| 1. |
- Bruce, Michael G, et al.
(författare)
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International Circumpolar Surveillance System for invasive pneumococcal disease, 1999-2005
- 2008
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Ingår i: Emerging Infectious Diseases. - Atlanta, GA : National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 14:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- The International Circumpolar Surveillance System is a population-based surveillance network for invasive bacterial disease in the Arctic. The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced for routine infant vaccination in Alaska (2001), northern Canada (2002-2006), and Norway (2006). Data for invasive pneumococcal disease (IPD) were analyzed to identify clinical findings, disease rates, serotype distribution, and antimicrobial drug susceptibility; 11,244 IPD cases were reported. Pneumonia and bacteremia were common clinical findings. Rates of IPD among indigenous persons in Alaska and northern Canada were 43 and 38 cases per 100,000 population, respectively. Rates in children <2 years of age ranged from 21 to 153 cases per 100,000 population. In Alaska and northern Canada, IPD rates in children <2 years of age caused by PCV7 serotypes decreased by >80% after routine vaccination. IPD rates are high among indigenous persons and children in Arctic countries. After vaccine introduction, IPD caused by non-PCV7 serotypes increased in Alaska.
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| 2. |
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| 3. |
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| 4. |
- Plymoth, Martin, et al.
(författare)
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Targeting tularemia : clinical, laboratory, and treatment outcomes from an 11-year retrospective observational cohort in northern sweden
- 2024
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 78:5, s. 1222-1231
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tularemia is an important re-emerging disease with a multimodal transmission-pattern. Treatment outcomes of current recommended antibiotic regimens (including ciprofloxacin and doxycycline) remain unclear. In this retrospective cohort study, we report clinical, laboratory, geographical, and treatment outcomes of laboratory-confirmed tularemia cases over an 11-year period in Northern Sweden.Methods: Data from reported tularemia cases (aged >10 years at time of study) in Norrbotten county between 2011-2021 were collected through review of electronic medical records and participant questionnaires; with 415 out of 784 accepting participation (52.9%). Of these, 327 were laboratory-confirmed cases (serology and/or PCR). A multivariable logistic regression model was used to investigate variables associated with re-treatment.Results: Median age of participants was 54 years (IQR 41.5-65) and 49.2% were female. While ulceroglandular tularemia was the predominant form (n=215, 65.7%), there were several cases of pulmonary tularemia (n=40; 12.2%). Inflammatory markers were largely non-specific, with monocytosis frequently observed (n=36/75; 48%). Tularemia was often misdiagnosed upon presentation (n=158, 48.3%), with 65 (19.9%) receiving initial inappropriate antibiotics, and 102 (31.2%) re-treated. Persistent lymphadenopathy was infrequent (n=22, 6.7%), with 10 undergoing surgical interventions. In multivariable analysis of variables associated with re-treatment, we highlight differences in time until receiving appropriate antibiotics (8 [IQR 3.25-20.75] vs. 7 [IQR 4-11.25] days; adjusted p=0.076), and doxycycline-based treatment regimen (vs. ciprofloxacin; adjusted p=0.084), although not significant after correction for multiple comparisons.Conclusion: We comprehensively summarize clinical, laboratory, and treatment outcomes of type B tularemia. Targeting tularemia requires clinical awareness, early diagnosis and timely commencement of treatment for an appropriate duration.
