Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma.

Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting TBXT expression is thought to be the key factor in controlling this tumour. Although the tumour is rare, distinct molecular differences and vulnerabilities have been described with regard to its location and the progression status of the disease, rendering it mandatory for novel cell lines to reflect all relevant chordoma subtypes. Here, we describe a novel chordoma cell line arising from the pleural effusion of a disseminated, poorly differentiated chordoma. This cell line, U-CH22, represents a highly aggressive terminal chordoma and, therefore, fills a relevant gap within the panel of available cell culture models for this orphan disease. CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum.

Soft tissue tumor imaging in adults: European Society of Musculoskeletal Radiology-Guidelines 2023-overview, and primary local imaging: how and where?

OBJECTIVES: Early, accurate diagnosis is crucial for the prognosis of patients with soft tissue sarcomas. To this end, standardization of imaging algorithms, technical requirements, and reporting is therefore a prerequisite. Since the first European Society of Musculoskeletal Radiology (ESSR) consensus in 2015, technical achievements, further insights into specific entities, and the revised WHO-classification (2020) and AJCC staging system (2017) made an update necessary. The guidelines are intended to support radiologists in their decision-making and contribute to interdisciplinary tumor board discussions. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements were scored online by level of agreement (0 to 10) during two iterative rounds. Either "group consensus," "group agreement," or "lack of agreement" was achieved. RESULTS: Eight sections were defined that finally contained 145 statements with comments. Overall, group consensus was reached in 95.9%, and group agreement in 4.1%. This communication contains the first part consisting of the imaging algorithm for suspected soft tissue tumors, methods for local imaging, and the role of tumor centers. CONCLUSION: Ultrasound represents the initial triage imaging modality for accessible and small tumors. MRI is the modality of choice for the characterization and local staging of most soft tissue tumors. CT is indicated in special situations. In suspicious or likely malignant tumors, a specialist tumor center should be contacted for referral or teleradiologic second opinion. This should be done before performing a biopsy, without exception. CLINICAL RELEVANCE: The updated ESSR soft tissue tumor imaging guidelines aim to provide best practice expert consensus for standardized imaging, to support radiologists in their decision-making, and to improve examination comparability both in individual patients and in future studies on individualized strategies. KEY POINTS: • Ultrasound remains the best initial triage imaging modality for accessible and small suspected soft tissue tumors. • MRI is the modality of choice for the characterization and local staging of soft tissue tumors in most cases; CT is indicated in special situations. Suspicious or likely malignant tumors should undergo biopsy. • In patients with large, indeterminate or suspicious tumors, a tumor reference center should be contacted for referral or teleradiologic second opinion; this must be done before a biopsy.

[Diagnostics and treatment of hourglass-like nerve constrictions and torsions in neuralgic amyotrophy]. / Diagnostik und Therapie sanduhrförmiger Nervenstrikturen und -torsionen bei neuralgischer Amyotrophie.

Neuralgic amyotrophy is a disease of the peripheral nervous system characterized by severe neuropathic pain followed by peripheral paralysis. A distinction is made between a hereditary and an idiopathic form, which is assumed to have an autoimmunological origin. Conservative medicinal treatment mainly consists of nonsteroidal anti-inflammatory drugs (NSAID), opioids and glucocorticoids; however, despite treatment, symptoms in the form of pain or paralysis persist in over 50% of cases. Inflammation can lead to strictures and torsions of peripheral nerves, which can be visualized by imaging using nerve sonography or magnetic resonance (MR) neurography and confirmed intraoperatively during surgical exploration. Based on the currently available data, patients with strictures and torsions of peripheral nerves can benefit from neurosurgical treatment.

Posttreatment Changes of the Elbow.

