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1.
BMJ Open ; 9(9): e027507, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511280

RESUMO

OBJECTIVE: To evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018. STUDY SELECTION: Randomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s. DATA EXTRACTION AND ANALYSIS: Data were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up. RESULTS: In total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) -1.32, 95% CI -2.23 to -0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator. CONCLUSION: Current evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo. PROSPERO REGISTRATION NUMBER: CRD42018095384.

2.
Bone Joint J ; 101-B(9): 1071-1080, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31474146

RESUMO

AIMS: The aim of this study was to determine the long-term risk of undergoing knee arthroplasty in a cohort of patients with meniscal tears who had undergone arthroscopic partial meniscectomy (APM). PATIENTS AND METHODS: A retrospective national cohort of patients with a history of isolated APM was identified over a 20-year period. Patients with prior surgery to the same knee were excluded. The primary outcome was knee arthroplasty. Hazard ratios (HRs) were adjusted by patient age, sex, year of APM, Charlson comorbidity index, regional deprivation, rurality, and ethnicity. Risk of arthroplasty in the index knee was compared with the patient's contralateral knee (with vs without a history of APM). A total of 834 393 patients were included (mean age 50 years; 37% female). RESULTS: Of those with at least 15 years of follow-up, 13.49% (16 256/120 493; 95% confidence interval (CI) 13.30 to 13.69) underwent subsequent arthroplasty within this time. In women, 22.07% (95% CI 21.64 to 22.51) underwent arthroplasty within 15 years compared with 9.91% of men (95% CI 9.71 to 10.12), corresponding to a risk ratio (RR) of 2.23 (95% CI 2.16 to 2.29). Relative to the general population, patients with a history of APM were over ten times more likely (RR 10.27; 95% CI 10.07 to 10.47) to undergo arthroplasty rising to almost 40 times more likely (RR 39.62; 95% CI 27.68 to 56.70) at a younger age (30 to 39 years). In patients with a history of APM in only one knee, the risk of arthroplasty in that knee was greatly elevated in comparison with the contralateral knee (no APM; HR 2.99; 95% CI 2.95 to 3.02). CONCLUSION: Patients developing a meniscal tear undergoing APM are at greater risk of knee arthroplasty than the general population. This risk is three-times greater in the patient's affected knee than in the contralateral knee. Women in the cohort were at double the risk of progressing to knee arthroplasty compared with men. These important new reference data will inform shared decision making and enhance approaches to treatment, prevention, and clinical surveillance. Cite this article: Bone Joint J 2019;101-B:1071-1080.


Assuntos
Artroplastia do Joelho/estatística & dados numéricos , Osteoartrite do Joelho/epidemiologia , Lesões do Menisco Tibial/epidemiologia , Adulto , Fatores Etários , Idoso , Progressão da Doença , Inglaterra/epidemiologia , Feminino , Seguimentos , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Risco , Fatores de Risco , Fatores Sexuais , Lesões do Menisco Tibial/complicações , Lesões do Menisco Tibial/cirurgia
3.
BMJ Open ; 9(8): e030229, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31467054

RESUMO

OBJECTIVES: To illustrate the need for better evaluation of surgical procedures, we investigated the use and cost of subacromial decompression in England over the last decade compared with other countries and explored how this related to the conduct and outcomes of randomised, placebo-controlled clinical trials. DESIGN: Longitudinal observational study using Hospital Episode Statistics linked to Payment by Results tariffs in England, 2007/2008 to 2016/2017. SETTING: Hospital care in England; Finland; New York State, USA; Florida State, USA and Western Australia. PARTICIPANTS: Patients with subacromial shoulder pain. INTERVENTIONS: Subacromial decompression. MAIN OUTCOME MEASURES: National procedure rates, costs and variation between clinical commissioning groups in England. RESULTS: Without robust clinical evidence, the use of subacromial decompression in England increased by 91% from 15 112 procedures (30 per 100 000 population) in 2007/2008, to 28 802 procedures (52 per 100 000 population) in 2016/2017, costing over £125 million per year. Rates of use of subacromial decompression are even higher internationally: Finland (131 per 100 000 in 2011), Florida State (130 per 100 000 in 2007), Western Australia (115 per 100 000 in 2013) and New York State (102 per 100 000 in 2006). Two randomised placebo-controlled trials have recently (2018) shown the procedure to be no more effective than placebo or conservative approaches. Health systems appear unable to avoid the rapid widespread use of procedures of unknown effectiveness, and methods for ceasing ineffective treatments are under-developed. CONCLUSIONS: Without good evidence, nearly 30 000 subacromial decompression procedures have been commissioned each year in England, costing over £1 billion since 2007/2008. Even higher rates of procedures are carried out in countries with less regulated health systems. High quality randomised trials need to be initiated before widespread adoption of promising operative procedures to avoid overtreatment and wasted resources, and methods to prevent or desist the use of ineffective procedures need to be expedited.

