| 1. |
- Andreasson, Jesper, et al.
(författare)
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Exhaled phospholipid transfer protein and hepatocyte growth factor receptor in lung adenocarcinoma
- 2022
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 23:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Screening decreases mortality among lung cancer patients but is not widely implemented, thus there is an unmet need for an easily accessible non-invasive method to enable early diagnosis. Particles in exhaled air offer a promising such diagnostic tool. We investigated the validity of a particles in exhaled air device (PExA) to measure the particle flow rate (PFR) and collect exhaled breath particles (EBP) to diagnose primary lung adenocarcinoma (LUAD).METHODS: Seventeen patients listed for resection of LUAD stages IA-IIIA and 18 non-cancer surgical control patients were enrolled. EBP were collected before and after surgery for LUAD, and once for controls. Proteomic analysis was carried out using a proximity extension assay technology. Results were validated in both plasma from the same cohort and with microarray data from healthy lung tissue and LUAD tissue in the GSE10072 dataset.RESULTS: Of the 92 proteins analyzed, levels of five proteins in EBP were significantly higher in the LUAD patients compared to controls. Levels of phospholipid transfer protein (PLTP) and hepatocyte growth factor receptor (MET) decreased in LUAD patients after surgery compared to control patients. PFR was significantly higher in the LUAD cohort at all timepoints compared to the control group. MET in plasma correlated significantly with MET in EBP.CONCLUSION: Collection of EBP and measuring of PFR has never been performed in patients with LUAD. In the present study PFR alone could distinguish between LUAD and patients without LUAD. PLTP and MET were identified as potential biomarkers to evaluate successful tumor excision.
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| 2. |
- Broberg, Ellen, et al.
(författare)
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Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients
- 2020
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Ingår i: Erj Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this cohort study, we evaluated whether the particles in exhaled air (PExA) device can be used in conjunction with mechanical ventilation during surgery. The PExA device consists of an optical particle counter and an impactor that collects particles in exhaled air. Our aim was to establish the feasibility of the PExA device in combination with mechanical ventilation (MV) during surgery and if collected particles could be analysed. Patients with and without nonsmall cell lung cancer (NSCLC) undergoing lung surgery were compared to normal breathing (NB) patients with NSCLC. Methods: A total of 32 patients were included, 17 patients with NSCLC (MV-NSCLC), nine patients without NSCLC (MV-C) and six patients with NSCLC and not intubated (NB). The PEx samples were analysed for the most common phospholipids in surfactant using liquid-chromatography-mass-spectrometry (LCMS). Results: MV-NSCLC and MV-C had significantly lower numbers of particles exhaled per minute ( particle flow rate; PFR) compared to NB. MV-NSCLC and MV-C also had a siginificantly lower amount of phospholipids in PEx when compared to NB. MV-NSCLC had a significantly lower amount of surfactant A compared to NB. Conclusion: We have established the feasibility of the PExA device. Particles could be collected and analysed. We observed lower PFR from MV compared to NB. High PFR during MV may be due to more frequent opening and closing of the airways, known to be harmful to the lung. Online use of the PExA device might be used to monitor and personalise settings for mechanical ventilation to lower the risk of lung damage.
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| 3. |
- Broberg, Ellen, et al.
(författare)
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Releasing high positive end-expiratory pressure to a low level generates a pronounced increase in particle flow from the airways
- 2023
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Ingår i: Intensive Care Medicine Experimental. - : Springer Science and Business Media LLC. - 2197-425X. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Detecting particle flow from the airways by a non-invasive analyzing technique might serve as an additional tool to monitor mechanical ventilation. In the present study, we used a customized particles in exhaled air (PExA) technique, which is an optical particle counter for the monitoring of particle flow in exhaled air. We studied particle flow while increasing and releasing positive end-expiratory pressure (PEEP). The aim of this study was to investigate the impact of different levels of PEEP on particle flow in exhaled air in an experimental setting. We hypothesized that gradually increasing PEEP will reduce the particle flow from the airways and releasing PEEP from a high level to a low level will result in increased particle flow. Methods: Five fully anesthetized domestic pigs received a gradual increase of PEEP from 5 cmH2O to a maximum of 25 cmH2O during volume-controlled ventilation. The particle count along with vital parameters and ventilator settings were collected continuously and measurements were taken after every increase in PEEP. The particle sizes measured were between 0.41 µm and 4.55 µm. Results: A significant increase in particle count was seen going from all levels of PEEP to release of PEEP. At a PEEP level of 15 cmH2O, there was a median particle count of 282 (154–710) compared to release of PEEP to a level of 5 cmH2O which led to a median particle count of 3754 (2437–10,606) (p < 0.009). A decrease in blood pressure was seen from baseline to all levels of PEEP and significantly so at a PEEP level of 20 cmH2O. Conclusions: In the present study, a significant increase in particle count was seen on releasing PEEP back to baseline compared to all levels of PEEP, while no changes were seen when gradually increasing PEEP. These findings further explore the significance of changes in particle flow and their part in pathophysiological processes within the lung.