Radiologists should be familiar with the typical surgical procedures applied at the elbow and aware of the spectrum of normal and pathologic appearances of posttreatment situations throughout all radiologic modalities. Most important in the case of posttraumatic surgical elbow procedures is correct postoperative elbow joint alignment, appropriate fixation of joint-forming fragments, and proper insertion of screws, plates, and anchor devices that do not conflict with intra-articular or bony structures. To report soft tissue repair procedures correctly, radiologists need to know the broad spectrum of different techniques applied and their appearance on magnetic resonance imaging.

Presurgical Perspective and Posttreatment Evaluation of Soft Tissue Tumors of the Ankle and Foot in Adults.

This article discusses soft tissue tumors of the ankle and foot region in adults, including tumors of the joints, and also briefly addresses tumor-simulating lesions. We offer general recommendations and describe specific aspects of common entities in that region, such as typical imaging appearance, therapeutic strategies, and posttherapeutic considerations. Focal masses and diffuse swelling are common in the foot and ankle region; most of them are non-neoplastic. Some of the tumors, such as plantar fibromatosis, tenosynovial giant cell tumor, synovial chondromatosis, or schwannoma, have a very typical appearance on magnetic resonance imaging. Sarcomas are rare among true soft tissue tumors; however, they can be small and well demarcated, may grow slowly, and are often misinterpreted as benign. This is especially true for synovial sarcoma, one of the most common sarcomas in this region. Densely packed tissues in the foot and ankle may hamper determining the tissue of origin. Adherence to diagnostic guidelines and cooperation with tumor centers is crucial including for posttherapeutic surveillance. We also describe typical posttherapeutic changes and complications after surgery, radiation therapy, and chemotherapy, as well as parameters for the detection and exclusion of recurrence of soft tissue tumors of the ankle and foot.

Soft Tissue Sarcoma Follow-up Imaging: Strategies to Distinguish Post-treatment Changes from Recurrence.

Soft tissue sarcomas encompass multiple entities with differing recurrence rates and follow-up intervals. The detection of recurrences and their differentiation from post-therapeutic changes is therefore complex, with a central role for the clinical radiologist. This article describes approved recommendations. Prerequisite is a precise knowledge of the current clinical management and surgical techniques. We review recurrence rates and treatment modalities. An adequate imaging technique is paramount, and comparison with previous imaging is highly recommended. We describe time-dependent therapy-related complications on magnetic resonance imaging compared with the spectrum of regular post-therapeutic changes. Early complications such as seromas, hematomas, and infections, late complications such as edema and fibrosis, and inflammatory pseudotumors are elucidated. The appearance of recurrences and radiation-associated sarcomas is contrasted with these changes. This systematic approach in follow-up imaging of soft tissue sarcoma patients will facilitate the differentiation of post-therapeutic changes from recurrences.

[Radiological diagnostics of lumbar spine fractures]. / Radiologische Frakturdiagnostik der Lendenwirbelsäule.

BACKGROUND: The lumbar spine forms the lowermost part of the mobile spinal column. Due to anatomical properties, the lumbar spine is highly flexible in the sagittal directions, thus, rendering it susceptible to both flexion and extension forces with the thoracolumbar junction being the most vulnerable part of it. To date, the modern thoracolumbar spine fracture classification is given by the AOSpine classification system based on the well-known Magerl classification of vertebral fracture morphology but now includes both neurological criteria and clinical modifiers, such as ankylosing spondylitis. DIAGNOSTICS: Whereas plain radiography remains a mainstay in the diagnostic evaluation of low-energy trauma patients, computed tomography (CT) exhibits its unsurpassed power in polytrauma and plays a decisive role in all equivocal cases where the osseous situation is unclear. However, magnetic resonance imaging (MRI) is increasingly gaining importance for assessing both discoligamentous integrity and intraspinal condition. Both CT and MRI have direct input in classifying fractures according to the AOSpine classification. RESULTS: Regarding fracture morphology, three main types (A-C) based on the stability are distinguished. C­type spinal injuries are all considered unstable, irrespective of type and severity of vertebral malalignment. Injuries to the anterior and posterior ligamentous complex are also considered to interfere with stability (B-type injuries). CONCLUSIONS: Special fracture patterns of the injured ankylosed and osteoporotic spine as well as of the pediatric lumbar spine are discussed. A survey is also given about several differential diagnoses (malignant fractures, anomalies, normal variants).