4.
Am J Pathol ; 189(11): 2258-2268, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437425

RESUMO

Tendon stromal cells isolated from patients with chronic shoulder rotator cuff tendon tears have dysregulated resolution responses. Current therapies do not address the biological processes concerned with persistent tendon inflammation; therefore, new therapeutic approaches that target tendon stromal cells are required. We examined whether two specialized proresolving mediators (SPMs), lipoxin B4 (LXB4) and resolvin E1 (RvE1), modulate the bioactive lipid mediator profiles of IL-1ß-stimulated tendon cells derived from patients with shoulder tendon tears and healthy volunteers. We also examined whether LXB4 or RvE1 treatments moderated the proinflammatory phenotype of tendon tear stromal cells. Incubation of IL-1ß-treated patient-derived tendon cells in LXB4 or RvE1 up-regulated concentrations of SPMs. RvE1 treatment of diseased tendon stromal cells increased 15-epi-LXB4 and regulated postaglandin F2α. LXB4 or RvE1 also induced expression of the SPM biosynthetic enzymes 12-lipoxygenase and 15-lipoxygenase. RvE1 treatment up-regulated the proresolving receptor human resolvin E1 compared with vehicle-treated cells. Incubation in LXB4 or RvE1 moderated the proinflammatory phenotype of patient-derived tendon tear cells, regulating markers of tendon inflammation, including podoplanin, CD90, phosphorylated signal transducer and activator of transcription 1, and IL-6. LXB4 and RvE1 counterregulate inflammatory processes in tendon stromal cells, supporting the role of these molecules as potential therapeutics to resolve tendon inflammation.

5.
J Orthop Res ; 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31329308

RESUMO

Intra-synovial tendon injuries are a common orthopedic problem with limited treatment options. The synovium is a specialized connective tissue forming the inner encapsulating lining of diarthrodial joints and intra-synovial tendons. It contains multipotent mesenchymal stromal cells that render it a viable source of progenitors for tendon repair. This study evaluated the effects of autologous implantation of cells derived from normal synovium (synovial membrane cells [SMCs]) in augmenting repair in an ovine model of intra-synovial tendon injury. For this purpose, synovial biopsies were taken from the right digital flexor tendon sheath following creation of a defect to the lateral deep digital flexor tendon. Mononuclear cells were isolated by partial enzymatic digestion and assessed for MSC characteristics. Cell tracking and tendon repair were assessed by implanting 5 × 106 cells into the digital flexor tendon sheath under ultrasound guidance with the effects evaluated using magnetic resonance imaging and histopathology. Synovial biopsies yielded an average 4.0 × 105 ± 2.7 × 105 SMCs that exhibited a fibroblastic morphology, variable osteogenic, and adipogenic responses but were ubiquitously strongly chondrogenic. SMCs displayed high expression of CD29 with CD271NEGATIVE and MHC-IILOW cell-surface marker profiles, and variable expression of CD73, CD90, CD105, CD166, and MHC-I. Implanted SMCs demonstrated engraftment within the synovium, though a lack of repair of the tendon lesion over 24 weeks was observed. We conclude healthy synovium is a viable source of multipotent cells, but that the heterogeneity of synovium underlies the variability between different SMC populations, which while capable of engraftment and persistence within the synovium exhibit limited capacity of influencing tendon repair. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res.

