| 1. |
- Barreto Henriksson, Helena, et al.
(författare)
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Determination of mechanical and rheological properties of a cell-loaded peptide gel during ECM production
- 2019
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 563, s. 437-444
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Tidskriftsartikel (refereegranskat)abstract
- The development of an injectable biomaterial that supports cell survival and maintains or promotes nucleus pulposus (NP) phenotype could aid delivery of cells to degenerated NPs causing low back pain. Mesenchymal cells were loaded and grown in a synthetic peptide gel, PuraMatrix (R). Cells were observed within the gels over 0-28 days, and accumulation of glycosaminoglycans were detected by histological staining. The mechanical properties of the cell-loaded constructs, and the change of the mechanical properties were studied using stress relaxation of the gels under compression and confinement. The PuraMatrix (R) gel was shown to relax fast on compression indicating that the fluid could easily flow out of the gel, and thus indicating the presence of large pores/voids. The presence of these pores/voids was further supported by high mobility of dextran molecules, determined using fluorescence recovery after photo bleaching. The stress required to deform the cell-loaded constructs to a specific strain increases at day 21, at which point the presence of glycosaminoglycans within the cell-loaded constructs was also observed. The results provide evidence of changes in mechanical properties of the PuraMatrix (R) matrix upon excretion of the extracellular matrix by the cells.
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| 2. |
- Barreto Henriksson, Helena, et al.
(författare)
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Development and Regeneration Potential of the Mammalian Intervertebral Disc
- 2013
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Ingår i: Cells Tissues and Organs. - : S. Karger AG. - 1422-6405 .- 1422-6421. ; 197:1
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Forskningsöversikt (refereegranskat)abstract
- At the present time, the normal cell proliferation rate and regeneration processes in the intervertebral disc (IVD) are not fully known. Historically, the IVD has been considered an organ with little or no regenerative capacity. However, several studies have identified the presence of cells expressing progenitor/stem cell markers in adult cartilage tissue and recent data suggest that adult mammalian IVDs have regenerative capacity, albeit slow. The aim of this review is to give an overview of the present knowledge regarding IVD development, regeneration and repair mechanisms in mammals, with a special focus on human discs. At a time when regenerative medicine is making progress and biological treatment options, such as stem cell therapy, are suggested for patients with degenerated discs causing chronic low back pain, basic knowledge about disc cells and their regenerative capacity form a useful basis for the exploration of new treatment options.
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| 3. |
- Barreto Henriksson, Helena, et al.
(författare)
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Identification of Cell Proliferation Zones, Progenitor Cells and a Potential Stem Cell Niche in the Intervertebral Disc Region: A Study in Four Species.
- 2009
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Ingår i: SPINE. - 0362-2436. ; 34:21, s. 2278-2287
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN.: Descriptive experimental study in 4 different mammals. OBJECTIVE.: To investigate cell proliferation/regeneration and localize stem cells/progenitor cells within the intervertebral disc (IVD). SUMMARY OF BACKGROUND DATA.: Disc degeneration (DD) is believed to play a major role in patients with chronic lumbar pain. Lately, biologic treatment options for DD have gained increasing interest. Normal regeneration processes within the IVD and have previously been sparsely described and therefore it is of great interest to increase the knowledge about these processes. METHODS.: Detection of cell proliferations zones and label-retaining cells were done by in vivo 5-bromo-2-deoxyuridine (BrdU) labeling in 18 rabbits, killed after 4, 6, 10, 14, 28, or 56 days. Results were visualized with immunohistochemistry and fluorescence/confocal microscopy. Localization of progenitor cell were further investigated by immunohistochemistry using antibodies towards Notch1, Delta4, Jagged1, C-KIT, KI67, and Stro-1 in normal IVD from rabbits (n = 3), rats (n = 2), minipigs (n = 2), and in human degenerated IVD (n = 4). Further, flowcytometry analysis using progenitor markers were performed on additional human IVD cells (n = 3). RESULTS.: BrdU positive cells were found in comparable numbers at early and late time points in most regions of the anulus fibrosus (AF) and nucleus pulposus demonstrating slow ongoing cell proliferation. In the AF border to ligament zone (AFo) and the perichondriumregion (P) a stem cell niche-like pattern was determined (a high number of BrdU positive cells at early time points vs. only a few label retaining cells at later time points). In normal and DD tissue from the 4 investigated species progenitor cell markers were detected. CONCLUSION.: The IVD is a tissue with ongoing slow cell proliferation both in the AF and the nucleus pulposus. The stem cell niche pattern detected in AFo and P can be suggested to play a role for IVD morphology and function. These findings may be of importance for the development of biologic treatment strategies. PMID: 19755937 [PubMed - as supplied by publisher]
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| 4. |
- Barreto Henriksson, Helena, et al.
(författare)
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Indications of that migration of stem cells is influenced by the extra cellular matrix architecture in the mammalian intervertebral disc region
- 2015
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Ingår i: Tissue & Cell. - : Elsevier BV. - 0040-8166 .- 1532-3072. ; 47:5, s. 439-455
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Tidskriftsartikel (refereegranskat)abstract
- Disc-degeneration is believed a major cause for lumbar pain. Previously, potential stem cell niches in the intervertebral disc (IVD) region, located adjacent to epiphyseal plate was reported. The aim of the study was to examine migration of mesenchymal stem cells (MSCs), extracellular matrix (ECM) architecture in a potential cellular migration route (CMR; area located between the niche and IVD) and in the IVD in non-degenerated lapine- and in human degenerated IVD tissues. Human MSCs (n = 3), human degenerated IVD tissues (n = 10) and lapine IVDs (n = 10) were collected. The samples were examined by immunohistochemistry for stem cell markers; CD90, OCT3/4, pre-chondrocytic marker; GDF5, catabolic markers; MMP9, MMP13, inflammatory marker; IL1R, cellular migration markers; SNAI1, SNAI2, adhesion markers; β1-INTEGRIN and DDR2. In addition, gene-expression analyses (Real time PCR) were performed on additional samples. Further, time lapse studies were performed with hMSCs cultured on aligned COLL-I-fibers-coated glass-slides in DMEM-LG, 10% human serum containing fibroblast growth factor (bFGF). Results: Presence of stem cells (CD90+, OCT3/4 + ), pre-chondocytic cells (GDF5 + )and cells positive for migration markers (SNAI1+, SNAI2 + ), catabolic markers (MMP9+, MMP13 + ), inflammatory marker (IL1R + ), adhesion markers (DDR2+, B1-INTEGRIN + ) were detected (gene- and protein level) in investigated CMR and IVD regions. In the time lapse studies, MSCs alignment and protrusions were observed orientated in the same direction as collagen fibres. Results displays influence of ECM collagen architecture and collagen fiber spatial direction on migration of stem cells. The results can be useful when developing tissue-engineering strategies for disc-degeneration.
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| 5. |
- Barreto Henriksson, Helena, et al.
(författare)
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Investigation of different cell types and gel carriers for cell-based intervertebral disc therapy, in vitro and in vivo studies.
- 2012
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Ingår i: Journal of tissue engineering and regenerative medicine. - : Hindawi Limited. - 1932-7005 .- 1932-6254. ; 6:9, s. 738-747
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Tidskriftsartikel (refereegranskat)abstract
- Biological treatment options for the repair of intervertebral disc damage have been suggested for patients with chronic low back pain. The aim of this study was to investigate possible cell types and gel carriers for use in the regenerative treatment of degenerative intervertebral discs (IVD). In vitro: human mesenchymal cells (hMSCs), IVD cells (hDCs), and chondrocytes (hCs) were cultivated in three gel types: hyaluronan gel (Durolane®), hydrogel (Puramatrix®), and tissue-glue gel (TISSEEL®) in chondrogenic differentiation media for 9days. Cell proliferation and proteoglycan accumulation were evaluated with microscopy and histology. In vivo: hMSCs or hCs and hyaluronan gel were co-injected into injured IVDs of six minipigs. Animals were sacrificed at 3 or 6months. Transplanted cells were traced with anti-human antibodies. IVD appearance was visualized by MRI, immunohistochemistry, and histology. Hyaluronan gel induced the highest cell proliferation in vitro for all cell types. Xenotransplanted hMSCs and hCs survived in porcine IVDs for 6months and produced collagen II in all six animals. Six months after transplantation of cell/gel, pronounced endplate changes indicating severe IVD degeneration were observed at MRI in 1/3 hC/gel, 1/3 hMSCs/gel and 1/3 gel only injected IVDs at MRI and 1/3hMSC/gel, 3/3hC/gel, 2/3 gel and 1/3 injured IVDs showed positive staining for bone mineralization. In 1 of 3 discs receiving hC/gel, in 1 of 3 receiving hMSCs/gel, and in 1 of 3 discs receiving gel alone. Injected IVDs on MRI results in 1 of 3 hMSC/gel, in 3 of 3 hC/gel, in 2 of 3 gel, and in 1 of 3 injured IVDs animals showed positive staining for bone mineralization. The investigated hyaluronan gel carrier is not suitable for use in cell therapy of injured/degenerated IVDs. The high cell proliferation observed in vitro in the hyaluronan could have been a negative factor in vivo, since most cell/gel transplanted IVDs showed degenerative changes at MRI and positive bone mineralization staining. However, this xenotransplantation model is valuable for evaluating possible cell therapy strategies for human degenerated IVDs. Copyright © 2011 John Wiley & Sons, Ltd.
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| 6. |
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| 7. |
- Barreto Henriksson, Helena, et al.
(författare)
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Support of Concept that Migrating Progenitor Cells from Stem Cell Niches Contribute to Normal Regeneration of the Adult Mammal Intervertebral Disc: A Descriptive study in the New Zeeland white Rabbit.
- 2012
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 37:9, s. 722-732
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: Study Design. Descriptive experimental study performed in rabbits of two age groups.Objective. To study and investigate presence of prechondrocytic cells and cell migration routes in the IVD region, to gain knowledge about the normal IVD regeneration pattern.Summary of Background Data. Disc degeneration is believed to play a major role in patients with chronic lumbar pain. Regeneration processes and cell migration within the intervertebral disc (IVD) have been sparsely described. Therefore it is of interest to increase knowledge of these processes in order to understand pathological conditions of the IVD.Methods. 5-bromo-2-deoxyuridine (BrdU) in vivo labelling was performed in two groups of rabbits, 3 and 9 months old at the beginning of the experiment, in total 27 rabbits. BrdU is incorporated into DNA during mitosis and then it is gradually diluted with each cell division until it finally disappears. Incorporation of BrdU was then visualized by immunohistochemistry (IHC) at different time points providing cell division pattern and presence of slow-cycling cells in the IVD region. IVD tissue was investigated by IHC for: Growth- and differentiation-factor-5 (GDF5), SOX9 (chondrogenic lineage markers), SNAIL homolog1 (SNAI1), SNAIL homolog2 (SLUG)(migration markers) and β1-INTEGRIN (cellular adhesion marker). In addition, GDF5, SOX9 and BMPRIB expression were investigated on genetic level.Results. BrdU+ cells were observed in early time points in the IVD niche, adjacent to the epiphyseal plate, at later time points mainly in outer region of the annulus fibrosus (AF) for both age groups of rabbits, indicating a gradual migration of cells. The presence of SLUG, SNAI1, GDF5, SOX9 and β1-INTEGRIN were found in same regions.Conclusion. The results suggest a cellular migration route from the IVD stem cell niche toward the AF and the inner parts of the IVD. These findings may be of importance for understanding IVD regenerative mechanisms and for future development of biological treatment strategies.
