The terminal complement complex (TCC) has been described as a potential driver in the pathogenesis of posttraumatic osteoarthritis (PTOA). However, sublytic TCC deposition might also play a crucial role in bone development and regeneration. Therefore, we elucidated the effects of TCC on joint-related tissues using a rabbit PTOA model. In brief, a C6-deficient rabbit breed was characterized on genetic, protein, and functional levels. Anterior cruciate ligament transection (ACLT) was performed in C6-deficient (C6−/−) and C6-sufficient (C6+/−) rabbits. After eight weeks, the progression of PTOA was determined histologically. Moreover, the structure of the subchondral bone was evaluated by µCT analysis. C6 deficiency could be attributed to a homozygous 3.6 kb deletion within the C6 gene and subsequent loss of the C5b binding site. Serum from C6−/− animals revealed no hemolytic activity. After ACLT surgery, joints of C6−/− rabbits exhibited significantly lower OA scores, including reduced cartilage damage, hypocellularity, cluster formation, and osteophyte number, as well as lower chondrocyte apoptosis rates and synovial prostaglandin E2 levels. Moreover, ACLT surgery significantly decreased the trabecular number in the subchondral bone of C6−/− rabbits. Overall, the absence of TCC protected from injury-induced OA progression but had minor effects on the micro-structure of the subchondral bone.
Objective: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration. Design: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content. Results: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements. Conclusion: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International.
Joint injuries are highly associated with the development of post-traumatic osteoarthritis. Previous studies revealed cell- and matrix-protective effects of N-acetylcysteine (NAC) after ex vivo cartilage trauma, while chondroanabolic stimulation with bone morphogenetic protein 7 (BMP7) enhanced type II collagen (COL2) expression. Here, as a next step, we investigated the combined and individual efficacy of intra-articular antioxidative and chondroanabolic treatment in a rabbit in vivo cartilage trauma model. Animals were randomly divided into group A (right joint: trauma (T); left joint: T+BMP7) and group B (right joint: T+NAC; left joint: T+BMP7+NAC). Condyles were impacted with the use of a spring-loaded impact device to ensure defined, single trauma administration. After 12 weeks, histopathological analysis was performed and the presence of matrix metalloproteinase 13 (MMP-13) and COL2 was assessed. Trauma-induced hypocellularity, MMP-13 expression, and cell cluster formation were reduced in NAC-treated animals. In contrast, BMP7 further increased cluster formation. Moreover, synovial concentrations of COL2 carboxy propeptide (CPII) and proteoglycan staining intensities were enhanced in NAC- and NAC+BMP7-treated joints. For the first time, the efficacy of NAC regarding early harm reduction after blunt cartilage trauma was demonstrated in vivo. However, parallel administration of BMP7 was not significantly superior compared to NAC alone.
Die Pfannenorientierung, welche sich neben der Positionierung im Becken aus der Pfanneninklination und Pfannenversion zusammensetzt, kann die kurz- und langfristigen Ergebnisse nach Hüft-Totalendoprothesen(TEP)-Implantation wesentlich beeinflussen. Die Pfanneninklinationsmessung im Röntgenbild nach Hüft-TEP-Implantation stellt im Rahmen der EndoCert-Zertifizierung in Deutschland einen radiologischen Qualitätsindikator dar. Ziel der Untersuchung war die Bestimmung der Intra- und Interrater-Reliabilität der von EndoCert empfohlenen Pfanneninklinationsmessung nach Hüft-TEP-Implantation.