6.
Sci Rep ; 9(1): 8941, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222078

RESUMO

There is emerging evidence of the impact of infections on rheumatoid arthritis pathogenesis and flares. We aimed to study the association between antibiotic use (and timing of use), and the occurrence of flares in patients with RA. We nested a self-controlled case series (SCCS) of patients who have RA flares within a newly diagnosed RA cohort (n = 31,992) from the UK Clinical Practice Research Datalink (CPRD) GOLD dataset. We determined associations between exposure to antibiotics (beta-lactam, imidazole, macrolide, nitrofurantoin, quinolone, sulphonamide and trimethoprim, and tetracycline) and the occurrence of RA flares. Conditional fixed-effects Poisson regression models were used to determine incidence rate ratios (IRR), offset by the natural logarithm of risk periods. A total of 1,192 (3.7%) of RA subjects had one or more flare/s during the study period, and were therefore included. Use of sulphonamide and trimethoprim was associated with an increased risk of RA flare at 29-90 days (IRR 1.71, CI 1.12-2.59, p = 0.012); 91-183 days (IRR 1.57, CI 1.06-2.33, p = 0.025); and 184-365 days (IRR 1.44, CI 1.03-2.02, p = 0.033) after commencement of antibiotic treatment. No other antibiotic group/s appear associated with RA flare/s risk. Usage of sulphonamide and trimethoprim antibiotics, is associated with a 70% increased risk of RA flare at 1-3 months, which decreases but remains significant up to 12 months after treatment. We hypothesise that the delayed onset of RA flares after specific antibiotics is mediated through the gut or urinary microbiomes. Further epidemiological and mechanistic research is needed to determine the role of infections in RA.

7.
PLoS One ; 14(4): e0214419, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31022203

RESUMO

Electrospun filaments are leading to a new generation of medical yarns that have the ability to enhance tissue healing through their biophysical cues. We have recently developed a technology to fabricate continuous electrospun filaments by depositing the submicron fibres onto a thin wire. Here we investigate the influence of pyridine on the fibre deposition. We have added pyridine to polydioxanone solutions at concentrations ranging from 0 to 100 ppm, increasing the conductivity of the solutions almost linearly from 0.04 uS/cm to 7 uS/cm. Following electrospinning, this led to deposition length increasing from 1 cm to 14 cm. The samples containing pyridine easily underwent cold drawing. The strength of drawn filaments increased from 0.8 N to 1.5 N and this corresponded to a decrease in fibre diameter, with values dropping from 2.7 µm to 1 µm. Overall, these findings are useful to increase the reliability of the manufacturing process of continuous electrospun filaments and to vary their biophysical properties required for their application as medical yarns such as surgical sutures.

8.
Arthritis Res Ther ; 21(1): 74, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30867043

RESUMO

BACKGROUND: Tendon disease is a significant global healthcare burden whereby patients experience pain and disability; however, the mechanisms that underlie inflammation and pain are poorly understood. Herein, we investigated the role of prostaglandins as important mediators of inflammation and pain in tissues and cells derived from patients with tendinopathy. METHODS: We studied supraspinatus and Achilles tendon biopsies from symptomatic patients with tendinopathy or rupture. Tendon-derived stromal cells (CD45negCD34neg) isolated from tendons were cultured and treated with interleukin-1ß (IL-1ß) to investigate prostaglandin production. RESULTS: Diseased tendon tissues showed increased expression of prostacyclin receptor (IP) and enzymes catalyzing the biosynthesis of prostaglandins, including cyclooxygenase-1 (COX-1), COX-2, prostacyclin synthase (PGIS), and microsomal prostaglandin E synthase-1 (mPGES-1). PGIS co-localized with cells expressing Podoplanin, a marker of stromal fibroblast activation, and the nociceptive neuromodulator NMDAR-1. Treatment with IL-1ß induced release of the prostacyclin metabolite 6-keto PGF1α in tendon cells isolated from diseased supraspinatus and Achilles tendons but not in cells from healthy comparator tendons. The same treatment induced profound prostaglandin E2 (PGE2) release in tendon cells derived from patients with supraspinatus tendon tears. Incubation of IL-1ß treated diseased tendon cells with selective mPGES-1 inhibitor Compound III, reduced PGE2, and simultaneously increased 6-keto PGF1α production. Conversely, COX blockade with naproxen or NS-398 inhibited both PGE2 and 6-keto PGF1α production. Tendon biopsies from patients in whom symptoms had resolved showed increased PTGIS compared to biopsies from patients with persistent tendinopathy. CONCLUSIONS: Our results suggest that PGE2 sustains inflammation and pain while prostacyclin may have a protective role in human tendon disease.