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| 8. |
- Barreto Henriksson, Helena, et al.
(författare)
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The Traceability of Mesenchymal Stromal Cells After Injection Into Degenerated Discs in Patients with Low Back Pain.
- 2019
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Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 28:17, s. 1203-1211
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is a major health issue and one main cause to this condition is believed to be intervertebral disc (IVD) degeneration. Stem cell therapy for degenerated discs using mesenchymal stromal cells (MSCs) has been suggested. The aim of the study was to investigate the presence and distribution pattern of autologous MSCs transplanted into degenerated IVDs in patients and explanted posttransplantation. IVD tissues from four patients (41, 45, 47, and 47 years of age) participating in a clinical feasibility study on MSC transplantation to degenerative discs were investigated. Three patients decided to undergo fusion surgery at time points 8 months and one patient at 28 months posttransplantation. Pretransplantation, MSCs from bone marrow aspirate were isolated by centrifugation in FICOLL® test tubes and cultured (passage 1). Before transplantation, MSCs were labeled with 1mg/mL iron sucrose (Venofer®) and 1×106 MSCs were transplanted into degenerated IVDs. At the time point of surgery, IVD tissues were collected. IVD tissue samples were fixated, embedded in paraffin, and sections prepared. IVD samples were stained with Prussian Blue, by which iron deposits are visualized and examined (light microscopy). Immunohistochemistry (IHC), including SOX9 (sex determining region Y box 9), Coll2A1 (collagen 2A1), and cell viability (TUNEL) were performed. Cells positive for iron deposits were observed in IVD tissues (3/4 patients). The cells/iron deposits were observed in clusters and/or as solitary cells in regions in IVD tissue samples [regions of interest (ROIs)]. By IHC, SOX9- and Coll2A1-positive cells were detected in the same regions as the detected cells/iron deposits. A few nonviable cells were detected by TUNEL assay in ROIs. Results demonstrated that MSCs, labeled with iron sucrose, transplanted into degenerated IVDs were detectable 8 months posttransplantation. The detected cellular activity indicates that MSCs have differentiated into chondrocyte-like cells and that the injected MSCs and/or their progeny have survived since the cells were found in large cluster and as solitary cells which were distributed at different parts of the IVD.
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| 9. |
- Barreto Henriksson, Helena, et al.
(författare)
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Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model.
- 2009
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Ingår i: Spine. - 1528-1159. ; 34:2, s. 141-8
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Experimental and descriptive study of a xenotransplantation model in minipigs. OBJECTIVE: To study survival and function of human mesenchymal stem cells (hMSCs) after transplantation into injured porcine spinal discs, as a model for cell therapy. SUMMARY OF BACKGROUND DATA: Biologic treatment options of the intervertebral disc are suggested for patients with chronic low back pain caused by disc degeneration. METHODS: Three lumbar discs in each of 9 minipigs were injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were injected in F12 media suspension (cell/med) or with a hydrogel carrier (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months. Disc appearance was visualized by magnetic resonance imaging. Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear antibody staining, and further performed for Collagen II, Aggrecan, and Collagen I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB human mRNA expression was analyzed by real-time PCR. RESULTS: At magnetic resonance imaging all injured discs demonstrated degenerative signs. Cell/gel discs showed fewer changes compared with cell/med discs and only injured discs at later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8 of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II expression were observed in NP after 3 and 6 months in gel/cell discs and colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA, Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR. CONCLUSION: hMSCs survive in the porcine disc for at least 6 months and express typical chondrocyte markers suggesting differentiation toward disc-like cells. As in autologous animal models the combination with a three-dimensional-hydrogel carrier seems to facilitate differentiation and survival of MSCs in the disc. Xenotransplantation seems to be valuable in evaluating the possibility for human cell therapy treatment for intervertebral discs.
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| 10. |
- Brisby, Helena, 1965, et al.
(författare)
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Moderate Physical Exercise Results in Increased Cell Activity in Articular Cartilage of the Knee Joint in Rats.
- 2013
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Ingår i: Cells, tissues, organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 198:3, s. 237-248
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Tidskriftsartikel (refereegranskat)abstract
- Background: Moderate exercise regimens have shown minor positive effects on matrix turnover in articular cartilage (AC), while effects at cellular level, e.g. proliferation, are scarcely described. Aim: The aim of this study was to investigate the effects of moderate exercise on cell proliferation and recruitment of cells possibly active in regeneration in different regions of cartilage in the rat knee joint. Methods: Eighteen rats were orally given 5-bromo-2-deoxyuridine (BrdU) for 14 days for in vivo DNA labeling. Nine rats underwent treadmill training for 50 min/day, 5 days/week (exercise group), and 9 rats served as controls (no exercise). Animals were sacrificed after 14, 56 and 105 days, and knee joints were harvested. BrdU+ cells were visualized immunohistochemically (IHC) and counted in AC, posterior stem cell niche (PN), potential migration route (PMR; area between PN and the AC border), potential migration area (PMA; region between PN and AC including PN) and epiphyseal cartilage plate (EP) of the tibia and femur. Results: Compared to controls, in the exercise group BrdU+ cells/mm(2) were increased on days 14 (p = 0.022) and 105 (p = 0.045) in AC of the tibia and on day 105 (p = 0.014) in AC of the femur. BrdU+ cell numbers were increased in the PMR region of the tibia on days 14 (p = 0.023) and 105 (p = 0.0018) and in the PMR region of the femur on day 105 (p = 0.0099) as well as in the PMA region of the tibia (p = 0.0008) and femur (p = 0.0080) on day 105. No significant differences in BrdU+ cells/mm(2) were seen in PN or EP between the groups at any time point. Regarding collagen 2A1 expression and proteoglycan accumulation, no significant differences between groups were detected. Conclusions: The results indicate increased cell activity in AC in response to physical exercise and may help to understand the complexity of AC regeneration in the normal mammal knee joint. © 2013 S. Karger AG, Basel.
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| 11. |
- Brisby, Helena, 1965, et al.
(författare)
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The presence of local mesenchymal progenitor cells in human degenerated intervertebral discs and possibilities to influence these in vitro: A descriptive study in humans
- 2013
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 22:5, s. 804-814
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is common and degenerated discs are believed to be a major cause. In non-degenerated intervertebral discs(IVDs) presence of stem-/progenitor cells was recently reported in different mammals (rabbit,rat,pig). Understanding processes of disc degeneration and regenerative mechanisms within degenerated discs(DDs) is important. The aim of the study was to examine presence of local stem-/progenitor cells in human DDs and if these cell-populations could respond to paracrin stimulation in vitro. Tissue biopsies from the IVD region (L3-S1) was collected from 15 patients, age 34-69 years, undergoing surgery (spinal fusion) and mesenchymal stem cells (MSCs)(iliac crest) from two donors. Non-degenerated disc cells were collected from one donor(scoliosis) and chordoma tissue was obtained from(positive control, stem cell markers) two donors. The IVD biopsies were investigated for gene- and protein expression of: OCT3/4, CD105, CD90, STRO-1 and NOTCH1. DD cell cultures(pellet mass) were performed with conditioned media from MSCs and non-degenerated IVD cells. Pellets were investigated after 7, 14, 28 days for the same stem cell markers as above. Gene expression of OCT3/4 and STRO-1 was detected in 13/15 patient samples, CD105 in 14/15 samples and CD90 and NOTCH1 was detected 15/15 samples. Immunohistochemistry analysis supported findings on protein level, in cells sparsely distributed in DDs tissues. DDs cell-cultures displayed more undifferentiated appearance with increased expression of CD105, CD90, STRO-1, OCT3/4, NOTCH1 and JAGGED1 which was observed when cultured in conditioned cell-culture media from MSC compared to cell-cultures cultured with conditioned media from non-degenerated disc cells. Expression of OCT3/4(multipotency marker) and NOTCH1(regulator of cell fate), MSC- markers CD105, CD90 and STRO-1 indicate that primitive cell populations are present within DDs. Furthermore, the possibility to influence cells from DDs by by paracrin signalling /soluble factors from MSCs and from non-degenerated IVD cells was observed in vitro indicating that repair processes within human degenerated discs may be stimulated.
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| 12. |
- Hansson, A., et al.
(författare)
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The direction of human mesenchymal stem cells into the chondrogenic lineage is influenced by the features of hydrogel carriers
- 2017
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Ingår i: Tissue and Cell. - : Elsevier BV. - 1532-3072 .- 0040-8166. ; 49:1, s. 35-44
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is a major public health issue in the Western world, one main cause is believed to be intervertebral disc (IVD) degeneration. To halt/diminish IVD degeneration, cell therapy using different biomaterials e.g. hydrogels as cell carriers has been suggested. In this study, two different hydrogels were examined (in vitro) as potential cell carriers for human mesenchymal stem cells (hMSCs) intended for IVD transplantation. The aim was to investigate cell- survival and chondrogenic differentiation of hMSCs when cultured in hydrogels Puramatrix((R)) or Hydromatrix((R)) and potential effects of stimulation with growth hormone (GH). hMSCs/hydrogel cultures were investigated for cell-viability, attachment, gene expressionof chondrogenic markers SOX9, COL2A1, ACAN and accumulation of extracellular matrix (ECM). In both hydrogel types, hMSCs were viable for 28 days, expressed integrin beta 1 which indicates adhesion of hMSCs. Differentiation was observed into chondrocyte-like cells, in a higher extent in hMSCs/Hydromatrix((R)) cultures when compared to hMSCs/Puramatrix ((R)) hydrogel cultures. Gene expression analyses of chondrogenic markers verified results. hMSCs/hydrogel cultures stimulated with GH displayed no significant effects on chondrogenesis. In conclusion, both hydrogels, especially Hydromatrix((R)) was demonstrated as a promising cell carrier in vitro for hMSCs, when directed into chondrogenesis. This knowledge could be useful in biological approaches for regeneration of degenerated human IVDs.