ZusammenfassungHintergrund und FragestellungDie Pfannenorientierung, welche sich neben der Positionierung im Becken aus der Pfanneninklination und Pfannenversion zusammensetzt, kann die kurz- und langfristigen Ergebnisse nach Huft-Totalendoprothesen(TEP)-Implantation wesentlich beeinflussen. Die Pfanneninklinationsmessung im Rontgenbild nach Huft-TEP-Implantation stellt im Rahmen der EndoCert-Zertifizierung in Deutschland einen radiologischen Qualitatsindikator dar. Ziel der Untersuchung war die Bestimmung der Intra- und Interrater-Reliabilitat der von EndoCert empfohlenen Pfanneninklinationsmessung nach Huft-TEP-Implantation.Studiendesign und UntersuchungsmethodenVier unabhangige Untersucher in unterschiedlichem Ausbildungsstand fuhrten Inklinationsmessungen an Rontgenbildern (Beckenubersicht a.-p.) von insgesamt 99Patienten retrospektiv durch. Zur Auswertung wurden der Intraklassen-Korrelationskoeffizient (ICC) sowie der Pearson-Korrelationskoeffizient bestimmt und bei einem r>0,8 und p<0,05 mit hoher ubereinstimmung als statistisch signifikant gewertet.Ergebnisse, Diskussion und SchlussfolgerungSowohl die Interrater- als auch die Intrarater-Reliabilitat wiesen bei Bestimmung des Pearson-Korrelationskoeffizienten und des ICC eine hohe ubereinstimmung mit einem r>0,9 und p<0,001 aller Messungen auf. Entsprechend den vorliegenden Ergebnissen zeigt sich die Pfanneninklinationsmessung als ein einfaches Messtool mit hoher Intra- und Interrater-Reliabilitat. Da sich die Pfannenorientierung neben der Pfanneninklination auch aus der Pfannenversion und Positionierung im Becken zusammensetzt, ist das alleinige Heranziehen der Inklinationsmessung zur radiologischen Qualitatsbeurteilung jedoch kritisch zu diskutieren. AbstractBackground and objectiveAcetabular cup orientation, consisting of pelvic positioning, version and inclination, can influence short-term and long-term results after total hip arthroplasty (THA). The radiographic measurement of acetabular cup inclination represents an indicator of quality for the EndoCert certification in Germany. The purpose of this study was to determine the intrarater and interrater reliability of radiographic measurements of acetabular cup inclination after THA.Material and methodsIn this study four independent investigators with different levels of expertise retrospectively performed measurements on radiograms (anteroposterior pelvic radiogram) from 99patients. The intraclass correlation coefficient (ICC) and Pearson's correlation coefficient were determined and were considered statistically significant with r>0.8 and p<0.05.Results and conclusionAhigh correlation was found for both intrarater and interrater reliability based on determination of Pearson's correlation coefficient and the ICC with r>0.9 and p<0.001 for all measurements. Based on these results the radiographic measurement of acetabular cup inclination can be considered as asimple measuring tool with high intrarater and interrater reliability. As cup orientation consists of inclination, version and positioning, the exclusive measurement of cup inclination for radiological quality assessment needs to be discussed critically.
Hibernomas are very rare benign soft tissue tumors arising from brown fat. Malignant transformation or metastases are unknown. Males seems to be affected more often. Most patients are aged 20 to 40, but patients with intraosseous hibernomas are older. In children, hibernomas are extremely rare. The tumors grow slowly and have usually been present for a few years on presentation. Hibernomas are typically located on the thigh, neck, axilla or in the peri- und interscapular region. Diagnostic work-up in symptomatic hibernomas usually includes conventional X-ray and magnetic resonance tomography (MRI) with contrast medium. Asymptomatic hibernomas are often found accidentally in the diagnostic work-up of other diseases. Important differential diagnoses are lipomas, well differentiated liposarcomas, rhabdomyomas, granular cell tumors and sebeceous adenomas. Incisional biopsy should be performed to allow definitive histological diagnosis before definitive therapy. According to the literature, histologically preserved hibernomas can be removed with curative intention and marginal resection. After complete tumor removal, local recurrence has not been described. The following article describes the case of a large hibernoma of the proximal arm, involving the axilla, and describes the epidemiology, clinical behavior, diagnostic work-up, therapy and prognosis of this very rare benign fatty soft tissue tumor, on the basis of a review of current literature.
Background: Sport injuries of the knee often lead to posttraumatic arthritis. In addition to direct damage of the cartilage, trauma-associated intra-articular bleeding may cause hemarthrosis. Both blood exposure and trauma are known to induce cell death and inflammation and to enhance proteoglycan release in cartilage. Hypothesis: Blood exposure increases chondrocyte death as well as inflammatory and degenerative processes in traumatized cartilage. Study Design: Controlled laboratory study. Methods: Human macroscopically intact osteoarthritic (OA) cartilage explants were impacted by a drop-tower system (0.59 J) and cultivated with or without 10% blood. Interactive effects were studied concerning cell survival, gene expression, and the release of mediators over 24 hours and 96 hours. To evaluate the effects of trauma and hemarthrosis in vivo, a newly established blunt cartilage trauma model in the rabbit was used. Treatment of the knee joints of mature New Zealand White rabbits consisted of the following groups: control (C), arthrotomy (A), arthrotomy with cartilage trauma (AT; 1.0 J), and arthrotomy with cartilage trauma and blood injection (ATH). After 1 and 12 weeks, inflammatory mediators in the synovial fluid and histological changes of the cartilage were determined, and immunohistological staining was performed. Results: The in vitro studies revealed a significant additional or synergistic effect of blood exposure on trauma-induced chondrocyte death, interleukin (IL)–1β and prostaglandin-E2 (PGE2) release, and matrix metalloproteinase (MMP)/pro-MMP level. Singular arthrotomy in vivo induced a temporary inflammation. Histologically, cartilage trauma caused significant OA changes that were not aggravated by an additional hemarthrosis. Trauma led to a persistent deposition of terminal complement complex (TCC), being enhanced by hemarthrosis. However, trauma-induced formation of osteophytes and arthrotomy-induced elevation of tumor necrosis factor–α release were reduced by hemarthrosis. Conclusion: While blood exposure clearly aggravated trauma-induced OA processes in the in vitro model, a singular blood injection revealed heterogeneous effects in vivo, enhancing TCC deposition but reducing trauma-induced osteophyte formation while the histological score of traumatized cartilage was not further impaired. Clinical Relevance: The results of this study indicate that a singular, limited bleeding event might not exacerbate early trauma-induced cartilage degeneration in joint injuries. An early removal of intra-articular blood may not prevent the final resulting cartilage damage.
