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1.
J Clin Med ; 13(8)2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38673660

ABSTRACT

Background: Non-surgical rhinoplasty is one of the best choices in mild cases of the saddle nose, and it represents a solution for the aesthetical amelioration of facial deformity; nevertheless, in most critical cases, surgical intervention is still required. This study reports the experience and results of a single facial plastic surgeon (M.G.) using a non-surgical technique for the correction of saddle noses in a large cohort of patients. Methods: This retrospective study assesses all patients injected from January 2017 through October 2023 in private clinics in Milan (Italy), London (UK), and Dubai (UAE). All patients were followed up for 12 months. The harvested adipose tissues were processed with different systems and with or without acoustic wave therapy (AWT). The extracted products have been characterized in terms of cellular yield and cell growth. Ninety-seven patients were injected with adipose-derived products or hyaluronic acid (HA). Patients were followed up for 12 months, and satisfaction data were analyzed. Results: The stem cells obtained from the patients who previously received AWT displayed a statistically higher cell growth ability in comparison with those of the cells derived from patients who did not receive AWT. The evolution of patient satisfaction during the time for each group of treatment was investigated, and cellular treatments show the best maintenance of patient satisfaction over time. Conclusions: Dermgraft and AWT approaches resulted in the highest patient satisfaction for the non-surgical correction of the saddle nose deformity.

2.
Atherosclerosis ; 390: 117335, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37872010

ABSTRACT

BACKGROUND AND AIMS: Heated tobacco products (HTPs) are novel alternative tobacco products being promoted as an alternative to cigarettes. To evaluate the impact of HTP use on vascular function, we investigated the effects of a brief HTP usage on arterial stiffness and platelet thrombus formation in healthy volunteers. METHODS: In a randomised crossover study, twenty-four healthy young adults with occasional tobacco use smoked the HTP IQOS 3 Multi (Phillip Morris Int.) and "no-exposure" was used as a control, with a wash-out period of at least one week in-between. Arterial stiffness was assessed through pulse wave velocity and pulse wave analysis. Blood samples, collected at baseline and 5 min following exposure, were analysed with the Total-Thrombus-formation analysis system evaluating platelet and fibrin-rich thrombus formation tendency. RESULTS: HTP exposure caused immediate heightened pulse wave velocity (+0.365 m/s, 95% CI: +0.188 to 0.543; p = 0.004) and enhanced augmentation index corrected to heart rate (+6.22%, 95% CI: +2.33 to 10.11; p = 0.003) compared to the no-exposure occasion. Similarly, blood pressure and heart rate transiently increased immediately following HTP inhalation. Platelet thrombus formation significantly increased following HTP exposure (area under the curve +59.5, 95% CI: +25.6 to 93.4; p < 0.001) compared to no-exposure. No effect was seen on fibrin-rich thrombus formation following HTP-exposure. CONCLUSIONS: Brief HTP use in healthy young adults had immediate adverse effects on vascular function resulting in increased arterial stiffness and platelet thrombus formation, known risk factors for the development of atherosclerosis. Further research is needed to address long term health impacts.


Subject(s)
Electronic Nicotine Delivery Systems , Thrombosis , Tobacco Products , Vascular Stiffness , Young Adult , Humans , Pulse Wave Analysis , Tobacco Products/adverse effects , Thrombosis/etiology , Fibrin
3.
BMC Med Inform Decis Mak ; 23(1): 265, 2023 11 17.
Article in English | MEDLINE | ID: mdl-37978393

