| 1. |
- Loftfield, Erikka, et al.
(author)
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Novel Biomarkers of Habitual Alcohol Intake and Associations With Risk of Pancreatic and Liver Cancers and Liver Disease Mortality
- 2021
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In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 113:11, s. 1542-1550
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Journal article (peer-reviewed)abstract
- BACKGROUND: Alcohol is an established risk factor for several cancers, but modest alcohol-cancer associations may be missed because of measurement error in self-reported assessments. Biomarkers of habitual alcohol intake may provide novel insight into the relationship between alcohol and cancer risk.METHODS: Untargeted metabolomics was used to identify metabolites correlated with self-reported habitual alcohol intake in a discovery dataset from the European Prospective Investigation into Cancer and Nutrition (EPIC; n = 454). Statistically significant correlations were tested in independent datasets of controls from case-control studies nested within EPIC (n = 280) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC; n = 438) study. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of alcohol-associated metabolites and self-reported alcohol intake with risk of pancreatic cancer, hepatocellular carcinoma (HCC), liver cancer, and liver disease mortality in the contributing studies.RESULTS: Two metabolites displayed a dose-response association with self-reported alcohol intake: 2-hydroxy-3-methylbutyric acid and an unidentified compound. A 1-SD (log2) increase in levels of 2-hydroxy-3-methylbutyric acid was associated with risk of HCC (OR = 2.54, 95% CI = 1.51 to 4.27) and pancreatic cancer (OR = 1.43, 95% CI = 1.03 to 1.99) in EPIC and liver cancer (OR = 2.00, 95% CI = 1.44 to 2.77) and liver disease mortality (OR = 2.16, 95% CI = 1.63 to 2.86) in ATBC. Conversely, a 1-SD (log2) increase in questionnaire-derived alcohol intake was not associated with HCC or pancreatic cancer in EPIC or liver cancer in ATBC but was associated with liver disease mortality (OR = 2.19, 95% CI = 1.60 to 2.98) in ATBC.CONCLUSIONS: 2-hydroxy-3-methylbutyric acid is a candidate biomarker of habitual alcohol intake that may advance the study of alcohol and cancer risk in population-based studies.
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| 2. |
- Porta, Miquel, et al.
(author)
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Plasma concentrations of persistent organic pollutants and pancreatic cancer risk
- 2022
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In: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 51:2, s. 479-490
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Journal article (peer-reviewed)abstract
- Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
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| 3. |
- Bergdahl, Carl, et al.
(author)
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No change in reoperation rates despite shifting treatment trends: a population-based study of 4,070 proximal humeral fractures
- 2021
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In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:6, s. 651-657
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Journal article (peer-reviewed)abstract
- Background and purpose - Clear and acknowledged treatment algorithms for proximal humeral fractures (PHFs) are lacking. Nevertheless, a change in treatment trends, including a change towards more reversed shoulder arthroplasties (RSA), has been observed during recent years. We examined the effect of these changes on reoperation rates. Patients and methods - Between 2011 and 2017, 4,070 PHFs treated at Sahlgrenska University Hospital were registered prospectively in the Swedish Fracture Register (SFR) and followed up until 2019 (mean follow-up of 4.5 years). Data on all reoperations were gathered from the SFR and from medical records. Results - The majority of PHFs were treated non-surgically and the proportion increased slightly, but not statistically significantly, during the study period (from 76% to 79%). Of the surgically treated fractures, the proportion fixed with a plate decreased from 47% to 25%, while the use of RSA increased 9-fold (from 2.0% to 19%). 221 patients underwent 302 reoperations. For those primarily treated surgically, the reoperation rate was 17%. Among treatment modalities, plate fixation was associated with the highest reoperation rate (21%). Rate of reoperations remained constant during the study period, both for the entire study cohort and for the surgically treated patients Interpretation - During the study period, treatment changes that are in accordance with recently published treatment recommendations were observed. However, these treatment changes did not affect the reoperation rate. Treatment with a plate, intramedullary nail, or hemiarthroplasty was associated with the highest reoperation rates. The fact that almost every 4th surgical procedure was a reoperation indicates a need for further improvement of modern treatment concepts for PHFs.
