv) medial tibial plateau; (v) patella; and (vi) trochlea. We used the asymmetry of the magnetization transfer ratio (MTRasym) parameter to quantify the gagCEST effects in these regions. RESULTS: Regional differences revealed high MTRasym values in the patellar (1.62% ± 1.19%) and the trochlear (1.17% ± 1.29%) cartilages, and low MTRasym values in the medial femoral condyle (0.41% ± 0.58%) and the lateral tibial plateau (0.52% ± 0.53%) cartilages. CONCLUSION: Regional differences in the gagCEST values must be considered when conducting gagCEST imaging of knee joint cartilage. In the future gagCEST imaging may be an additional feature in the evaluation of the biochemical composition of knee joint cartilage.

Effects of thromboprophylaxis on mesenchymal stromal cells during osteogenic differentiation: an in-vitro study comparing enoxaparin with rivaroxaban.

BACKGROUND: Low-molecular-weight heparins (e.g. Enoxaparin) are widely used to prevent venous thromboembolism after orthopaedic surgery, but there are reports about serious side effects including reduction in bone density and strength. In recent years new oral antithrombotic drugs (e.g. direct Factor Xa-inhibitor, Rivaroxaban) have been used to prevent venous thromboembolism. However, there is lack of information on the effects of these new drugs on human mesenchymal stromal cells during osteogenic differentiation and, therefore, effects during postoperative bone healing. METHODS: We evaluated the effects of Rivaroxaban and Enoxaparin on the proliferation, mRNA and surface receptor expression as well as differentiation capacity of primary human mesenchymal stromal cells during their osteogenic differentiation. RESULTS: Enoxaparin, but not Rivaroxaban treatment significantly increased human mesenchymal stromal cell (hMSC) proliferation during the first week of osteogenic differentiation while suppressing osteogenic marker genes, surface receptor expression and calcification. CONCLUSIONS: This is the first paper to demonstrate that Rivaroxaban had no significant influence on hMSC differentiation towards the osteogenic lineage, indicating a less affected bone healing process compared with Enoxaparin in vitro. Based on these findings Rivaroxaban seems to be superior to Enoxaparin in early stages of bone healing in vitro.

Current knowledge and importance of dGEMRIC techniques in diagnosis of hip joint diseases.

Accurate assessment of early hip joint cartilage alterations may help optimize patient selection and follow-up of hip joint preservation surgery. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) is sensitive to the glycosaminoglycan content in cartilage that is lost early in the development of osteoarthritis (OA). Hence, the dGEMRIC technique holds promise for the development of new diagnostic and therapeutic procedures. However, because of the location of the hip joint deep within the body and due to the fairly thin cartilage layers that require high spatial resolution, the diagnosis of early hip joint cartilage alterations may be problematic. The purpose of this review is to outline the current status of dGEMRIC in the assessment of hip joint cartilage. A literature search was performed with PubMed, using the terms "cartilage, osteoarthritis, hip joint, MRI, and dGEMRIC", considering all levels of studies. This review revealed that dGEMRIC can be reliably used in the evaluation of early stage cartilage pathology in various hip joint disorders. Modifications in the technique, such as the operation of three-dimensional imaging and dGEMRIC after intra-articular contrast medium administration, have expanded the range of application. Notably, the studies differ considerably in patient selection and technical prerequisites. Furthermore, there is a need for multicenter prospective studies with the required technical conditions in place to establish outcome based dGEMRIC data to obtain, in conjunction with clinical data, reliable threshold values for normal and abnormal cartilage, and for hips that may benefit from conservative or surgical treatment.

Opioids as an alternative to amide-type local anaesthetics for intra-articular application.