ABSTRACT

BACKGROUND: Despite the globally reducing hospitalization rates and the much lower risks of Covid-19 mortality, accurate diagnosis of the infection stage and prediction of outcomes are clinically of interest. Advanced current technology can facilitate automating the process and help identifying those who are at higher risks of developing severe illness. This work explores and represents deep-learning-based schemes for predicting clinical outcomes in Covid-19 infected patients, using Visual Transformer and Convolutional Neural Networks (CNNs), fed with 3D data fusion of CT scan images and patients' clinical data. METHODS: We report on the efficiency of Video Swin Transformers and several CNN models fed with fusion datasets and CT scans only vs. a set of conventional classifiers fed with patients' clinical data only. A relatively large clinical dataset from 380 Covid-19 diagnosed patients was used to train/test the models. RESULTS: Results show that the 3D Video Swin Transformers fed with the fusion datasets of 64 sectional CT scans + 67 clinical labels outperformed all other approaches for predicting outcomes in Covid-19-infected patients amongst all techniques (i.e., TPR = 0.95, FPR = 0.40, F0.5 score = 0.82, AUC = 0.77, Kappa = 0.6). CONCLUSIONS: We demonstrate how the utility of our proposed novel 3D data fusion approach through concatenating CT scan images with patients' clinical data can remarkably improve the performance of the models in predicting Covid-19 infection outcomes. SIGNIFICANCE: Findings indicate possibilities of predicting the severity of outcome using patients' CT images and clinical data collected at the time of admission to hospital.


Subject(s)
COVID-19 , Humans , COVID-19/diagnostic imaging , Hospitalization , Hospitals , Neural Networks, Computer , Tomography, X-Ray Computed
4.
Cardiovasc Toxicol ; 23(7-8): 255-264, 2023 08.
Article in English | MEDLINE | ID: mdl-37548804

ABSTRACT

Electronic cigarette (EC) vaping is increasingly popular, despite growing evidence of adverse health effects. To further evaluate the impact of EC use on vascular health, we investigated the effects of brief EC inhalation on flow-dependent thrombus formation and microcirculation in healthy volunteers. The study was performed with a randomised double-blind crossover design. Twenty-two healthy subjects aged between 18 and 45 years with occasional tobacco use were recruited. Subjects inhaled 30 puffs of EC aerosol with and without nicotine on two occasions separated by a wash-out period of at least 1 week. Blood samples were collected at baseline and at 15 and 60 min following exposure and analysed with the Total-Thrombus-formation analysis system evaluating fibrin-rich thrombus formation and platelet thrombus formation in whole blood under flow. Microvascular function was assessed at baseline and 30 min after exposure by laser speckle contrast imaging and iontophoresis of acetylcholine and sodium nitroprusside (SNP) to evaluate the endothelium-dependent and independent pathways of vasodilation. Compared with nicotine free EC aerosol, exposure to EC aerosol with nicotine significantly increased platelet thrombus formation and fibrin-rich thrombus formation at 15 min (p = 0.017 and p = 0.037, respectively) with normalisation after 60 min. Peak SNP-mediated microvascular perfusion, i.e. endothelium-independent vasodilation, was reduced following EC vaping with nicotine compared with baseline (p = 0.006). Thirty puffs of EC aerosol with nicotine increased platelet and fibrin-dependent thrombus formation and reduced microvascular dilatation capacity. No compelling effects of EC vaping without nicotine were observed, indicating nicotine as the main effector. Trial registration: ClinicalTrials.gov Identifier: NCT04175457 URL: https://clinicaltrials.gov/ct2/show/NCT04175457.


Subject(s)
Electronic Nicotine Delivery Systems , Vaping , Humans , Adolescent , Young Adult , Adult , Middle Aged , Nicotine/adverse effects , Vaping/adverse effects , Aerosols , Fibrin
5.
Am J Med ; 136(8): 814-823.e8, 2023 08.
Article in English | MEDLINE | ID: mdl-37156347