[Radiological diagnosis of pelvic ring fractures]. / Radiologische Diagnostik von Beckenringfrakturen.

EPIDEMIOLOGY: Traumatic fractures of the pelvic ring are relatively rare, but are associated with increased risk of mortality. Depending on injury mechanism and main vector of energy impact, a distinction is made between anteroposterior compression, lateral compression, and vertical shear (Young and Burgess classification), while the stability-related classification according to Tile distinguishes between type A (stable), type B (rotationally unstable) and type C (completely unstable). A comprehensive modern classification is given by the AO/OTA. RADIOLOGICAL FRACTURE DIAGNOSIS: Plain pelvis x­rays lack sufficient sensitivity but are still used to detect highly unstable pelvic fractures. CT has superior sensitivity and specificity. In addition to fracture classification, CT allows reliable assessment of associated vascular and bladder/urethral injuries and large soft tissue hemorrhage. MRI is unparalleled in showing bone marrow edema, cauda and plexus complications, and peripelvic soft tissue damage. MRI may also prove to be a valuable diagnostic tool for pelvic ring injuries in children, adolescents and young women, provided they are hemodynamically stable. Angiography, ultrasonography and bone scintigraphy are additional important diagnostic and therapeutic options. PRACTICAL RECOMMENDATIONS: Knowledge of basic pelvic trauma mechanisms is important to understand the potential severity of traumatic pelvic fractures and to classify them correctly in terms of stability. Being familiar with typical concomitant injuries in pelvic ring fractures allows reliable diagnosis and their communication with the clinician. CT remains the "diagnostic workhorse". In fragile pelvic fractures, the often prolonged course with fracture progression must be taken into account, which is why MRI is of particular importance herein.

[Management of Rib Fractures]. / Management der Rippenfraktur.

The therapy of rib fractures is controversially discussed. Neither does an osteosynthesis have to be performed for each individual rib fracture, nor is the internal splinting by ventilation or respiratory therapy sufficient for each patient. Rib fractures are common in polytrauma patients after car and motorcycle accidents or falls from great heights. However, rib fractures are also increasingly occurring in older patients with falls from low heights. Anamnesis and clinical examination are groundbreaking for the diagnosis and therapy decision of rib fractures. In radiological diagnostics, projection radiography comes first, followed by sonography and CT. Computed tomography should be required for planning an operation. Accompanying injuries must be taken into account when deciding on therapy. We see a complicated organ injury, dislocated rib serial fractures, flail chest and respiratory insufficiency as indications for rib stabilization. As a relative indication for rib stabilization, we see a high suffering pressure due to pain and an intrathoracic volume restriction due to dislocated rib serial fractures. New osteosynthesis material and minimally invasive techniques standardize the procedure and minimize surgical trauma. In any case, adequate pain and respiratory therapy are always crucial for successful treatment.

Do overhead sports increase risk for rotator cuff tears in wheelchair users?