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| 13. |
- Hingert, Daphne, et al.
(författare)
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BMP-3 Promotes Matrix Production in Co-cultured Stem Cells and Disc Cells from Low Back Pain Patients
- 2020
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Ingår i: Tissue Engineering Part A. - : Mary Ann Liebert Inc. - 1937-3341 .- 1937-335X. ; 26:1-2, s. 47-56
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is one of the most common disorders and believed to be due to intervertebral disc degeneration. Transplantation of human mesenchymal stem cells (hMSCs) is suggested as potential treatment option. Bone morphogenetic growth factor 3 (BMP-3) promotes chondrogenesis and is proven effective in enhancing chondrogenesis in hMSCs pretreated with interleukin-1 beta (IL-1β) in hydrogel model. Three-dimensional co-cultures of hMSCs and disc cells (DCs) have previously been demonstrated to result in increased proteoglycan production. The aim was to study the effects of BMP-3 on hMSCs, DCs, as well as hMSCs and DCs in co-culture in a pellet system, both as single treatment and after pretreatment of IL-1β. Cell pellet cultures with hMSCs, DCs, and co-culture (1:1 ratio) were performed and stimulated with BMP-3 at 1 or 10ng/mL concentrations. For pretreatment (PRE-T), cell pellets were first stimulated with IL-1β, for 24h, and then BMP-3. The pellets were harvested on day 7, 14, and 28. Results demonstrated that BMP-3 stimulation at 10ng/mL promoted cell viability, proteoglycan accumulation, as well as chondrogenesis in all pellet groups compared to 1ng/mL. Cellular proliferation and chondrogenic differentiation of hMSCs were best promoted by PRE-T at 10ng/mL, whereas BMP-3 best enhanced chondrogenesis in DC and co-culture pellets at the same concentration.
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| 14. |
- Hingert, Daphne, et al.
(författare)
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Human mesenchymal stem cells pre-treated with IL-1β and stimulated with BMP-3 enhance chondrogenesis.
- 2018
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Ingår i: Tissue engineering. Part A. - 1937-335X. ; 24:9-10
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Tidskriftsartikel (refereegranskat)abstract
- Low back pain is one of the most common ailments in western countries afflicting more than 80% of the population and the main cause is considered to be degeneration of intervertebral discs (IVDs). IL-1β is a vital inflammatory cytokine found in abundance in degenerated disc environment whereas BMP-3 is believed to promote chondrogenesis through TGF-β pathway.The aim was to study the effects of BMP-3, IL-1β and combination (pre-treatment with IL-1β) on hMSCs encapsulated in PuraMatrix™ hydrogel (Phg) especially in the absence of TGF-β in order to investigate the proliferation, and differentiation ability of hMSCs over 28 days period.100µL of hMSCs cell suspension was encapsulated between two layers of 100 µL hydrogels forming a sandwich-like structure. The encapsulated hMSCs were cultured in two sets of media, chondrogenic (C) and non-chondrogenic (nC) media along with addition of BMP-3 (10ng/mL) and IL-1β (10ng/mL). To study the combined effects of BMP-3 and IL-1β, the encapsulated hMSCs were first pre-treated with relevant media containing IL-1β for 24 hours, and then the media was replaced by media containing BMP-3 for the remaining experimental time period. IL-1β pre-treatment was carried out in both C and nC media. The samples were collected at day 7, 14, and 28.Proliferation and differentiation of hMSCs into chondrocyte-like cells was observed in all samples. Proteoglycans accumulation was observed in pre-treatment samples in C media. The protein and gene expression of Sox-9 and COL2A1 respectively, showed the occurrence of chondrogenesis in all samples.High cell viability, proliferation and differentiation was achieved in this in vitro model confirming that BMP-3 alone in the absence of TGF-β could drive hMSCs into chondrogenic lineage. Pre-treatment with IL-1β followed by BMP-3 stimulation resulted in high proteoglycans accumulation compared to stimulation with growth factors or cytokine alone. This suggests that pre-treatment with a pro-inflammatory cytokine before driving them into a chondrogeneic lineage might be of importance also in vivo.
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| 15. |
- Hingert, Daphne, et al.
(författare)
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Pathological Effects of Cortisol on Intervertebral Disc Cells and Mesenchymal Stem Cells from Lower Back Pain Patients
- 2019
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Ingår i: Cells Tissues Organs. - : S. Karger AG. - 1422-6421 .- 1422-6405. ; 207:1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- In western countries, lower back pain (LBP) is one of the most common disorders, experienced by more than 80% of the population. Chronic LBP due to disc degeneration has been linked to ongoing inflammatory processes in the disc and endplates. Pain effects the body in different ways, inducing a general stress response in which the body responds by releasing the stress hormone cortisol. Little is known about the impact of pain-induced stress on the progression of disc degeneration. Thus, the effects of cortisol on disc cells (DCs) and human mesenchymal stem cells (hMSCs) were explored in vitro with the objective of investigating the repercussions of cortisol on these cell types involved in de- and regenerative mechanisms of the disc. DC and hMSC pellet cultures were exposed to cortisol at two concentrations (150 and 300 ng/mL) for 28 days to simulate pain-induced stress. Cell viability, histological staining, and GAG DNA, along with apo-ptotic assays were conducted. Detection of OCT4, SOX9, IL-1R, and CXCR2 expressions was performed by immunohistochemistry. With cortisol treatment, restricted cell proliferation and less GAG production in both DCs and hMSCs were observed. Suppression of the differentiation and immunomodulatory efficacy of hMSCs was also detected. Moreover, elevated expressions of IL-1R and CXCR2 were detected in both cell types. To conclude, constant exposure to cortisol even at a physiological level enhanced pathological cellular processes in both DCs and hMSCs, which further jeopardized chondrogenesis. This suggests that cortisol resulting from pain-induced stress is a contributing component of intervertebral disc degeneration and may negatively affect regenerative attempts of the disc.
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| 16. |
- Nicolaos, Papadimitriou, 1972, et al.
(författare)
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Intradiscal Injection of Iron-Labeled Autologous Mesenchymal Stromal Cells in Patients With Chronic Low Back Pain: A Feasibility Study With 2 Years Follow-Up
- 2021
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Ingår i: International Journal of Spine Surgery. - : International Journal of Spine Surgery. - 2211-4599. ; 15:6, s. 1201-1209
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Degeneration of the intervertebral disc is considered to be central in pain pathogenesis in patients suffering from chronic low back pain (LBP). In recent years, the injection of mesenchymal stromal cells (MSCs) into the disc to arrest or reverse the degenerative process has been proposed as an alternative therapy. The aim of the present study was to investigate the feasibility of using iron-labeled MSCs for intradiscal injection in patients with long-standing LBP. Methods: Ten patients (7 men, 3 women, mean age 40 years, range 26-53) with chronic LBP and confirmed disc degeneration on magnetic resonance imaging (MRI) were recruited from the waiting list for planned surgery. Injection of autologous, expanded, and iron-labeled bone marrow-derived MSCs (BM-MSCs) into 1 or 2 disc levels was undertaken. Follow-up consisted of monitoring of adverse events, regular MRI examinations, and collection of patient-reported outcome measures (PROMs) for a minimum of 2 years. Results: No complications could be detected, neither clinically nor on MRI. No statistically significant improvement was seen for PROMs on a group level up to 2 years postinjection. Three of 10 patients opted to proceed with the initially planned surgery within the first year and 2 more within 3 years postinjection. Conclusion: Results from this pilot cohort study show that injection of autologous expanded iron-labeled BM-MSCs is a safe procedure, in accordance with the existing body of evidence. The clinical result warrants further larger studies. © 2021 ISASS.
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| 17. |
- Suzuki, Nobuyuki, 1971, et al.
(författare)
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Physical exercise affects cell proliferation in lumbar intervertebral disc regions in rats
- 2012
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Ingår i: Spine. - 0362-2436. ; 37:17, s. 1440-1447
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Tidskriftsartikel (refereegranskat)abstract
- Study Design. Descriptive experimental study.Objective. The aim of this study was to investigate the effect of exercise on cell proliferation in different areas of the IVD and recruitment of cells possibly active in regeneration of normal rat lumbar IVDs.Summary of Background Data. Little is known about the effects of physical exercise on lumbar intervertebral disc (IVD) tissue. Recently, stem cell niches in the perichondrium area of the IVD were identified and cells in these niches have been suggested to be involved in the normal regeneration of the IVD.Methods. Thirty Sprague-Dawley rats were exposed to 5-bromo-2-deoxyuridine (BrdU) diluted in the drinking water during 14 days. Fifteen rats ran on a treadmill daily for 50 min/day, 5 days/week (exercise group) and 15 non-exercised rats served as controls. Immunohistochemical analyses (anti-BrdU antibody) were performed at 9, 14, 28, 56 and 105 days after the start of the exercise protocol. BrdU positive cells were counted in the stem cell niche area (SN), peripheral region of epiphyseal cartilage area (pEC), the annulus fibrous outer and inner area (AFo and AFi). Data were analyzed by two-way ANOVA (significance level; p<0.05).Results. The BrdU positive cell numbers in the SN and AFo region were increased in discs from the exercising group on days 14 (p<0.01) and 105 (p<0.05) and at day 14 (p<0.01) in the pEC region as compared to controls.Conclusions. Physical exercise was shown to have positive effects on cell proliferation in intervertebral discs with involvement of various disc regions, indicating a differential response by disc tissue to exercise depending on anatomical location and tissue characteristics.
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| 18. |
- Svanvik, Teresia, et al.
(författare)
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Human Disk Cells from Degenerated Disks and Mesenchymal Stem Cells in Co-Culture Result in Increased Matrix Production.
- 2009
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Ingår i: Cell Tissues and Organs. - 1422-6405. ; 191:1, s. 2-11
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of mesenchymal stem cells (MSCs) has been suggested for disk degeneration, which is characterized by dysfunctional cells and low proteoglycan production. The aim of this study was to examine the effects of a 3D co-culture system using human disk cells (DCs) and MSCs on collagen and proteoglycan production. DCs and MSCs were expanded in monolayer and grown in pellet cultures for 7, 14 and 28 days and analyzed for hydroxyproline (HP), reflecting total collagen production, and glycosaminoglycan (GAG) accumulation. DCs and MSCs co-cultured at different ratios (25/75, 50/50 and 75%/25%) were examined for GAG accumulation. Collagen type II expression was analyzed immunohistochemically. In a second series, conditioned media were added to pellet cultures of degenerated DCs or MSCs. DCs from degenerated disks and MSCs demonstrated lower total collagen production than non-degenerated DC pellets. GAG production was comparable in DCs and MSCs, except in the youngest donor, with MSC producing about 10 times higher GAG/DNA. Co-cultures resulted in approximately 1.5 times higher GAG/DNA production than DCs. Increased collagen type II expression was seen in co-cultures compared to DC or MSC culture alone, except in the case with highly active MSCs. No positive effect of conditioned media was seen. In conclusion, co-culture of MSCs with degenerated DCs increased proteoglycan and collagen-type ceII production, indicating that in future clinical therapy MSCs can be transplanted without pre-differentiation in vitro. The lack of effect of conditioned media suggests that the positive effect of co-culture on matrix production is not due to soluble factors.