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| 5. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
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Genomic Characterization of the Barnacle Balanus improvisus Reveals Extreme Nucleotide Diversity in Coding Regions
- 2021
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Ingår i: Marine Biotechnology. - : Springer Science and Business Media LLC. - 1436-2228 .- 1436-2236. ; 23, s. 402-416
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Tidskriftsartikel (refereegranskat)abstract
- Barnacles are key marine crustaceans in several habitats, and they constitute a common practical problem by causing biofouling on man-made marine constructions and ships. Despite causing considerable ecological and economic impacts, there is a surprising void of basic genomic knowledge, and a barnacle reference genome is lacking. We here set out to characterize the genome of the baybarnacle Balanus improvisus (= Amphibalanus improvisus) based on short-read whole-genome sequencing and experimental genome size estimation. We show both experimentally (DNA staining and flow cytometry) and computationally (k-mer analysis) that B. improvisus has a haploid genome size of ~ 740 Mbp. A pilot genome assembly rendered a total assembly size of ~ 600 Mbp and was highly fragmented with an N50 of only 2.2 kbp. Further assembly-based and assembly-free analyses revealed that the very limited assembly contiguity is due to the B. improvisus genome having an extremely high nucleotide diversity (π) in coding regions (average π ≈ 5% and average π in fourfold degenerate sites ≈ 20%), and an overall high repeat content (at least 40%). We also report on high variation in the α-octopamine receptor OctA (average π = 3.6%), which might increase the risk that barnacle populations evolve resistance toward antifouling agents. The genomic features described here can help in planning for a future high-quality reference genome, which is urgently needed to properly explore and understand proteins of interest in barnacle biology and marine biotechnology and for developing better antifouling strategies. © 2021, The Author(s).
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| 6. |
- Almlöf, Jonas Carlsson, et al.
(författare)
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Whole-genome sequencing identifies complex contributions to genetic risk by variants in genes causing monogenic systemic lupus erythematosus
- 2019
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Ingår i: Human Genetics. - : SPRINGER. - 0340-6717 .- 1432-1203. ; 138:2, s. 141-150
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Tidskriftsartikel (refereegranskat)abstract
- Systemic lupus erythematosus (SLE, OMIM 152700) is a systemic autoimmune disease with a complex etiology. The mode of inheritance of the genetic risk beyond familial SLE cases is currently unknown. Additionally, the contribution of heterozygous variants in genes known to cause monogenic SLE is not fully understood. Whole-genome sequencing of DNA samples from 71 Swedish patients with SLE and their healthy biological parents was performed to investigate the general genetic risk of SLE using known SLE GWAS risk loci identified using the ImmunoChip, variants in genes associated to monogenic SLE, and the mode of inheritance of SLE risk alleles in these families. A random forest model for predicting genetic risk for SLE showed that the SLE risk variants were mainly inherited from one of the parents. In the 71 patients, we detected a significant enrichment of ultra-rare (0.1%) missense and nonsense mutations in 22 genes known to cause monogenic forms of SLE. We identified one previously reported homozygous nonsense mutation in the C1QC (Complement C1q C Chain) gene, which explains the immunodeficiency and severe SLE phenotype of that patient. We also identified seven ultra-rare, coding heterozygous variants in five genes (C1S, DNASE1L3, DNASE1, IFIH1, and RNASEH2A) involved in monogenic SLE. Our findings indicate a complex contribution to the overall genetic risk of SLE by rare variants in genes associated with monogenic forms of SLE. The rare variants were inherited from the other parent than the one who passed on the more common risk variants leading to an increased genetic burden for SLE in the child. Higher frequency SLE risk variants are mostly passed from one of the parents to the offspring affected with SLE. In contrast, the other parent, in seven cases, contributed heterozygous rare variants in genes associated with monogenic forms of SLE, suggesting a larger impact of rare variants in SLE than hitherto reported.
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| 7. |
- Carlsson Almlöf, Jonas, et al.
