Essentials
Androgen deprivation increases the rate of venous thromboembolism in prostate cancer patients.
We characterized androgen receptor‐mediated tissue factor regulation in prostate epithelial ...cells.
Androgen receptor is dampening tissue factor expression in prostate epithelial cells.
Androgen deprivation could enhance tissue factor expression and raise venous thromboembolism rates.
Summary
Background
Prostate cancer is one of the leading causes of cancer death in men. Advanced prostate cancer is usually treated by androgen deprivation therapy (ADT), which is aimed at reducing circulating testosterone levels to reduce cancer growth. There is growing evidence that ADT can increase the rate of venous thromboembolism (VTE) in prostate cancer patients. The tissue factor (TF) gene is one of the most important mediators of coagulation and VTE, but, so far, there are limited data on androgen receptor (AR)‐mediated TF gene expression.
Objectives
To characterize AR‐mediated TF regulation in vitro and in vivo.
Methods
We used the androgen‐dependent prostate cancer cell lines LNCaP and MyC‐CaP to test whether TF expression is regulated by AR. Furthermore, we cloned the TF gene promoter into a luciferase reporter vector to identify the transcription factor‐binding sites that mediate TF regulation downstream of AR. Finally, we used castration experiments in mice to characterize AR‐mediated TF regulation in vivo.
Results
TF is directly regulated by AR. In LNCaP cells, nuclear factor‐κB signaling and EGR1 mediate TF expression. By using castration experiments in mice, we could detect upregulation of TF and early growth response protein 1 mRNA and protein expression in prostate epithelial cells.
Conclusion
AR is crucial for dampening TF expression, which could be important for increased TF expression and TF‐positive microvesicle release in androgen‐deprived prostate cancer patients.
Objective
The aim of this systematic review was to analyze the evidence about the efficacy of the several synovial fluid (SF) biomarkers proposed for knee osteoarthritis (OA), categorizing them by ...both molecular characteristics and clinical use according to the BIPEDs criteria, to provide a comprehensive and structured overview of the current literature.
Design
A systematic review was performed in May 2020 on PubMed, Cochrane Library, and Embase databases about SF biomarkers in patients with knee OA. The search was limited to articles in the last 20 years on human studies, involving patients with knee OA, reporting SF biomarkers. The evidence for each selected SF biomarker was quantified according to the 6 categories of BIPEDs classification.
Results
A total of 159 articles were included in the qualitative data synthesis and 201 different SF biomarkers were identified. Among these, several were investigated multiple times in different articles, for a total of 373 analyses. The studies included 13,557 patients with knee OA. The most promising SF biomarkers were C4S, IL-6, IL-8, Leptin, MMP-1/3, TIMP-1, TNF-α, and VEGF. The “burden of disease” and “diagnostic” categories were the most represented with 132 and 106 different biomarkers, respectively.
Conclusions
The systematic review identified numerous SF biomarkers. However, despite the high number of studies on the plethora of identified molecules, the evidence about the efficacy of each biomarker is supported by limited and often conflicting findings. Further research efforts are needed to improve the understanding of SF biomarkers for a better management of patients with knee OA.
Purpose We report the 2-year clinical results and identify prognostic factors in patients treated with autologous chondrocyte transplantation by use of a collagen membrane to seed the chondrocytes ...(ACT-CS). Methods This is a prospective study of 59 patients who were treated with ACT-CS and followed up for 24 months. Clinical function was assessed by International Knee Documentation Committee (IKDC-2000), objective International Cartilage Repair Society, and Lysholm scores before surgery and at 6, 12, and 24 months after surgery. Results On the basis of objective International Cartilage Repair Society (ICRS) rating, the percentage of patients rated A (normal) and B (nearly normal) increased from 33.9% preoperatively to 92.5% at 24 months after ACT-CS. IKDC and Lysholm scores increased from 50.1 points (SD, 13.4) and 60.5 points (SD, 9.4), respectively, to 76.1 points (SD, 15.2) ( P < .001) and 82.5 points (SD, 13.7) ( P < .001), respectively, at 24 months. The failure rate was highest, at 26.7% at 2 years' follow-up, in the subgroup of patients who underwent ACT-CS as a salvage procedure. The rate of failures in patients with isolated cartilage defects was 5.9%. Conclusions ACT-CS represents a technical modification of membrane-associated autologous chondrocyte transplantation that combines easy handling and attractive application properties with reliable clinical results 24 months after surgery, especially in patients with isolated cartilage defects. Even though the failure rate was higher in patients with kissing lesions or mild osteoarthritis, ACT-CS also seems to improve function in a large proportion of such patients. Level of Evidence Level IV, prospective case series.