9.
FASEB J ; 33(7): 8043-8054, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30916999

RESUMO

Resolution of inflammation is poorly understood in Achilles tendon disorders. Herein, we investigated the bioactive lipid mediator profiles of tendon-derived stromal cells isolated from patients with Achilles tendinopathy (AT) or Achilles rupture (AR) under baseline and IL-1ß-stimulated conditions. We also determined whether incubating these cells with 2 of the mediators produced by tendon-derived stromal cells, 15-epi-Lipoxin A4 (15-epi-LXA4) or maresin (MaR)-1, moderated their proinflammatory phenotype. Under baseline conditions, AT cells showed concurrent increased levels of proinflammatory eicosanoids and proresolving mediators compared with AR cells. IL-1ß treatment induced profound prostaglandin E2 release in AR compared with AT cells. Incubation of IL-1ß treated AT and AR tendon-derived stromal cells in 15-epi-LXA4 or MaR1 reduced proinflammatory eicosanoids and potentiated the release of proresolving mediators. These mediators also induced specialized proresolving mediator (SPM) biosynthetic enzymes arachidonate lipoxygenase (ALOX) 12 and ALOX15 and up-regulated the proresolving receptor ALX compared with vehicle-treated cells. Incubation in 15-epi-LXA4 or MaR1 also moderated the proinflammatory phenotype of AT and AR cells, regulating podoplanin, CD90, signal transducer and activator of transcription (STAT)-1, IL-6, IFN regulatory factor (IRF) 5, and TLR4 and suppressed c-Jun N-terminal kinase 1/2/3, Lyn, STAT-3, and STAT-6 phosphokinase signaling. In summary, we identify proresolving mediators that are active in AT and AR and propose SPMs, including 15-epi-LXA4 or MaR1, as a potential strategy to counterregulate inflammatory processes in these cells.-Dakin, S. G., Colas, R. A., Newton, J., Gwilym, S., Jones, N., Reid, H. A. B., Wood, S., Appleton, L., Wheway, K., Watkins, B., Dalli, J., Carr, A. J. 15-Epi-LXA4 and MaR1 counter inflammation in stromal cells from patients with Achilles tendinopathy and rupture.

