| 1. |
- Simán, Henrik, et al.
(författare)
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Association between Helicobacter pylori and gastric carcinoma in the city of Malmo, Sweden. A prospective study
- 1997
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 32:12, s. 1215-1221
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We have investigated the association between Helicobacter pylori and gastric carcinoma through a nested case-control study in a single city. METHODS: From a cohort of 32,906 residents recruited from 1974 through 1992, 56 cases of gastric adenocarcinoma and 224 matched controls were selected. The mean interval between serum collection and diagnosis was 5.7 years. Frozen serum or plasma samples were analysed for IgG antibodies against H. pylori with an enzyme-linked immunosorbent assay. RESULTS: The overall seropositivity prevalence in gastric cancer cases was 82%, compared with 49% in controls, giving an odds ratio (OR) of 5.0 (95% confidence interval (CI), 2.2-11.5). Partial gastrectomy because of peptic ulcer 5 to 36 year before diagnosis of gastric cancer could be a confounding factor. With exclusion of 10 such cases, H. pylori seropositivity among cases was 78%, as compared with 50% in matched controls (OR, 3.9; 95% CI, 1.7-9.2). Tumours of the cardia were not associated with H. pylori (OR, 0.92; 95% CI, 0.23-3.7), which is in contrast to tumours of the fundus, corpus, and antrum, which were significantly associated (OR, 11.1; 95% CI, 2.4-71.8). This difference in location was significant (P < 0.01). CONCLUSION: There is a significant association between prior infection with H. pylori and later development of gastric carcinoma, and the association is related to noncardia gastric cancer.
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| 2. |
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| 3. |
- Simán, Henrik, et al.
(författare)
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Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma.
- 2007
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 42:8, s. 933-940
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Helicobacter pylori infection is an established risk factor for non-cardia gastric adenocarcinoma. Infection with H. pylori strains harbouring the cagA pathology island may augment this association. H. pylori infection may at the same time reduce the risk for oesophageal carcinoma. However, prospective data on the association between CagA seropositivity and gastric or oesophageal carcinomas are limited. The purpose of this study was to investigate whether CagA seropositivity among H. pylori seropositive subjects is associated with gastric or oesophageal carcinomas. Material and methods. A nested case-control study was performed in the Malmo Preventive Medicine cohort consisting of 32,906 middle-aged subjects. Tumour cases were identified by the Swedish National Cancer Registry. The Western blot method Helicoblot 2.1 was used to detect H. pylori and CagA seropositivity. Results. Non-cardia gastric adenocarcinoma was associated with H. pylori seropositivity, odds ratio 17.8 (95% CI: 4.2 - 74.8; 67 cases). The odds ratio for CagA seropositivity among H. pylori seropositive subjects was 9.7 ( 95% CI: 1.5 - infinity). No significant associations were found between cardia gastric adenocarcinoma and H. pylori or CagA seropositivity among H. pylori seropositive subjects; odds ratios were 1.5 ( 95% CI: 0.51 - 4.8) and 2.7 ( 95% CI: 0.38 - infinity), respectively ( 24 cases). Oesophageal adenocarcinoma and oesophageal squamous cell carcinoma were not significantly associated with H. pylori seropositivity or with CagA seropositivity among H. pylori seropositive subjects; the odds ratios associated with oesophageal adenocarcinoma were 0.46 ( 95% CI: 0.07 - 2.6) and 0.38 ( 95% CI: 0.02 - 24), respectively. Corresponding odds ratios for oesophageal squamous cell carcinoma were 0.44 ( 95% CI: 0.15 - 1.2; 37 cases) and 2.0 ( 95% CI: 0.24 - infinity), respectively. Conclusions. CagA seropositivity among H. pylori seropositive subjects is a risk factor for non-cardia gastric adenocarcinoma.
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| 4. |
- Simán, Henrik, et al.
(författare)
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Helicobacter pylori infection is associated with a decreased risk of developing oesophageal neoplasms
- 2001
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Ingår i: Helicobacter. - : Wiley. - 1083-4389 .- 1523-5378. ; 6:4, s. 310-316
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Tidskriftsartikel (refereegranskat)abstract
- Background. The role of Helicobacter pylori infection in the development of oesophageal malignancies was investigated through a multivariate conditional logistic regression analysis in a nested case-control study. Methods. Blood samples and a questionnaire on smoking and alcohol habits were collected from a cohort of 32,906 city residents during a health-screening programme between 1974 and 1992. Forty-four cases of oesophageal cancer and 149 matched controls were selected. The mean interval between screening and cancer diagnosis was 11.9 years. H. pylori seropositivity was determined by an enzyme-linked immunosorbant assay measuring IgG. Occupation was included in the statistical analysis as an indicator of socio-economic status. Results. Helicobacter pylori seropositivity was present in 10 of the cases (22.7%) and 67 of the controls (45.0%). In a multivariate model, vith adjustment for occupation, tobacco and alcohol consumption, the odds ratio for developing in oesophageal malignancy when infected with H. pylori was 0.29 (95% confidence interval (CI): 0.12-0.67). Current smokers had an odds ratio of 17.3 (95% Cl: 3.0-99.4) and the odds ratio for ex-smokers was 5.9 (95% CI: 1.15-29.9). High alcohol consumption was no longer significantly, associated with oesophageal neoplasms after tobacco smoking was included into the model, odds ratio 1.22 (95% CI: 0.46-3.2). The protective effect of H. pylori was more pronounced for oesophageal adenocarcinoma (seven cases, odds ratio 0.16, 95% Cl: 0.00-1.06) than for squamous-cell carcinoma (29 cases, odds ratio 0.41, 95% Cl: 0.14-1.2). Conclusions. Helicobacter pylori infection is associated with a decreased risk of developing an oesophageal malignancy. Current smokers and ex-smokers have instead a definite increased risk of oesophageal neoplasms.
