| 1. |
- Munkvold, Bodil Karoline Ravn, et al.
(författare)
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Variations in the management of diffuse low-grade gliomas : A Scandinavian multicenter study
- 2021
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Ingår i: Neuro-Oncology Practice. - : Oxford University Press. - 2054-2577 .- 2054-2585. ; 8:6, s. 706-717
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Tidskriftsartikel (refereegranskat)abstract
- Background. Early extensive surgery is a cornerstone in treatment of diffuse low-grade gliomas (DLGGs), and an additional survival benefit has been demonstrated from early radiochemotherapy in selected "high-risk" patients. Still, there are a number of controversies related to DLGG management. The objective of this multicenter population-based cohort study was to explore potential variations in diagnostic work-up and treatment between treating centers in 2 Scandinavian countries with similar public health care systems.Methods. Patients screened for inclusion underwent primary surgery of a histopathologically verified diffuse WHO grade II glioma in the time period 2012 through 2017. Clinical and radiological data were collected from medical records and locally conducted research projects, whereupon differences between countries and inter-hospital variations were explored.Results. A total of 642 patients were included (male:female ratio 1:4), and annual age-standardized incidence rates were 0.9 and 0.8 per 100 000 in Norway and Sweden, respectively. Considerable inter-hospital variations were observed in preoperative work-up, tumor diagnostics, surgical strategies, techniques for intraoperative guidance, as well as choice and timing of adjuvant therapy.Conclusions. Despite geographical population-based case selection, similar health care organizations, and existing guidelines, there were considerable variations in DLGG management. While some can be attributed to differences in clinical implementation of current scientific knowledge, some of the observed inter-hospital variations reflect controversies related to diagnostics and treatment. Quantification of these disparities renders possible identification of treatment patterns associated with better or worse outcomes and may thus represent a step toward more uniform evidence-based care.
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| 2. |
- Stepien, M., et al.
(författare)
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Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study
- 2021
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 148:3, s. 609-625
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Tidskriftsartikel (refereegranskat)abstract
- Hepatocellular carcinoma (HCC) development entails changes in liver metabolism. Current knowledge on metabolic perturbations in HCC is derived mostly from case-control designs, with sparse information from prospective cohorts. Our objective was to apply comprehensive metabolite profiling to detect metabolites whose serum concentrations are associated with HCC development, using biological samples from within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (>520 000 participants), where we identified 129 HCC cases matched 1:1 to controls. We conducted high-resolution untargeted liquid chromatography-mass spectrometry-based metabolomics on serum samples collected at recruitment prior to cancer diagnosis. Multivariable conditional logistic regression was applied controlling for dietary habits, alcohol consumption, smoking, body size, hepatitis infection and liver dysfunction. Corrections for multiple comparisons were applied. Of 9206 molecular features detected, 220 discriminated HCC cases from controls. Detailed feature annotation revealed 92 metabolites associated with HCC risk, of which 14 were unambiguously identified using pure reference standards. Positive HCC-risk associations were observed forN1-acetylspermidine, isatin,p-hydroxyphenyllactic acid, tyrosine, sphingosine,l,l-cyclo(leucylprolyl), glycochenodeoxycholic acid, glycocholic acid and 7-methylguanine. Inverse risk associations were observed for retinol, dehydroepiandrosterone sulfate, glycerophosphocholine, gamma-carboxyethyl hydroxychroman and creatine. Discernible differences for these metabolites were observed between cases and controls up to 10 years prior to diagnosis. Our observations highlight the diversity of metabolic perturbations involved in HCC development and replicate previous observations (metabolism of bile acids, amino acids and phospholipids) made in Asian and Scandinavian populations. These findings emphasize the role of metabolic pathways associated with steroid metabolism and immunity and specific dietary and environmental exposures in HCC development.
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| 3. |
- Ohlsson, Bodil, et al.
(författare)
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Patients with irritable bowel syndrome and dysmotility express antibodies against gonadotropin-releasing hormone in serum.
- 2011
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925. ; 23, s. 459-1000
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Tidskriftsartikel (refereegranskat)abstract
- Background The etiology of irritable bowel syndrome (IBS) and dysmotility is in most cases unknown. Organic, pathognomonic changes have not been described. We have previously demonstrated sporadic expressions of antibodies against gonadotropin-releasing hormone (GnRH) in serum from these patients. The aim of this study was to screen for the presence of GnRH antibodies in healthy subjects and patients with gastrointestinal (GI) diseases. Methods Consecutive patients suffering from either IBS, idiopathic dysmotility, GI complaints secondary to diabetes mellitus, celiac disease or inflammatory bowel disease (IBD) were included. Healthy blood donors served as controls. Blood samples were taken for analyzing IgM and IgG antibodies against GnRH using an ELISA method. Medical records were scrutinized with respect to duration of symptoms, co-existing diseases, drug treatments, hereditary factors, and laboratory analyses. Key Results Healthy controls expressed low levels of GnRH IgM antibodies in a prevalence of 23%. The prevalence of GnRH IgM antibodies in IBS and dysmotility patients was 42% (P = 0.008), and the levels were higher (P = 0.000). Patients with diabetes mellitus expressed GnRH IgM antibodies in the same prevalence as controls (25%), but in higher levels (P = 0.02). Patients with celiac disease or IBD had the same or lower levels of antibodies. There were no associations between antibodies, other co-existing diseases or laboratory analyses. Conclusions & Inferences Higher levels of GnRH IgM antibodies were detected in patients with IBS and dysmotility, but not organic GI diseases, compared with healthy controls. These findings suggest that IBS and dysmotility to some extent may be of an autoimmune origin.