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| 19. |
- Teixeira, G. Q., et al.
(författare)
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Terminal complement complex formation is associated with intervertebral disc degeneration
- 2021
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 30, s. 217-226
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The complement system is a crucial part of innate immunity. Recent work demonstrated an unexpected contribution to tissue homeostasis and degeneration. This study investigated for the first time, in human disc tissues, the deposition profile of the complement activation product terminal complement complex (TCC), an inflammatory trigger and inducer of cell lysis, and its inhibitor CD59, and their correlation with the degree of disc degeneration (DD). Methods Disc biopsies were collected from patients diagnosed with DD (n = 39, age 63 +/- 12) and adolescent idiopathic scoliosis (AIS,n = 10, age 17 +/- 4) and compared with discs from healthy Young (n = 11, age 7 +/- 7) and Elder (n = 10, age 65 +/- 15) donors. Immunohistochemical detection of TCC and CD59 in nucleus pulposus (NP), annulus fibrosus (AF) and endplate (EP) was correlated with age, Pfirrmann grade and Modic changes. Results Higher percentage of TCC+ cells was detected in the NP and EP of DD compared to Elder (P < 0.05), and in the EP of Young versus Elder (P < 0.001). In DD, TCC deposition was positively correlated with Pfirrmann grade, but not with Modic changes, whereas for Young donors, a negative correlation was found with age, indicating TCC's involvement not only in DD, but also in early stages of skeletal development. Higher CD59 positivity was found in AIS and DD groups compared to Young (P < 0.05), and it was negatively correlated with the age of the patients. Conclusion TCC deposition positively correlated with the degree of disc degeneration. A functional relevance of TCC may exist in DD, representing a potential target for new therapeutics.
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| 20. |
- Vukusic, Kristina, 1979, et al.
(författare)
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Physical exercise affects slow cycling cells in the rat heart and reveals a new potential niche area in the atrioventricular junction
- 2015
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Ingår i: Journal of Molecular Histology. - : Springer Science and Business Media LLC. - 1567-2379 .- 1567-2387. ; 46:4, s. 387-398
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Tidskriftsartikel (refereegranskat)abstract
- Physical exercise has several beneficial effects on the heart. In other tissues it has been shown to activate endogenous stem cells. There is however a lack of knowledge how exercise affects the distribution of progenitor cells as well as overall cell turnover within the heart. Therefore, proliferating cells were identified using BrdU DNA labeling in a rat exercise model. Slow cycling cells were identified by label retention. BrdU+ nuclei were counted in apex, ventricle and atrioventricular junction (AV junction), as well as in skin tissue where label retaining cells (LRC) have been described previously. After 13 weeks of chasing, the cells with the highest intensity were identified and considered as LRC. Heart tissue showed slower proliferation compared to skin. The highest number of BrdU+ cells was found in the AV junction. Here, a sub region in close proximity to the valvular insertion point was observed, where density of BrdU+ cells was high at all time points. Physical exercise increased proliferation in AV junction at the early stage. Furthermore, the sub region was found to harbor a significant higher number of LRC compared to other regions of the heart in the exercised animals. Progenitor markers MDR1 and Sca-1 were detected in the same area by immunohistochemistry. In conclusions, our data shows that physical exercise affects cell turnover and distribution of LRC in the heart. Furthermore, it reveals a region within the AV junction of the heart that shows features of a stem cell niche.
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| 21. |
- Åberg, Jonas, 1982-, et al.
(författare)
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Biocompatibility and resorption of a radiopaque premixed calcium phosphate cement
- 2012
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Ingår i: Journal of Biomedical Materials Research. Part A. - : Wiley. - 1549-3296 .- 1552-4965. ; 100A:5, s. 1269-1278
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Tidskriftsartikel (refereegranskat)abstract
- Calcium phosphate cements (CPC) are used as bone void filler in various orthopedic indications; however, there are some major drawbacks regarding mixing, transfer, and injection of traditional CPC. By using glycerol as mixing liquid, a premixed calcium phosphate cement (pCPC), some of these difficulties can be overcome. In the treatment of vertebral fractures the handling characteristics need to be excellent including a high radio-opacity for optimal control during injection. The aim of this study is to evaluate a radiopaque pCPC regarding its resorption behavior and biocompatibility in vivo. pCPC and a water-based CPC were injected into a circle divide 4-mm drilled femur defect in rabbits. The rabbits were sacrificed after 2 and 12 weeks. Cross sections of the defects were evaluated using histology, electron microscopy, and immunohistochemical analysis. Signs of inflammation were evaluated both locally and systemically. The results showed a higher bone formation in the pCPC compared to the water-based CPC after 2 weeks by expression of RUNX-2. After 12 weeks most of the cement had been resorbed in both groups. Both materials were considered to have a high biocompatibility since no marked immunological response was induced and extensive bone ingrowth was observed. The conclusion from the study was that pCPC with ZrO2 radiopacifier is a promising alternative regarding bone replacement material and may be suggested for treatment of, for example, vertebral fractures based on its high biocompatibility, fast bone ingrowth, and good handling properties.
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| 22. |
- Åberg, Jonas, 1982-, et al.
(författare)
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In vitro and in vivo evaluation of an injectable premixed calcium phosphate cement : cell viability and immunological response from rat
- 2010
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Ingår i: International Journal of Nano and Biomaterials. - 1752-8941. ; 3:3, s. 203-221
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Tidskriftsartikel (refereegranskat)abstract
- By using premixed calcium phosphate cement (CPC) the handling properties of the cement are drastically improved, which is a challenge for traditional injectable CPC. In this article, a premixed acidic CPC has been compared to a conventional water mixed brushite cement to evaluate whether the premixed concept affects the biological response. The cements were evaluated regarding the pH-variation in simulated body fluid (SBF). Further, the biocompatibility of the cement with human mesenchymal stem cells (MSC) was studied in vitro and eventual inflammation properties studied in vivo, after subcutaneous material injections in rats. A larger pH decrease was seen for the conventional cement than the premixed cement in SBF. For both materials, > 90% of the MSC remained alive in vitro. No systemic or macroscopic inflammation was detected, only a mild microscopic inflammation was detected around both materials. In addition to the handling benefit of premixed cements compared to conventional water mixed CPC, the premixed CPC in the present study demonstrated high and in comparison to conventional CPC comparable biocompability, both in vitro and in vivo.
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| 23. |
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| 24. |
- Åberg, Jonas, et al.
(författare)
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Premixed acidic calcium phosphate cement: Characterization of strength and microstructure.
- 2010
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Ingår i: Journal of biomaterials research. Part B. Applied biomaterials. - : Wiley. - 1552-4981. ; 93B:2, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- By using a premixed calcium phosphate cement (CPC), the handling properties of the cement are drastically improved, which is a challenge for traditional injectable CPCs. Previously premixed cements have been based on apatitic cements. In this article, acidic cement has been developed and evaluated. Monocalcium phosphate monohydrate and beta-tricalcium phosphate were mixed with glycerol to form a paste. As the paste does not contain water, no setting reaction starts and thus the working time is indefinite. Powder/liquid ratios (P/L) of 2.25, 3.5 and 4.75 were evaluated. Setting time (ST) and compressive strength (CS) were measured after 1 day, 1 week and 4 weeks in phosphate buffered saline (PBS) solution, and the corresponding microstructure was evaluated using electron microscopy and X-ray diffraction. The ST started when the cements were placed in PBS and ranged from 28 to 75 min, higher P/L gave a lower ST. Higher P/L also gave a higher CS, which ranged from 2 to 16 MPa. The microstructure mainly consisted of monetite, 1-5 mum in grain size. After 4 weeks in PBS, the strength increased. As acidic cements are resorbed faster in vivo, this cement should allow faster bone regeneration than apatitic cements. Premixed cements show a great handling benefit when compared with normal CPCs and can be formulated with similar ST and mechanical properties. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 2010.
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| 25. |
- Aaen, J., et al.
(författare)
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Clinical and MRI findings in lumbar spinal stenosis: baseline data from the NORDSTEN study
- 2022
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:6, s. 1391-1398
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The aim was to describe magnetic resonance imaging findings in patients planned for lumbar spinal stenosis surgery. Further, to describe possible associations between MRI findings and patient characteristics with patient reported disability or pain. Methods The NORDSTEN spinal stenosis trial included 437 patients planned for surgical decompression of LSS. The following MRI findings were evaluated before surgery: morphological (Schizas) and quantitative (cross-sectional area) grade of stenosis, disk degeneration (Pfirrmann), facet joint tropism and fatty infiltration of the multifidus muscle. Patients were dichotomized into a moderate or severe category for each radiological parameter classification. A multivariable linear regression analysis was performed to investigate the association between MRI findings and preoperative scores for Oswestry Disability Index, Zurich Claudication Questionnaire and Numeric rating scale for back and leg pain. The following patient characteristics were included in the analysis: gender, age, smoking and weight. Results The percentage of patients with severe scores was as follows: Schizas (C + D) 71.3%, cross-sectional area (< 75 mm(2)) 86.8%, Pfirrmann (4 + 5) 58.1%, tropism (>= 15 degrees) 11.9%, degeneration of multifidus muscle (2-4) 83.7%. Regression coefficients indicated minimal changes in severity of symptoms when comparing the groups with moderate and severe MRI findings. Only gender had a significant and clinically relevant association with ODI score. Conclusion In this cross-sectional study, the majority of the patients had MRI findings classified as severe LSS changes, but the findings had no clinically relevant association with patient reported disability and pain at baseline. Patient characteristics have a larger impact on disability and pain than radiological findings.
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| 26. |
- Aaen, J., et al.