ABSTRACT

BACKGROUND: Previous studies using cardiac troponin levels to investigate the relationship between myocardial injury and mortality in sepsis patients have been conflicting. Our aim was to investigate the relationship between plasma high-sensitive cardiac troponin T (hs-cTnT) level and 30-day and 1-year mortality in sepsis patients and 30- to 365-day mortality in sepsis survivors. METHODS: Sepsis patients requiring vasopressor support and admitted to our institution between 2012 and 2021 (n = 586) were included in this retrospective cohort study. Elevated hs-cTnT values (≥15 ng/L) were divided into quartiles (Q): Q1 15-35 ng/L; Q2 36-61 ng/L; Q3 62-125 ng/L; Q4 126-8630 ng/L. Stratified Kaplan-Meier curves and multivariable Cox regression were used for survival analyses. RESULTS: First sampled hs-cTnT was elevated in 529 (90%) patients. One-year mortality was 45% (n = 264). Increasing level of hs-cTnT was independently associated with higher adjusted hazard ratios (HR) for 1-year mortality compared with normal levels: Q1 HR 2.9 (95% confidence interval [CI], 1.03-8.1); Q2 HR 3.5 (95% CI, 1.2-9.8); Q3 HR 4.8 (95% CI, 1.7-13.4); Q4 HR 5.7 (95% CI, 2.1-16). In acute phase survivors, first sampled hs-cTnT was an independent predictor of 30- to 365-day mortality (HR 1.3; 95% CI, 1.1-1.6 per loge hs-cTnT). CONCLUSIONS: First sampled plasma hs-cTnT in critically ill sepsis patients was independently associated with 30-day and 1-year mortality. Importantly, first sampled hs-cTnT was associated with mortality during the convalescence phase (30- to 365-day) and could be a feasible marker to identify acute phase survivors at high risk of death.


Subject(s)
Sepsis , Troponin T , Humans , Retrospective Studies , Hospitalization , Biomarkers , Prognosis
6.
Crit Care Explor ; 4(2): e0643, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35198986

ABSTRACT

Severe coronavirus disease 2019 is characterized by infected microvascular endothelial cells. The primary aim of this study was to investigate microvascular function in patients with critical coronavirus disease 2019. DESIGN: A prospective observational study was conducted in which patients with critical and severe COVID-19 were investigated during acute disease phase and at least 3 months after disease onset. SETTING: Single-center study at Danderyd University Hospital. PATIENTS: Twenty-three patients with critical coronavirus disease 2019 treated with noninvasive or invasive mechanical ventilation, seven patients with severe COVID-19 with dyspnea or need of oxygen supply up to 8 L/min, and 15 noncoronavirus disease controls. INTERVENTIONS: None. MEASUREMENTS: Skin perfusion was investigated through laser speckle contrast imaging before and after iontophoresis of acetylcholine and sodium nitroprusside for determination of the endothelial-dependent and the endothelial-independent vasodilation, respectively. MAIN RESULTS: Patients with critical COVID-19 had higher basal skin perfusion during both the acute (34 ± 9 perfusion unit; p = 0.0003) and the postinfectious phase (29 ± 8 perfusion unit; p = 0.04), compared with noncoronavirus disease controls (23 ± 7 perfusion unit). In addition, endothelial-dependent and endothelial-independent vasodilation were reduced in patients with critical COVID-19 during the acute disease phase (p < 0.001 for both), whereas no significant differences between patients and controls were found during the postinfectious phase. In patients with severe COVID-19, basal skin perfusion and endothelial-dependent vasodilatation were not significantly changed, whereas endothelial-independent vasodilatation was reduced (p = 0.02) compared with controls. CONCLUSIONS: Changes in skin microcirculation in patients with critical COVID-19 indicate that the infection induces a systemic microvascular impairment with persisting long-term effects on the microvascular function.

