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- Kandolf-Sekulovic, L, et al.
(författare)
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Which medical disciplines diagnose and treat melanoma in Europe in 2019? A survey of experts from melanoma centres in 27 European countries.
- 2021
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Ingår i: Journal of the European Academy of Dermatology and Venereology : JEADV. - : Wiley. - 1468-3083 .- 0926-9959. ; 35:5, s. 1129-1132
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of melanoma is increasing. This places significant burden on societies to provide efficient cancer care. The European Cancer Organisation recently published the essential requirements for quality melanoma care. The present study is aimed for the first time to roughly estimate the extent to which these requirements have been met in Europe.A web-based survey of experts from melanoma centres in 27 European countries was conducted from 1 February to 1 August 2019. Data on diagnostic techniques, surgical and medical treatment, organization of cancer care and education were collected and correlated with national health and economic indicators and mortality-to-incidence ratio (MIR) as a surrogate for survival. Univariate linear regression analysis was performed to evaluate the correlations. SPSS software was used. Statistical significance was set at P<0.05.The MIR was lower in countries with a high health expenditure per capita and with a higher numbers of general practitioners (GPs) and surgeons (SURG) per million inhabitants. In these countries, GPs and dermatologists (DER) were involved in melanoma detection; high percentage of DER used dermatoscopy and were involved in the follow-up of all melanoma stages; both medical oncologists (ONC) and dermato-oncologists administered systemic treatments; and patients had better access to sentinel lymph node biopsy and were treated within multidisciplinary tumour boards.Based on these first estimates, the greater involvement of GPs in melanoma detection; the greater involvement of highly trained DER in dermatoscopy, dermatosurgery, follow-up and the systemic treatment of melanoma; and the provision of ongoing dermato-oncology training for pathologists, SURG, DER and ONC are necessary to provide an optimal melanoma care pathway. A comprehensive analysis of the melanoma care pathway based on clinical melanoma registries will be needed to more accurately evaluate these first insights.
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- Schadendorf, D., et al.
(författare)
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Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma : quality-of-life analyses of the METRIC study
- 2014
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 25:3, s. 700-706
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Tidskriftsartikel (refereegranskat)abstract
- We report the first quality-of-life assessment of a MEK inhibitor in metastatic melanoma from a phase III study. Trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Less functional impairment, smaller declines in health status, and less exacerbation of symptoms were observed with trametinib.In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.
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- Longo, C., et al.
(författare)
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Delphi Consensus Among International Experts on the Diagnosis, Management, and Surveillance for Lentigo Maligna
- 2023
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Ingår i: Dermatology Practical & Conceptual. - 2160-9381. ; 13:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Melanoma of the lentigo maligna (LM) type is challenging. There is lack of consensus on the optimal diagnosis, treatment, and follow-up. Objectives: To obtain general consensus on the diagnosis, treatment, and follow-up for LM. Methods: A modified Delphi method was used. The invited participants were either members of the International Dermoscopy Society, academic experts, or authors of published articles relating to skin cancer and melanoma. Participants were required to respond across three rounds using a 4-point Likert scale). Consensus was defined as >75% of participants agreeing/strongly agreeing or disagreeing/strongly disagreeing. Results: Of the 31 experts invited to participate in this Delphi study, 29 participants completed Round 1 (89.9% response rate), 25/31 completed Round 2 (77.5% response rate), and 25/31 completed Round 3 (77.5% response rate). Experts agreed that LM diagnosis should be based on a clinical and dermatoscopic approach (92%) followed by a biopsy. The most appropriate primary treatment of LM was deemed to be margin-controlled surgery (83.3%), although non-surgical modalities, especially imiquimod, were commonly used either as alternative off-label primary treatment in selected patients or as adjuvant therapy following surgery; 62% participants responded life-long clinical follow-up was needed for LM. Conclusions: Clinical and histological diagnosis of LM is challenging and should be based on macroscopic, dermatoscopic, and RCM examination followed by a biopsy. Different treatment modalities and follow-up should be carefully discussed with the patient.
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- Dekov, Vesselin, et al.
(författare)
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Ferrihydrite precipitation in goundwater-fed river systems (Nete and Demer river basins, Belgium): Insights from a combined Fe-Zn-Sr-Nd-Pb-isotope study.