(författare)
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Is the presence of foraminal stenosis associated with outcome in lumbar spinal stenosis patients treated with posterior microsurgical decompression
- 2023
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Ingår i: ACTA NEUROCHIRURGICA. - 0001-6268. ; 165, s. 2121-2129
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Tidskriftsartikel (refereegranskat)abstract
- Background We aim to investigate associations between preoperative radiological findings of lumbar foraminal stenosis with clinical outcomes after posterior microsurgical decompression in patients with predominantly central lumbar spinal stenosis (LSS). Methods The study was an additional analysis in the NORDSTEN Spinal Stenosis Trial. In total, 230 men and 207 women (mean age 66.8 ( SD 8.3)) were included. All patients underwent an MRI including T1- and T2-weighted sequences. Grade of foraminal stenosis was dichotomized into none to moderate (0-1) and severe (2-3) category using Lee's classification system. The Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ), and numeric rating scale (NRS) for back and leg pain were collected at baseline and at 2-year follow-up. Primary outcome was a reduction of 30% or more on the ODI score. Secondary outcomes included the mean improvement on the ODI, ZCQ, and NRS scores. We performed multivariable regression analyses with the radiological variates foraminal stenosis, Pfirrmann grade, Schizas score, dural sac cross-sectional area, and the possible plausible confounders: patients' gender, age, smoking status, and BMI. Results The cohort of 437 patients presented a high degree of degenerative changes at baseline. Of 414 patients with adequate imaging of potential foraminal stenosis, 402 were labeled in the none to moderate category and 12 in the severe category. Of the patients with none to moderate foraminal stenosis, 71% achieved at least 30% improvement in ODI. Among the patients with severe foraminal stenosis, 36% achieved at least 30% improvement in ODI. A significant association between severe foraminal stenosis and less chance of reaching the target of 30% improvement in the ODI score after surgery was detected: OR 0.22 (95% CI 0.06, 0.83), p=0.03. When investigating outcome as continuous variables, a similar association between severe foraminal stenosis and less improved ODI with a mean difference of 9.28 points (95%CI 0.47, 18.09; p=0.04) was found. Significant association between severe foraminal stenosis and less improved NRS pain in the lumbar region was also detected with a mean difference of 1.89 ( 95% CI 0.30, 3.49; p=0.02). No significant association was suggested between severe foraminal stenosis and ZCQ or NRS leg pain. Conclusion In patients operated with posterior microsurgical decompression for LSS, a preoperative severe lumbar foraminal stenosis was associated with higher proportion of patients with less than 30% improvement in ODI. Trial registration The study is registered at ClinicalTrials. gov (22.11.2013) under the identifier NCT02007083.
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| 27. |
- Aaen, J., et al.
(författare)
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The association between preoperative MRI findings and clinical improvement in patients included in the NORDSTEN spinal stenosis trial
- 2022
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Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 31:10, s. 2777-2785
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To investigate potential associations between preoperative MRI findings and patient reported outcome measures (PROMs) after surgery for lumbar spinal stenosis (LSS). Methods The NORDSTEN trial included 437 patients. We investigated the association between preoperative MRI findings such as morphological grade of stenosis (Schizas grade), quantitative grade of stenosis (dural sac cross-sectional area), disc degeneration (Pfirrmann score), facet joint tropism and fatty infiltration of the multifidus muscle, and improvement in patient reported outcome measures (PROMs) 2 years after surgery. We dichotomized each radiological parameter into a moderate or severe category. PROMs i.e., Oswestry Disability Index (ODI), Zurich Claudication Questionnaire (ZCQ) and Numeric rating scale (NRS) for back and leg pain were collected before surgery and at 2 year follow-up. In the primary analysis, we investigated the association between MRI findings and ODI score (dichotomized to >= 30% improvement or not). In the secondary analysis, we investigated the association between MRI findings and the mean improvement on the ODI-, ZCQ- and NRS scores. We used multivariable regression models adjusted for patients' gender, age, smoking status and BMI. Results The primary analysis showed that severe disc degeneration (Pfirrmann score 4-5) was significantly associated with less chance of achieving a 30% improvement on the ODI score (OR 0.54, 95% CI 0.34, 0.88). In the secondary analysis, we detected no clinical relevant associations. Conclusion Severe disc degeneration preoperatively suggest lesser chance of achieving 30% improvement in ODI score after surgery for LSS. Other preoperative MRI findings were not associated with patient reported outcome.
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| 28. |
- Andersson Shams Hakimi, Caroline, et al.
(författare)
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The Effect of Ex Vivo Factor XIII Supplementation on Clot Formation in Blood Samples From Cardiac and Scoliosis Surgery Patients.
- 2018
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Ingår i: Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. - : SAGE Publications. - 1938-2723. ; 24:4, s. 677-683
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Tidskriftsartikel (refereegranskat)abstract
- Excessive perioperative bleeding remains a substantial problem. Factor XIII (FXIII) contributes to clot stability, and it has therefore been suggested that supplementation with FXIII concentrate may improve perioperative hemostasis. We evaluated the effects of increasing doses of FXIII, alone or in combination with fibrinogen or platelet concentrate, in blood samples from 2 considerably different groups of surgical patients: cardiac and scoliosis surgery patients. Whole-blood samples were collected immediately after operation from cardiac and scoliosis surgery patients. The samples were supplemented with 3 clinically relevant doses of FXIII concentrate (+20%, +40%, and +60%), alone or in combination with a fixed dose of fibrinogen concentrate (+1.0 g/L) or fresh apheresis platelets (+92 × 10(9)/L). Clot formation was assessed with rotational thromboelastometry (ROTEM). When the highest dose of FXIII concentrate was added, EXTEM clotting time was shortened by 10% in both cardiac and scoliosis surgery patients (95% confidence intervals: 2.4%-17% and 3.3%-17%, respectively), and FIBTEM maximum clot firmness was increased by 25% (9.3%-41%) in cardiac patients, relative to baseline. When fibrinogen was added, the dose-dependent effect of FXIII on clot stability was maintained, but the total effect was markedly greater than with FXIII alone, +150% (100%-200%) and +160% (130%-200%) for the highest FXIII dose in cardiac and scoliosis patients, respectively. Ex vivo supplementation with clinically relevant doses of FXIII improved clot formation moderately in blood samples from cardiac and scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelet concentrate.
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| 29. |
- Angelini, Eva, 1964, et al.
(författare)
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Evaluating a targeted person-centred pain management intervention programme in lumbar spine surgery - a controlled segment-specific before-and-after interventional design
- 2024
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Ingår i: BMC Health Services Research. - 1472-6963. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Postoperative pain management in lumbar spine surgery care remains a challenge. The aim of this study was to evaluate the impact of a person-centred postoperative pain management intervention programme on lumbar spine surgery patients on postoperative pain, shared decision-making, and satisfaction with postoperative pain management. Methods: The study was performed with a controlled before-and-after interventional design in an orthopaedic unit at a university hospital. Person-centred pain management for patients undergoing spine surgery was developed in co-creation by a multi-professional team and implemented throughout the care pathway. The usual care group (pre-intervention) served as a comparison to the intervention group. Pain intensity, shared decision-making in pain management, and patient satisfaction with results of pain management, served as patient-reported measures, collected using the International Pain Outcomes questionnaire and analysed using descriptive statistics. Results: The intervention showed no benefit for patients’ pain and satisfaction, while shared decision-making in pain management was significant lower in the intervention group than in the conventional group. The per-protocol analysis showed no significant differences between groups. Conclusion: The initial assumption of the study, that the implementation of a co-created structured person-centred care pathway would improve patient-reported outcomes, was not confirmed. The periodically low fidelity to the intervention due to organizational constraints (due to sub-optimal organizational conditions and managerial support) may have affected the results.
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| 30. |
- Angelini, Eva, 1964, et al.
(författare)
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Healthcare practitioners’ experiences of postoperative pain management in lumbar spine surgery care—A qualitative study
- 2020
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Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 29, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd Aims and objective: To explore and describe healthcare practitioners’ experiences of postoperative pain management to patients undergoing planned lumbar spine surgery by identifying the healthcare practitioners’ behaviours, attitudes and strategies. Background: Poorly managed postoperative pain continues to cause suffering and prolong hospital care and may affect individual and team practitioners’ strategies and attitudes. The impact of these strategies and attitudes needs greater understanding. Design: Descriptive qualitative study. Methods: In-depth interviews were conducted at a university hospital in Sweden during January–March 2016 with 9 healthcare practitioners (ages: 29–61years; gender: male 3 and female 6; professions: medical doctor 3, registered nurse 3 and physiotherapist 3; professional experience: 1.5months to 25years). The interviews were analysed using Braun and Clarke's thematic analysis. The study adhered to the Consolidated Criteria for Reporting Qualitative Research COREQ. Results: The interviews revealed healthcare practitioners’ attitudes and strategies. Three themes were identified: (a) Connecting with the person was recognised as the key component in postoperative pain management; (b) Professionalism: a balancing act, accentuated health care practitioners’ duality in being both vulnerable and strong in delicate care situations; and (c) Collaboration: being constantly responsive, the necessity for healthcare practitioners to be constantly responsive to their environment. Conclusions: The findings pinpoint the need for healthcare organisations to build structures enabling practitioners to deliver adequate pain management in acknowledging the practitioners’ delicate situation when facing patients in pain. Relevance to clinical practice: Given the global need for postoperative pain management, our findings have international relevance. Preconceived expectations on specific pain need to be depicted and postoperative pain taken seriously to protect the patient as well as the healthcare practitioners.
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| 31. |
- Angelini, Eva, 1964, et al.
(författare)
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Patients' Experiences of Pain Have an Impact on Their Pain Management Attitudes and Strategies
- 2018
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Ingår i: Pain Management Nursing. - : Elsevier BV. - 1524-9042. ; 19:5, s. 464-473
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Postoperative pain remains undermanaged in orthopedic surgery. To identify areas of improvement for future structural changes in pain management, patients' experiences of pain and pain management when undergoing elective lumbar spine surgery were explored, using a qualitative method with focus group interviews. Setting: The study setting was an orthopedic spine surgery department at a University Hospital in Sweden. Methods: This study consisted of two focus group interviews with patients (n = 6/group, a total of 12 patients) who had undergone lumbar spine surgery 4 days to 5 weeks prior to the focus group interviews. The interviews were semi-structured, and the analysis was performed using qualitative content analysis. Results: The main result of this study revealed that patients' experiences of pain influenced their attitudes and strategies for pain management. Three main categories emerged from the focus group interviews: I. Coping with pain while waiting for surgery; II. Using different pain-relieving strategies after surgery; and III. How organizational structures influence the pain experiences. Conclusions: In conclusion the results from this study acknowledge that postoperative pain experiences and coping strategies after spine surgery are highly diverse and individual. This calls for staff having a more personalized approach to pain management in order to optimize pain relief, which was stressed as highly valued by the patients. (C) 2018 by the American Society for Pain Management Nursing
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| 32. |
- Angelini, Eva, 1964, et al.