OBJECTIVE: To analyze whether frequent overhead-sports activity increases the risk for rotator cuff disease in patients with spinal cord injuries (SCIs) who are wheelchair dependent. DESIGN: Cross-sectional study, risk analysis. SETTING: Department of Orthopaedic Surgery, Trauma Surgery and Spinal Cord Injury. PARTICIPANTS: Patients (N=296) with SCI requiring the full-time use of a manual wheelchair were recruited for this study. The total population was divided into 2 groups (sports vs no sports), among them 103 patients playing overhead sports on a regular basis (at least 1-2 times/wk) and 193 patients involved in overhead sports less than once a week or in no sports activity at all. The mean age of the sports group was 49.1 years. The mean duration of wheelchair dependence was 26.5 years. The mean age of the no-sports group was 48 years. The mean duration of wheelchair dependence was 25.2 years. Each individual completed a questionnaire designed to identify overhead-sports activity on a regular basis and was asked about shoulder problems. Magnetic resonance imaging scans of both shoulders were performed in each patient and analyzed in a standardized fashion. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Possible differences in continuous data between patients with and without rotator cuff tear were evaluated. The relative risk of suffering from a rotator cuff tear between patients playing overhead sports and those not playing overhead sports was calculated. RESULTS: One hundred three patients played overhead sports regularly and 193 did not. There was no difference between groups regarding age, sex, level of SCI, and duration of wheelchair dependence. The body mass index was significantly lower in the sports group than in the no-sports group (P<.0001). A rotator cuff tear was present in 75.7% of the patients in the sports group and in 36.3% of the patients in the no-sports group (P<.0001). Rotator cuff tears were symptomatic in 92.6% of the patients. The estimated risk increase for the sports group to develop rotator cuff tears was twice as high as for the no-sports group (95% confidence interval, 1.7-2.6; P<.001). Similar results were found for the neurological level of lesion (T2-7/

Etiology of rotator cuff tears in paraplegic patients: a case-control study.

BACKGROUND: The purpose of this study was to investigate the etiology and the demographic and functional characteristics of rotator cuff tears (RCTs) in 100 paraplegic patients as compared with 100 able-bodied volunteers. METHODS: The magnetic resonance imaging examination results of 200 shoulders in each group were analyzed. Clinical examination included the Constant score and a visual analog scale for pain intensity. RESULTS: The prevalence of RCTs was 63% in paraplegic patients versus 15% in able-bodied volunteers (P < .0001). All RCTs in the paraplegic group were associated with symptoms. Among the patients with RCTs, full-thickness tears were detected in 78% of cases in the paraplegic patient group versus 73% of cases in the volunteer group. The rate of partial-thickness tears was 22% in the paraplegic group versus 27% in the volunteer group. Paraplegic patients had a lower Constant score; Disabilities of the Arm, Shoulder and Hand score; and range of motion and a higher pain intensity than the volunteer cohort. The mean tear width in paraplegic patients was 14.4 mm (range, 8-28 mm) versus 9.9 mm (range, 8-14 mm) in the volunteers (P < .01). CONCLUSION: The etiology of RCTs in paraplegic patients seems to be based on wear-and-tear mechanisms rather than aging. These results are important for our understanding of shoulder pathology in long-term paraplegic patients and show the impact of this problem.

A cross-sectional study of demographic and morphologic features of rotator cuff disease in paraplegic patients.

BACKGROUND: This study analyzed the demographic and morphologic features of rotator cuff disease in paraplegic patients who presented with or without shoulder pain. METHODS: Clinical and magnetic resonance imaging examinations of both shoulders were performed in 317 paraplegic patients. Mean age was 49 (range, 19-76) years. The level of spinal cord injury was between T2 and T7 In 54% of patients and between T8 and L3 in 46%. Constant scores were measured for all shoulders. Pain was analyzed using a visual analog scale. RESULTS: Rotator cuff tears were not present in 51%, were unilateral in 20%, and were bilateral in 29%. Age was older and duration of spinal cord injury was significantly longer in patients with bilateral tears than in patients without or with unilateral tears (P < .001). In patients with unilateral tears, a full-thickness rupture of the supraspinatus tendon was found in 67%, whereas a partial-rupture was detected in 33%. Of the patients with bilateral tears, 75% presented with a full-thickness rupture and 25% with a partial rupture. The mean Constant score was 76 (range, 37-98) in patients without cuff tears, 69 (range, 16-94) for patients with unilateral tears, and 64 (16-96) for patients with bilateral tears (P < .001). CONCLUSIONS: Rotator cuff disease is common and correlates highly with age and duration of spinal cord injury, which underlines the theory of "wear and tear" in wheelchair-dependent patients.