10.
BMJ ; 364: l298, 2019 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-30786996

RESUMO

OBJECTIVES: To provide accurate risk estimates of serious adverse events after elective shoulder replacement surgery for arthritis, including age and sex specific estimates of the lifetime risk of revision surgery. DESIGN: Population based cohort study. SETTING: Hospital episode statistics for NHS England, including civil registration mortality data. PARTICIPANTS: 58 054 elective shoulder replacements in 51 895 adults (aged ≥50 years) between April 1998 and April 2017. MAIN OUTCOME MEASURES: The lifetime risk of revision surgery, calculated using an actuarial life table approach and the cumulative probability method. Rates of serious adverse events at 30 and 90 days post-surgery: pulmonary embolism, myocardial infarction, lower respiratory tract infection, acute kidney injury, urinary tract infection, cerebrovascular events, and all cause death. Secondary outcome measures were the number of surgeries performed each year and Kaplan-Meier estimates of revision risk at 3, 5, 10, and 15 years. RESULTS: The number of shoulder replacements performed each year increased 5.6-fold between 1998 and 2017. Lifetime risks of revision surgery ranged from 1 in 37 (2.7%, 95% confidence interval 2.6% to 2.8%) in women aged 85 years and older to 1 in 4 (23.6%, 23.2% to 24.0%) in men aged 55-59 years. The risks of revision were highest during the first five years after surgery. The risk of any serious adverse event at 30 days post-surgery was 1 in 28 (3.5%, 3.4% to 3.7%), and at 90 days post-surgery was 1 in 22 (4.6%, 4.4% to 4.8%). At 30 days, the relative risk of pulmonary embolism compared with baseline population risk was 61 (95% confidence interval 50 to 73) for women aged 50-64. Serious adverse events were associated with increasing age, comorbidity, and male sex. 1 in 5 (21.2%, 17.9% to 25.1%) men aged 85 years and older experienced at least one serious adverse event within 90 days. CONCLUSIONS: Younger patients, particularly men, need to be aware of a higher likelihood of early failure of shoulder replacement and the need for further and more complex revision replacement surgery. All patients should be counselled about the risks of serious adverse events. These risks are higher than previously considered, and for some could outweigh any potential benefits. Our findings caution against unchecked expansion of shoulder replacement surgery in both younger and older patients. The more accurate age and sex specific estimates of risk from this study are long overdue and should improve shared decision making between patients and clinicians. STUDY REGISTRATION: ClinicalTrials.gov NCT03573765.


Assuntos
Artroplastia do Ombro/efeitos adversos , Hospitais/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos , Medição de Risco/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Ombro/estatística & dados numéricos , Inglaterra/epidemiologia , Cuidado Periódico , Feminino , Humanos , Estimativa de Kaplan-Meier , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/cirurgia , Período Pós-Operatório , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Falha de Tratamento
11.
BMJ ; 364: l185, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30733197

RESUMO

OBJECTIVE: To compare arthroscopic hip surgery with physiotherapy and activity modification for improving patient reported outcome measures in patients with symptomatic femoroacetabular impingement (FAI). DESIGN: Two group parallel, assessor blinded, pragmatic randomised controlled trial. SETTING: Secondary and tertiary care centres across seven NHS England sites. PARTICIPANTS: 222 participants aged 18 to 60 years with symptomatic FAI confirmed clinically and with imaging (radiography or magnetic resonance imaging) were randomised (1:1) to receive arthroscopic hip surgery (n=112) or a programme of physiotherapy and activity modification (n=110). Exclusion criteria included previous surgery, completion of a physiotherapy programme targeting FAI within the preceding 12 months, established osteoarthritis (Kellgren-Lawrence grade ≥2), and hip dysplasia (centre-edge angle <20 degrees). INTERVENTIONS: Participants in the physiotherapy group received a goal based programme tailored to individual patient needs, with emphasis on improving core stability and movement control. A maximum of eight physiotherapy sessions were delivered over five months. Participants in the arthroscopic surgery group received surgery to excise the bone that impinged during hip movements, followed by routine postoperative care. MAIN OUTCOME MEASURES: The primary outcome measure was the hip outcome score activities of daily living subscale (HOS ADL) at eight months post-randomisation, with a minimum clinically important difference between groups of 9 points. Secondary outcome measures included additional patient reported outcome measures and clinical assessment. RESULTS: At eight months post-randomisation, data were available for 100 patients in the arthroscopic hip surgery group (89%) and 88 patients in the physiotherapy programme group (80%). Mean HOS ADL was 78.4 (95% confidence interval 74.4 to 82.3) for patients randomised to arthroscopic hip surgery and 69.2 (65.2 to 73.3) for patients randomised to the physiotherapy programme. After adjusting for baseline HOS ADL, age, sex, and study site, the mean HOS ADL was 10.0 points higher (6.4 to 13.6) in the arthroscopic hip surgery group compared with the physiotherapy programme group (P<0.001)). No serious adverse events were reported in either group. CONCLUSIONS: Patients with symptomatic FAI referred to secondary or tertiary care achieve superior outcomes with arthroscopic hip surgery than with physiotherapy and activity modification. TRIAL REGISTRATION: ClinicalTrials.gov NCT01893034.