(författare)
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The impact of implementing a person-centred pain management intervention on resistance to change and organizational culture
- 2021
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Ingår i: BMC Health Services Research. - : Springer Science and Business Media LLC. - 1472-6963. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Resistance to change and organizational culture are essential factors to consider in change management in health care settings. Implementation of structural change remains a challenge. There is a lack of studies providing information on the impact of implementation processes on the organization. The aim of this study was to describe the impact of implementing a systematic change process concerning postoperative person-centred pain management on resistance to change and organizational culture in an orthopaedic spine surgery unit. Methods: The study was set in an orthopaedic spine surgery unit at a university hospital. Person-centred bundles of care for postoperative pain management of spine surgery patients were developed in co-creation by a multi-professional expert group and implemented throughout the care pathway. The intervention was underpinned by theories on organizational culture and inspired by principles of person-centred care. Quantitative data were collected using the Resistance to Change Scale and the Organizational Culture Assessment Instrument and analysed using descriptive statistics. Results: The findings showed a low resistance to change decreasing during the study. The organizational culture shifted from a result-oriented to a formalized and structured culture after the implementation. The culture preferred by the staff was team-oriented and participation-focused throughout the study. The discrepancy between the current and preferred cultures remained extensive over time. Conclusion: It is challenging to describe the influence of the development and implementation of a postoperative pain management program on organizational culture as well as in terms of resistance to change, in a complex health care setting. In the current study the unit was under organizational strain during the implementation. Albeit, the important discrepancy between the current and preferred organizational culture could imply that structural changes aren’t enough when implementing person-centred pain management structures and needs to be combined with relational aspects of change.
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| 33. |
- Austevoll, I. M., et al.
(författare)
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Decompression with or without Fusion in Degenerative Lumbar Spondylolisthesis
- 2021
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 385:6, s. 526-538
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with lumbar spinal stenosis and degenerative spondylolisthesis, it is uncertain whether decompression surgery alone is noninferior to decompression with instrumented fusion. Methods We conducted an open-label, multicenter, noninferiority trial involving patients with symptomatic lumbar stenosis that had not responded to conservative management and who had single-level spondylolisthesis of 3 mm or more. Patients were randomly assigned in a 1:1 ratio to undergo decompression surgery (decompression-alone group) or decompression surgery with instrumented fusion (fusion group). The primary outcome was a reduction of at least 30% in the score on the Oswestry Disability Index (ODI; range, 0 to 100, with higher scores indicating more impairment) during the 2 years after surgery, with a noninferiority margin of -15 percentage points. Secondary outcomes included the mean change in the ODI score as well as scores on the Zurich Claudication Questionnaire, leg and back pain, the duration of surgery and length of hospital stay, and reoperation within 2 years. Results The mean age of patients was approximately 66 years. Approximately 75% of the patients had leg pain for more than a year, and more than 80% had back pain for more than a year. The mean change from baseline to 2 years in the ODI score was -20.6 in the decompression-alone group and -21.3 in the fusion group (mean difference, 0.7; 95% confidence interval [CI], -2.8 to 4.3). In the modified intention-to-treat analysis, 95 of 133 patients (71.4%) in the decompression-alone group and 94 of 129 patients (72.9%) in the fusion group had a reduction of at least 30% in the ODI score (difference, -1.4 percentage points; 95% CI, -12.2 to 9.4), showing the noninferiority of decompression alone. In the per-protocol analysis, 80 of 106 patients (75.5%) and 83 of 110 patients (75.5%), respectively, had a reduction of at least 30% in the ODI score (difference, 0.0 percentage points; 95% CI, -11.4 to 11.4), showing noninferiority. The results for the secondary outcomes were generally in the same direction as those for the primary outcome. Successful fusion was achieved with certainty in 86 of 100 patients (86.0%) who had imaging available at 2 years. Reoperation was performed in 15 of 120 patients (12.5%) in the decompression-alone group and in 11 of 121 patients (9.1%) in the fusion group. Conclusions In this trial involving patients who underwent surgery for degenerative lumbar spondylolisthesis, most of whom had symptoms for more than a year, decompression alone was noninferior to decompression with instrumented fusion over a period of 2 years. Reoperation occurred somewhat more often in the decompression-alone group than in the fusion group. (NORDSTEN-DS ClinicalTrials.gov number, .) Decompression versus Fusion for Lumbar Spondylolisthesis In a randomized trial conducted in Norway, decompression surgery alone was noninferior to decompression with instrumented fusion with respect to the percentage of patients who had a 30% reduction on a scale of pain and disability over a period of 2 years, with a noninferiority margin of -15 percentage points.
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| 34. |
- Banitalebi, H., et al.
(författare)
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A novel MRI index for paraspinal muscle fatty infiltration: reliability and relation to pain and disability in lumbar spinal stenosis: results from a multicentre study
- 2022
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Ingår i: European Radiology Experimental. - : Springer Science and Business Media LLC. - 2509-9280. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fatty infiltration of the paraspinal muscles may play a role in pain and disability in lumbar spinal stenosis. We assessed the reliability and association with clinical symptoms of a method for assessing fatty infiltration, a simplified muscle fat index (MFI). Methods: Preoperative axial T2-weighted magnetic resonance imaging (MRI) scans of 243 patients aged 66.6 +/- 8.5 years (mean +/- standard deviation), 119 females (49%), with symptomatic lumbar spinal stenosis were assessed. Fatty infiltration was assessed using both the MFI and the Goutallier classification system (GCS). The MFI was calculated as the signal intensity of the psoas muscle divided by that of the multifidus and erector spinae. Observer reliability was assessed in 102 consecutive patients for three independent investigators by intraclass correlation coefficient (ICC) and 95% limits of agreement (LoA) for continuous variables and Gwet's agreement coefficient (AC1) for categorical variables. Associations with patient-reported pain and disability were assessed using univariate and multivariate regression analyses. Results: Interobserver reliability was good for the MFI (ICC 0.79) and fair for the GCS (AC1 0.33). Intraobserver reliability was good or excellent for the MFI (ICC range 0.86-0.91) and moderate to almost perfect for the GCS (AC1 range 0.55-0.92). Mean interobserver differences of MFI measurements ranged from -0.09 to -0.04 (LoA -0.32 to 0.18). Adjusted for potential confounders, none of the disability or pain parameters was significantly associated with MFI or GCS. Conclusion: The proposed MFI demonstrated high observer reliability but was not associated with preoperative pain or disability.
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| 35. |
- Banitalebi, H., et al.
(författare)
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Reliability of preoperative MRI findings in patients with lumbar spinal stenosis
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Magnetic Resonance Imaging (MRI) is an important tool in preoperative evaluation of patients with lumbar spinal stenosis (LSS). Reported reliability of various MRI findings in LSS varies from fair to excellent. There are inconsistencies in the evaluated parameters and the methodology of the studies. The purpose of this study was to evaluate the reliability of the preoperative MRI findings in patients with LSS between musculoskeletal radiologists and orthopaedic spine surgeons, using established evaluation methods and imaging data from a prospective trial. Methods: Consecutive lumbar MRI examinations of candidates for surgical treatment of LSS from the Norwegian Spinal Stenosis and Degenerative Spondylolisthesis (NORDSTEN) study were independently evaluated by two musculoskeletal radiologists and two orthopaedic spine surgeons. The observers had a range of experience between six and 13 years and rated five categorical parameters (foraminal and central canal stenosis, facet joint osteoarthritis, redundant nerve roots and intraspinal synovial cysts) and one continuous parameter (dural sac cross-sectional area). All parameters were re-rated after 6 weeks by all the observers. Inter- and intraobserver agreement was assessed by Gwet's agreement coefficient (AC1) for categorical parameters and Intraclass Correlation Coefficient (ICC) for the dural sac cross-sectional area. Results: MRI examinations of 102 patients (mean age 66 +/- 8 years, 53 men) were evaluated. The overall interobserver agreement was substantial or almost perfect for all categorical parameters (AC1 range 0.67 to 0.98), except for facet joint osteoarthritis, where the agreement was moderate (AC1 0.39). For the dural sac cross-sectional area, the overall interobserver agreement was good or excellent (ICC range 0.86 to 0.96). The intraobserver agreement was substantial or almost perfect/excellent for all parameters (AC1 range 0.63 to 1.0 and ICC range 0.93 to 1.0). Conclusions: There is high inter- and intraobserver agreement between radiologists and spine surgeons for preoperative MRI findings of LSS. However, the interobserver agreement is not optimal for evaluation of facet joint osteoarthritis.
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| 36. |
- Baranto, Adad, 1966, et al.
(författare)
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Interspinous Process Implants Causes Wear of the Spinous Processes in Patients Treated for Spinal Stenosis—An Experimental Biomechanical Study with Comparison to Clinical Cases
- 2016
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Ingår i: Open Journal of Orthopedics. - : Scientific Research Publishing, Inc.. - 2164-3008 .- 2164-3016. ; :6, s. 201-210
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Tidskriftsartikel (refereegranskat)abstract
- There are few biomechanical studies on Interspinous Process Implants (IPD); however none investigate the amount of wear on spinous processes. Therefore the objective of the present study was to investigate the effect of repetitive loading of the IPD Aperius on the spinous processes in a biomechanical porcine model. For comparison, three patients treated surgically with the same device have been followed for one to two years clinically and with image analyses (X-rays, MRI, CT-scans). Four lumbar spines from 6 months old porcine were divided into seven segments, which received IPD. The segments were exposed to 20,000 cyclical loads. Afterwards the deformation (wear) of the segments was registered. The wear of the spinous processes was measured in mm on a following CT-scan. Additionally, the wear of the ex-vivo was compared to that of the spinous processes investigated by CT-scans or X-ray in three patients treated surgically with the same interspinous implant. The mean maximal deformation of porcine specimens was 1.79 mm (SD 0.25) with the largest deformation occurring in the first quarter of the loading (<5000 cycles). The mean wear of the spinous processes after loading was 6.57 mm. A similar level of wear (mean 12.7 mm) of the spinous processes was detected in the patients. The Aperius IPD creates significant wear on the spinous processes in an experimental biomechanical study. Similar wear of the spinous pro-
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| 37. |
- Beck, Joel, et al.
