| 1. |
- Diarbakerli, E., et al.
(författare)
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Learning from the past to plan for the future: A scoping review of musculoskeletal clinical research in Sweden 2010-2020
- 2022
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 127:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aims of this study are to 1) determine the scope of musculoskeletal (MSK)-related clinical research in Sweden; 2) collate the amount of first-tier funding received; 3) discuss strategies and infrastructure supporting future MSK clinical trials in Sweden. Methods: A systematic scoping review protocol was applied in PubMed, Scopus, and SweCRIS databases. The articles were examined, and data were extracted in multiple stages by three blinded authors. Results: The search strategy resulted in 3,025 publications from 479 Swedish-affiliated authors. Primary health care was the basis for 14% of the publications, 84% from secondary health care, and 2% from occupational health care with a similar proportional distribution of first-tier research grant financing. Approximately one in six publications were randomized controlled trials (RCTs), while the majority were of observational cohort design. The majority of publications in primary and occupational health care were related to pain disorders (51 and 67%, respectively), especially diagnosis, prognosis, and healthcare organizational-related interventions (34%) and rehabilitation (15%) with similar proportional distribution of first-tier research grant financing. In secondary health care, rheumatic inflammatory disorder-related publications were most prevalent (30%), most frequently concerning diagnosis, prognosis, and healthcare organizational-related interventions (20%), attracting approximately half of all first-tier funding. Publications related to degenerative joint disorders (25%), fractures (16%), and joint, tendon, and muscle injuries (13%) frequently concerned surgical and other orthopedic-related interventions (16, 6, and 8%, respectively). Pain disorder-related publications (10%) as well as bone health and osteoporosis-related publications (4%) most frequently concerned diagnosis, prognosis, and healthcare organizational-related interventions (5 and 3%, respectively). Conclusions: Swedish-affiliated MSK disorder research 2010-2020 was predominantly observational cohort rather than RCT based. There was skewed first-tier funding allocation considering prevalence/incidence and burden of disease. Use of infrastructure supporting register-based RCTs, placebo-controlled RCTs, and hybrid effectiveness-implementation studies on prevention and clinical intervention is important strategies for the future in all healthcare sectors.
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| 2. |
- Diarbakerli, Elias, et al.
(författare)
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Swedish musculoskeletal researchers view on a collaborative network and future research priorities in Swedish healthcare
- 2024
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Ingår i: Musculoskeletal Care. - : John Wiley & Sons. - 1478-2189 .- 1557-0681. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Musculoskeletal disorders (MSK) are a global burden causing significant suffering and economic impact. Systematic identification and targeting of research questions of highest interest for stakeholders can aid in improving MSK disorder knowledge and management.Objective: To obtain Swedish MSK researchers' opinions and views on a collaborative Swedish MSK network (SweMSK) and identify future research areas of importance for Swedish MSK research.Methods: A web-based survey was conducted July to September 2021 to collect data from 354 Swedish MSK researchers. The survey focused on the need, objectives, and structure of a SweMSK network and identified prioritised areas for future MSK research.Results: The study included 141 respondents, of which 82 were associate professors or professors. The majority (68%) supported the creation of a new musculoskeletal network. The most supported element was increased collaboration regarding nationwide and multicenter studies. Respondents recommended the creation of a homepage and the establishment of national work groups with different specific interests as the primary elements of a new network.Conclusion: The results demonstrated a need and desire for increased national research collaboration and the creation of a new musculoskeletal network. The high academic experience and active research participation of the respondents suggest the need for MSK disorder knowledge and management improvement in Sweden. Therefore, the SweMSK network may help facilitate effective collaboration and research efforts that can contribute to the advancement of MSK disorder management and care. This study may provide valuable insights for policymakers, clinicians, and researchers to improve MSK disorder care and management in Sweden.
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| 3. |
- Kvist, Martin, et al.
(författare)
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Costimulation blockade in transplantation of nerve allografts: long-term effects.