Die diffuse idiopathische skelettale Hyperostose (Synonym DISH-Syndrom, Morbus Forestier-Ott, Spondylosis hyperostotica) ist eine häufige systemische Entität mit Ausbildung ankylosierender Formationen an der Wirbelsäule sowie Ossifikationen an den peripheren Enthesen, welche bevorzugt bei der älteren Bevölkerung auftritt. Die Erkrankung wird trotz der steigenden Prävalenz im Alter wegen ihres schleichenden Verlaufs häufig verkannt. Die diffuse idiopathische skelettale Hyperostose kann einen asymptomatischen radiographischen Zufallsbefund darstellen oder in Form multilokulärer Beschwerden, wie Rücken- und Nackenschmerzen, Einschränkung der Beweglichkeit, peripherer Gelenkbefall, Dysphagie, Globusgefühl, Adipositas, Hyperurikämie und kardiovaskuläre Komorbiditäten manifest werden. Der folgende Artikel präsentiert eine aktuelle Übersicht über die interdisziplinären Aspekte dieser Erkrankung.
Background: Clinically oriented and easy to handle animal models are urgently needed to test pharmacologic treatment of cartilage trauma to reduce the resulting tissue damage by chondrocyte apoptosis and induction of matrix-degrading enzymes. Aim: To develop a biomechanically defined cartilage trauma model. Material and Methods: We constructed a novel trauma device that allows biomechanically defined force application to the load-bearing region of the medial and lateral femoral condyles in adult rabbits. The fixation to the femur was specially designed to avoid uncontrolled influx of blood into the joint. The device was tested on the articular femoral surface of cadaveric rabbits. Results: At a lower energy (1.0 J), the tests showed that superficial and partially deep fissuring, partial necrosis of the chondrocytes, and early proteoglycan loss occurred at the region of impact. Subchondral fractures could be excluded by micro CT. At higher energy (≥1.4 J), we observed more pronounced deep fissuring and in some cases complete shearing of the articular cartilage from the subchondral bone. Conclusion: Our model represents an easy to use method to create a biomechanically defined cartilage trauma and offers some advantages with respect to handling under aseptic surgical conditions and prevention of uncontrolled intra-articular bleeding from the bone marrow compartment for pharmacologic studies.
Diffuse idiopathic skeletal hyperostosis (DISH) is a common but often unrecognized systemic disorder observed mainly in the middle-aged and elderly population, characterized by ankylosing formations of the spine and ossifications of peripheral ligaments, tendons and joint capsule insertion points (entheses). Despite the increase of prevalence with age, the condition often remains undiagnosed. It can be an asymptomatic incidental radiographic finding but can also manifest in several multiorgan complications, such as back and neck pain, restriction of mobility of the spine, peripheral joint affection, dysphagia, dyspnea, foreign body sensation, hoarseness, neurologic manifestations due to compression of the spinal cord, hyperuricemia, obesity, hypercholesterinemia and resulting cardiovascular comorbidities, implicating a multidisciplinary approach. The following article presents a current overview of the condition.
Spontaneous spinal haematoma is a rare cause of sciatica. We present a case of a 73 year old patient, who was admitted to our department and suffered from spontaneous sciatica over 24 hours. During the examination, the patient presented undulating symptoms of paraplegia, varying from incomplete loss of power in the left lower limb to complete plegia. The patient presented multiple diseases like biological aortic valve replacement, diabetes, hypertonia in her medical history, etc. Due to an additional absolute arrhythmia she ingested a cumarine medication. The tomographic imaging revealed a spontaneous lumbar and cranial subarachnoidal haematoma.