Besides their primary role in haemostasis, platelets are actively involved in immune responses as they respond to various inflammatory stimuli, including microbial infection. Further, platelets ...contain intracellular IgG, but their physiologic function remains unknown. Thus, we aimed to elucidate the function of platelet-derived IgGs and their effect on viral infections. Human and murine platelets contained IgG which were released upon shear stress. However, IgG loss did not correlate with P-Selectin exposure or CXCL4 release and α-granule deficient (Nbeal2-/-) platelets failed to show reduced IgG content and release, indicating an extragranular IgG storage site within platelets. While platelet IgG could derive from megakaryocytes that have taken up IgG from the bone marrow microenvironment, naïve platelets also took up IgG directly from plasma in vitro and in vivo. Murine platelets from anti-IAV IgG seropositive mice reduced IAV infection in vitro and in vivo more efficiently than plasma containing comparable IgG levels. Further, human platelets from anti-CMV IgG seropositive but not seronegative donors also potently neutralized in vitro CMV-infection of HUVEC under microvascular shear stress. Our data indicate that IgG storage in platelets may not be restricted to α-granules. Further, our results show that platelets have the potential to mediate potent IgG-mediated antiviral effects both in vitro and in vivo directly at foci of infection. This indicates that platelet-derived IgG may represent a yet unexplored mechanism for focused serological immunity.
Background
For the reconstruction of acromioclavicular (AC) joint separation, several operative procedures have been described; however, the anatomic reconstruction of both coracoclavicular ligaments ...has rarely been reported.
Purpose
The aim of this biomechanical study is to describe a new procedure for anatomic reconstruction of the AC joint.
Study Design
Controlled laboratory study.
Materials and Methods
Forty fresh-frozen cadaveric shoulders were tested. Cyclic loading and a load-to-failure protocol was performed in vertical (native, n = 10; reconstructed, n = 10) and anterior directions (native, n = 10; reconstructed, n = 10) on 20 AC joints and repeated after anatomic reconstruction. Reconstruction of conoid and trapezoid ligaments was achieved by 2 TightRope devices (Arthrex, Naples, Florida). Dynamic, cyclic, and static loading until failure in vertical (n = 5) and horizontal (n = 5) directions were tested in native as well as reconstructed joints in a standardized setting.
Results
The native coracoclavicular ligaments in static load for vertical force measured 598 N (range, 409–687), elongation 10 mm (range, 6–14), and stiffness 99 N/mm (range, 67–130); static load for anterior force was 338 N (range, 186–561), elongation 4 mm (range, 3–7), and stiffness 140 N/mm (range, 70–210). The mean maximum static load until failure in reconstruction for vertical force was 982 N (range, 584–1330) (P = .001), elongation 4 mm (range, 3–6) (P < .001), and stiffness 80 N/mm (range, 66.6–105) (P = .091); and for anterior static force 627 N (range, 364–973) (P < .001), elongation 6.5 mm (range, 4–10) (P = .023), and stiffness 78 N/mm (range, 46–120) (P = .009). During dynamic testing of the native coracoclavicular ligaments, the mean amount of repetitions (100 repetitions per stage, stage 0–100 N, 100–200 N, 200–300 N, etc, and a frequency of 1.5 Hz) in native vertical direction was 593 repetitions (range, 426–683) and an average of 552 N (range, 452–683) load until failure. In vertical reconstructed testing, there were 742 repetitions (range, 488–893) (P = .222; with a load until failure of 768 N (range, 486–900) (P = .095). In the anterior direction load, the native ligament failed after an average of 365 repetitions (range, 330–475) and an average load of 360 N (range, 307–411), while reconstructed joints ended in 549 repetitions (range, 498–566) (P = .008J with a load until failure of 547 N (range, 490–585) (P = .008). In all testing procedures, a preload of 5 N was performed.