7.
Shock ; 56(6): 964-968, 2021 12 01.
Article in English | MEDLINE | ID: mdl-33958544

ABSTRACT

BACKGROUND: Endothelial and microvascular dysfunction may be a key pathogenic feature of severe COVID-19. The aim of this study was to investigate endothelial-dependent and endothelial-independent skin microvascular reactivity in patients with critical COVID-19. METHODS: Twelve patients with COVID-19 treated with non-invasive or invasive mechanical ventilation were included in the study. We investigated skin microvascular reactivity on 2 separate days during hospitalization (study day 1 and 2) and at least 3 months after disease onset (study day 3). Twelve controls with no confirmed or suspected COVID-19 infection during 2020 were also examined. Skin perfusion was investigated through Laser Speckle Contrast Imaging before and after iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to determine the endothelial-dependent and the endothelial-independent vasodilation, respectively. RESULTS: Compared to controls, patients with critical COVID-19 had higher basal skin perfusion and reduced responses to endothelial-dependent (ACh, P = 0.002) and endothelial-independent (SNP, P = 0.01) vasodilator drugs on study day 1. In addition, the ACh/SNP ratio was significantly reduced in patients (0.50 ±â€Š0.36 vs. 0.91 ±â€Š0.49 in controls, P = 0.02). Three months after disease onset, surviving patients tended to have reduced ACh-mediated vasodilation compared to controls (P = 0.08). CONCLUSIONS: This small-sized pilot study demonstrates that critical COVID-19 infection is associated with microvascular impairment and, in particular, a markedly reduced endothelial function. Our results also suggest that microvascular function may not be fully recovered 3 months after disease onset.


Subject(s)
COVID-19/epidemiology , Critical Illness/epidemiology , Endothelium, Vascular/physiopathology , Microcirculation/physiology , Regional Blood Flow/physiology , Vasodilation/physiology , Aged , COVID-19/physiopathology , Comorbidity , Female , Follow-Up Studies , Humans , Male , Microvessels/physiopathology , Middle Aged , Pilot Projects , Prospective Studies , SARS-CoV-2
8.
Int J Infect Dis ; 102: 415-421, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33130213

ABSTRACT

OBJECTIVES: This study investigated demographics, comorbidities, and death rate in hospitalized patients with confirmed COVID-19. In addition, we hypothesized that functional status, according to the Clinical Frailty Scale (CFS), in patients aged 65 years or older is a better predictor of poor outcome than age and comorbidities. METHODS: A total of 255 randomly selected COVID-19 patients admitted to a university hospital were included and followed up for 60 days. Patient data were extracted manually from the electronic health records with use of a standardized protocol. RESULTS: The age of the study population ranged between 20 and 103 years (mean age 66 years ± 17 years). Hypertension, diabetes mellitus, and obesity were the three most prevalent comorbidities. At the 60-day follow-up, 70 patients (27%) had died. In multivariate analyses, age, chronic kidney disease, and previous stroke were associated with death. Most fatal cases (90%) occurred in patients aged 65 years or older. Among such patients, CFS level was the only predictor of death in multivariate analyses. CONCLUSIONS: This study shows that increasing age, chronic kidney disease, and previous stroke significantly contribute to a fatal outcome in hospitalized patients with COVID-19. In patients aged 65 years or older, CFS level was the strongest prognostic factor for death.


Subject(s)
COVID-19/mortality , Frailty , SARS-CoV-2 , Adult , Age Factors , Aged , Aged, 80 and over , Comorbidity , Female , Humans , Male , Middle Aged , Renal Insufficiency, Chronic/complications , Risk Factors , Stroke/complications , Young Adult
9.
Thromb Res ; 196: 78-86, 2020 12.
Article in English | MEDLINE | ID: mdl-32853980

