| 1. |
- Brinck, Jonas W., et al.
(author)
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High-density lipoprotein from end-stage renal disease patients exhibits superior cardioprotection and increase in sphingosine-1-phosphate
- 2018
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 48:2
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Journal article (peer-reviewed)abstract
- Background: Chronic kidney disease (CKD) exacerbates the risk of death due to cardiovascular disease (CVD). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high-density lipoprotein (HDL) cholesterol are thought to contribute to increased risk. In CKD patients, higher HDL cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which HDL could favourably influence CVD risk. In this study, we compared plasma levels of sphingosine-1-phosphate (S1P), HDL-associated S1P (HDL-S1P) and HDL-mediated protection against oxidative stress between CKD and control patients. Methods: High-density lipoprotein was individually isolated from 20 CKD patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, HDL-S1P content and the capacity of HDL to protect cardiomyocytes against doxorubicin-induced oxidative stress in vitro were measured. Results: Chronic kidney disease patients showed a typical profile with significant reductions in plasma HDL cholesterol and albumin and an increase in triglycerides and pro-inflammatory cytokines (TNF-alpha and IL-6). Unexpectedly, HDL-S1P content (P = .001) and HDL cardioprotective capacity (P = .034) were increased significantly in CKD patients. Linear regression analysis of which factors could influence HDL-S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively. Discussion: The novel and unexpected observation in this study is that uremic HDL is more effective than control HDL for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of HDL-mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in CKD are associated with higher HDL-S1P.
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| 2. |
- Chirinos, Julio A., et al.
(author)
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Reduced Apolipoprotein M and Adverse Outcomes across the Spectrum of Human Heart Failure
- 2020
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In: Circulation. - 0009-7322. ; , s. 1463-1476
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Journal article (peer-reviewed)abstract
- Background: Apo (apolipoprotein) M mediates the physical interaction between high-density lipoprotein (HDL) particles and sphingosine-1-phosphate (S1P). Apo M exerts anti-inflammatory and cardioprotective effects in animal models. Methods: In a subset of PHFS (Penn Heart Failure Study) participants (n=297), we measured apo M by Enzyme-Linked ImmunoSorbent Assay (ELISA). We also measured total S1P by liquid chromatography-mass spectrometry and isolated HDL particles to test the association between apo M and HDL-associated S1P. We confirmed the relationship between apo M and outcomes using modified aptamer-based apo M measurements among 2170 adults in the PHFS and 2 independent cohorts: the Washington University Heart Failure Registry (n=173) and a subset of TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial; n=218). Last, we examined the relationship between apo M and ≈5000 other proteins (SomaScan assay) to identify biological pathways associated with apo M in heart failure. Results: In the PHFS, apo M was inversely associated with the risk of death (standardized hazard ratio, 0.56 [95% CI, 0.51-0.61]; P<0.0001) and the composite of death/ventricular assist device implantation/heart transplantation (standardized hazard ratio, 0.62 [95% CI, 0.58-0.67]; P<0.0001). This relationship was independent of HDL cholesterol or apo AI levels. Apo M remained associated with death (hazard ratio, 0.78 [95% CI, 0.69-0.88]; P<0.0001) and the composite of death/ventricular assist device/heart transplantation (hazard ratio, 0.85 [95% CI, 0.76-0.94]; P=0.001) in models that adjusted for multiple confounders. This association was present in both heart failure with reduced and preserved ejection fraction and was replicated in the Washington University cohort and a cohort with heart failure with preserved ejection fraction only (TOPCAT). The S1P and apo M content of isolated HDL particles strongly correlated (R=0.81, P<0.0001). The top canonical pathways associated with apo M were inflammation (negative association), the coagulation system (negative association), and liver X receptor/retinoid X receptor activation (positive association). The relationship with inflammation was validated with multiple inflammatory markers measured with independent assays. Conclusions: Reduced circulating apo M is independently associated with adverse outcomes across the spectrum of human heart failure. Further research is needed to assess whether the apo M/S1P axis is a suitable therapeutic target in heart failure.
