| 11. |
- Drobin, Kimi, et al.
(författare)
-
Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer
- 2020
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 12:3
-
Tidskriftsartikel (refereegranskat)abstract
- Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depending on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.
|
|
| 12. |
- Halle, Martin
(författare)
-
Vascular inflammation : implications for microvascular reconstructive surgery after irradiation
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Better treatment has led to a rapidly increasing population of cancer survivors. A growing body of clinical evidence has shown that radiotherapy is associated with adverse effects on the cardiovascular system, such as myocardial infarction and stroke, depending on the previous treatment site. However, there is a paucity of experimental evidence linked to these clinical findings since the pathology, not evident until years after exposure, precludes adequate investigation through cell- and animal-experiments. We present a differential global gene expression strategy, by comparing irradiated with nonirradiated conduit arteries and veins, harvested simultaneously from the same patient during microvascular free tissue transfers for cancer reconstruction. We could thereby benefit from the true advantages of microarray technology, bypassing the common problem of inter-individual variability and furthermore exclude the influence of other risk factors and study the effect of irradiation only. Surgery at different time-points after radiotherapy did furthermore give us the opportunity to study temporal aspects, a key-factor for the understanding of delayed vascular disease. Temporal aspects of vascular alterations caused by irradiation are furthermore of importance for the timing of surgery in relation to radiotherapy, since there has been a debate about treatment order and timing between the two. In paper I, we could demonstrate that preoperative, compared to postoperative, radiotherapy was associated with microvascular occlusion after autologous free tissue transfers for head and neck reconstructions, and furthermore increased with the time elapsed from last radiotherapy session to surgery. In paper II, we utilized Affymetrix® microarray technology to unravel gene expression patterns in irradiated, compared to non-irradiated, arteries. Based on Gene Ontology Tree Machine®- analysis, target genes were selected and further confirmed with RT-PCR and immunohistochemistry. A major part of differentially expressed genes related to increased NF-kappaB activation, confined to cells within the arterial wall. The observed NF-kappaB activation, together with invading macrophages and T-cells, was evident even years after radiation exposure. Since microvascular occlusions after free tissue transfers are more likely to occur on the venous side, further analyses were performed in veins in paper III, utilizing a Taqman® tissue low density array, including 45 selected target-genes involved in inflammation and coagulation. An acute NF-kappaB activation was detected in irradiated veins, confined to the endothelium, whereas in contrast to arteries, no sustained NF-kappaB activity was observed more than 15 weeks from last radiotherapy session. Neither was any detectable invasion of inflammatory cells observed. Immunohistochemistry indicated decreased staining of endothelial nitric oxide synthase (eNOS) in irradiated veins, compared to controls, in further support for an endothelial dysfunction caused by irradiation. A sustained activation was detected for plasminogen activator-1 (PAI-1) in irradiated veins. In study IV, we detected a decreased eNOS activity in endothelial cells after incubation with the free fatty acids (FFAs) palmitic and oleic, but not linolenic, acid, whereas a triglyceride-rich fat emulsion increased the eNOS activity. This is interesting since FFAs are markedly elevated during surgery. With support from clinical and experimental data, we clearly advocate postoperative radiotherapy for microvascular reconstructive surgery, whenever possible for oncological reasons. Vascular inflammation may, together with increased PAI-1 gene expression observed in radiated veins, explain the increased risk for vascular complications when radiotherapy is administered prior to microvascular surgery. Moreover, the finding of a sustained NF-kappaB activation, together with presence of macrophages and T-cells, in irradiated arteries supports radiotherapy as an independent risk factor for cardiovascular disease and contributes to the search for therapeutic adjuncts to cope with the adverse effects of radiotherapy.
|
|
| 13. |
|
|
| 14. |
- Mont, Lluís, et al.
(författare)
-
Pre-participation cardiovascular evaluation for athletic participants to prevent sudden death: Position paper from the EHRA and the EACPR, branches of the ESC. Endorsed by APHRS, HRS, and SOLAECE.
- 2017
-
Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092 .- 1099-5129. ; 19:1, s. 139-163
-
Tidskriftsartikel (refereegranskat)
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Piepoli, Massimo F., et al.
(författare)
-
Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology
- 2022
-
Ingår i: European Journal of Heart Failure. - : WILEY. - 1388-9842 .- 1879-0844. ; 24:1, s. 143-168
-
Tidskriftsartikel (refereegranskat)abstract
- The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present position paper aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing heart failure are listed.
|
|
| 19. |
- Piepoli, Massimo F., et al.
(författare)
-
Preventing heart failure: a position paper of the Heart Failure Association in collaboration with the European Association of Preventive Cardiology
- 2022
-
Ingår i: European Journal of Preventive Cardiology. - : OXFORD UNIV PRESS. - 2047-4873 .- 2047-4881. ; 29:1, s. 275-300
-
Tidskriftsartikel (refereegranskat)abstract
- The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed.
|
|
| 20. |
- Sartelli, Massimo, et al.
(författare)
-
Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
|
|