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| 5. |
- Simán, Henrik, et al.
(författare)
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Tobacco smoking increases the risk for gastric adenocarcinoma among Helicobacter pylori-infected individuals
- 2001
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Ingår i: Scandinavian Journal of Gastroenterology. - 1502-7708. ; 36:2, s. 208-213
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The importance of tobacco smoking and Helicobacter pylori infection as risk factors in the development of gastric carcinoma was investigated through multivariate conditional logistic regression analysis in a nested case-control study. METHODS: Blood samples and a questionnaire on smoking habits were collected from a cohort of 32,906 city residents during a health screening programme from 1974 to 1992. Fifty-six cases of gastric cancer and 224 matched controls were selected. The mean interval between screening and cancer diagnosis was 5.7 years. H. pylori infection was determined by IgG-serology. Occupation categorized into blue-collar workers, white-collar workers, self-employed and unknown occupation was included in the statistical analysis as an indicator of socio-economic status. RESULTS: The proportion of current smokers was 61% among gastric cancer cases, versus 41% among controls. H. pylori seropositivity was present in 82% of the cases and 49% of the controls. In a multivariate model current smokers had an odds ratio (OR) of 2.2 (95% confidence interval (CI): 1.2-4.2). With different levels of tobacco consumption, smoking less than 20 g tobacco each day gave the OR of 2.1 (95% CI: 0.98-4.4), and the OR when smoking more than 20 g tobacco per day was 2.5 (95% CI: 1.1-5.6). The OR of H. pylori infection was 5.0 (95% CI: 2.2-11.2). Among H. pylori-seropositive citizens, current smoking was associated with an increased risk of 2.3 (95% CI: 1.1-4.7) compared with non-smoking H. pylori-positive persons. CONCLUSIONS: Tobacco smoking and H. pylori are both risk factors in the development of gastric cancer, and tobacco smoking is still a risk factor among H. pylori-infected individuals. The risk of gastric cancer among H. pylori-infected current smokers is 11 times that of non-infected individuals not currently smoking.
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| 6. |
- Trupp, Miles, et al.
(författare)
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Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson's disease
- 2014
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Ingår i: Journal of Parkinson's Disease. - : Taylor & Francis. - 1877-7171 .- 1877-718X. ; 4:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a progressive, multi-focal neurodegenerative disease for which there is no effective disease modifying treatment. A critical requirement for designing successful clinical trials is the development of robust and reproducible biomarkers identifying PD in preclinical stages. Objective: To investigate the potential for a cluster of biomarkers visualized with multiple analytical platforms to provide a clinically useful tool. Methods: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics and immunoassay-based protein/peptide analyses on samples from patients with PD diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients at the time of diagnosis (baseline) were analyzed. Results: In plasma, we found a significant increase in several amino acids and a decrease in C16-C18 saturated and unsaturated fatty acids in patients as compared to control subjects. We also observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate (ketoleucine) that may be indicative of increased metabolic stress in patients. In CSF, there was a generally lower level of metabolites in PD as compared to controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and creatinine. Multivariate analysis and modeling of metabolites indicates that while the PD samples can be separated from control samples, the list of detected compounds will need to be expanded in order to define a robust predictive model. CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a significant decrease in the levels of A beta-38 and A beta-42, and an increase in soluble APP alpha in CSF of patients. Furthermore, these peptides showed significant correlations to each other, and positive correlations to the CSF levels of several 5- and 6-carbon sugars. However, combining these metabolites and proteins/peptides into a single model did not significantly improve the statistical analysis. Conclusions: Together, this metabolomics study has detected significant alterations in plasma and CSF levels of a cluster of amino acids, fatty acids and sugars based on clinical diagnosis and levels of known protein and peptide biomarkers.
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| 7. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 8. |
- Brännvall, Rickard, 1975-, et al.