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| 4. |
- Fakhro, Mohammed, et al.
(författare)
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25-year follow-up after lung transplantation at Lund University Hospital in Sweden : superior results obtained for patients with cystic fibrosis
- 2016
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : Oxford University Press (OUP). - 1569-9285 .- 1569-9293. ; 23:1, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: In Sweden, two centres perform lung transplantation for a population of about 9 million and the entire population is covered for lung transplantation by government health insurance. Lund University Hospital is one of these centres. This retrospective report reviews the 25-year experience of the Skåne University Hospital Lung Transplant Program with particular emphasis on short-term outcome and long-term survival but also between different subgroups of patients and types of transplant [single-lung transplantation (SLTx) versus double-lung transplantation (DLTx)] procedure performed.METHODS: Between January 1990 and June 2014, 278 patients underwent lung transplantation at the Skåne University Hospital Sweden. DLTx was performed in 172 patients, SLTx was performed in 97 patients and heart-lung transplantation was performed in 9 patients. In addition, 15 patients required retransplantation (7 DLTx and 8 SLTx).RESULTS: Overall 1-, 5-, 10-, 15- and 20-year survival rates were 88, 65, 49, 37 and 19% for the whole cohort. DLTx recipients showed 1-, 5-, 10- and 20-year survival rates of 90, 71, 60 and 30%, compared with SLTx recipients with 1-, 5-, 10- and 20-year survival rates of 83, 57, 34 and 6% (P < 0.05), respectively. Comparing the use of intraoperative extracorporeal membrane oxygenation, extracorporeal circulation (ECC) and no circulatory support in the aspect of survival, a significant difference in favour of intraoperative ECC was seen.CONCLUSIONS: Superior long-term survival rates were seen in recipients diagnosed with cystic fibrosis, α1-antitrypsin deficiency and pulmonary hypertension. DLTx showed better results compared with SLTx especially at 10 years post-transplant. In the present study, we present cumulative incidence rates of bronchiolitis obliterans syndrome of 15% at 5 years, 26% at 10 years and 32% at 20 years post-transplant; these figures are in line with the lowest rates presented internationally.
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| 5. |
- Fakhro, Mohammed, et al.
(författare)
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ABO-identical matching has no superiority in long-term survival in comparison to ABO-compatible matching in lung transplantation
- 2019
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Even though identical blood group matching between recipient and donor is preferred, it is still not clear by how much this improves the outcome for patients who received a lung transplant (LTx), or whether there is any survival benefit. Earlier studies have yielded ambiguous results and few have investigated long-term survival. The aim of this study is, therefore, to explore the different outcomes of identical and compatible recipient and donor blood group matching to determine whether identical matching is superior (LTx). Method: Between January 1990 to June 2016, 297 patients underwent primary LTx, 10 patients underwent heart and lung transplantation (HLTx), and 18 patients required re-transplantation (Re-LTx) at Skåne University Hospital in Lund. With a total of 325 transplantations at our center, 262 were ABO-identically matched while 53 were ABO-compatible. For survival analyses, the end-point used was retransplantation-free survival in addition to excluding HLTx (n = 10), assessed by Cox regression and Kaplan-Meier. Results: ABO-compatible patients had a median of 49 days (2-641), and ABO-identical patients had a median of 89 days (1-1717) (p = 0.048) on the transplant waiting list. Patients with a limited survival up to 1-year showed significant difference in survival rate for ABO-compatible recipients compared to ABO-identical recipients (p < 0.05), however no significant difference was shown in overall survival between the two groups (p > 0.05), with the same pattern shown in patients with a limited survival rate up to ten years, emphysema-patients, when excluding single-LTx and patients transplanted before 2005 and after 2005, respectively (p > 0.05). Conclusion: Recipients who received ABO-compatible matched grafts showed a similar survival rate to recipients who received ABO-identical matched grafts in the present study. Cytolomegalovirus and Ebstein Barr Virus mismatch were also identified as risk factors particular among emphysema patients. Since ABO-identical transplantations and ABO-compatible transplantations showed similar results, the present selection-bias of preferring ABO-identical lungs could be adjusted to increase organ allocation. It might also be possible to shorten recipient waiting list time, as an identical match showed over 80% higher time on the waiting list than a compatible, non-identical match.