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| 4. |
- Fedirko, Veronika, et al.
(författare)
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Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma : a nested case-control study
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 72:15
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking.METHODS: We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression.RESULTS: = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses.CONCLUSIONS: These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
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| 5. |
- Wallerstedt, Sven, 1944, et al.
(författare)
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Moderate hyperkalemia in hospitalized patients with cirrhotic ascites indicates a poor prognosis
- 2013
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 48:3, s. 358-365
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Development of ascites in patients with liver cirrhosis is an ominous sign with a poor outcome. A liver transplantation must be considered, and it then becomes important to know if there are any factors indicating a worsened prognosis. Material and methods. We used official registers for a follow-up study of at least 5 years considering the prognosis of 155 prospectively recruited in-patients with cirrhotic ascites from medical units at nine Swedish university hospitals. All patients had undergone at least one diagnostic ascites tap, and had initially been questioned about background factors and physically examined according to a standardized case record form, followed by sampling of blood, urine, and ascites. Results. Death occurred within 1 year after inclusion in 53% of the cases, and was primarily liver-related in 70%. In a multivariable analysis, the two ordinary variables that showed the strongest correlation with risk of death were serum potassium and abdominal tenderness. All 22 patients with a serum potassium concentration of at least 4.8 mmol/L (maximum 5.8 mmol/L) died within 1 year after inclusion. Potassium concentration was related to renal function and potassium-saving drugs. Conclusion. This follow-up study of a prospectively recruited cohort of in-patients with cirrhotic ascites confirms their poor prognosis. Awareness of an elevated serum potassium value, which would reflect a threatened renal function, seems essential, because it may offer a simple way to identify cases with the worst prognosis. An area for further research should be to explore the significance of including serum potassium in prognostic models.
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| 6. |
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| 7. |
- Bohm-Starke, Nina, et al.
(författare)
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Treatment of provoked vulvodynia : A systematic review
- 2022
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Ingår i: Journal of Sexual Medicine. - : Elsevier. - 1743-6095 .- 1743-6109. ; 19:5, s. 789-808
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Forskningsöversikt (refereegranskat)abstract
- Background: Treatment recommendations for provoked vulvodynia (PVD) are based on clinical experiences and there is a need for systematically summarizing the controlled trials in this field.Aim: To provide an overview of randomized controlled trials and non-randomized studies of intervention for PVD, and to assess the certainty of the scientific evidence, in order to advance treatment guidelines.Data Sources: The search was conducted in CINAHL (EBSCO), Cochrane Library, Embase (Embase.com), Ovid MEDLINE, PsycINFO (EBSCO) and Scopus. Databases were searched from January 1, 1990 to January 29, 2021.Study Eligibility Criteria: Population: Premenopausal women with PVD. Interventions: Pharmacological, surgical, psychosocial and physiotherapy, either alone or as combined/team-based interventions. Control: No treatment, waiting-list, placebo or other defined treatment. Outcomes: Pain during intercourse, pain upon pressure or touch of the vaginal opening, sexual function/satisfaction, quality of life, psychological distress, adverse events and complications. Study design: Randomized controlled trials and non-randomized studies of interventions with a control group.Study Appraisal and Synthesis Methods: 2 reviewers independently screened citations for eligibility and assessed relevant studies for risk of bias using established tools. The results from each intervention were summarized. Studies were synthesized using a narrative approach, as meta-analyses were not considered appropriate. For each outcome, we assessed the certainty of evidence using grading of recommendations assessment, development, and evaluation (GRADE).Results: Most results of the evaluated studies in this systematic review were found to have very low certainty of evidence, which means that we are unable to draw any conclusions about effects of the interventions. Multimodal physiotherapy compared with lidocaine treatment was the only intervention with some evidential support (low certainty of evidence for significant treatment effects favoring physiotherapy). It was not possible to perform meta-analyses due to a heterogeneity in interventions and comparisons. In addition, there was a heterogeneity in outcome measures, which underlines the need to establish joint core outcome sets.Clinical Implications: Our result underscores the need of stringent trials and defined core outcome sets for PVD.Strength and Limitations: Standard procedures for systematic reviews and the Population Intervention Comparison Outcome model for clinical questions were used. The strict eligibility criteria resulted in limited number of studies which might have resulted in a loss of important information.Conclusion: This systematic review underlines the need for more methodologically stringent trials on interventions for PVD, particularly for multimodal treatments approaches. For future research, there is a demand for joint core outcome sets.
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| 8. |
- Carlsson, Annelie, et al.
(författare)
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Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome
- 1998
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 101:2, s. 5-272
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study was undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome.MATERIAL AND METHODS: Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be either AGA- or EMA-positive were investigated further with intestinal biopsy.RESULTS: None of the 43 patients had known celiac disease at entry into the study; 37% (16/43) were found to have AGA levels above normal, and 16% (7/43) to be EMA-positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy. Villous atrophy was present in all 7 of the EMA-positive patients, whereas the villi were normal in 7 of the 13 AGA-positive patients who underwent biopsy.CONCLUSIONS: EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome.
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| 9. |
- Duarte-Salles, Talita, et al.
(författare)
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Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
- 2016
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Ingår i: Cancer Prevention Research. - 1940-6207 .- 1940-6215. ; 9:9, s. 758-765
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Tidskriftsartikel (refereegranskat)abstract
- We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis.
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| 10. |
- Duarte-Salles, Talita, et al.
(författare)
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Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort
- 2015
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:11, s. 2715-2728
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Tidskriftsartikel (refereegranskat)abstract
- The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.
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