(författare)
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Contributions of de novo variants to systemic lupus erythematosus
- 2021
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Ingår i: European Journal of Human Genetics. - : Springer Nature. - 1018-4813 .- 1476-5438. ; 29:1, s. 184-193
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Tidskriftsartikel (refereegranskat)abstract
- By performing whole-genome sequencing in a Swedish cohort of 71 parent-offspring trios, in which the child in each family is affected by systemic lupus erythematosus (SLE, OMIM 152700), we investigated the contribution of de novo variants to risk of SLE. We found de novo single nucleotide variants (SNVs) to be significantly enriched in gene promoters in SLE patients compared with healthy controls at a level corresponding to 26 de novo promoter SNVs more in each patient than expected. We identified 12 de novo SNVs in promoter regions of genes that have been previously implicated in SLE, or that have functions that could be of relevance to SLE. Furthermore, we detected three missense de novo SNVs, five de novo insertion-deletions, and three de novo structural variants with potential to affect the expression of genes that are relevant for SLE. Based on enrichment analysis, disease-affecting de novo SNVs are expected to occur in one-third of SLE patients. This study shows that de novo variants in promoters commonly contribute to the genetic risk of SLE. The fact that de novo SNVs in SLE were enriched to promoter regions highlights the importance of using whole-genome sequencing for identification of de novo variants.
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| 8. |
- Förnegård, Per
(författare)
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Le Miroir historial de Jean de Noyal : Livre X : édition du ms. Paris, BnF, fr. 10138 avec introduction, notes et index
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In the 1380s, Jean de Noyal, Abbot of the Benedictine monastery of Saint Vincent in Laon between 1367 and 1396, authored his universal history, the Miroir Historial. The mirror, which described the history of the world from the creation until the year 1380, originally comprised 12 books, presumably organized into three volumes. However, only the three final books, X, XI and XII, have been preserved for posterity and are to be found in a sole manuscript: Paris, BnF, fr. 10138. Until today, only short excerpts of Jean de Noyal’s history have been published. In all cases, except one, these excerpts have been taken from books XI and XII. This thesis provides a critical edition of book X, the longest of the three, which comprises the initial 101 folio pages of the manuscript’s total 191. The edited text is preceded by an introduction, followed by a complete index verborum including all of the words found in the text, as well as a complete index nominum.Book X describes the period from 1223 to 1328. Its contents cover the history of Western Europe and the north and eastern Mediterranean fairly well. Although France and its kings maintain a privileged position in the book, the Holy Roman Empire, the Holy See and the Iberian Peninsula are devoted considerable space. The geography of the Near East, the Muslim rulers and the Mongols are also described in brief. The mirror also has a local perspective – in part, Jean de Noyal provides a rather detailed account of Philip the Fair’s Flemish campaign, which took place not far from the place in which the history was authored and, in part the Abbot’s predecessors at Saint Vincent are presented, albeit laconically.Like other universal histories of the same period, the Abbot’s mirror is a compilation. The original passages in book X are particularly few and quite brief. Apart from a few passages dealing with the history of Laon, the original material in the mirror is generally limited to explanatory sub-clauses. The remaining material is entirely comprised of borrowings from other French texts or of translations from Latin works. Eight sources have been used for book X. The work from which the largest amount of text has been borrowed is the Chronique amplifiée des rois de France by Guillaume de Nangis, and no less than three quarters of book X have been borrowed from this source. Other sources used are Martin of Troppau’s and Bernard Gui’s chronicles of popes and emperors and the Chronique normande du XIVe siècle. The remaining four sources are probably secondary and have quite likely been taken from another compilation, possibly Vincent of Beauvais’ Speculum historiale. The third chapter of the introduction includes a presentation of the eight sources for book X that it has been possible to identify. Finally, this work gives a tabular account of the book’s sources excerpt by excerpt.Jean de Noyal’s narrative style is thematic rather than chronological – events are retold only partly in chronological order. Furthermore, the Abbot sometimes gives two or three different versions of the same event. The fact that these repetitions are, without doubt, a deliberate method of compilation is proven by the references inserted by the Abbot in these instances. This method provides the reader with several interpretations of the same event.Linguistically, the mirror is very heterogeneous – the parts that have been borrowed from Guillaume de Nangis differ considerably from those taken from the Chronique normande. There are lexical differences and morphosyntactic differences – including the use of the two-case system, which is highly sporadic in the former but entirely consistent in the latter. The remaining parts of book X, which Jean de Noyal probably translated from Latin himself, form a third group, which, in turn, contrast with the parts borrowed from the two French sources.