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| 6. |
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| 7. |
- Fakhro, Mohammed, et al.
(författare)
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Double lung, unlike single lung transplantation might provide a protective effect on mortality and bronchiolitis obliterans syndrome
- 2017
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Survival after lung transplantation (LTx) is often limited by bronchiolitis obliterans syndrome (BOS).METHOD: Survey of 278 recipients who underwent LTx. The endpoint used was BOS (BOS grade ≥ 2), death or Re-lung transplantation (Re-LTx) assessed by competing risk regression analyses.RESULTS: The incidence of BOS grade ≥ 2 among double LTx (DLTx) recipients was 16 ± 3% at 5 years, 30 ± 4% at 10 years, and 37 ± 5% at 20 years, compared to single LTx (SLTx) recipients whose corresponding incidence of BOS grade ≥ 2 was 11 ± 3%, 20 ± 4%, and 24 ± 5% at 5, 10, and 20 years, respectively (p > 0. 05). The incidence of BOS grade ≥ 2 by major indications ranked in descending order: other, PF, CF, COPD, PH and AAT1 (p < 0. 05). The mortality rate by major indication ranked in descending order: COPD, PH, AAT1, PF, Other and CF (p < 0. 05).CONCLUSION: No differences were seen in the incidence of BOS grade ≥ 2 regarding type of transplant, however, DLTx recipients showed a better chance of survival despite developing BOS compared to SLTx recipients. The highest incidence of BOS was seen among CF, PF, COPD, PH, and AAT1 recipients in descending order, however, CF and PF recipients showed a better chance of survival despite developing BOS compared to COPD, PH, and AAT1 recipients.
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| 8. |
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| 9. |
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| 10. |
- Fakhro, Mohammed, et al.
(författare)
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Impact of Forced Expiratory Volume in 1 Second (FEV1) and 6-Minute Walking Distance at 3, 6, and 12 Months and Annually on Survival and Occurrence of Bronchiolitis Obliterans Syndrome (BOS) After Lung Transplantation
- 2017
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Ingår i: Annals of Transplantation. - 2329-0358. ; 22, s. 532-540
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Development of bronchiolitis obliterans syndrome (BOS) is a great limitation for patient survival in lung transplantation (LTx). A curative treatment for BOS is still missing, and in terminal stages re-transplantation (Re-LTx) is the only salvation. It is possible to slow the progress of BOS if it is detected at an early stage. This might be possible by assessing pulmonary function pattern. MATERIAL AND METHODS Between 1990 and 2014, 278 patients underwent LTx at Skåne University Hospital, Sweden. Pulmonary function was followed using spirometry (FEV1) and 6-minute walking test (6MWT) measured at 3, 6, and 12 months and annually. The endpoint used was freedom from BOS (BOS grade ≤1), BOS (BOS grade ≥2), and death or Re-LTx. RESULTS Double-lung transplantation (DLTx) showed a hazard ratio (HR) of 0.514 (p=0.001) versus recipients who underwent single-lung transplantation (SLTx). Regarding freedom from BOS, FEV1 showed an HR of 0.597 and 6MWT an HR of 0.982 (p<0.001). Regarding combined endpoint BOS ≥2 and Re-LTx, FEV1 showed an HR of 0.618 and 6MWT an HR of 0.972 (p<0.001). CONCLUSIONS Recipients with higher FEV1 or 6MWT values had better chances of survival. Recipients with DLTx had a significant survival benefit and a protective effect against development of BOS. As the distance that the patient can walk in 6 minutes increases, risk for death or Re-LTx is significantly lower, as is incidence of developing BOS grade ≥2. Understanding changes within pulmonary function are probably key to understanding patient prognosis.
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| 11. |
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| 12. |
- Ghaidan, Haider, et al.
(författare)
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Impact of allograft ischemic time on long-term survival in lung transplantation : a Swedish monocentric study
- 2020
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 54:5, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regression and Kaplan–Meier survival. Results: Kaplan–Meier survival for mean IT (min) between subgroups ≤120, 121–240, 241–360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p <.05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.