Assuntos
Artroscopia/métodos , Terapia por Exercício/métodos , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/cirurgia , Atividades Cotidianas , Adolescente , Adulto , Inglaterra , Feminino , Impacto Femoroacetabular/reabilitação , Articulação do Quadril/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento , Adulto Jovem
12.
Nat Rev Rheumatol ; 2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30498256

RESUMO

In the originally published version of this article, the acknowledgements and affiliations contained errors. In the acknowledgements, "NIHR Oxford and Birmingham Biomedical Research Centres" and "the Department of Health and Social Care" were incorrectly presented as "NIHR Oxford Biomedical Research Centres" and "the Department of Health". For affiliation 4, "NIHR Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust and University of Birmingham, Institute of Inflammation and Ageing, Birmingham, UK" was incorrectly presented as "Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK". For affiliation 3, "Institute" was incorrectly spelt. These errors have now been corrected in the HTML and PDF versions of the manuscript.

13.
Nat Rev Rheumatol ; 14(12): 714-726, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30420750

RESUMO

Knowledge of how the joint functions as an integrated unit in health and disease requires an understanding of the stromal cells populating the joint mesenchyme, including fibroblasts, tissue-resident macrophages and endothelial cells. Knowledge of the physiological and pathological mechanisms that involve joint mesenchymal stromal cells has begun to cast new light on why joint inflammation persists. The shared embryological origins of fibroblasts and endothelial cells might shape the behaviour of these cell types in diseased adult tissues. Cells of mesenchymal origin sustain inflammation in the synovial membrane and tendons by various mechanisms, and the important contribution of newly discovered fibroblast subtypes and their associated crosstalk with endothelial cells, tissue-resident macrophages and leukocytes is beginning to emerge. Knowledge of these mechanisms should help to shape the future therapeutic landscape and emphasizes the requirement for new strategies to address the pathogenic stroma and associated crosstalk between leukocytes and cells of mesenchymal origin.

14.
Nat Biotechnol ; 36(11): 1043-1047, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30412195

RESUMO

The reporting quality of patent landscapes is inadequate. The Reporting Items for Patent Landscapes (RIPL) checklist can improve reporting quality.

15.
Lancet ; 392(10144): 281-282, 2018 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-30064650

Assuntos
Artroscopia , Ombro
16.
Stem Cell Res Ther ; 9(1): 169, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29921317

RESUMO

BACKGROUND: Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs. METHODS: A lesion was made in the lateral border of the lateral branch of the ovine deep digital flexor tendon within the digital sheath and 2 weeks later 5 million autologous bone marrow MSCs were injected under ultrasound guidance into the digital sheath. Tendons were recovered post mortem at 1 day, and 1-2, 4, 12 and 24 weeks after MSC injection. For the 1-day and 1-2-week groups, MSCs labelled with fluorescent-conjugated magnetic iron-oxide nanoparticles (MIONs) were tracked with MRI, histology and flow cytometry. The 4, 12 and 24-week groups were implanted with non-labelled cells and compared with saline-injected controls for healing. RESULTS: The MSCs displayed no reduced viability in vitro to an uptake of 20.0 ± 4.6 pg MIONs per cell, which was detectable by MRI at minimal density of ~ 3 × 104 cells. Treated limbs indicated cellular distribution throughout the tendon synovial sheath but restricted to the synovial tissues, with no MSCs detected in the tendon or surgical lesion. The lesion was associated with negligible morbidity with minimal inflammation post surgery. Evaluation of both treated and control lesions showed no evidence of healing of the lesion at 4, 12 and 24 weeks on gross and histological examination. CONCLUSIONS: Unlike other laboratory animal models of tendon injury, this novel model mimics the failed tendon healing seen clinically intra-synovially. Importantly, however, implanted stem cells exhibited homing to synovium niches where they survived for at least 14 days. This phenomenon could be utilised in the development of novel physical or biological approaches to enhance localisation of cells in augmenting intra-synovial tendon repair.