- 2008
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1529-8027 .- 1085-9489. ; 13:3, s. 200-207
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Tidskriftsartikel (refereegranskat)abstract
- Costimulation blockade can prevent rejection of nerve allografts in short-term studies. We tested if costimulation blockade also prevented rejection of nerve allografts in long-term experiments, thereby improving functional recovery. A 7-mm sciatic nerve defect in C57/BL6 mice was bridged either by nerve allografts from Balb/C mice or by isogenic nerve grafts (isografts) from C57/BL6 mice. Costimulation blockade in the form of a triple treatment with anti-LFA-1, anti-CD40L, and CTLA4Ig was given at post-operative days 0, 2, 4, and 6 (intraperitoneal). Control mice (placebo; allografts) with nerve grafts were treated with isotype antibodies during the same time period. After 49 days, tetanic muscle force, wet weight of gastrocnemius muscle, histology, and morphometry in the tibial nerve were evaluated. Costimulation blockade diminished rejection of the nerve allografts. Axons bridged the graft. Treatment increased wet weight of the gastrocnemius muscle and resulted in a higher mean myelin area/nerve fiber in the tibial nerve distal to the nerve grafts. Tetanic muscle force and number of axons in tibial nerve showed no differences between groups. We conclude that rejection is suppressed by costimulation blockade. Treatment improves recovery of target muscle and myelination after nerve allografting.
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| 4. |
- Kvist, Martin, et al.
(författare)
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Immunomodulation by costimulation blockade inhibits rejection of nerve allografts
- 2007
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Ingår i: Journal of the Peripheral Nervous System. - : Wiley. - 1085-9489 .- 1529-8027. ; 12:2, s. 83-90
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate if costimulation blockade could be used to modulate the immune response, to prevent rejection, and to stimulate regeneration into nerve allografts. Nerve allografts from Balb/C mice, and isogenic nerve grafts (isografts) from C57/BL6 mice, were used to bridge a 7-mm gap of the sciatic nerve in C57/BL6 mice. Allograft recipients were treated with either a triple treatment with anti-lymphocyte function antigen-1 (anti-LFA), anti-CD40 ligand (anti-CD40L), and cytotoxic T-lymphocyte antigen 4 immunoglobulin (anti-CTLA4Ig) or isotype antibodies (placebo) at postoperative days 0, 2, 4, and 6 (intraperitoneal). After 5 or 9 days, the nerve grafts, together with the proximal and the distal nerve segments, were evaluated by histology and immunocytochemistry for inflammatory cells [CD4-positive (CD4+) and CD8-positive (CD8+) staining cells] and axonal outgrowth (neurofilaments). The immune response was inhibited by costimulation blockade with less extensive inflammation and a lower number of CD4+ staining cells in triple-treated allografts at 9 days. The regeneration rate was significantly faster in isografts (0.75 mm/day) compared with allografts with placebo treatment (0.39 mm/day), but not when compared with triple-treated allografts (0.49 mm/day). At 9 days, the axons were significantly longer in nerve isografts than in nerve allografts, irrespective of treatment. Hence, costimulation blockade neither increased the regeneration rate nor the outgrowth length in triple-treated allografts. We conclude that costimulation blockade inhibits the immune response in nerve allografts without deterring early axonal outgrowth.
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| 5. |
- Kvist, Martin, et al.
(författare)
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Regeneration in, and properties of, extracted peripheral nerve allografts and xenografts.
- 2011
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Ingår i: Journal of Plastic Surgery and Hand Surgery. - 2000-656X .- 2000-6764. ; 45:3, s. 122-128
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Tidskriftsartikel (refereegranskat)abstract
- Abstract When not enough conventional autologous nerve grafts are available, alternatives are needed to bridge nerve defects. Our aim was to study regeneration of nerves in chemically-extracted acellular nerve grafts from frogs, mice, humans (fresh and stored sural nerve), pigs and rats when defects in rat sciatic nerves were bridged. Secondly, we compared two different extraction procedures (techniques described by Sondell et al. and Hudson et al.) with respect to how efficiently they supported axonal outgrowth, and remaining laminin and myelin basic protein (MBP), after extraction. Isografts (rat) and xenografts (mouse) were transplanted into defects in rat sciatic nerves. Acellular nerve allografts from rats, extracted by the Sondell et al's technique, had an appreciably longer axonal outgrowth based on immunohistochemical staining of neurofilaments, than acellular nerve xenografts except those from the pig. Among acellular xenografts there was considerably longer axonal outgrowth in the grafts from pigs compared with those from humans (fresh), but there were no other differences among the xenografts with respect to axonal outgrowth. Axonal outgrowth in acellular nerve xenografts from mice, extracted by the method described by Sondell et al. was longer than in those extracted by Hudson et al's method, while there was no difference in outgrowth between extracted nerve isografts from rats. Electrophoretic analysis of extracted acellular nerve grafts showed remaining laminin, but not MBP, after both extraction procedures. These preserved laminin and removed MBP in acellular nerve grafts. Such grafts can be used to reconstruct short defects in nerves irrespective of their origin. However, selecting and matching a suitable combination of graft and host species may improve axonal outgrowth.