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| 9. |
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| 10. |
- Kåberg, Martin, et al.
(författare)
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High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder
- 2020
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Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:5, s. 574-580
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.
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| 11. |
- Mårtensson, Johan, et al.
(författare)
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Structural changes on mri demonstrate specific cerebellar involvement in sle patients—a vbm study
- 2021
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to investigate possible differences in brain structure, as measured by T1-weighted MRI, between patients with systemic lupus erythematosus (SLE) and healthy controls (HC), and whether any observed differences were in turn more severe in SLE patients with neuropsychiatric manifestations (NPSLE) than those without (non-NPSLE). Structural T1weighted MRI was performed on 69 female SLE patients (mean age = 35.8 years, range = 18–51 years) and 24 age-matched female HC (mean age = 36.8 years, range = 23–52 years) in conjunction with neuropsychological assessment using the CNS Vital Signs test battery. T1-weighted images were preprocessed and analyzed by FSL-VBM. The results show that SLE patients had lower grey matter probability values than the control group in the VIIIa of the cerebellum bilaterally, a region that has previously been implied in sensorimotor processing in human and non-human primates. No structural differences for this region were found between NPSLE and non-NPSLE patients. VBM values from the VIIIa region showed a weak positive correlation with the psychomotor speed domain from CNS Vital Signs (p = 0.05, r = 0.21), which is in line with its presumed role as a sensorimotor processing area.
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| 12. |
- Nystedt, Jessika, et al.
(författare)
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Altered white matter microstructure in lupus patients : A diffusion tensor imaging study
- 2018
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Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms. Methods: Structural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2-52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3-51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE). Results: Comparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p=0.038), the mid-sagittal corpus callosum (CC) (p=0.050), and the forceps minor of the CC (p=0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p=0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p<0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report. Conclusions: We found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.
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| 13. |
- Nystedt, Jessika, et al.
(författare)
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Functional Connectivity Changes in Systemic Lupus Erythematosus : A Resting-State Study
- 2018
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Ingår i: Brain Connectivity. - : Mary Ann Liebert Inc. - 2158-0014 .- 2158-0022. ; 8:4, s. 220-234
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Tidskriftsartikel (refereegranskat)abstract
- To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.
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| 14. |
- Sayyab, Shumaila, et al.
(författare)
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Mutational patterns and clonal evolution from diagnosis to relapse in pediatric acute lymphoblastic leukemia
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The mechanisms driving clonal heterogeneity and evolution in relapsed pediatric acute lymphoblastic leukemia (ALL) are not fully understood. We performed whole genome sequencing of samples collected at diagnosis, relapse(s) and remission from 29 Nordic patients. Somatic point mutations and large-scale structural variants were called using individually matched remission samples as controls, and allelic expression of the mutations was assessed in ALL cells using RNA-sequencing. We observed an increased burden of somatic mutations at relapse, compared to diagnosis, and at second relapse compared to first relapse. In addition to 29 known ALL driver genes, of which nine genes carried recurrent protein-coding mutations in our sample set, we identified putative non-protein coding mutations in regulatory regions of seven additional genes that have not previously been described in ALL. Cluster analysis of hundreds of somatic mutations per sample revealed three distinct evolutionary trajectories during ALL progression from diagnosis to relapse. The evolutionary trajectories provide insight into the mutational mechanisms leading relapse in ALL and could offer biomarkers for improved risk prediction in individual patients.
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| 15. |
- Söderholm, Jonas, et al.