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| 4. |
- Ladfors, S. W., et al.
(author)
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Longitudinal Follow-Up on Cardiopulmonary Exercise Capacity Related to Cardio-Metabolic Risk Factors in Children With Renal Transplants
- 2021
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In: Frontiers in Sports and Active Living. - : Frontiers Media SA. - 2624-9367. ; 3
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Journal article (peer-reviewed)abstract
- Background: Children with chronic kidney disease, including those treated with kidney transplantation (KT), have an increased risk of cardiovascular disease. The aim of this study was to examine the cardiopulmonary exercise capacity after KT compared to matched controls, to relate the results to physical activity, blood pressure and biochemical findings and to follow exercise capacity over time. & nbsp; Methods: Patients with KT (n = 38, age 7.7-18 years), with a mean time from transplantation of 3.7 years (0.9-13.0) and mean time in dialysis 0.8 years, were examined at inclusion and annually for up to three years. Healthy controls (n = 17, age 7.3-18.6 years) were examined once. All subjects underwent a cardiopulmonary exercise test, resting blood pressure measurement, anthropometry and activity assessment. Patients also underwent echocardiography, dual-energy X-ray absorptiometry (DXA), 24-h ambulatory BP measurements (ABPM), assessment of glomerular filtration rate (GFR) and blood sampling annually. & nbsp; Results: As compared to healthy controls, KT patients showed decreased exercise capacity measured both as VO2peak (34.5 vs. 43.9 ml/kg/min, p < 0.001) and maximal load (2.6 vs. 3.5 W/kg, p < 0.0001), similarly as when results were converted to z-scores. No significant difference was found in weight, but the KT patients were shorter and had higher BMI z-score than controls, as well as increased resting SBP and DBP z-scores. The patient or parent reported physical activity was significantly lower in the KT group compared to controls (p < 0.001) In the combined group, the major determinants for exercise capacity z-scores were activity score and BMI z-score (beta = 0.79, p < 0.0001 and beta = -0.38, p = 0.007, respectively). Within the KT group, low exercise capacity was associated with high fat mass index (FMI), low activity score, low GFR and high blood lipids. In the multivariate analysis FMI and low GFR remained predictors of low exercise capacity. The longitudinal data for the KT patients showed no change in exercise capacity z-scores over time. & nbsp; Conclusion: Patients with KT showed decreased exercise capacity and increased BP as compared to healthy controls. Exercise capacity was associated to GFR, physical activity, FMI and blood lipids. It did not improve during follow-up.
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| 5. |
- Möller, Michael, 1957, et al.
(author)
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The Swedish Fracture Register - ten years of experience and 600,000 fractures collected in a National Quality Register
- 2022
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 23:1
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Journal article (peer-reviewed)abstract
- Background Before the creation of the Swedish Fracture Register (SFR), there was no national quality register that prospectively collects data regarding all types of fractures regardless of treatment in an emergency setting. Observational data on fractures registered in a sustainable way may provide invaluable tools for quality improvements in health care and research. Description Ten years after its implementation, the Swedish Fracture Register has 100% coverage among orthopaedic and trauma departments in Sweden. The completeness of registrations reached in 2020 69-96% for hip fractures at the different departments, with the majority reporting a completeness above 85%. The Swedish Fracture Register is a fully web-based national quality register created and run by orthopaedic professionals, with financial support from public healthcare providers and the government. All users have full access to both the registration platform and all aggregated statistics in real time. The web-based platform was created for use in health quality registers and it has easily gained acceptance among users. The register has gradually developed by the addition of more fracture types and skeletal parts. Research activity is high and 31 scientific publications have been published since 2016. The strategy from the start was to publish validation data and basic epidemiological data. However, over the past few years, publications on outcomes, such as re-operations and mortality, have been published and four register-based, randomised, controlled trials are ongoing. Conclusion It is possible to create a fracture register, to gain professional acceptance and to collect fracture data in a sustainable way on a national level if the platform is easy to use. Such a platform can also be used as a randomisation platform for prospective studies.