(författare)
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Association of extended duration of sciatic leg pain with worse outcome after lumbar disc herniation surgery: a register study in 6216 patients
- 2021
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Ingår i: Journal of Neurosurgery-Spine. - 1547-5654. ; 34, s. 759-767
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Sciatica is the hallmark symptom of a lumbar disc herniation (LDH). Up to 90% of LDH patients recover within 12 weeks regardless of treatment. With continued deteriorating symptoms and low patient quality of life, most surgeons recommend surgical discectomy. However, there is not yet a clear consensus regarding the proper timing of surgery. The aim of this study was to evaluate how the duration of preoperative leg pain (sciatic neuralgia) is associated with patient-reported levels of postoperative leg pain reduction and other patient-reported outcome measures (PROMs) in a prospectively collected data set from a large national cohort. METHODS All patients aged 18?65 years undergoing a lumbar discectomy during 2013?2016 and registered in Swespine (the Swedish national spine registry) with 1 year of postoperative follow-up data were included in the study (n = 6216). The patients were stratified into 4 groups according to preoperative pain duration: < 3, 3?12, 12?24, or > 24 months. Patient results assessed with the numeric rating scale (NRS) for leg pain (rated from 0 to 10), global assessment of leg pain, EQ-5D, Oswestry Disability Index (ODI), and patient satisfaction with the final surgical outcome were analyzed and compared with preoperative values and between groups. RESULTS A significant improvement was seen 1 year postoperatively regardless of preoperative pain duration (change in NRS score: mean ?4.83, 95% CI ?4.73 to ?4.93 in the entire cohort). The largest decrease in leg pain NRS score (mean ?5.59, 95% CI ?5.85 to ?5.33) was seen in the operated group with the shortest sciatica duration (< 3 months). The patients with a leg pain duration in excess of 12 months had a significantly higher risk of having unchanged radiating leg pain 1 year postoperatively compared with those with < 12-month leg pain duration at the time of surgery (OR 2.41, 95% CI 1.81?3.21, p < 0.0001). CONCLUSIONS Patients with the shortest leg pain duration (< 3 months) reported superior outcomes in all measured parameters. More significantly, using a 12-month pain duration as a cutoff, patients who had a lumbar discectomy with a preoperative symptom duration < 12 months experienced a larger reduction in leg pain and were more satisfied with their surgical outcome and perception of postoperative leg pain than those with > 12 months of sciatic leg pain.
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| 38. |
- Beck, Joel, et al.
(författare)
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Low lordosis is a common finding in young lumbar disc herniation patients
- 2020
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Ingår i: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The sagittal alignment of the lumbar spine and pelvis can be classified into several subtypes. It has been suggested that the risk of developing certain pathologies, such as a lumbar disc herniation (LDH) is affected by spinal sagittal profiles. The main aim of this study was to investigate the sagittal profile in young patients surgically treated for a lumbar disc herniation and if a discectomy would alter the sagittal parameters. Methods: Sixteen active young patients (mean age 18.3 ± 3.2 SD) with a lumbar disc herniation having a discectomy were included. A classification according to Roussouly of the sagittal parameters was made by two senior spinal surgeons, both pre-operatively and post-operatively on radiographs. The distribution of sagittal parameters and spinopelvic profiles were analysed and compared to a previous established healthy normal population. Results: This series of active young patients with LDH exhibited a low lumbar lordosis dominance, with Roussouly sagittal profiles type 1 and type 2 accounting for more than 75% of the examined patients. An analysis of the erect radiographs revealed no significant changes in the post-operative sagittal profile. Conclusions: This study showed that sagittal spinal alignment according to Roussouly in a young population with LDH is skewed compared with a normal population cohort. Furthermore, the lack of post-operative correction is suggestive of a non-ephemeral response to a LDH. Roussouly type 2 spinal sagittal profile may be a risk factor in young individuals suffering a disc herniation. © 2020, The Author(s).
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| 39. |
- Belavy, D. L., et al.
(författare)
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Characterization of Intervertebral Disc Changes in Asymptomatic Individuals with Distinct Physical Activity Histories Using Three Different Quantitative MRI Techniques
- 2020
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 9:6
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Assessments of intervertebral disc (IVD) changes, and IVD tissue adaptations due to physical activity, for example, remains challenging. Newer magnetic resonance imaging techniques can quantify detailed features of the IVD, where T2-mapping and T2-weighted (T2w) and Dixon imaging are potential candidates. Yet, their relative utility has not been examined. The performances of these techniques were investigated to characterize IVD differences in asymptomatic individuals with distinct physical activity histories. (2) Methods: In total, 101 participants (54 women) aged 25-35 years with distinct physical activity histories but without histories of spinal disease were included. T11/12 to L5/S1 IVDs were examined with sagittal T2-mapping, T2w and Dixon imaging. (3) Results: T2-mapping differentiated Pfirrmann grade-1 from all other grades (p< 0.001). Most importantly, T2-mapping was able to characterize IVD differences in individuals with different training histories (p< 0.005). Dixon displayed weak correlations with the Pfirrmann scale, but presented significantly higher water content in the IVDs of the long-distance runners (p< 0.005). (4) Conclusions: Findings suggested that T2-mapping best reflects IVD differences in asymptomatic individuals with distinct physical activity histories changes. Dixon characterized new aspects of IVD, probably associated with IVD hypertrophy. This complementary information may help us to better understand the biological function of the disc.
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| 40. |
- Belavy, Daniel L, et al.
(författare)
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Disc herniations in astronauts: What causes them, and what does it tell us about herniation on earth?
- 2016
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Ingår i: European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. - : Springer Science and Business Media LLC. - 1432-0932. ; 25:1, s. 144-154
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Forskningsöversikt (refereegranskat)abstract
- Recent work showed an increased risk of cervical and lumbar intervertebral disc (IVD) herniations in astronauts. The European Space Agency asked the authors to advise on the underlying pathophysiology of this increased risk, to identify predisposing factors and possible interventions and to suggest research priorities.
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| 41. |
- Berger, Christina, et al.
(författare)
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High Risk for Persistent Peri-Prosthetic Infection and Amputation in Mega-Prosthesis Reconstruction
- 2023
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Ingår i: Journal of Clinical Medicine. ; 12:10
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Tidskriftsartikel (refereegranskat)abstract
- A peri-prosthetic joint infection is a feared complication after mega-prosthesis reconstruction of large bone defects. The current study investigates how patients operated with a mega-prosthesis due to sarcoma, metastasis, or trauma, are affected by a deep infection focusing on re-operations, risk for persistent infection, arthrodesis, or subsequent amputation. Time to infection, causative bacterial strains, mode of treatment and length of hospital stay are also reported. A total of 114 patients with 116 prostheses were evaluated, a median of 7.6 years (range 3.8-13.7) after surgery, of which 35 (30%) were re-operated due to a peri-prosthetic infection. Of the infected patients, the prosthesis was still in place in 51%, 37% were amputated, and 9% had an arthrodesis. The infection was persistent in 26% of the infected patients at follow-up. The mean total length of hospital stay was 68 (median 60) days and the mean number of reoperations was 8.9 (median 6.0). The mean length of antibiotic treatment was 340 days (median 183). Coagulase-negative staphylococci and Staphylococcus aureus were the most frequent bacterial agents isolated in deep cultures. No MRSA- or ESBL-producing Enterobacterales were found but vancomycin-resistant Enterococcus faecium was isolated in one patient. In summary, there is a high risk for peri-prosthetic infection in mega-prostheses, resulting in persistent infection or amputation relatively often.
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| 42. |
- Berger, Christina, et al.
(författare)
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The risk for complications and reoperations with the use of mega prostheses in bone reconstructions
- 2021
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite a relatively high risk for complications and reoperations, mega prostheses are considered a useful method for reconstruction of bone defects after tumour resections. The total number of reoperations has not previously been described, and little is known about the complication rate of mega prostheses used for other indications than primary bone tumours. Questions/purposes The current retrospective observational study aimed to describe the patient population treated with mega prostheses at Sahlgrenska University Hospital, Sweden, during 14 consecutive years, reports the complications leading to reoperation and the number and type of reoperations for different kinds of complications, and reports on implant survival. Methods All patients treated with a mega prosthesis, regardless of surgical indication and anatomical location, at Sahlgrenska University Hospital during the period 2006-2019 were identified. The medical records for all patients were reviewed. Data regarding age, sex, diagnosis, site of disease, bone resection length, chemotherapeutical treatment and postoperative complications including infections and oncological outcome, were collected and evaluated. Results One hundred and fourteen patients treated with 116 mega prostheses were included in the study. The predominant indication for primary surgery with a mega prosthesis was sarcoma of either bone or soft tissue (53.5% of the patients). In total 51 prostheses (44%) did not require any reoperation after the primary surgery. The most common reason for reoperation was infection (22%) followed by soft tissue failure (13%). The risk for prosthetic infection was significantly higher in the group of patients operated due to sarcoma compared with all other indications for surgery regardless of surgical site (p = 0.004). Conclusion The study reveals a total reoperation rate of 56% after reconstructive surgery using mega prostheses. Despite the high reoperation rates, at the end of the study period, 83% of the patients had still a functioning prosthesis. Therefore, the use of mega prostheses can be considered a reliable method for reconstruction of large bone defects in selected patients.
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| 43. |
- Bergh, Camilla, et al.
(författare)
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30-day and 1-year mortality after skeletal fractures: a register study of 295,713 fractures at different locations
- 2021
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:6, s. 739-745
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Few studies have reported the mortality rate after skeletal fractures involving different locations, within the same population. We analyzed the 30-day and 1-year mortality rates following different fractures. Patients and methods - We included 295,713 fractures encountered in patients 16-108 years of age, registered in the Swedish Fracture Register (SFR) from 2012 to 2018. Mortality rates were obtained by linkage of the SFR to the Swedish Tax Agency population register. The standardized mortality ratios (SMR) at 30 days and 1 year were calculated for fractures in any location and for each of 27 fracture locations, using age- and sex-life tables from Statistics Sweden (www.scb.se). Results - The overall SMR at 30 days was 6.8 (95% CI 6.7-7.0) and at 1 year 2.2 (CI 2.2-2.2). The SMR was > 2 for 19/27 and 13/27 of the fracture locations at 30 days and 1 year, respectively. Humerus, femur, and tibial diaphysis fractures were all associated with high SMR, at both 30 days and 1 year. Interpretation - Patients sustaining a fracture had approximately a 7-fold increased mortality at 30 days and over 2-fold increased mortality at 1 year as compared with what would be expected in the general population. High mortality rates were seen for patients with axial skeletal and proximal extremity fractures, indicating frailty in these patient groups.
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| 44. |
- Bergh, Camilla, et al.