PURPOSE: Recently, the safety profile of local anaesthetics in intra-articular use became into focus of investigation. Opioid drugs have a different mode of action and may be a safe and potent alternative for intra-articular application. The purpose of this in vitro study is to provide evidence for significant chondrotoxicity of amide-type local anaesthetics even after short-term application on human chondrocytes and to demonstrate the absence of such negative effects for opioids [morphine, morphine-6-glucuronide (M6G)]. METHOD: Visually intact cartilage explants of human, mainly osteoarthritic joints (n = 9), were harvested and cultivated in monolayer for expansion and transferred into alginate bead. The beads were incubated for increasing incubation times (15 min, 1 and 4 h) in decreasing concentrations (full, ½, » for 15 min) of bupivacaine, ropivacaine, morphine, M6G or saline control. Adenosine triphosphate content of 798 beads was measured 3 days post-incubation to assess cell viability. RESULTS: A clear ranking of cytotoxic potency: bupivacaine > ropivacaine > morphine = M6G = saline was observed. Results reveal a dose- and time-dependent manner of cytotoxic effects on human chondrocytes for bupivacaine and ropivacaine but not for opioids. Cell viability after exposure to morphine and M6G was comparable to exposure to saline. CONCLUSION: The results confirm dose- and time-dependent cytotoxic effects on human chondrocytes for amide-type local anaesthetics. This study confirms the safety of morphine and M6G in terms of an absence of cytotoxic effects after intra-articular application, making them safe potential alternatives in clinical practice.

T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of humeral articular cartilage--a histologically controlled study.

BACKGROUND: Cartilage biochemical imaging modalities that include the magnetic resonance imaging (MRI) techniques of T2* mapping (sensitive to water content and collagen fiber network) and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC, sensitive to the glycosaminoglycan content) can be effective instruments for early diagnosis and reliable follow-up of cartilage damage. The purpose of this study was to provide T2* mapping and dGEMRIC values in various histologic grades of cartilage degeneration in humeral articular cartilage. METHODS: A histologically controlled in vitro study was conducted that included human humeral head cartilage specimens with various histologic grades of cartilage degeneration. High-resolution, 3-dimensional (3D) T2* mapping and dGEMRIC were performed that enabled the correlation of MRI and histology data. Cartilage degeneration was graded according to the Mankin score, which evaluates surface morphology, cellularity, toluidine blue staining, and tidemark integrity. SPSS software was used for statistical analyses. RESULTS: Both MRI mapping values decreased significantly (P < .001) with increasing cartilage degeneration. Spearman rank analysis revealed a significant correlation (correlation coefficients ranging from -0.315 to 0.784; P < .001) between the various histologic parameters and the T2* and T1Gd mapping values. CONCLUSION: This study demonstrates the feasibility of 3D T2* and dGEMRIC to identify various histologic grades of cartilage damage of humeral articular cartilage. With regard to the advantages of these mapping techniques with high image resolution and the ability to accomplish a 3D biochemically sensitive imaging, we consider that these imaging techniques can make a positive contribution to the currently evolving science and practice of cartilage biochemical imaging.

Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells.

Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. We show that hematopoietic stem and progenitor cells (HSPCs), in particular megakaryocyte-erythrocyte progenitors, are diminished in the BM of MM patients. Genomic profiling of HSPC subsets revealed deregulations of signaling cascades, most notably TGFß signaling, and pathways involved in cytoskeletal organization, migration, adhesion, and cell-cycle regulation in the patients. Functionally, proliferation, colony formation, and long-term self-renewal were impaired as a consequence of activated TGFß signaling. In accordance, TGFß levels in the BM extracellular fluid were elevated and mesenchymal stromal cells (MSCs) had a reduced capacity to support long-term hematopoiesis of HSPCs that completely recovered on blockade of TGFß signaling. Furthermore, we found defective actin assembly and down-regulation of the adhesion receptor CD44 in MM HSPCs functionally reflected by impaired migration and adhesion. Still, transplantation into myeloma-free NOG mice revealed even enhanced engraftment and normal differentiation capacities of MM HSPCs, which underlines that functional impairment of HSPCs depends on MM-related microenvironmental cues and is reversible. Taken together, these data implicate that hematopoietic suppression in MM emerges from the HSPCs as a result of MM-related microenvironmental alterations.

Direct comparison of intra-articular versus intravenous delayed gadolinium-enhanced MRI of hip joint cartilage.