ABSTRACT

INTRODUCTION: Patients with type 1 diabetes have high risk of developing microvascular complications, and microangiopathy contributes to premature cardiovascular disease in this population. The role that microvesicles (MVs) may play in the development of microangiopathy in type 1 diabetes remains unclear. MATERIALS AND METHODS: Plasma levels of endothelial MVs (EMVs) and platelet MVs (PMVs) in 130 patients with type 1 diabetes without microangiopathy, 106 patients with microangiopathy and 100 matched healthy controls were analyzed using flow cytometry. MV expression of procoagulant phosphatidylserine (PS) and proinflammatory high mobility group box-1 protein (HMGB1) was also assessed. RESULTS: Patients with type 1 diabetes had markedly elevated levels of EMVs and PS+ EMVs as well as PMVs and PS+ PMVs compared to healthy controls (p < .001 for all). Furthermore, HMGB1+ EMVs and HMGB1+ PMVs were significantly increased in patients (p < .001 for all). After adjusting for potential confounders, there were no clear differences between patients with or without microvascular complications for any of the MV parameters. CONCLUSION: Type 1 diabetes is a prothrombotic and proinflammatory disease state that, regardless of the presence of clinical microangiopathy, is associated with elevated levels of plasma MVs, in particular those of an endothelial origin. We have for the first time demonstrated that patients with type 1 diabetes have higher levels of HMGB1+ MVs. HMGB1 is an alarmin with potent proinflammatory effects that drive endothelial dysfunction, and it would therefore be of interest to further study the role of HMGB1+ MVs in the development of macrovascular complications in type 1 diabetes.


Subject(s)
Cell-Derived Microparticles , Diabetes Mellitus, Type 1 , HMGB1 Protein , Blood Platelets , Diabetes Mellitus, Type 1/complications , Humans , Phosphatidylserines
10.
Diab Vasc Dis Res ; 17(3): 1479164120928303, 2020.
Article in English | MEDLINE | ID: mdl-32538145

ABSTRACT

AIM: The aim of this study was to investigate the correlation between skin microvascular reactivity and clinical microangiopathy in patients with type 1 diabetes. METHODS: We included 61 patients with type 1 diabetes, that is, 31 patients with and 30 without clinical microangiopathy, and 31 healthy controls. A microangiopathy scoring system was introduced for comparison of data between patients with microangiopathy. Responses to iontophoresis of acetylcholine and sodium nitroprusside were assessed by laser Doppler imaging. RESULTS: Patients with microangiopathy had reduced acetylcholine- and sodium nitroprusside-mediated flux in forearm skin microcirculation compared to healthy controls (p = 0.03 and p < 0.001, respectively, repeated measures analysis of variance), whereas no significant differences were found between patients without microangiopathy and controls. Skin reactivity was reduced in patients with microangiopathy compared to patients without microangiopathy: 1.43 ± 0.38 versus 1.59 ± 0.39 arbitrary units for acetylcholine-mediated peak flux and 1.44 ± 0.46 versus 1.74 ± 0.34 arbitrary units for sodium nitroprusside-mediated peak flux (p < 0.05 for both). A tendency of gradual decrease in acetylcholine and sodium nitroprusside responses was found in patients with increasing microangiopathy scores. CONCLUSION: We conclude that skin microvascular reactivity is associated with clinical microangiopathy in patients with type 1 diabetes. Impaired skin microvascular function in type 1 diabetes seems to be multifactorial and involves both endothelial-dependent and endothelial-independent pathways. We introduce a novel microangiopathy score that could easily be used in a clinical setting for comparison of patients with various degrees of microangiopathy.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/etiology , Microcirculation , Skin/blood supply , Vasodilation , Administration, Cutaneous , Adult , Aged , Blood Flow Velocity , Case-Control Studies , Cross-Sectional Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/physiopathology , Female , Forearm , Humans , Iontophoresis , Laser-Doppler Flowmetry , Male , Microcirculation/drug effects , Microscopic Angioscopy , Middle Aged , Pilot Projects , Predictive Value of Tests , Risk Factors , Vasodilation/drug effects , Vasodilator Agents/administration & dosage
11.
Thromb Res ; 172: 158-164, 2018 12.
Article in English | MEDLINE | ID: mdl-30447538