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| 6. |
- Arundale, Amelia, et al.
(författare)
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Jump performance in male and female football players
- 2020
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : SPRINGER. - 0942-2056 .- 1433-7347. ; 28, s. 606-613
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To examine differences between men and women football players in clinically feasible jumping measures. Methods Female football players (N=46, ages 16-25) were matched based on age, training frequency, and playing position with 46 male players. All players performed the tuck jump and drop vertical jump (DVJ). DVJ was assessed quantitatively for valgus knee motion and probability of a high peak knee abduction moment (pKAM), as well as sagittal plane hip, knee, and ankle angles, and qualitatively with visual assessment of the players knees upon landing; graded as good, reduced, or poor control. Result Women had higher total tuck jump scores (52) (more technique flaws), than men (3 +/- 2, Pamp;lt;0.01). The quantitative analysis of the DVJ found that men had greater asymmetries between limbs, but women landed bilaterally in more knee valgus (interaction P=0.04, main effect of sex P=0.02). There was no difference in pKAM (interaction n.s.). Women also landed in less hip flexion (P=0.01) and ankle dorsiflexion (P=0.01) than men. The qualitative DVJ analysis found that more women (48%) had poor knee control compared to men (11%, Pamp;lt;0.01). Conclusions The results indicate that women perform worse on the tuck jump assessment than men. The results support previous findings that women land in more knee valgus than men, but also found that men may have larger asymmetries in knee valgus. These results from clinically feasible measures provide some suggestions for clinicians to consider during ACL reconstruction rehabilitation to enhance performance.
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| 7. |
- Arundale, Amelia, 1965-, et al.
(författare)
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Jumping performance based on duration of rehabilitation in female football players after anterior cruciate ligament reconstruction
- 2019
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Berlin/Heidelberg. - 0942-2056 .- 1433-7347. ; 27:2, s. 556-563
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo determine if female football players who had longer durations of rehabilitation, measured in months, after anterior cruciate ligament reconstruction would have lower tuck jump scores (fewer technique flaws) and smaller asymmetries during drop vertical jump landing.MethodsOne-hundred-and-seventeen female football players, aged 16ￜ25 years, after primary unilateral ACL reconstruction (median 16 months, range 6ￜ39) were included. Athletes reported the duration of rehabilitation they performed after anterior cruciate ligament reconstruction. Athletes also performed the tuck jump and drop vertical jump tests. Outcome variables were: tuck jump score, frontal plane knee motion and probability of peak knee abduction moment during drop vertical jump landing.ResultsThere was no difference in tuck jump score based on duration of rehabilitation (n.s.). No interaction (n.s.), difference between limbs (n.s.), or duration of rehabilitation (n.s.) was found for peak knee abduction moment during drop vertical jump landing. No interaction (n.s.) or difference between limbs (n.s.) was found for frontal plane knee motion, but there was a difference based on duration of rehabilitation (P?=?0.01). Athletes with >?9 months of rehabilitation had more frontal plane knee motion (medial knee displacement) than athletes with ConclusionAs there was no difference in tuck jump score or peak knee abduction moment based on duration of rehabilitation, the results of this study press upon clinicians the importance of using objective measures to progress rehabilitation and clear athletes for return to sport, rather than time alone.
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| 8. |
- Arundale, Amelia, et al.