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| 3. |
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| 4. |
- Cukalevski, Risto, et al.
(author)
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Structural Changes in Apolipoproteins Bound to Nanoparticles
- 2011
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In: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:23, s. 14360-14369
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Journal article (peer-reviewed)abstract
- Nanoparticles are widely used in the pharmaceutical and food industries, but the consequences of exposure to the human body have not been thoroughly investigated. Apolipoprotein A-I (apoAI), the major protein in high-density lipoprotein (HDL), and other lipoproteins are found in the corona around many nanopartides, but data on protein structural and functional effects are lacking. Here we investigate the structural consequences of the adsorption of apoAI, apolipoprotein B100 (apoB100), and HDL on polystyrene nanoparticles with different surface charges. The results of circular dichroism, fluorescence spectroscopy, and limited proteolysis experiments indicate effects on both secondary and tertiary structures. Plain and negatively charged nanoparticles induce helical structure in apoAI (negative net charge) whereas positively charged nanoparticles reduce the amount of helical structure. Plain and negatively charged partides induce a small blue shift in the tryptophan fluorescence spectrum, which is not noticed with the positively charged particles. Similar results are observed with reconstituted HDL. In apoB100, both secondary and tertiary structures are perturbed by all particles. To investigate the generality of the role of surface charge, parallel experiments were performed using human Serum albumin (HSA, negative net charge) and lysozyme (positive net charge). Again, the secondary structure is most affected by nanoparticles carrying an opposite surface charge relative to the protein. Nanoparticles carrying the same net charge as the protein induce only minor structural changes in lysozyme whereas a moderate change is observed for HSA. Thus, surface charge is a critical parameter for predicting structural changes in adsorbed proteins, yet the effect is specific for each protein.
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| 5. |
- Dahlbäck, Cecilia, et al.
(author)
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Accuracy of magnetic resonance imaging staging of tumour and nodal stage in rectal cancer treated by primary surgery : a population-based study
- 2022
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In: Colorectal Disease. - : Wiley. - 1462-8910 .- 1463-1318. ; 24:9, s. 1047-1053
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Journal article (peer-reviewed)abstract
- Aim: The preoperative stage of rectal cancer is an important prognostic factor affecting treatment recommendations. Currently, magnetic resonance imaging (MRI) is used for clinical staging to identify patients who should be recommended for neoadjuvant oncological treatment. The aim of this work was to investigate the accuracy of the preoperative T- and N-stage and also involvement of the mesorectal fascia (MRF) as determined by MRI in a Swedish national cohort. Method: Patients who had undergone resectional surgery for rectal cancer without neoadjuvant treatment in Sweden in the period 2013–2017 were identified through the Swedish Colorectal Cancer Registry (n = 2062). The T- and N-stage determined by preoperative MRI were compared with the histopathological results. The MRI-assessed MRF status was compared with the circumferential resection margin. Results: Sensitivity for differentiating T1-2 from T3-4 was 69% and specificity 77%. Sensitivity to detect N1-2 was 42% and specificity 81%. Sensitivity for MRF positivity was 50% and specificity 92%. Agreement analysed by weighted kappa analysis was 0.47 for T-stage [confidence interval (CI) 0.44–0.51], 0.24 for N-stage (CI 0.19–0.24) and 0.20 for MRF status (CI 0.12–0.29). Conclusion: In this study, accuracy of the preoperative MRI was lower than expected for rectal cancers. Overstaging might lead to potentially harmful neoadjuvant treatment and understaging can lead to a higher risk of tumour recurrence. The results of this study show that efforts should be made to increase the accuracy of the preoperative evaluation in order to optimize treatment recommendations.
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| 6. |
- Dahlbäck, Cecilia, et al.