ABSTRACT

INTRODUCTION: Type 1 diabetes is a prothrombotic state strongly linked to vascular complications. The role of microvesicles (MVs) as mediators and potential biomarkers in microangiopathy in type 1 diabetes remains unclear. MATERIALS AND METHODS: MV levels in plasma samples from 106 patients with type 1 diabetes with microangiopathy, 130 patients without microangiopathy and 100 healthy controls were analysed using flow cytometry. Phosphatidylserine (PS) expression in MVs was assessed by lactadherin, and the ability of MVs to induce thrombin generation was investigated in vitro. Endogenous plasma lactadherin levels were measured using ELISA. RESULTS: Patients with type 1 diabetes had higher MV levels compared to healthy controls, with no significant differences between patients with and without microangiopathy. MV-induced thrombin generation in normal-pooled plasma was blocked by addition of lactadherin. Endogenous lactadherin levels were higher in patients compared to controls, and the highest levels were found in patients with microangiopathy. Plasma lactadherin levels did not correlate with levels of PS positive/negative MVs. CONCLUSION: Patients with type 1 diabetes with and without microangiopathy have higher levels of circulating MVs than healthy controls, probably reflecting higher cellular activation and turnover. However, we found no associations between clinical microangiopathy and levels of MVs in total or PS-expressing MVs. Plasma levels of lactadherin, which is a glycoprotein important in the clearance of cells and MVs, are increased in patients with type 1 diabetes and correlate with microangiopathy.


Subject(s)
Cell-Derived Microparticles/pathology , Diabetes Mellitus, Type 1/complications , Microvessels/pathology , Phosphatidylserines/analysis , Adult , Antigens, Surface/analysis , Antigens, Surface/blood , Blood Coagulation , Cell-Derived Microparticles/metabolism , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/pathology , Female , Humans , Male , Microvessels/metabolism , Middle Aged , Milk Proteins/analysis , Milk Proteins/blood , Phosphatidylserines/metabolism , Thrombin/metabolism
12.
Growth Horm IGF Res ; 29: 78-82, 2016 08.
Article in English | MEDLINE | ID: mdl-27400272

ABSTRACT

INTRODUCTION: Insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 (IGFBP-1) play an important role in vascular health. Many patients with type 1 diabetes are medicated with HMG-CoA reductase inhibitors, statins, in order to prevent vascular complications. Yet little is known about the effect of statins on the IGF-1/IGFBP-1 axis in these patients. OBJECTIVES: The aim of this study was to evaluate the effect of atorvastatin treatment on IGF-1 and IGFBP-1 with regards to microvascular function. DESIGN: Twenty patients with type 1 diabetes received either placebo or 80mg atorvastatin for two months in a double-blinded cross-over study. IGF-1 and IGFBP-1 levels were assessed before and after each treatment period. Skin microcirculation was studied using Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. RESULTS: Treatment with high-dose atorvastatin was associated with a significant decrease in IGF-1 levels compared to placebo (p<0.05, ANOVA repeated measures), whereas no effect was seen on IGFBP-1 or the IGF-1/IGFBP-1 ratio. These variables did not correlate with measurements of skin microvascular reactivity. CONCLUSIONS: The study found that treatment with high-dose atorvastatin was associated with reduced IGF-1 levels, which may indicate a potential negative effect on microvascular function and long-term risk of microangiopathy development.


Subject(s)
Atorvastatin/administration & dosage , Diabetes Mellitus, Type 1/drug therapy , Diabetic Angiopathies/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Insulin-Like Growth Factor Binding Protein 1/metabolism , Insulin-Like Growth Factor I/metabolism , Acetylcholine/pharmacology , Adult , Cross-Over Studies , Diabetes Mellitus, Type 1/metabolism , Double-Blind Method , Female , Humans , Iontophoresis , Laser-Doppler Flowmetry , Male , Microcirculation/drug effects , Middle Aged , Nitroprusside/pharmacology , Risk Factors , Skin/blood supply , Skin/diagnostic imaging , Vasodilation/drug effects , Vasodilator Agents/pharmacology
13.
Thromb Haemost ; 113(2): 312-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25318636

ABSTRACT

The increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the fibrin clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20-70 years and without any history of cardiovascular disease. Fibrin clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable fibrin clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher fibrinogen concentrations and denser and less permeable fibrin clots. Thus, we conclude that in vitro fibrin clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter fibrin clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.