(författare)
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ELEVATED RISK FOR LIVER RELATED MORTALITY IN CHRONIC HEPATITIS C PATIENTS BOTH WITH OR WITHOUT ILLICIT SUBSTANCE USE DISORDER : A NATION-WIDE REGISTER STUDY
- 2019
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Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 70:Suppl. 1, s. 366A-366A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hepatitis C is a slowly progressive disease mainly transmitted in people who inject drugs . This cohort has a high mortality from drug related causes, such as overdoses or external causes. We investigated the relative risk for liver related death in chronic hepatitis C (CHC) patients with or without illicit substance use disorders (SUD) .Methods: Patients with CHC were identified using the Swedish National Patient Registry (contains all inpatient, day surgery, and outpatient non-primary care visits) according to the International Classification of Diseases-10 (ICD-10) code B18.2. The baseline observation was set to the first CHC visit from 2001, and person-time continued until death, emigration or December 31, 2013, whichever came first. Patients with ≥2 non-primary care visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have illicit SUD . The underlying cause of death was obtained from the Cause of Death Register . A six months lag-period between CHC diagnosis and death was introduced to reduce surveillance bias. Non-alcoholic liver disease was defined using ICD-10 codes K71–K77, B15–B19, B94.2, R17-R18, I85 .0, I98 .2, and I98 .3 . The relative risk for death was determined using standardized mortality ratio (SMR) where the observed number of deaths was divided by the expected number of deaths taken from five comparators from the general population (matched for age/sex/place of residency) .Results: In total 38,186 patients with CHC were included in the study whereof 11,818 (31%) were considered to have illicit SUD . The CHC patients with SUD were younger (37 .7 vs . 46 .9 years) with a greater proportion of men (72% vs . 62%) than CHC patients without SUD . The SMRs for CHC patients with SUD were 10 .5, 33 .8, 18 .1, 123 .2, 61 .6, and 13 .2, for all-causes, liver cancer, alcoholic or non-alcoholic liver disease, drug-related, or external causes, respectively (Table 1) . The corresponding SMRs for CHC patients without SUD were 4 .1, 52 .8, 18 .0, 69 .4, 11 .2, and 4 .9, respectively (Table 1) .Conclusion: The relative risks for all investigated parameters were elevated for CHC patients whether they had illicit SUD or not . Furthermore, although the CHC patients with SUD had a high relative risk to die from both drug-related and external causes, the relative risk to die from non-alcoholic liver disease was also greatly elevated .
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| 16. |
- Zervides, Kristoffer A, et al.
(författare)
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Plasma and cerebrospinal fluid neurofilament light concentrations reflect neuronal damage in systemic lupus Erythematosus
- 2022
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Ingår i: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 22:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuronal damage in systemic lupus erythematosus (SLE) is common, but the extent and mechanisms are unclear. Neurofilament light (NfL) concentrations rise in plasma and cerebrospinal fluid (CSF) during neuronal damage in various neurological disorders. In this cross-sectional study, plasma and CSF concentrations of NfL were explored as a marker of neuronal damage in SLE.METHODS: Seventy-two consecutive SLE out-patients and 26 healthy controls, all female, aged < 55 years, underwent magnetic resonance imaging (MRI) and neurocognitive testing. NfL concentrations in plasma from all individuals and in CSF from 32 patients were measured with single-molecule array technology. Patients were assessed by a rheumatologist and neurologist to define neuropsychiatric involvement (NPSLE) according to three attribution models: SLICC A, SLICC B and ACR.RESULTS: Plasma and CSF NfL concentrations correlated strongly (r = 0.72, p < 0.001). Both NPSLE and non-NPSLE patients in all attribution models had