(author)
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Aesthetic result after breast-conserving therapy is associated with quality of life several years after treatment. Swedish women evaluated with BCCT.core and BREAST-Q (TM)
- 2017
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 164:3, s. 679-687
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Journal article (peer-reviewed)abstract
- A gold standard for evaluation of aesthetic outcome after breast-conserving therapy (BCT) is still lacking. The BCCT.core software has been developed to assess aesthetic result in a standardised way. We aimed to study how the result of BCCT.core after BCT is associated with quality of life, measured with the BREAST-Q (TM), a validated questionnaire. Women eligible for BCT were consecutively recruited between February 1st 2008 and January 31st 2012 (n = 653). Photographs of 310 women, taken one year after BCT, were evaluated using the BCCT.core software. The postoperative BCT module of the BREAST-Q (TM) questionnaire was administered by mail and 348 questionnaires were returned (median 5.5 years after BCT). In all, 216 women had both BCCT.core results and completed BREAST-Q (TM) questionnaires available. The results from the BCCT.core evaluation were: excellent n = 49 (15.8%); good n = 178 (57.4%); fair n = 73 (23.5%); poor n = 10 (3.2%). The median BREAST-Q (TM) score for satisfaction with breasts was 66 [interquartile range (IQR) 57-80] and for psychosocial well-being 82 (IQR 61-100). Poor/fair results on BCCT.core were associated with Q-scores below median for both satisfaction with breasts [odds ratio (OR) 3.4 (confidence interval (CI) 1.7-6.8)] as well as for psychosocial well-being [OR 2.2 (CI 1.1-4.2)]. A statistically significant association between BCCT.core results one year after BCT and quality of life ratings using BREAST-Q (TM) several years later is shown in this study. This implies that the BCCT.core may be valuable in BCT follow-up and used as a standardised instrument in the evaluation of aesthetic results.
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| 8. |
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| 9. |
- Dahlbäck, Cecilia, et al.
(author)
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Long-term outcome of lymph vessel transplantation after chronic lymphorrhea
- 2021
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In: Case Reports in Plastic Surgery and Hand Surgery. - : Informa UK Limited. - 2332-0885. ; 8:1, s. 169-174
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Journal article (peer-reviewed)abstract
- A 52-year-old male patient developed a chronic fistula with excessive lymph leakage in the left axilla following removal of an enlarged lymph node with chronic local adipose tissue inflammation due to infection. After multiple surgeries, treatment with lymphatic vessel transplantation was successful. No recurrence occurred over 20 years of follow-up.
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| 10. |
- Dahlbäck, Cecilia, et al.
(author)
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Muscle mass and quality as predictors for complications, recurrence and length of hospital stay in acute uncomplicated diverticulitis: a retrospective cohort study
- 2023
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:4, s. 375-379
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Journal article (peer-reviewed)abstract
- ObjectivesThe aim of this study was to investigate the potential correlation between muscle mass/muscle quality and risk of complications or recurrence in patients presenting with acute uncomplicated diverticulitis. It was also to study if low muscle mass/quality correlated to prolonged hospital stay.Materials and methodsThe study population comprised 501 patients admitted to Helsingborg Hospital or Skåne University Hospital between 1 January 2015 and 31 December 2017, who had been diagnosed with acute uncomplicated diverticulitis and undergone computed tomography upon admission. The scans were used to estimate skeletal muscle mass and muscle radiation attenuation (an indicator for muscle quality). Skeletal muscle index was obtained by adjusting skeletal muscle mass to the patients’ height. Values of below the fifth percentile of a normal population were considered low.ResultsThere were no differences between the patients with normal versus those with low skeletal muscle mass, skeletal muscle index or muscle radiation attenuation regarding risk of complications or recurrence of diverticular disease. However, as only 11 patients had complications, no conclusion as to a potential correlation can be made. Low muscle quality correlated to longer hospital stay, also when adjusting for other potential confounders.ConclusionsMuscle mass/quality do not seem to serve as predictor of risk for recurrent disease in patients with acute uncomplicated diverticulitis. However, low muscle radiation attenuation was associated with prolonged hospital stay. This indicates that muscle quality, assessed by computed tomography scan, might be used in clinical practise to identify patients at risk of longer hospitalisation.
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