Subject(s)
Blood Coagulation , Diabetes Mellitus, Type 1/blood , Fibrin/chemistry , Adult , Aged , Blood Coagulation Tests , Cardiovascular Diseases/blood , Diabetes Complications/blood , Female , Fibrinogen/pharmacology , Fibrinolysis , Hemostasis , Humans , Hyperglycemia/blood , Male , Microcirculation , Middle Aged , Nephelometry and Turbidimetry , Permeability , Risk Factors , Thrombin/chemistry , Thrombosis/blood , Young Adult
14.
Diab Vasc Dis Res ; 10(6): 483-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23823849

ABSTRACT

AIMS: The present study investigated the effects of lipid-lowering therapy with atorvastatin on skin microvascular function in patients with type 1 diabetes and dyslipidaemia. METHODS: Twenty patients received daily treatment with atorvastatin 80 mg or placebo during 2 months in a randomised, double-blind, cross-over study. Forearm skin microcirculation was investigated with laser Doppler perfusion imaging during iontophoresis of acetylcholine and sodium nitroprusside to assess endothelium-dependent and endothelium-independent microvascular reactivity, respectively. Various biochemical markers of endothelial function were also investigated. RESULTS: Endothelium-dependent microvascular reactivity decreased during atorvastatin (p < 0.001), showing a significant treatment effect compared with placebo (p = 0.04). Atorvastatin treatment was also associated with increased haemoglobin A1C levels from 7.45% to 7.77% (p = 0.008). CONCLUSIONS: The present study shows impaired endothelium-dependent skin microvascular function during high-dose atorvastatin treatment in patients with type 1 diabetes, thus implicating a risk for deterioration of microvascular function during such therapy in these patients.


Subject(s)
Diabetes Mellitus, Type 1/complications , Diabetic Angiopathies/etiology , Dyslipidemias/drug therapy , Endothelium, Vascular/drug effects , Heptanoic Acids/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Microcirculation/drug effects , Pyrroles/adverse effects , Skin/blood supply , Administration, Cutaneous , Adult , Atorvastatin , Biomarkers/blood , Cell-Derived Microparticles/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Diabetic Angiopathies/blood , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/physiopathology , Double-Blind Method , Dyslipidemias/blood , Dyslipidemias/complications , Dyslipidemias/diagnosis , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Female , Glycated Hemoglobin/metabolism , Heptanoic Acids/administration & dosage , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Iontophoresis , Laser-Doppler Flowmetry , Male , Middle Aged , Pyrroles/administration & dosage , Risk Factors , Sweden , Time Factors , Treatment Outcome , Vasodilator Agents/administration & dosage
15.
Diabetes Care ; 35(2): 404-8, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22148098