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| 6. |
- Puthia, Manoj, et al.
(author)
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Antibacterial and Anti-Inflammatory Effects of Apolipoprotein E
- 2022
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In: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:6, s. 1430-1430
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Journal article (peer-reviewed)abstract
- Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We observed that APOE exhibits anti-bacterial activity against several Gram-negative bacterial strains of Pseudomonas aeruginosa and Escherichia coli. In addition, we showed that APOE exhibits a significant binding affinity for lipopolysaccharide (LPS) and lipid A as well as heparin. MD simulations identified the low-density lipoprotein receptor (LDLR) binding region in helix 4 of APOE as a primary binding site for these molecules via electrostatic interactions. Together, our data suggest that APOE may have an important role in controlling inflammation during Gram-negative bacterial infection.
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| 7. |
- Späth, Florentin, 1980-, et al.
(author)
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Intraindividual long-term immune marker stability in plasma samples collected in median 9.4 Years apart in 304 adult cancer-free individuals
- 2021
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In: Cancer Epidemiology, Biomarkers and Prevention. - Philadephia : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 30:11, s. 2052-2058
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Journal article (peer-reviewed)abstract
- Background: Changes in immune marker levels in the blood could be used to improve the early detection of tumor-associated inflammatory processes. To increase predictiveness and utility in cancer detection, intraindividual long-term stability in cancer-free individuals is critical for biomarker candidates as to facilitate the detection of deviation from the norm.Methods: We assessed intraindividual long-term stability for 19 immune markers (IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sVEGF-R2, sTNF-R1, sTNF-R2, sCD23, sCD27, and sCD30) in 304 cancer-free individuals. Repeated blood samples were collected up to 20 years apart. Intraindividual reproducibility was assessed by calculating intraclass correlation coefficients (ICC) using a linear mixed model.Results: ICCs indicated fair to good reproducibility (ICCs ≥ 0.40 and < 0.75) for 17 of 19 investigated immune markers, including IL10, IL13, TNFa, CXCL13, MCP-3, MIP-1a, MIP-1b, fractalkine, VEGF, FGF-2, TGFa, sIL2Ra, sIL6R, sTNF-R1, sTNF-R2, sCD27, and sCD30. Reproducibility was strong (ICC ≥ 0.75) for sCD23, while reproducibility was poor (ICC < 0.40) for sVEGF-R2. Using a more stringent criterion for reproducibility (ICC ≥ 0.55), we observed either acceptable or better reproducibility for IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30.Conclusions: IL10, IL13, CXCL13, MCP-3, MIP-1a, MIP-1b, VEGF, FGF-2, sTNF-R1, sCD23, sCD27, and sCD30 displayed ICCs consistent with intraindividual long-term stability in cancer-free individuals. Impact: Our data support using these markers in prospective longitudinal studies seeking early cancer detection biomarkers.
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| 8. |
- Vuori, Matti A., et al.
(author)
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Diabetes status-related differences in risk factors and mediators of heart failure in the general population : results from the MORGAM/BiomarCaRE consortium
- 2021
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In: Cardiovascular Diabetology. - : BioMed Central. - 1475-2840. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers.Methods: In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure.Results: Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49–2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59–2.69]; non-diabetes: HR 1.85 [1.68–2.02]), BMI (diabetes: HR 1.30 [1.18–1.42]; non-diabetes: HR 1.40 [1.35–1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55–2.75]; non-diabetes: HR 2.86 [2.50–3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82–2.80]; non-diabetes: HR 2.97 [2.21–4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19–1.34]; non-diabetes: HR 1.43 [1.39–1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04–1.16]; non-diabetes: HR 1.13 [1.10–1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03–1.24]; non-diabetes: HR 1.29 [1.25–1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9–52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3–16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7–17.4]), and hyperglycemia (glucose, 12.0% [4.2–19.9]).Conclusions: The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.