17.
Curr Stem Cell Res Ther ; 13(8): 619-631, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29380705

RESUMO

INTRODUCTION: Rotator Cuff tears affect 15% of 60 year olds and carry a significant social and financial burden. Current operative techniques and repair adjuncts are associated with unacceptably high failure rates, stimulating investigation into novel tissue engineering and regenerative medicine (TERM) approaches in the field of rotator cuff surgery. In this review we explore the most recent advances in the field of electrospinning, focussing on proposed tissue-engineered solutions in tendon, specifically the rotator cuff. METHODS: The MEDLINE/PubMed database was reviewed for English language papers and publication date within the last 5 years, using the search string "electrospinning AND tendon". RESULTS: Of 38 results, eighteen studies were included in the final analysis. Common themes identified included (1) drug/biological molecule delivery (2) using novel and biological materials in manufacture (3) increased mechanical strengths of materials, and, (4) techniques to improve the nanotopographical properties - of electrospun scaffolds. Human tissue was used in less than 15% of studies to determine cytocompatibility. Varying study designs were observed often employing differing outcome measures making direct comparisons and conclusions challenging. CONCLUSION: This review summarises the most current scientific knowledge in the study of TERM in tendon and the rotator cuff field and electrospinning techniques. We found that as knowledge of the pathology behind rotator cuff tears is furthered, specific molecules, mechanical properties and nanotopographical features are being incorporated into electrospun scaffolds.

18.
Lancet ; 391(10118): 329-338, 2018 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-29169668

RESUMO

BACKGROUND: Arthroscopic sub-acromial decompression (decompressing the sub-acromial space by removing bone spurs and soft tissue arthroscopically) is a common surgery for subacromial shoulder pain, but its effectiveness is uncertain. We did a study to assess its effectiveness and to investigate the mechanism for surgical decompression. METHODS: We did a multicentre, randomised, pragmatic, parallel group, placebo-controlled, three-group trial at 32 hospitals in the UK with 51 surgeons. Participants were patients who had subacromial pain for at least 3 months with intact rotator cuff tendons, were eligible for arthroscopic surgery, and had previously completed a non-operative management programme that included exercise therapy and at least one steroid injection. Exclusion criteria included a full-thickness torn rotator cuff. We randomly assigned participants (1:1:1) to arthroscopic subacromial decompression, investigational arthroscopy only, or no treatment (attendance of one reassessment appointment with a specialist shoulder clinician 3 months after study entry, but no intervention). Arthroscopy only was a placebo as the essential surgical element (bone and soft tissue removal) was omitted. We did the randomisation with a computer-generated minimisation system. In the surgical intervention groups, patients were not told which type of surgery they were receiving (to ensure masking). Patients were followed up at 6 months and 1 year after randomisation; surgeons coordinated their waiting lists to schedule surgeries as close as possible to randomisation. The primary outcome was the Oxford Shoulder Score (0 [worst] to 48 [best]) at 6 months, analysed by intention to treat. The sample size calculation was based upon a target difference of 4·5 points (SD 9·0). This trial has been registered at ClinicalTrials.gov, number NCT01623011. FINDINGS: Between Sept 14, 2012, and June 16, 2015, we randomly assigned 313 patients to treatment groups (106 to decompression surgery, 103 to arthroscopy only, and 104 to no treatment). 24 [23%], 43 [42%], and 12 [12%] of the decompression, arthroscopy only, and no treatment groups, respectively, did not receive their assigned treatment by 6 months. At 6 months, data for the Oxford Shoulder Score were available for 90 patients assigned to decompression, 94 to arthroscopy, and 90 to no treatment. Mean Oxford Shoulder Score did not differ between the two surgical groups at 6 months (decompression mean 32·7 points [SD 11·6] vs arthroscopy mean 34·2 points [9·2]; mean difference -1·3 points (95% CI -3·9 to 1·3, p=0·3141). Both surgical groups showed a small benefit over no treatment (mean 29·4 points [SD 11·9], mean difference vs decompression 2·8 points [95% CI 0·5-5·2], p=0·0186; mean difference vs arthroscopy 4·2 [1·8-6·6], p=0·0014) but these differences were not clinically important. There were six study-related complications that were all frozen shoulders (in two patients in each group). INTERPRETATION: Surgical groups had better outcomes for shoulder pain and function compared with no treatment but this difference was not clinically important. Additionally, surgical decompression appeared to offer no extra benefit over arthroscopy only. The difference between the surgical groups and no treatment might be the result of, for instance, a placebo effect or postoperative physiotherapy. The findings question the value of this operation for these indications, and this should be communicated to patients during the shared treatment decision-making process. FUNDING: Arthritis Research UK, the National Institute for Health Research Biomedical Research Centre, and the Royal College of Surgeons (England).