PURPOSE: To investigate the potential of delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) after intra-articular (ia) contrast agent administration at 3 Tesla (T), a paired study comparing intravenous (iv) dGEMRIC (standard) with ia-dGEMRIC was performed. MATERIALS AND METHODS: Thirty-five symptomatic patients with suspected cartilage damage underwent ia- and iv-dGEMRIC. MRI was performed with a 3T system wherein the interval between both measurements was 2 weeks. For iv-dGEMRIC, FDA approved Gd-DOTA(-) was injected intravenously 45 min before the MRI scan. For ia-dGEMRIC, 10-20 mL of a 2 mM solution of Gd- DOTA(-) was injected under fluoroscopic guidance 30 min before the MRI scan. RESULTS: Both ia- and iv-dGEMRIC demonstrated the typical T1Gd pattern in hip joint cartilage with increasing values toward the superior regions in acetabular cartilage reflecting the higher glycosaminoglycan (GAG) content in the main weight-bearing area. Correlation analysis revealed a moderate correlation between both techniques (r = 0.439, P-value < 0.001), whereas the T1Gd values for iv-dGEMRIC were significantly higher than those for ia-dGEMRIC. This corresponds with the Bland-Altman plot analysis, which revealed a systemic bias (higher T1Gd values after iv gadolinium application) of ∼70 ms. CONCLUSION: Ia-dGEMRIC was able to reveal the characteristic T1Gd pattern in hip joint cartilage confirming the sensitivity of ia-dGEMRIC for GAG. In addition, there was a significant correlation between iv-dGEMRIC and ia-dGEMRIC. However, the T1Gd values after ia contrast media application were significantly lower than those after iv application that has to be considered for future studies.

T2* mapping for articular cartilage assessment: principles, current applications, and future prospects.

With advances in joint preservation surgery that are intended to alter the course of osteoarthritis by early intervention, accurate and reliable assessment of the cartilage status is critical. Biochemically sensitive MRI techniques can add robust biomarkers for disease onset and progression, and therefore, could be meaningful assessment tools for the diagnosis and follow-up of cartilage abnormalities. T2* mapping could be a good alternative because it would combine the benefits of biochemical cartilage evaluation with remarkable features including short imaging time and the ability of high-resolution three-dimensional cartilage evaluation-without the need for contrast media administration or special hardware. Several in vitro and in vivo studies, which have elaborated on the potential of cartilage T2* assessment in various cartilage disease patterns and grades of degeneration, have been reported. However, much remains to be understood and certain unresolved questions have become apparent with these studies that are crucial to the further application of this technique. This review summarizes the principles of the technique and current applications of T2* mapping for articular cartilage assessment. Limitations of recent studies are discussed and the potential implications for patient care are presented.

Spectrum of T2* values in knee joint cartilage at 3 T: a cross-sectional analysis in asymptomatic young adult volunteers.

OBJECTIVE: To establish baseline T2* values in healthy knee joint cartilage at 3 T. MATERIALS AND METHODS: Thirty-four volunteers (mean age: 24.6 ± 2.7 years) with no history or clinical findings indicative of any knee joint disease were enrolled. The protocol included a double-echo steady-state (DESS) sequence for morphological cartilage evaluation and a gradient-echo multi-echo sequence for T2* assessment. Bulk and zonal T2* values were assessed in eight regions: posterior lateral femoral condyle; central lateral femoral condyle; trochlea; patella; lateral tibial plateau; posterior medial femoral condyle; central medial femoral condyle; and medial tibial plateau. Statistical evaluation comprised a two-tailed t test and a one-way analysis of variance to identify zonal and regional differences. RESULTS: T2* mapping revealed higher T2* values in the superficial zone in all regions (P values ≤ 0.001) except for the posterior medial femur condyle (P = 0.087), and substantial regional differences demonstrating superior values in trochlear cartilage, intermediate values in patellar and central femoral condylar cartilage, and low T2* values in posterior femoral condylar cartilage and tibial plateau cartilage. CONCLUSION: Substantial regional differences in T2* measures should be taken into consideration when conducting T2* mapping of knee joint cartilage.