Die spinale epidurale Lipomatose (SEL) der thorakalen und lumbalen Wirbelsäule ist eine seltene Entität, bei der es zu einer extraduralen Hypertrophie und Neubildung von vaskularisiertem Fettgewebe im Spinalkanal kommt. Die genaue Pathogenese der Erkrankung ist bis dato nicht geklärt. Die SEL tritt gehäuft bei Adipositas, Kortikoideinnahme sowie metabolischen Störungen im ACTH-Kortikoidstoffwechsel (ACTH adrenokortikotropes Hormon) auf. Der Prozess kann klinisch inapparent verlaufen oder sich in Form von unspezifischen Rückenschmerzen, Schwäche der Extremitäten, Dysästhesien, Radikulopathien, Claudicatio spinalis bis hin zum Cauda-equina-Syndrom manifestieren. Die Therapie der symptomatischen Formen ist interdisziplinär und besteht in Gewichtsreduktion und „weaning“ der Kortikoide, bei Persistenz oder neurologischen Defiziten in der Dekompression des Spinalkanals. Der folgende Artikel bietet eine aktuelle Literaturübersicht sowie eine Kasuistik zu dieser seltenen Erkrankung.
Background Chronic low back pain (CLBP) and chronic neck pain (CNP) have become a serious medical and socioeconomic problem in recent decades. Patients suffering from chronic pain seem to have a higher prevalence of sleep disorders. Purpose To calculate the prevalence of sleep deprivation in patients with CLBP and CNP and to evaluate the factors that may contribute to sleep impairment. Methods This study was a retrospective evaluation of 1016 patients with CNP and CLBP who consulted an orthopedic department at a university hospital. Factors assessed were gender, age, diagnosis, grade of sleep deprivation, pain intensity, chronification grade, and migrational background. Pearson’s chi-squared test was performed to calculate the relationship between these factors and the grade of sleep deprivation. Regression analysis was performed to explore the correlation between the grade of sleep deprivation and age, pain intensity, and chronification grade. Results A high prevalence of sleep deprivation (42.22%) was calculated in patients with CNP and CLBP, even when analgesics had been taken. About 19.88% of the patients reported serious sleep impairments (ie, <4 hours of sleep per night). The grade of sleep deprivation did not correlate with the gender or age distribution. A significant relationship was found between the grade of sleep deprivation and pain intensity, failed back surgery syndrome, and patients with a migrational background. There was a moderate relationship with intervertebral disc disease and no relationship with spinal stenosis. Conclusion Sleep disturbance should be assessed when treating patients with CNP or CLBP, especially in patients with higher pain intensity, failed back surgery syndrome, and a migrational background. Further research is needed to explore the complex relationship of sleep disturbance and chronic pain.
Spinal epidural lipomatosis (SEL) is a rare condition affecting the thoracic and lumbar spine, characterized by a hypertrophy and hyperplasia of the rich vascularized fat tissue inside the spinal canal. The etiology of SEL is unknown. A high number of cases are associated with obesity, corticosteroid intake and a dysbalance in adrenocorticotropic hormone (ACTH)-cortisone metabolism. It can be an incidental radiographic finding or present with symptoms, such as low back pain, weakness of the lower limbs, dysesthesia, radiculopathy, claudication or even cauda equina syndrome. The interdisciplinary treatment consists of weight reduction, weaning from corticosteroids and in persisting cases or neurologic alterations in surgical decompression of the spinal canal. The following article presents a current review and a case report of this rare entity.
Vascular endothelial growth factor (VEGF) has been indicated to play a role during endochondral ossification by stimulation of blood vessel invasion into hypertrophic cartilage resulting in its replacement by trabecular bone. We could demonstrate a dose-dependent chemoattractive effect of VEGF-A and PlGF-1, but not VEGF-E or VEGF-C, on human mesenchymal progenitor cells. Quantitative realtime PCR revealed the expression of VEGFR-1 (Flt-1), VEGFR-2 (KDR/Flk-1), and VEGFR-3 (Flt-4), which markedly declined during osteogenic differentiation. In addition, expression of neuropilin-1 and -2 was detected by RT-PCR. In an in vitro kinase assay, we could demonstrate activation of VEGFR-1 and VEGFR-2 upon stimulation with specific ligands. These findings are consistent with the idea that the chemotactic effect of VEGF-A on MPC is mediated via VEGFR-1, and that VEGF-A and PlGF-1, have a functional role for recruitment of osteoprogenitor cells in the course of endochondral bone formation or remodeling.