- 2014
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Ingår i: Chemical Geology. - : Elsevier. - 0009-2541 .- 1872-6836. ; 386, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Two groundwater-fed river systems (Nete and Demer, Belgium) carry red suspended material that settles on the river bed forming red sediments. The local aquifer that feeds these river systems is a glauconite-rich sand, which provides most of the dissolved Fe to the rivers. The solid component of these systems, i.e., the red suspended material and sediments, has a simple mineralogy (predominantly ferrihydrite), but shows a complex geochemistry pointing out the different processes contributing to the river chemistry: (1) the red sediments have higher transition metal (excluding Cu) and detrital element (e.g., Si, Al, K, Rb, etc.) concentrations than the red suspended matter because of their longer residence time in the river and higher contribution of the background (aquifer) component, respectively; (2) the red suspended material and sediments have inherited their rare earth element (REE) patterns from the aquifer; (3) the origin of Sr present in the red suspended matter and red sediments is predominantly marine (i.e., Quaternary calcareous rocks), but a small amount is geogenic (i.e., from detrital rocks); (4) Pb in both solids originates mostly from anthropogenic and geogenic sources; (5) all of the anthropogenic Pb in the red suspended material and sediments is hosted by the ferrihydrite; (6) Nd budget of the red riverine samples is controlled by the geogenic source and shows little anthropogenic component; (7) the signi- ficant Fe- and Zn-isotope fractionations are in line with the previous studies. Their fractionation patterns do not correlate, suggesting that the processes controlling the isotope geochemistry of Fe and Zn are different: oxidation/reduction most likely governs the Fe-isotope fractionation, whereas adsorption/desorption or admixing of anthropogenic sources controls the isotope fractionation of Zn.
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| 22. |
- Garbe, C.S., et al.
(författare)
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Estimation of complex motion from thermographic image sequences
- 2003
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 5073, s. 303-317
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- In this contribution a novel technique for computing complex motion involving heat transport processes will be presented. The proposed technique is a local gradient based approach, combining transport models with motion analysis. It allows for the simultaneous estimation of both motion and parameter of an underlying transport model. Since the analysis is based on thermal image sequences, estimates are computed to a high temporal and spatial resolution, limited only by the resolution and frame rate of the employed IR camera. This novel technique was utilized on exchange processes at the atmosphere/ocean boundary, where significant parameters of heat transfer could be measured and a transport model verified. Using the presented algorithms, surface flows as well as convergences and divergences on air-water interfaces can be measured accurately. Apart from applications in oceanography and botany, relevant benefits of the proposed technique to NDT will be presented. It is possible to compensate for motion to reach accuracies much better than 1/10th of a pixel. Through the direct estimation of locally resolved diffusivities in materials, insights can be gained about defects present. By estimating not only isotropic diffusion but also the whole matrix of anisotropic diffusion, the technique is highly relevant to measurements of composite materials.
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| 23. |
- 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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| 24. |
- Luiken, Ina, et al.
(författare)
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Pleuropulmonary pathologies in the early phase of acute pancreatitis correlate with disease severity
- 2022
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 17:2 February
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Tidskriftsartikel (refereegranskat)abstract
- Background Respiratory failure worsens the outcome of acute pancreatitis (AP) and underlying factors might be early detectable. Aims To evaluate the prevalence and prognostic relevance of early pleuropulmonary pathologies and pre-existing chronic lung diseases (CLD) in AP patients. Methods Multicentre retrospective cohort study. Caudal sections of the thorax derived from abdominal contrast enhanced computed tomography (CECT) performed in the early phase of AP were assessed. Independent predictors of severe AP were identified by binary logistic regression analysis. A one-year survival analysis using Kaplan-Meier curves and log rank test was performed. Results 358 patients were analysed, finding pleuropulmonary pathologies in 81%. CECTs were performed with a median of 2 days (IQR 1–3) after admission. Multivariable analysis identified moderate to severe or bilateral pleural effusions (PEs) (OR = 4.16, 95%CI 2.05–8.45, p<0.001) and pre-existing CLD (OR = 2.93, 95%CI 1.17–7.32, p = 0.022) as independent predictors of severe AP. Log rank test showed a significantly worse one-year survival in patients with bilateral compared to unilateral PEs in a subgroup. Conclusions Increasing awareness of the prognostic impact of large and bilateral PEs and pre-existing CLD could facilitate the identification of patients at high risk for severe AP in the early phase and thus improve their prognosis.
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| 25. |
- Nelson, Daniel C., et al.
(författare)
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Cysteine proteinase SpeB from Streptococcus pyogenes - a potent modifier of immunologically important host and bacterial proteins
- 2011
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Ingår i: Biological Chemistry. - 1437-4315. ; 392:12, s. 1077-1088
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Forskningsöversikt (refereegranskat)abstract
- Group A streptococcus (Streptococcus pyogenes) is an exclusively human pathogen that causes a wide spectrum of diseases ranging from pharyngitis, to impetigo, to toxic shock, to necrotizing fasciitis. The diversity of these disease states necessitates that S. pyogenes possess the ability to modulate both the innate and adaptive immune responses. SpeB, a cysteine proteinase, is the predominant secreted protein from S. pyogenes. Because of its relatively indiscriminant specificity, this enzyme has been shown to degrade the extracellular matrix, cytokines, chemokines, complement components, immunoglobulins, and serum protease inhibitors, to name but a few of the known substrates. Additionally, SpeB regulates other streptococcal proteins by degrading them or releasing them from the bacterial surface. Despite the wealth of literature on putative SpeB functions, there remains much controversy about this enzyme because many of reported activities would produce contradictory physiological results. Here we review all known host and bacterial protein substrates for SpeB, their cleavage sites, and discuss the role of this enzyme in streptococcal pathogenesis based on the current literature.
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