Prospective randomised comparison of arthroscopic versus mini-open rotator cuff repair of the supraspinatus tendon.

PURPOSE: The aim of the study was to evaluate whether arthroscopic (ASC) repair of rotator cuff ruptures causes less postoperative pain and better range of motion (ROM) in the early postoperative period than a mini-open (MO) technique. METHODS: Inclusion criteria were a rupture of the supraspinatus tendon with retraction with a maximum to the apex of the humeral head and minor fatty degeneration and atrophy of the muscle. Each group (n = 17) had similar demographics and preoperative magnetic resonance imaging (MRI) findings (mean age 60.1 years, SD 8.8, range 43-71). The ASC group underwent double-row repair with resorbable anchors; the MO group received a transosseous repair. The postoperative rehabilitation was standardised and equivalent in both groups. RESULTS: In the first week fewer nonsteroidal anti-inflammatory drug (NSAID) tablets were needed in the ASC group. Pain scores on the visual analogue scale were similar in the first three weeks; however, from week four to eight the MO group had less pain (p < 0.05). After six months, the Constant-Murley score and the ROM improved significantly (p < 0.05) in both groups without differences between the groups. Postoperative MRI revealed in three of 16 patients a discontinuity of the tendon in both groups; in the ASC group there were more patients (n = 9) with a thinning of the tendon compared to the MO group (n = 6). CONCLUSIONS: There was less use of NSAIDs in the first postoperative week in the ASC group, indirectly indicating less pain, but higher pain scores in the later course (weeks four to eight) compared to the MO group. ROM, MRI findings and the scores were similar after six months, demonstrating that both techniques are equivalent regarding the outcome in this period.

Neurological and functional recovery in multiple injured patients with paraplegia: outcome after 1 year.

BACKGROUND: Injuries of thoracic vertebrae in multiple trauma patients are often accompanied by severe thoracic injuries and sensorimotor deficits. However, until now, it is not clear whether and how the severity of trauma influences the neurologic and functional outcome in paraplegic patients during the first year after the trauma. The aim of the study was to compare two cohorts of multiple injured paraplegic patients with and without conversion in the American Spinal Injury Association Impairment Scale (AIS) with regard to the severity of spinal trauma, the severity of thorax trauma, the type of fracture, and the functional outcome 1 year after the date of injury. METHODS: Twenty-one traumatic paraplegic patients (neurologic level T1-T12) were included in the study based on a retrospective analysis of the Heidelberg European Multicenter Study about Spinal Cord Injury database (www.emsci.org) from 2002 to 2007. In all patients, the Polytraumaschluessel (PTS), the AO classification, the AIS, and the Spinal Cord Independence Measure were collected. Patients with no change in the AIS (group 1, n=14) were compared with patients with AIS changes (group 2, n=7), and t test and χ test were performed (p<0.05). RESULTS: Differences in both groups concerning fracture classification were confirmed (p=0.046). A relation between neurologic improvement in the AIS and the severity of trauma (p=0.058) after 1 year was not found. The subitem PTST in the thoracic area showed statistical significance comparing the two groups (p=0.005). Both groups significantly improved functionally (Spinal Cord Independence Measure, p=0.035) during the first year but with no significant difference between the groups after 1 year. CONCLUSIONS: Our data suggest that functional improvement is achieved independently from neurologic recovery. The combined assessment of the PTS, the AO classification, and the AIS in multiple-injured paraplegic patients can contribute to provide a better prognostication of the neurologic changes during rehabilitation and the outcome after 1 year than the AIS alone.

Prevalence of rotator cuff tear in paraplegic patients compared with controls.