(författare)
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Fracture incidence in adults in relation to age and gender: A study of 27,169 fractures in the Swedish Fracture Register in a well-defined catchment area
- 2020
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 Bergh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Studies on fracture incidence have mostly been based on retrospectively registered data from local hospital databases. The Swedish Fracture Register (SFR) is a national quality register collecting data prospectively on fractures, at the time of care-seeking. In the present study the incidence of all different fractures, regardless of location, in adults’ > 16 years treated at the only care provider for patients with fractures within a catchment area of approximately 550,000 inhabitants, during 2015–2018 are described. Age, gender, and fracture location (according to AO/OTA classification) was used for the analyses and presentation of fracture incidences. During the 4-year study period, 23,917 individuals sustained 27,169 fractures. The mean age at fracture was 57.9 years (range 16–105 years) and 64.5% of the fractures occurred in women. The five most common fractures accounted for more than 50% of all fractures: distal radius, proximal femur, ankle, proximal humerus, and metacarpal fractures. Seven fracture incidence distribution groups were created based on age- and gender-specific incidence curves, providing visual and easily accessible information on fracture distribution. This paper reports on incidence of all fracture locations based on prospectively collected data in a quality register. The knowledge on fracture incidence related to age and gender may be of importance for the planning of orthopaedic care, involving both in- and out-patients as well as allocating surgical resources. Further, this might be useful for organizing preventive measures, especially in countries with similar socioeconomic structure and fracture burden.
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| 45. |
- Bergh, Camilla, et al.
(författare)
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Mortality after Sustaining Skeletal Fractures in Relation to Age
- 2022
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Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Age-related mortality across fractures in different anatomical regions are sparsely described, since most studies focus on specific age groups or fracture locations. The aim here was to investigate mortality at 30 days and 1 year post-fracture within four different age groups. All patients >= 16 years registered in the Swedish Fracture Register (SFR) 2012-2018 were included (n = 262,598 patients) and divided into four age groups: 16-49, 50-64, 65-79, and >= 80 years of age. Standardized mortality ratios (SMR) at 30 days and 1 year after sustaining a fracture were calculated using age- and gender-specific life tables from Statistics Sweden for each of the 27 fracture locations in the four age groups. Absolute mortality rates for the youngest age group for all locations were below 1% and 2% at 30 days and 1 year, respectively. For the patients in the two oldest age groups (65 and older), mortality rates were as high as 5% at 30 days and up to 25% at 1 year for certain fracture locations. For younger patients a few localizations were associated with high SMRs, whereas for the oldest age group 22 out of 27 fracture locations had an SMR of >= 2 at 30 days. Fractures of the femur (proximal, diaphysis, and distal) and humerus diaphysis fractures were among the fractures associated with the highest mortality rates and SMRs within each age group. Moderately high SMRs were further seen for pelvic, acetabulum, spine, and tibia fractures within all age groups. Regardless of age, any type of femur fractures and humerus diaphysis fractures were associated with increased mortality. In the oldest age groups, about twice as many patients died within 1 year after sustaining a fracture in almost any location, as compared with the expected mortality rates, whereas in the youngest age group only fractures in a few locations were associated with a high SMR.
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| 46. |
- Bergh, Camilla, et al.
(författare)
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Preoperative dual-energy X-ray absorptiometry and FRAX in patients with lumbar spinal stenosis
- 2018
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Ingår i: Journal of Orthopaedic Surgery and Research. - : Springer Science and Business Media LLC. - 1749-799X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOsteoporosis implies an increased risk of complications after orthopedic surgery. For the mostly elderly group of patients undergoing lumbar spinal stenosis surgery (LSS), it is important to include skeletal health evaluation in the preoperative planning. The aim of this study was to assess spine and femoral neck (FN) bone mineral density (BMD) in LSS patients and to evaluate whether the World Health Organization (WHO) fracture risk assessment tool (FRAX) can identify patients with reduced BMD levels in the spine.MethodsThe study involved 65 LSS patients and 53 patients with hip osteoarthritis (HOA) for comparison. BMD was measured with dual-energy X-ray absorptiometry (DXA) in the lumbar spine in three projections: anterior-posterior (AP), lateral and lateral-mid (the mid-portion of the vertebrae), and FN. The LSS patients filled out the FRAX questionnaire.ResultsIn the LSS group, 43% of the women and 8% of the men were classified as being osteoporotic/osteopenic by AP spine measurement. The corresponding proportions using the lateral spine T-score -2.5 were 87% and 57%, respectively, and 82% and 53%, respectively, for the FN. The FN BMD T-score was significantly lower in the LSS group compared with the HOA group. The FRAX questionnaire identified 40% of the LSS patients with a moderate/high risk of sustaining an osteoporotic fracture within 10years, with or without simultaneous FN BMD, while 71% of these patients were classified as being osteoporotic with DXA lateral spine measurement.ConclusionIt is common with osteoporosis/osteopenia in patients undergoing spine surgery, and the identification may influence the surgical treatment why the evaluation of BMD is important preoperatively. FRAX evaluation could not replace DXA measurement of the spine regarding the identification of osteoporosis patients in the preoperative planning phase.
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| 47. |
- Brisby, Helena, 1965, et al.
(författare)
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Cell therapy for disc degeneration--potentials and pitfalls
- 2004
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Ingår i: Orthop Clin North Am. - 0030-5898. ; 35:1, s. 85-93
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Tidskriftsartikel (refereegranskat)abstract
- Disc degeneration is considered a major source of pain in patients with chronic low back pain. Novel strategies to cure or decrease the symptoms and increase the patient's quality of life and function are under development. Until recently conservative treatment and fusion surgery were the main therapeutic options. Disc prostheses are undergoing clinical evaluation. The potential for cell transplantation to the intervertebral disc with mature autologous disc cells, chondrocytes, or stem cells is in early stages of investigation. Cell transplantation potentially can increase proteoglycan production and induce disc regeneration or slow down the degeneration process. In animal models, transplantation of autologous disc cells and chondrocytes (derived from costal cartilage) has been demonstrated to be feasible and may slow disc degeneration.
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| 48. |
- Brisby, Helena, 1965, et al.
(författare)
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Cerebrospinal fluid leakage after elective disc surgery
- 2012
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Ingår i: ArgoSpine News and Journal. - : Springer Science and Business Media LLC. - 1957-7729 .- 1957-7737. ; 24, s. 162-165
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Forskningsöversikt (refereegranskat)abstract
- For patients undergoing elective disc herniation surgery the risk to experience a dural tear is somewhere around 1% both for the cervical and the thoracic regions and probably slightly higher for the lumbar region. In most cases a dural tear is diagnosed and taken care of peroperatively. When a leakage of cerebrospinal fluid is suspected postoperatively a combination of the patient's history and imaging investigations/laboratory tests usually gives the diagnosis and it is mostly treated by closure in a new surgical procedure or by a subdural lumbar drainage. There is conflicting data on the long-term effect of a dural tear in relation to disc herniation surgery. This review exemplifies, describes and discusses how to diagnose, treat a dural tear and what the results are when dealing with it during or after disc herniation surgery.
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| 49. |
- Brisby, Helena, 1965, et al.
(författare)
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In vivo measurement of facet joint nitric oxide in patients with chronic low back pain.
- 2007
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Ingår i: Spine. - 1528-1159. ; 32:14, s. 1488-92
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Tidskriftsartikel (refereegranskat)abstract
- Prospective case-control study testing a new diagnostic method.The aim of the present study was to investigate the concentration of nitric oxide (NO) in the perifacetal region in patients with chronic low back pain and healthy controls.Facet joint arthrosis may be a pain source in chronic back pain. Increased concentrations of NO, an oxygen-free radical, have been demonstrated in temporomandibular and knee joints with osteoarthritis.Patients with at least 6 months' duration of chronic low back pain and signs of facet joint osteoarthrosis (n = 24) and healthy volunteers (n = 7) were included. A detailed questionnaire, including visual analogue scale, was completed before and 6 weeks after the measurements. NO was measured with a custom-designed electrochemical real-time NO sensor inserted under fluoroscopic guidance. All patients received corticosteroids and local anesthetics after NO measurements.NO measurements were obtained from all participants. No adverse effects were noted. The patients with chronic low back pain demonstrated higher concentrations of NO in the perifacetal region compared with healthy controls (1.66 +/- 0.28 vs. 0.46 +/- 0.14 nmol/L, P = 0.007). No association between NO concentration and pain duration or pain level was detected. Patients with a positive response to local anesthetics and corticosteroid injection (defined as a >or=20 mm reduction of visual analogue scale at the 6-week follow-up visit) had higher NO concentrations than patients without positive response.The study demonstrates that it is feasible and safe to measure NO with a real time-sensor in or around the facet joints. The findings of higher concentrations of NO in the perifacetal region in chronic low back patients compared with healthy controls indicate that the degenerative process of the joints in these patients may cause increased NO production. The observation of higher NO concentrations in the perifacetal region in patients responding to corticosteroid/local anesthetic infiltration indirectly suggest a more pronounced inflammatory process in these patients.
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| 50. |
- Brisby, Helena, 1965
(författare)
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Nerve tissue injury markers, inflammatory mechanisms and immunologic factors in lumbar disc herniation. Clinical and experimental studies
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The general concept for sciatic pain has for many decades been mechanical nerve root compression caused by a herniated disc. Recently evidence has indicated a more complex process, with a combination of mechanical and inflammatory/immunologic factors involved. The aim of these investigations was to analyze markers of nerve tissue injury, inflammation and immunologic factors in cerebrospinal fluid (CSF) and serum in patients with sciatica. Furthermore, the aim was to analyze the possible role of such inflammatory and immunologic factors in the pathophysiology of lumbar disc herniation and sciatica. The concentrations of four nerve tissue injury markers, neurofilament (NFL), S-100, glial fibrillary acidic protein (GFAp) and neuron specific enolase (NSE), were measured in CSF in patients with lumbar disc herniation and compared to control patients. The concentrations of NFL and S-100 were increased in CSF from patients with lumbar disc herniation, preferably in patients with short pain duration. In a disc herniation model in pig, changes in these nerve tissue injury markers, total protein and immunoglobulins were investigated in CSF. Nerve root compression was shown to induce an increase of NFL in CSF. Concentrations of five proinflammatory cytokines, IL-1b, IL-6, IL-8, IFN-g and TNF-a were assessed in CSF and serum from patients with disc herniation. The concentration of IL-8 was increased in CSF in 1/3 of the disc herniation patients, preferably in those with short pain duration. The involvement of nitric oxide (NO) in nucleus pulposus (NP) induced effects on spinal nerve roots were investigated in two animal models. Evidence was found for involvement of NO. The presence of auto-antibodies against glycosphingolipids was investigated in three groups of patients with sciatica. Increased serum titers of glycosphingolipid antibodies were found in approximately 2/3 of these patients. In summary, biomarkers of nerve root injury related to compression, inflammation and activation of the immune system can be detected in CSF and serum from patients with disc herniation, as well as in animal experimental models of disc herniation. Both inflammatory and immunologic mechanisms seem to be involved in the pathophysiology of sciatica caused by disc herniation.
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