(författare)
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HEIDA : Software Examples for Rapid Introduction of Homomorphic Encryption for Privacy Preservation of Health Data
- 2023
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Ingår i: Studies in health technology and informatics. - : IOS Press. ; 302, s. 267-271
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Tidskriftsartikel (refereegranskat)abstract
- Adequate privacy protection is crucial for implementing modern AI algorithms in medicine. With Fully Homomorphic Encryption (FHE), a party without access to the secret key can perform calculations and advanced analytics on encrypted data without taking part of either the input data or the results. FHE can therefore work as an enabler for situations where computations are carried out by parties that are denied plain text access to sensitive data. It is a scenario often found with digital services that process personal health-related data or medical data originating from a healthcare provider, for example, when the service is delivered by a third-party service provider located in the cloud. There are practical challenges to be aware of when working with FHE. The current work aims to improve accessibility and reduce barriers to entry by providing code examples and recommendations to aid developers working with health data in developing FHE-based applications. HEIDA is available on the GitHub repository: https://github.com/rickardbrannvall/HEIDA.
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| 9. |
- Brännvall, Rickard, 1975-, et al.
(författare)
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Homomorphic encryption enables private data sharing for digital health : Winning entry to the Vinnova innovation competition Vinter 2021-22
- 2022
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Ingår i: 34th Workshop of the Swedish Artificial Intelligence Society, SAIS 2022. - : Institute of Electrical and Electronics Engineers Inc.. - 9781665471268
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Konferensbidrag (refereegranskat)abstract
- People living with type 1 diabetes often use several apps and devices that help them collect and analyse data for a better monitoring and management of their disease. When such health related data is analysed in the cloud, one must always carefully consider privacy protection and adhere to laws regulating the use of personal data. In this paper we present our experience at the pilot Vinter competition 2021-22 organised by Vinnova. The competition focused on digital services that handle sensitive diabetes related data. The architecture that we proposed for the competition is discussed in the context of a hypothetical cloud-based service that calculates diabetes self-care metrics under strong privacy preservation. It is based on Fully Homomorphic Encryption (FHE)-a technology that makes computation on encrypted data possible. Our solution promotes safe key management and data life-cycle control. Our benchmarking experiment demonstrates execution times that scale well for the implementation of personalised health services. We argue that this technology has great potentials for AI-based health applications and opens up new markets for third-party providers of such services, and will ultimately promote patient health and a trustworthy digital society.
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| 10. |
- Bäckström, David C, et al.
(författare)
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Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease
- 2015
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Ingår i: JAMA Neurology. - : American Medical Association. - 2168-6149 .- 2168-6157. ; 72:10, s. 1175-1182
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Alterations in cerebrospinal fluid (CSF) have been found in Parkinson disease (PD) and in PD dementia (PDD), but the prognostic importance of such changes is not well known. In vivo biomarkers for disease processes in PD are important for future development of disease-modifying therapies. OBJECTIVE: To assess the diagnostic and prognostic value of a panel of CSF biomarkers in patients with early PD and related disorders. DESIGN, SETTING, AND PARTICIPANTS: Regional population-based, prospective cohort study of idiopathic parkinsonism that included patients diagnosed between January 1, 2004, and April 30, 2009, by amovement disorder team at a university hospital that represented the only neurology clinic in the region. Participants were 128 nondemented patients with new-onset parkinsonism (104 with PD, 11 with multiple system atrophy, and 13 with progressive supranuclear palsy) who were followed up for 5 to 9 years. At baseline, CSF from 30 healthy control participants was obtained for comparison. MAIN OUTCOMES AND MEASURES: Cerebrospinal fluid concentrations of neurofilament light chain protein, Aβ1-42, total tau, phosphorylated tau, α-synuclein, and heart fatty acid-binding protein were quantified by 2 blinded measurements (at baseline and after 1 year). Follow-up included an extensive neuropsychological assessment. As PD outcome variables, mild cognitive impairment and incident PDD were diagnosed based on published criteria. RESULTS: Among the 128 study participants, the 104 patients with early PD had a different CSF pattern compared with the 13 patients with progressive supranuclear palsy (baseline area under the receiver operating characteristic curve, 0.87; P < .0001) and the 30 control participants (baseline area under the receiver operating characteristic curve, 0.69; P = .0021). A CSF biomarker pattern associated with the development of PDD was observed. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein at baseline were related to future PDD as analyzed by Cox proportional hazards regression models. Combined, these early biomarkers predicted PDD with high accuracy (hazard ratio, 11.8; 95% CI, 3.3-42.1; P = .0001) after adjusting for possible confounders. CONCLUSIONS AND RELEVANCE: The analyzed CSF biomarkers have potential usefulness as a diagnostic tool in patients with parkinsonism. In PD, high neurofilament light chain protein, low Aβ1-42, and high heart fatty acid-binding protein were related to future PDD, providing new insights into the etiology of PDD.
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