Assuntos
Acrômio/lesões , Artroscopia/métodos , Descompressão Cirúrgica/métodos , Dor de Ombro , Adulto , Inglaterra , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteófito/complicações , Dor de Ombro/fisiopatologia , Dor de Ombro/cirurgia , Resultado do Tratamento
19.
BMJ Open ; 7(11): e016112, 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29138197

RESUMO

OBJECTIVE: This cohort study evaluates the unknown age-specific and gender-specific incidence of primary shoulder dislocations in the UK. SETTING: UK primary care data from the Clinical Practice Research Datalink (CPRD) were used to identify patients aged 16-70 years with a shoulder dislocation during 1995-2015. Coding of primary shoulder dislocations was validated using the CPRD general practitioner questionnaire service. PARTICIPANTS: A cohort of 16 763 patients with shoulder dislocation aged 16-70 years during 1995-2015 were identified. PRIMARY OUTCOME MEASURE: Incidence rates per 100 000 person-years and 95% CIs were calculated. RESULTS: Correct coding of shoulder dislocation within CPRD was 89% (95% CI 83% to 95%), and confirmation that the dislocation was a 'primary' was 76% (95% CI 67% to 85%). Seventy-two percent of shoulder dislocations occurred in men. The overall incidence rate in men was 40.4 per 100 000 person-years (95% CI 40.4 to 40.4), and in women was 15.5 per 100 000 person-years (95% CI 15.5 to 15.5). The highest incidence was observed in men aged 16-20 years (80.5 per 100 000 person-years; 95% CI 80.5 to 80.6). Incidence in women increased with age to a peak of 28.6 per 100 000 person-years among those aged 61-70 years. CONCLUSIONS: This is the first time the incidence of shoulder dislocations has been studied using primary care data from a national database, and the first time the results for the UK have been produced. While most primary dislocations occurred in young men, an unexpected finding was that the incidence increased in women aged over 50 years, but not in men. The reasons for this are unknown. Further work is commissioned by the National Institute for Health Research to examine treatments and predictors for recurrent shoulder dislocation. STUDY REGISTRATION: The design of this study was approved by the Independent Scientific Advisory Committee (15_260) for the Medicines & Healthcare products Regulatory Agency.


Assuntos
Bases de Dados Factuais , Luxação do Ombro/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Confiabilidade dos Dados , Bases de Dados Factuais/normas , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Reino Unido/epidemiologia , Adulto Jovem
20.
BMC Musculoskelet Disord ; 18(1): 414, 2017 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-29037237

RESUMO

BACKGROUND: The serious adverse events associated with metal on metal hip replacements have highlighted the importance of improving methods for monitoring surgical implants. The new European Union (EU) device regulation will enforce post-marketing surveillance based on registries among other surveillance tools. Europe has a common regulatory environment, a common market for medical devices, and extensive experience with joint replacement registries. In this context, we elaborate how joint replacement registries, while building on existing structure and data, can better ensure safety and balance risks and benefits. MAIN TEXT: Actions to improve registry-based implant surveillance include: enriching baseline and diversifying outcomes data collection; improving methodology to limit bias; speeding-up failure detection by active real-time monitoring; implementing risk-benefit analysis; coordinating collaboration between registries; and translating knowledge gained from the data into clinical decision-making and public health policy. CONCLUSIONS: The changes proposed here will improve patient safety, enforce the application of the new legal EU requirements, augment evidence, improve clinical decision-making, facilitate value-based health-care delivery, and provide up-to-date guidance for public health.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Sistema de Registros , Humanos , Próteses Articulares Metal-Metal
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