Biometrical analysis of the shoulder joint regarding glenoid implant dimensions for arthroplasty.

PURPOSE: Reduced bone stock and difficult intraoperative orientation are challenges in glenoid replacement surgery. New implant designs and methods for fixation, such as locking screws, extra-long central pegs and/or central compression screws are targeting these issues. The objective of this study is the analysis of the glenoid dimension regarding maximum central peg diameter and peg length (PL), and maximum screw length (SL) for glenoid fixation. METHODS: Retrospective analysis of magnetic resonance imaging (n = 50) scans. Measurement of the maximum inferior glenoid diameter (GD), SL, maximum length of a 9.9, 10 and 11.4 mm central peg (PL) in the transverse plane; glenoid version (GV), humeral head diameter (HHD). Two independent measurements. RESULTS: Mean age: 49.0 ± 15.7 years (17-80) (n = 20 female, 49.6 ± 16.0; n = 30 male, 48.6 ± 15.7). Mean values of measurement were GD: 28.9 ± 3.7 mm (21-39); SL: 34.1 ± 4.9 mm (26-44); PL 9.9 mm: 19.4 ± 4.3 mm (9-30); PL 10 mm: 19.0 ± 4.4 mm (8-30); PL 11.4 mm: 16.5 ± 4.1 mm (7-26) with significant gender differences (p = 0.001; p = 0.022; p = 0.001); GV: -0.6° ± 4.9° (-10 to 11); HHD: 50.0 mm ± 4.9 (41-61). There was good correlation between PL and SL (r = 0.32, p = 0.024) and for GD and PL (r = 0.61, p = 0.001; r = 0.57, p = 0.001; r = 0.96, p = 0.001). The ratio of HHD and GD was very constant with 0.6 ± 0.07. CONCLUSIONS: These data indicate the high interindividual variability of glenoid morphology including significant gender-related differences. The good correlation between humeral head size and GD and maximum central PL can be helpful for cases with reduced bone stock in decision-making about implant size and bone grafting.

T2* mapping and delayed gadolinium-enhanced magnetic resonance imaging in cartilage (dGEMRIC) of glenohumeral cartilage in asymptomatic volunteers at 3 T.

OBJECTIVES: To establish baseline T2* and T1Gd values of glenohumeral cartilage at 3 T. METHODS: Forty asymptomatic volunteers (mean age: 24.8 ± 2.2 years) without shoulder abnormalities were included. The MRI protocol comprised a double-echo steady-state (DESS) sequence for morphological cartilage evaluation, a gradient-echo multiecho sequence for T2* assessment, and a gradient-echo dual-flip-angle sequence for T1Gd mapping. Statistical assessment involved a one-way analysis of variance (ANOVA) to identify the differences between various regions of the glenohumeral joint and intraclass correlation (ICC) analysis comparing repetitive T2* and T1Gd measures to assess intra- and interobserver reliability. RESULTS: Both techniques revealed significant differences between superior and inferior glenohumeral cartilage demonstrating higher T2* (26.2 ms vs. 23.2 ms, P value < 0.001) and T1Gd (750.1 ms vs. 720.2 ms, P value = 0.014) values in the superior regions. No trend was observed in the anterior-posterior measurement (P value range: 0.279-1.000). High intra- and interobserver agreement (ICC value range: 0.895-0.983) was noted for both T2* and T1Gd mapping. CONCLUSIONS: T2* and T1Gd mapping are reliable in the assessment of glenohumeral cartilage. The values from this study can be used for comparison to identify cartilage degeneration in patients suffering from shoulder joint abnormalities. KEY POINTS: • T2* mapping and dGEMRIC are sensitive to collagen degeneration and proteoglycan depletion. • This study aimed to establish baseline T2*/dGEMRIC values of glenohumeral cartilage. • Both techniques revealed significant differences between superior and inferior glenohumeral cartilage. • High intra-/interreader agreement was noted for both T2* mapping and dGEMRIC. • These baseline normal values should be useful when identifying potential degeneration.