Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes.

Modic type 1 changes (MC1) are painful vertebral bone marrow lesions frequently found in patients suffering from chronic low-back pain. Marrow fibrosis is a hallmark of MC1. Bone marrow stromal cells (BMSCs) are key players in other fibrotic bone marrow pathologies, yet their role in MC1 is unknown. The present study aimed to characterise MC1 BMSCs and hypothesised a pro-fibrotic role of BMSCs in MC1. BMSCs were isolated from patients undergoing lumbar spinal fusion from MC1 and adjacent control vertebrae. Frequency of colony-forming unit fibroblast (CFU-F), expression of stem cell surface markers, differentiation capacity, transcriptome, matrix adhesion, cell contractility as well as expression of pro-collagen type I alpha 1, α-smooth muscle actin, integrins and focal adhesion kinase (FAK) were compared. More CFU-F and increased expression of C-X-C-motif-chemokine 12 were found in MC1 BMSCs, possibly indicating overrepresentation of a perisinusoidal BMSC population. RNA sequencing analysis showed enrichment in extracellular matrix proteins and fibrosis-related signalling genes. Increases in pro-collagen type I alpha 1 expression, cell adhesion, cell contractility and phosphorylation of FAK provided further evidence for their pro-fibrotic phenotype. Moreover, a leptin receptor high expressing (LEPRhigh) BMSC population was identified that differentiated under transforming growth factor beta 1 stimulation into myofibroblasts in MC1 but not in control BMSCs. In conclusion, pro-fibrotic changes in MC1 BMSCs and a LEPRhigh MC1 BMSC subpopulation susceptible to myofibroblast differentiation were found. Fibrosis is a hallmark of MC1 and a potential therapeutic target. A causal link between the pro-fibrotic phenotype and clinical characteristics needs to be demonstrated.

The Restless Spinal Cord in Degenerative Cervical Myelopathy.

BACKGROUND AND PURPOSE: The spinal cord is subject to a periodic, cardiac-related movement, which is increased at the level of a cervical stenosis. Increased oscillations may exert mechanical stress on spinal cord tissue causing intramedullary damage. Motion analysis thus holds promise as a biomarker related to disease progression in degenerative cervical myelopathy. Our aim was characterization of the cervical spinal cord motion in patients with degenerative cervical myelopathy. MATERIALS AND METHODS: Phase-contrast MR imaging data were analyzed in 55 patients (37 men; mean age, 56.2 [SD,12.0] years; 36 multisegmental stenoses) and 18 controls (9 men, P = .368; mean age, 62.2 [SD, 6.5] years; P = .024). Parameters of interest included the displacement and motion pattern. Motion data were pooled on the segmental level for comparison between groups. RESULTS: In patients, mean craniocaudal oscillations were increased manifold at any level of a cervical stenosis (eg, C5 displacement: controls [n = 18], 0.54 [SD, 0.16] mm; patients [n = 29], monosegmental stenosis [n = 10], 1.86 [SD, 0.92] mm; P < .001) and even in segments remote from the level of the stenosis (eg, C2 displacement: controls [n = 18], 0.36 [SD, 0.09] mm; patients [n = 52]; stenosis: C3, n = 21; C4, n = 11; C5, n = 18; C6, n = 2; 0.85 [SD, 0.46] mm; P < .001). Motion at C2 differed with the distance to the next stenotic segment and the number of stenotic segments. The motion pattern in most patients showed continuous spinal cord motion throughout the cardiac cycle. CONCLUSIONS: Patients with degenerative cervical myelopathy show altered spinal cord motion with increased and ongoing oscillations at and also beyond the focal level of stenosis. Phase-contrast MR imaging has promise as a biomarker to reveal mechanical stress to the cord and may be applicable to predict disease progression and the impact of surgical interventions.

[Spinal tumors - part 1: extradural tumors. Epidemiology, clinical aspects and therapy]. / Spinale Tumoren - Teil 1: Extradurale Tumoren. Epidemiologie, klinische Aspekte und Therapie.

Spinal tumors are classified according to their location in extradural, intradural-extramedullary, and intradural-intramedullary tumors. The most frequent extradural tumors are metastases. Primary spinal tumors are rare and predominantly benign. Independent of their origin, spinal tumors manifest themselves with progressive local or radicular pain and neurological deficits. A preferably early diagnosis and subsequent therapy is important to improve the prognosis. The treatment of choice for most of these tumors is the complete surgical resection. In particular with the occurrence of neurological deficits a fast surgical intervention is indicated, since the prognosis depends on duration and severity of the preoperative existing deficits. Below, clinical presentation and relevant treatment options of spinal extradural tumors are discussed.

[Spinal tumors - part 2: intradural tumors. Epidemiology, clinical aspects and therapy]. / Spinale Tumoren - Teil 2: Intradurale Tumoren. Epidemiologie, klinische Aspekte und Therapie.

Intradural spinal tumors are classified in extra- and intramedullary tumors. The most frequent intradural-extramedullary tumors are meningiomas and neurinomas. Among the intradural-intramedullary tumors the most frequent ones are ependymomas and astrocytomas. Independent of their origin, spinal tumors usually manifest with progressive local or radicular pain and neurological deficits. The treatment of choice for most of these tumors is a complete surgical resection. In tumors with infiltrative growth into the intramedullary area, a marginal tumor tissue has to be left in situ in order to avoid additional neurological deficits. In particular if neurological deficits appear, a fast surgical intervention is indicated, since the prognosis depends on duration and severity of the preoperative existing deficits. Below, clinical presentation and relevant treatment options of spinal intradural tumors are discussed.

Human resource information systems: helping to meet Section 89 requirements.

After January 1, 1989, firms offering comprehensive benefits plans to employees must demonstrate that such plans do not discriminate against non-highly compensated workers. This article presents human resource information systems as a solution to Section 89 compliance problems and suggests integrating benefits and payroll information.