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| 9. |
- Wen, Qingfeng, et al.
(author)
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Lead-exposure associated miRNAs in humans and Alzheimer’s disease as potential biomarkers of the disease and disease processes
- 2022
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 12:1
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is a neurodegenerative disease that eventually affects memory and behavior. The identification of biomarkers based on risk factors for AD provides insight into the disease since the exact cause of AD remains unknown. Several studies have proposed microRNAs (miRNAs) in blood as potential biomarkers for AD. Exposure to heavy metals is a potential risk factor for onset and development of AD. Blood cells of subjects that are exposed to lead detected in the circulatory system, potentially reflect molecular responses to this exposure that are similar to the response of neurons. In this study we analyzed blood cell-derived miRNAs derived from a general population as proxies of potentially AD-related mechanisms triggered by lead exposure. Subsequently, we analyzed these mechanisms in the brain tissue of AD subjects and controls. A total of four miRNAs were identified as lead exposure-associated with hsa-miR-3651, hsa-miR-150-5p and hsa-miR-664b-3p being negatively and hsa-miR-627 positively associated. In human brain derived from AD and AD control subjects all four miRNAs were detected. Moreover, two miRNAs (miR-3651, miR-664b-3p) showed significant differential expression in AD brains versus controls, in accordance with the change direction of lead exposure. The miRNAs’ gene targets were validated for expression in the human brain and were found enriched in AD-relevant pathways such as axon guidance. Moreover, we identified several AD relevant transcription factors such as CREB1 associated with the identified miRNAs. These findings suggest that the identified miRNAs are involved in the development of AD and might be useful in the development of new, less invasive biomarkers for monitoring of novel therapies or of processes involved in AD development.
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| 10. |
- Wennergren, David, et al.
(author)
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Treatment and re-operation rates in one thousand and three hundred tibial fractures from the Swedish Fracture Register
- 2021
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In: European Journal of Orthopaedic Surgery and Traumatology. - : Springer Science and Business Media LLC. - 1633-8065 .- 1432-1068. ; 31:1, s. 143-154
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Journal article (peer-reviewed)abstract
- Purpose: Approximately, 50 persons per 100,000 per year sustain a tibial fracture. There is, however, a lack of large cohort studies that describe the treatment and re-operation frequencies of tibial fractures. The aim of this study was to describe the treatment and re-operation rates of tibial fractures in all segments of the tibia. Methods: Data related to all patients aged 16 and above treated for tibial fractures (ICD-10 S82.10-31) at Sahlgrenska University Hospital in 2011–2015 were extracted from the Swedish Fracture Register. To make sure all re-operations were included in the study, the operation planning system was checked for all patients included in the study. Results: The study comprised 1371 tibial fractures − 712 proximal, 417 diaphyseal and 242 distal tibial fractures. Among the proximal and distal tibial fractures, plate fixation was the most commonly used surgical method, whereas among tibial shaft fractures, an intramedullary nail was the most commonly used surgical method. Almost 30% (29.8%) of all surgically treated tibial fractures underwent re-operation. Among proximal tibial fractures, 24.0% underwent re-operation; tibial shaft fractures 37.0% and distal tibial fractures 26.8%. Re-operations due to infection were more or less equally common in all segments (3.9–5.4%). Conclusion: This study describes the treatment and re-operation rates after tibial fractures in a cohort of 1371 tibial fractures at Sahlgrenska University Hospital during a period of 5years. The study shows an overall re-operation rate of 29.8% for fractures in all segments of the tibia. © 2020, The Author(s).
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