Conclusion
The anatomic reconstruction of the AC joint using TightRope is a stable and functional anatomic reconstruction procedure. The reconstruction technique led to favorable in vitro results with equal or even higher forces than native ligaments.
Clinical Relevance
Through anatomic repair, stable function of the AC joint can be achieved in an anatomic manner.
Background The purpose of the study was to report early functional and radiographic results of a small series of patients who underwent autologous chondrocyte transplantation–collagen membrane ...seeding (ACT-Cs) for focal chondral defects of the shoulder. Methods The outcome of 4 consecutive male patients (mean age, 29.3 ± 6.2 years; range, 21-36 years) who underwent ACT-Cs for treatment of large symptomatic glenohumeral cartilage defects was retrospectively evaluated with clinical and radiographic measures at a mean of 41.3 ± 24.9 months (range, 11-71 months) after surgery. The evaluation included a visual analog scale for pain, the Constant score, the American Shoulder and Elbow Surgeons shoulder index, the Rowe score, and a satisfaction scale. Magnetic resonance imaging evaluation was performed according to the Magnetic Resonance Observation of Cartilage Repair Tissue scoring system. Results There were 3 humeral full-thickness cartilage defects (each 6.0 cm2 ) and 1 glenoid full-thickness cartilage defect (2.0 cm2 ). The mean postoperative visual analog scale score (0.3 of 10), the mean unweighted Constant score (83.3 ± 9.9), and the mean American Shoulder and Elbow Surgeons index (95.3 ± 8.1) were representative of satisfactory shoulder function. The Magnetic Resonance Observation of Cartilage Repair Tissue score was indicative of satisfactory defect coverage with signs of fibrocartilaginous repair tissue. Conclusions Autologous chondrocyte transplantation at the glenohumeral joint is a remote option for young adults with symptomatic, isolated, large-diameter cartilage lesions. Potential complications as a result of the open approach and 2-step procedure have to be considered carefully. Long-term data, larger patient populations, and randomized studies are required to determine the potential for chondrocyte transplantation techniques to be standard procedure for treatment of symptomatic, large-diameter, full-thickness cartilage defects in the glenohumeral joint.
Quadriceps neuromuscular function remains impaired in the short- and long-term following knee arthroscopy for meniscal surgery and/or anterior cruciate ligament (ACL) reconstruction. The aim of this ...study was to compare quadriceps neuromuscular impairments in patients following meniscal surgery with and without ACL reconstruction. Thirty patients were tested six months after meniscal surgery with (
= 15) and without (
= 15) ACL reconstruction. We bilaterally assessed knee extension maximal voluntary contraction (MVC) torque using dynamometry, vastus lateralis thickness using ultrasound, quadriceps voluntary activation and evoked knee extension torque with transcutaneous electrical stimulation. Patient-reported outcomes were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS). Compared with meniscus patients, ACL patients demonstrated larger asymmetries in MVC torque (15% vs. 5%,
= 0.049) and vastus lateralis thickness (6% vs. 0%,
= 0.021). In ACL patients, asymmetries in MVC torque correlated with asymmetries in evoked torque (
= 0.622,
= 0.013). In meniscus patients, asymmetries in muscle activation correlated with KOOS quality of life (
= 0.619,
= 0.018). Patients demonstrated persistent quadriceps muscle weakness six months after ACL reconstruction, but not after isolated meniscal surgery. Quantitative and/or qualitative muscular changes likely underlie quadriceps muscle weakness in ACL patients, whereas activation failure is associated with poor quality of life in some meniscus patients.
PDF