ABSTRACT

OBJECTIVE: Patients with type 1 diabetes form a less permeable fibrin network, which could contribute to their increased risk of cardiovascular disease (CVD). Low-dose aspirin treatment is the standard in the management of CVD; however, the effect seems reduced in patients with diabetes. We investigated the effects of low- and high-dose aspirin treatment on fibrin network formation in patients with type 1 diabetes (primary aim) and the possible interaction between the treatment effects of aspirin on fibrin network permeability and glycemic control in these patients (secondary aim). RESEARCH DESIGN AND METHODS: Forty-eight patients (24 subjects with good [HbA(1c) <7.4%] and 24 subjects with poor [HbA(1c) >8.4%] glycemic control) were randomly assigned to treatment with 75 or 320 mg/day aspirin during 4 weeks in a crossover fashion. A 4-week washout period separated the treatment periods. The plasma fibrin network was assessed by determination of the permeability coefficient (K(s)). RESULTS: Treatment with 75 mg aspirin did not influence fibrin network permeability (K(s)). However, K(s) increased significantly during treatment with 320 mg aspirin (P = 0.004), and a significant treatment effect was seen compared with treatment with 75 mg aspirin (P = 0.009). The increase in K(s) during high-dose aspirin treatment was significant in patients with poor glycemic control (P = 0.02), whereas K(s) only tended to increase in patients with good glycemic control (P = 0.06). CONCLUSIONS: A high dose of aspirin is required to influence fibrin network permeability in patients with type 1 diabetes. The observed lack of effect with low-dose aspirin may contribute to aspirin treatment failure in diabetes.


Subject(s)
Aspirin/therapeutic use , Diabetes Mellitus, Type 1/metabolism , Fibrin/metabolism , Aspirin/administration & dosage , Chromatography, High Pressure Liquid , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Drug Administration Schedule , Female , Glycated Hemoglobin/metabolism , Humans , Male
16.
Thromb Res ; 126(3): e225-31, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20637495

ABSTRACT

INTRODUCTION: Diabetes is a prothrombotic state involving a more thrombogenic fibrin network. In the present study we investigated the effects of lipid-lowering therapy with atorvastatin on fibrin network structure and platelet-derived microparticles in patients with type 1 diabetes and dyslipidemia. MATERIALS AND METHODS: Twenty patients were treated with atorvastatin (80 mg daily) or placebo during 2 months in a randomized, double-blind, cross-over study. Fibrin network permeability, expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles, plasma endogenous thrombin potential, plasminogen activator inhibitor-1 and tissue plasminogen activator antigen levels were assessed. Additionally, levels of plasma fibrinogen, high-sensitivity C-reactive protein and glycated haemoglobin were measured. RESULTS: During treatment with atorvastatin, fibrin network permeability increased (p=0.01), while endogenous thrombin potential and expression of glycoprotein IIIa, P-selectin and tissue factor decreased (p<0.01). In vitro experiments indicated that platelet-derived microparticles influence the fibrin network formation as fibrin network permeability decreased significantly when platelet-derived microparticles were added to normal plasma. Baseline levels of plasminogen activator inhibitor-1 and tissue plasminogen activator antigen as well as plasma fibrinogen and high-sensitivity C-reactive protein were within reference values and not significantly changed during atorvastatin treatment, while glycated haemoglobin increased 0.3% (p<0.001). CONCLUSIONS: Novel treatment effects were found in patients with type 1 diabetes and dyslipidemia during atorvastatin therapy, i.e. a more porous fibrin network, to which reduced expression of glycoprotein IIIa, P-selectin and tissue factor on platelet-derived microparticles may contribute. The observed impairment of glycemic control during long-term statin treatment deserves attention.


Subject(s)
Diabetes Mellitus, Type 1/complications , Dyslipidemias/drug therapy , Fibrinolytic Agents/therapeutic use , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pyrroles/therapeutic use , Thrombosis/drug therapy , Adult , Aged , Atorvastatin , Biomarkers/blood , Blood Platelets/drug effects , Blood Platelets/metabolism , C-Reactive Protein/metabolism , Cell-Derived Microparticles/drug effects , Cell-Derived Microparticles/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Double-Blind Method , Dyslipidemias/blood , Dyslipidemias/complications , Fibrin/metabolism , Glycated Hemoglobin/metabolism , Humans , Integrin beta3/blood , Middle Aged , P-Selectin/blood , Plasminogen Activator Inhibitor 1/blood , Sweden , Thrombin/metabolism , Thromboplastin/metabolism , Thrombosis/blood , Thrombosis/etiology , Time Factors , Treatment Outcome
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