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| 13. |
- Ghaidan, Haider, et al.
(författare)
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Ten year follow-up of lung transplantations using initially rejected donor lungs after reconditioning using ex vivo lung perfusion
- 2019
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2006 and 2007 we performed double lung transplantation with marginal donor lungs assessed and reconditioned by Ex Vivo Lung Perfusion (EVLP), using a technique developed by Professor Stig Steen. Here we present a 10-year follow-up comparing the outcomes of lung transplantations performed at our clinic using EVLP lungs vs. conventional lungs. Method: Between 2006 and 2007, 21 patients (6 EVLP, 15 conventional) underwent double lung transplantation (LTx) with follow-up on May 2017 at Lund University Hospital, Sweden. Pulmonary function was measured at 3/6/12 months, and annually thereafter for a period of 10 years in addition to survival and freedom from chronic lung allograft dysfunction (CLAD) being analyzed. Results: Regarding Forced Expiratory Volume in 1 s (FEV1) and 6MWT at 3, 6, and 12 months and annually thereafter, no difference in median FEV1 nor 6MWT was found for EVLP-LTx vs. conventional-LTx (p > 0.05). No difference was shown in post-operative survival between EVLP-LTx vs. conventional LTx for patients with an overall survival up to 10-years (p > 0.05). The same pattern was shown in sub analyses for patients with a limited survival up to 1 and 5 years (p > 0.05). Conclusion: No superiority was found in conventional-LTx over EVLP-LTx, neither in long-term survival nor pulmonary function. No difference in CLAD-free survival was seen between the two groups. We believe that EVLP is a safe and effective method to use in LTx, greatly increasing the donor pool by improving marginal lungs and providing an objective assessment of the viability of marginal donor lungs.
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| 14. |
- Liersch-Nordqvist, Annika, et al.
(författare)
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The impact of alteplase on pulmonary graft function in donation after circulatory death - An experimental study
- 2017
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Ingår i: Annals of Medicine and Surgery. - : Ovid Technologies (Wolters Kluwer Health). - 2049-0801. ; 22, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Lung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function.METHODS: Twelve Swedish domestic pigs were randomized into two groups. All animals underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. None of the animals received heparin. The lungs were then harvested and flush-perfused with Perfadex(®) solution and the organs were then stored at 8 °C for 4 h. In one group alteplase was added to the Perfadex(®) solution (donation after cardiac death with alteplase (DCD-A)) and in the other, it was not (DCD). Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance.RESULTS: During EVLP, there were no significant differences between groups in PaO2 at any investigated FiO2 level (1.0, 0.5, or 0.21). At FiO2 1.0, the PaO2 in the DCD and DCD-A was 51.7 ± 2.05 kPa and 60.3 ± 3.67 kPa, respectively (p = 0.1320). There were no significant differences between groups PVR levels, in the DCD (372 ± 31 dyne x s/cm(5)) and in the DCD-A (297 ± 37 dyne x s/cm(5)) groups (p = 0.1720). There was no significant difference between groups in macroscopic appearance.CONCLUSIONS: All the lungs showed excellent blood gases after EVLP, and they all meet the criteria's for clinical lung transplantation. The use of alteplase did not seem to have any obvious benefit to the donor lungs in a DCD situation. The donor lungs treated with alteplas showed slightly better blood gases and slightly lower PVR compared to the group without alteplas, however the difference was not significant. DCD appears to be a safe and effective method to expand the donor pool.
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| 15. |
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| 16. |
- Wlosinska, Martine, et al.
(författare)
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Aged garlic extract preserves cutaneous microcirculation in patients with increased risk for cardiovascular diseases : A double-blinded placebo-controlled study
- 2019
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Ingår i: International Wound Journal. - : Wiley. - 1742-4801 .- 1742-481X. ; 16:6, s. 1487-1493
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Tidskriftsartikel (refereegranskat)abstract
- Laser Doppler velocimetry estimates tissue perfusion providing a record of microvascular blood flow. Patients with heart disease or diabetes mellitus have impaired microvascular perfusion leading to impaired wound healing. Aged garlic extract (AGE) has a positive effect on vascular elasticity. This study aimed to assess the effect of long-term treatment with AGE on cutaneous tissue perfusion. A total of 122 patients with Framingham Risk Score ≥ 10 were randomised in a double-blinded manner to placebo or 2400 mg AGE daily for 1 year and monitored. Cutaneous microcirculation was measured at 0 and 12 months using laser Doppler velocimetry. A repeated measures analysis of variance (ANOVA) with a Greenhouse–Geisser correction determined that mean post-occlusive reactive hyperaemia differed significantly between time points. The mean percent change between the two time points 0 and 12 months was 102, 64 (174, 15)% change for AGE and 78, 62 (107, 92)% change for the placebo group (F[1, 120] = 5. 95, P < 0.016), 12 months of AGE increases the microcirculation in patients with an increased risk for cardiovascular events estimated using the Framingham risk score. Increased microcirculation could hypothetically facilitate wound healing.