(författare)
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TUCK JUMP SCORE IS NOT RELATED TO HOPPING PERFORMANCE OR PATIENT-REPORTED OUTCOME MEASURES IN FEMALE SOCCER PLAYERS
- 2020
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Ingår i: INTERNATIONAL JOURNAL OF SPORTS PHYSICAL THERAPY. - : AMER PHYSICAL THERAPY ASSOC. - 2159-2896. ; 15:3, s. 395-406
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Tidskriftsartikel (refereegranskat)abstract
- Background: The tuck jump assessment was developed to identify players at risk for anterior cruciate ligament (ACL) injuries or gauge a players progress through rehabilitation after ACL reconstruction. A tuck jump score of >= 6 out of 10 has been labeled poor and thought to identify players with high risk landing patterns. Purpose: The purpose of this exploratory study was to examine if there was a relationship between tuck jump score, particularly tuck jump scores >= 6, hopping performance, and patient-reported outcome measures in female soccer players with ACL reconstruction (ACLR) and knee-healthy controls. Study Design: Secondary analysis of prospective cohort study Methods: Female soccer players (117 after ACLR, 117 knee-healthy) performed the single hop for distance, tuck jump assessment, and drop vertical jump (DVJ). All players were categorized based on as having a total tuck jump score >= 6 or < 6. Analyzing all players together, Spearmans rank correlations assessed if there were relationships between total tuck jump score or tuck jump scores >= 6 and single-legged hop limb symmetry or DVJ measures. Players with an ACLR also filled out the International Knee Documentation Committee 2000 Subjective Knee Form and the Knee injury Osteoarthritis Outcome Score. Spearmans rank correlations assessed if there were relationships between total tuck jump score or tuck jump scores >= 6 and patient-reported outcome measures. Results: The mean tuck jump scores was 4.8 +/- 1.8 (tuck jump score >= 6, 6.7 +/- 0.9, tuck jump score < 6, 3.7 +/- 1.1) with 87 (37%) athletes having tuck jump score >= 6. There were no significant relationships between tuck jump score or tuck jump score >= 6 and hopping performance or patient-reported outcome measures. Conclusion: The results of this current study indicate that tuck jump scores, including tuck jump scores >= 6, may not be related to functional or patient-reported outcome measures. Further work is needed to examine the clinical utility of the tuck jump assessment.
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| 9. |
- Cirenajwis, Helena, et al.
(författare)
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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
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Tidskriftsartikel (refereegranskat)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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| 10. |
- Cirenajwis, Helena, et al.
(författare)
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NF1-mutated melanoma tumors harbor distinct clinical and biological characteristics
- 2017
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 11:4, s. 438-451
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Tidskriftsartikel (refereegranskat)abstract
- In general, melanoma can be considered as a UV-driven disease with an aggressive metastatic course and high mutational load, with only few tumors (acral, mucosal, and uveal melanomas) not induced by sunlight and possessing a lower mutational load. The most commonly activated pathway in melanoma is the mitogen-activated protein kinase (MAPK) pathway. However, the prognostic significance of mutational stratification is unclear and needs further investigation. Here, in silico we combined mutation data from 162 melanomas subjected to targeted deep sequencing with mutation data from three published studies. Tumors from 870 patients were grouped according to BRAF, RAS, NF1 mutation or triple-wild-type status and correlated with tumor and patient characteristics. We found that the NF1-mutated subtype had a higher mutational burden and strongest UV mutation signature. Searching for co-occurring mutated genes revealed the RASopathy genes PTPN11 and RASA2, as well as another RAS domain-containing gene RASSF2 enriched in the NF1 subtype after adjustment for mutational burden. We found that a larger proportion of the NF1-mutant tumors were from males and with older age at diagnosis. Importantly, we found an increased risk of death from melanoma (disease-specific survival, DSS; HR, 1.9; 95% CI, 1.21-3.10; P = 0.046) and poor overall survival (OS; HR, 2.0; 95% CI, 1.28-2.98; P = 0.01) in the NF1 subtype, which remained significant after adjustment for age, gender, and lesion type (DSS P = 0.03, OS P = 0.06, respectively). Melanoma genomic subtypes display different biological and clinical characteristics. The poor outcome observed in the NF1 subtype highlights the need for improved characterization of this group.
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