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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Conte, Michael S, et al.
(författare)
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Global vascular guidelines on the management of chronic limb-threatening ischemia.
- 2019
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 69:6S, s. 3S-125S.e40
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Tidskriftsartikel (refereegranskat)abstract
- Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.
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| 6. |
- Conte, Michael S., et al.
(författare)
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Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia
- 2019
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 58:1, s. S1-S109
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Tidskriftsartikel (refereegranskat)abstract
- Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.
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| 7. |
- Geraghty, A., et al.
(författare)
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Internet-based vestibular rehabilitation for older adults with chronic dizziness : A randomised controlled trial in primary care
- 2017
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Konferensbidrag (refereegranskat)abstract
- Introduction: Vestibular dysfunction occurs in 50% of those over age 60, and with an ageing population the health burden will increase. Vestibular Rehabilitation (VR) has been shown to be effective for dizziness caused by vestibular dysfunction, but it is seldom provided in primary care. The rapid growth in internet access provides a promising vehicle for VR to achieve widespread health impact. We aimed to determine the effectiveness of internet-based VR on chronic dizziness in older adults in primary care.Method: We conducted a single centre randomised controlled trial comparing an internet-based VR intervention with usual primary care. 296 primary care patients aged 50 years and over with current dizziness exacerbated by head movements were recruited from 54 primary care practices from southern England. Patients in the intervention arm accessed an automated internet-based intervention that taught VR exercises and suggested cognitive behavioural management strategies. Dizziness was measured by the Vertigo Symptom Short-Form (VSS-SF) at baseline, 3 and 6 months. The primary outcome was VSS-SF score at 6 months (ISRCTN: 86912968).Results: The VSS-SF was completed by 250 (84%) at 3 months and 230 (78%) at 6 months. Dizziness symptoms were significantly lower in the internet-based VR group compared to usual care at 3 (2.75, 95% CI:1.39, 4.12; p<0.001 and 6 months (2.26, 95% CI: 0.39, 4.12; p=0.018). Dizziness-related disability was also significantly lower in the internet-based VR condition, at 3 (5.33, 95% CI: 1.41, 9.26; p=0.008) and 6 month (5.58 95% CI: 1.19, 10.0; p=0.013).Discussion: Internet-based VR improves dizziness and reduces dizziness-based disability in older primary care patients without requiring structured guidance. The effectiveness without the need for health professional support indicates that this intervention could be made rapidly available to GPs for provision to their patients and wider dissemination in the community.
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| 8. |
- Lanigan, Fiona, et al.
(författare)
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Delineating Transcriptional Networks of Prognostic Gene Signatures Refines Treatment Recommendations for Lymph Node-negative Breast Cancer Patients.
- 2015
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Ingår i: The FEBS Journal. - : Wiley. - 1742-464X. ; 282:18, s. 3455-3473
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Tidskriftsartikel (refereegranskat)abstract
- The majority of women diagnosed with lymph node-negative breast cancer are unnecessarily treated with damaging chemotherapeutics following surgical resection. This highlights the importance of understanding and more accurately predicting patient prognosis. Here, we define the transcriptional networks regulating well-established prognostic gene expression signatures. We find that the same set of transcriptional regulators consistently lie upstream of both 'prognosis' and 'proliferation' gene signatures, suggesting that a central transcriptional network underpins a shared phenotype within these signatures. Strikingly, the master transcriptional regulators within this network predict recurrence risk for lymph node-negative breast cancer better than currently used multi-gene prognostic assays, particularly in lymph node-negative, estrogen receptor-positive patients. Simultaneous examination of p16(INK) (4A ) expression, which predicts tumors that have bypassed cellular senescence, revealed that intermediate levels of p16(INK) (4A) correlate with an intact pRB pathway and improved survival. A combination of these master transcriptional regulators and p16(INK) (4A) , termed the OncoMasTR score, stratifies tumours based on their proliferative and senescence capacity, facilitating a clearer delineation of lymph node-negative breast cancer patients at high risk of recurrence, and thus requiring chemotherapy. Furthermore, OncoMasTR accurately classifies over 60% of patients as 'low risk', an improvement on existing prognostic assays, which has the potential to reduce overtreatment in early-stage patients. Taken together, this study provides new insights into the transcriptional regulation of cellular proliferation in breast cancer and provides an opportunity to enhance and streamline breast cancer prognosis. This article is protected by copyright. All rights reserved.
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| 9. |
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| 10. |
- van Kuilenburg, Andre B. P., et al.
(författare)
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Glutaminase Deficiency Caused by Short Tandem Repeat Expansion in GLS
- 2019
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 380:15, s. 1433-1441
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Tidskriftsartikel (refereegranskat)abstract
- We report an inborn error of metabolism caused by an expansion of a GCA-repeat tract in the 5′ untranslated region of the gene encoding glutaminase (GLS) that was identified through detailed clinical and biochemical phenotyping, combined with whole-genome sequencing. The expansion was observed in three unrelated patients who presented with an early-onset delay in overall development, progressive ataxia, and elevated levels of glutamine. In addition to ataxia, one patient also showed cerebellar atrophy. The expansion was associated with a relative deficiency of GLS messenger RNA transcribed from the expanded allele, which probably resulted from repeat-mediated chromatin changes upstream of the GLS repeat. Our discovery underscores the importance of careful examination of regions of the genome that are typically excluded from or poorly captured by exome sequencing.
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