higher plasma NfL concentrations compared with healthy controls (log-NfL, pg/ml, mean (SD); healthy controls (0.71 (0.17)); SLICC A model: NPSLE (0.87 (0.13), p = 0.003), non-NPSLE (0.83 (0.18), p = 0.005); SLICC B model: NPSLE (0.87 (0.14), p = 0.001), non-NPSLE (0.83 (0.18), p = 0.008); ACR model: NPSLE (0.86 (0.16), p < 0.001), non-NPSLE (0.81 (0.17), p = 0.044)). Plasma and CSF NfL concentrations did not differ between NPSLE and non-NPSLE patients. Higher plasma NfL concentrations correlated with larger CSF volumes on MRI (r = 0.34, p = 0.005), and was associated with poorer cognitive performance in the domains of simple attention, psychomotor speed and verbal memory. SLICC/ACR-Damage Index ≥1 was independently associated with higher plasma NfL concentrations (β = 0.074, p = 0.038). Higher plasma creatinine concentrations, anti-dsDNA-positivity, low complement C3 levels, or a history of renal involvement were associated with higher plasma NfL concentrations (β = 0.003, p = 0.009; β = 0.072, p = 0.031; β = 0.077, p = 0.027; β = 0.069, p = 0.047, respectively).CONCLUSIONS: Higher plasma NfL concentrations in NPSLE and non-NPSLE patients may indicate a higher degree of neuronal damage in SLE in general, corresponding to cognitive impairment and organ damage development. Furthermore, our results may indicate a higher degree of neuronal breakdown in patients with active SLE, also without overt clinical symptoms. NfL may serve as an indicator of neuronal damage in SLE in further studies.
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| 17. |
- Zervides, Kristoffer A, et al.
(författare)
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Serum S100A8/A9 concentrations are associated with neuropsychiatric involvement in systemic lupus erythematosus: a cross-sectional study
- 2022
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Ingår i: BMC Rheumatology. - : Springer Science and Business Media LLC. - 2520-1026. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuropsychiatric (NP) involvement and fatigue are major problems in systemic lupus erythematosus (SLE). S100A8/A9 is a marker of inflammation and responds to therapy in SLE patients. S100A8/A9 has an immunopathogenic role in various neurological diseases. We investigated S100A8/A9 in relation to NP-involvement and fatigue in SLE.METHODS: 72 consecutive SLE outpatients at a tertiary centre and 26 healthy controls were included in this cross-sectional study. NPSLE was determined by specialists in rheumatology and neurology and defined according to three attribution models: "ACR", "SLICC A" and "SLICC B". Cerebral MRI was assessed by a neuroradiologist and neurocognitive testing by a neuropsychologist. The individuals were assessed by scores of pain (VAS), fatigue (VAS and FSS), and depression (MADRS-S). Concentrations of S100A8/A9 in serum and cerebrospinal fluid were measured with ELISA. Statistical calculations were performed using non-parametric methods.RESULTS: Serum concentrations of S100A8/A9 were higher in SLE patients compared with controls (medians 1230 ng/ml; 790 ng/ml, p = 0.023). The concentrations were higher in NPSLE patients compared with non-NPSLE patients when applying the SLICC A and ACR models, but not significant when applying the SLICC B model (medians 1400 ng/ml; 920 ng/ml, p = 0.011; 1560 ng/ml; 1090 ng/ml, p = 0.050; 1460 ng/ml; 1090 ng/ml, p = 0.083, respectively). No differences of CSF S100A8/A9 concentrations were observed between NPSLE and non-NPSLE patients. SLE patients with depression or cognitive dysfunction as an ACR NPSLE manifestation had higher serum S100A8/A9 concentrations than non-NPSLE patients (median 1460 ng/ml, p = 0.007 and 1380 ng/ml, p = 0.013, respectively). Higher serum S100A8/A9 correlated with higher VAS fatigue (r = 0.31; p = 0.008) and VAS pain (r = 0.27, p = 0.021) in SLE patients. Serum S100A8/A9 was not independently associated with NPSLE when adjusting for scores of fatigue (FSS) and pain (VAS) (OR 1.86, 95% CI 0.93-3.73, p = 0.08).CONCLUSIONS: Serum S100A8/A9 concentrations may be associated with NPSLE and fatigue. S100A8/A9 may be of interest in evaluating NPSLE, although further investigations are needed.
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