BACKGROUND: Musculoskeletal injuries of the shoulder in paraplegic patients with long-term survival can result from overuse and/or inappropriate use of wheelchairs. The purpose of the present study was to evaluate the prevalence and risk of pathological changes in the weight-bearing shoulder girdle of paraplegic patients who have been wheelchair-dependent for more than thirty years in comparison with able-bodied volunteers. METHODS: One hundred paraplegic patients were matched for sex and age with a group of 100 able-bodied volunteers. Two hundred shoulders from each group were evaluated with use of magnetic resonance imaging. Collected outcome measures included a standardized clinical examination protocol, the Constant score, and a visual analog score for pain intensity. RESULTS: Shoulder function according to the Constant score was significantly worse in the paraplegic patients than in the able-bodied volunteers. Similarly, the visual analog scale pain scores were significantly worse for the paraplegic patients. Magnetic resonance imaging showed that the prevalence of rotator cuff tears in either shoulder was significantly higher in the paraplegic patients than in the able-bodied volunteers (63% compared with 15%), resulting in a tenfold higher risk of rotator cuff rupture among paraplegic patients. CONCLUSIONS: The present study demonstrates that the structural and functional changes of the shoulder joint are more severe and the risk of development of shoulder girdle damage is significantly higher in individuals with long-term paraplegia than in age-matched controls.

The role of kyphoplasty in the management of osteogenesis imperfecta: risk or benefit?

Kyphoplasty is a recognized treatment option in the management of symptomatic osteoporotic compression fractures, osteolytic vertebral metastases or haemangioma. To our knowledge, kyphoplasty with polymethylmethacrylate in a patient with type I osteogenesis imperfecta (OI) and a vertebral compression fracture has not been reported so far. We report on a 58-year-old patient with type I OI and a vertebral compression fracture at L2 with undislocated posterior vertebral wall and an additional older L1 fracture. Because of severe back pain resistant to conservative therapy over 5 months the indication for percutaneous kyphoplasty was made. Preoperative adjacent endplates of L2 were nearly parallel. Radiologically a minimal loss of height of the L2 vertebra was seen without adjacent fractures at 9 months follow-up. A slight increase of the preoperative kyphotic angle of overlying vertebrae L1 (8.7 degrees/10.3 degrees) and T12 (10.4 degrees/11.0 degrees) was apparent. The visual analogue scale showed decrease of low back pain from 10 to 2 allowing mobilization with a walking frame. Kyphoplasty constitutes a minimal invasive therapeutic alternative in the treatment of vertebral fractures in type I OI and pain, resistant to conservative treatment. Similar to the results of osteoporotic fractures the immediate reduction of pain and stabilization of the fracture in undislocated fragments can be achieved. No adjacent fractures occurred 9 months postoperatively after kyphoplasty in type I OI. Preoperative parallelism of the endplates seems to protect from adjacent fractures.

Depiction of the triangular fibro-cartilage in patients with ulnar-sided wrist pain: comparison of direct multi-slice CT arthrography and direct MR arthrography.

To compare direct multi-slice CT arthrography (MSCT-AG) and direct MR arthrography (MR-AG) of the wrist with regard to the depiction of the triangular fibro-cartilage (TFC). Fifteen consecutive patients with ulnar-sided wrist pain suspicious for TFC tear underwent both MSCT-AG and MR-AG of the wrist. Images obtained were evaluated by two radiologists in a blinded fashion for the depiction of six anatomical areas (radial, central and ulnar portion on the proximal and distal side) of the TFC by means of a five-point scoring system (1 = excellent visibility to 5 = not visible). Scores for MSCT-AG and MR-AG were compared using the Student's t-test. Mean scores for MSCT-AG and MR-AG, respectively, were 2.5/2.0, 3.2/2.5 and 2.8/2.4 for the radial, central and ulnar portion of the TFC on its proximal side, and 2.7/2.0, 3.1/2.3 and 2.9/2.4 for the radial, central and ulnar portion on its distal side (n = 15). Paired Student's t-test showed no significant difference between MSCT-AG and MR-AG (P > 0.05). In a first, small series, depiction of the TFC with MSCT-AG is comparable to that of MR-AG. Further evaluation of direct multi-slice CT arthrography of the wrist in a larger patient population would be promising.