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| 17. |
- Wlosinska, Martiné, et al.
(författare)
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Aged garlic extract reduces IL-6 : A double-blind placebo-controlled trial in females with a low risk of cardiovascular disease
- 2021
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Ingår i: Evidence-based Complementary and Alternative Medicine. - : Hindawi Limited. - 1741-427X .- 1741-4288. ; 2021
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Tidskriftsartikel (refereegranskat)abstract
- Background. Chronic inflammation is a risk factor for cardiovascular disease. The aim of the study was to evaluate whether a daily supplementation of aged garlic extract (AGE) could reduce inflammation in females with low risk for cardiovascular disease. The study was conducted at a single center, as a parallel randomized placebo-controlled trial. Method. 63 females with a Framingham risk score over 10 underwent cardiac computed tomography (CT) scan. Of those, patients with a coronary artery calcium (CAC) scores less than 5 (n = 31) met the inclusion criteria and were randomized, in a double-blind manner to an intake of placebo or AGE (2400 mg daily) for 1 year. Results. Main outcome measure was changes in inflammatory biomarkers, blood pressure, fastening blood glucose, and blood lipids. A total of 29 patients (14 in the AGE group and 15 in the placebo group) completed the study and were analyzed. Females treated with AGE showed lower levels of inflammatory marker IL-6 after 12 months of treatment compared to females receiving placebo (p < 0.05). The blood lipids had a trend towards a lowering effect in females treated with AGE; however, this trend was not significant. Conclusion. The present study concludes that AGE lowers IL-6 in females with a risk profile of cardiovascular disease. We could also conclude that risk prediction with cardiac CT scan turned out to be superior in estimating the risk of cardiac disease compared to Framingham risk score.
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| 18. |
- Wlosinska, Martiné, et al.
(författare)
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The effect of aged garlic extract on the atherosclerotic process-A randomized double-blind placebo-controlled trial
- 2020
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Ingår i: BMC Complementary Medicine and Therapies. - : Springer Science and Business Media LLC. - 2662-7671. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: One of the most serious secondary manifestations of Cardiovascular Disease (CVD) is coronary atherosclerosis. This study aimed to evaluate whether aged garlic extract (AGE) can influence coronary artery calcification (CAC) and to predict the individual effect of AGE using a standard process for data mining (CRISP-DM). Method: This was a single-center parallel randomized controlled study in a university hospital in Europe. Patients were randomized, in a double-blind manner, through a computer-generated randomization chart. Patients with a Framingham risk score≥10 after CT scan (n=104) were randomized to an intake of placebo or AGE (2400 mg daily) for 1 year. Main outcome measures were changes in CAC score and secondary outcome measures changes in blood pressure, fasting blood glucose, blood lipids and inflammatory biomarkers. Result: 104 patients were randomized and 46 in the active group and 47 in the placebo group were analyzed. There was a significant (p < 0.05) change in CAC progression (OR: 2.95 [1.05-8.27]), blood glucose (OR: 3.1 [1.09- 8.85]) and IL-6 (OR 2.56 [1.00-6.53]) in favor of the active group. There was also a significant (p=0.027) decrease in systolic blood pressure in the AGE group, from a mean of 148 (SD: 19) mmHg at 0 months, to 140 (SD: 15) mmHg after 12 months. The AGE Algorithm, at a selected probability cut-off value of 0.5, the accuracy score for CAC progression was 80%, precision score of 79% and recall score 83%. The score for blood pressure was 74% (accuracy, precision and recall). There were no side-effects in either group. Conclusions: AGE inhibits CAC progression, lowers IL-6, glucose levels and blood pressure in patients at increased risk of cardiovascular events in a European cohort. An algorithm was made and was used to predict with 80% precision which patient will have a significantly reduced CAC progression using AGE. The algorithm could also predict with a 74% precision which patient will have a significant blood pressure lowering effect pressure using AGE.
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