| 1. |
- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 2. |
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| 4. |
- Sachdev, P. S., et al.
(författare)
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STROKOG (stroke and cognition consortium): An international consortium to examine the epidemiology, diagnosis, and treatment of neurocognitive disorders in relation to cerebrovascular disease
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 7, s. 11-23
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The Stroke and Cognition consortium (STROKOG) aims to facilitate a better understanding of the determinants of vascular contributions to cognitive disorders and help improve the diagnosis and treatment of vascular cognitive disorders (VCD). Methods Longitudinal studies with ≥75 participants who had suffered or were at risk of stroke or TIA and which evaluated cognitive function were invited to join STROKOG. The consortium will facilitate projects investigating rates and patterns of cognitive decline, risk factors for VCD, and biomarkers of vascular dementia. Results Currently, STROKOG includes 25 (21 published) studies, with 12,092 participants from five continents. The duration of follow-up ranges from 3months to 21years. Discussion Although data harmonization will be a key challenge, STROKOG is in a unique position to reuse and combine international cohort data and fully explore patient level characteristics and outcomes. STROKOG could potentially transform our understanding of VCD and have a worldwide impact on promoting better vascular cognitive outcomes. © 2016 The Authors
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| 5. |
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| 6. |
- Lorenz, M. W., et al.
(författare)
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Carotid Intima-Media Thickness Progression and Risk of Vascular Events in People With Diabetes: Results From the PROG-IMT Collaboration
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:10, s. 1921-1929
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVECarotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.RESEARCH DESIGN AND METHODSIn a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.RESULTSAverage mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).CONCLUSIONSDespite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.
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| 7. |
- Ståhlman, Marcus, 1975, et al.
(författare)
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Clinical dyslipidaemia is associated with changes in the lipid composition and inflammatory properties of apolipoprotein-B-containing lipoproteins from women with type 2 diabetes.
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:4, s. 1156-66
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The aim of this study was to use lipidomics to determine if the lipid composition of apolipoprotein-B-containing lipoproteins is modified by dyslipidaemia in type 2 diabetes and if any of the identified changes potentially have biological relevance in the pathophysiology of type 2 diabetes. Methods VLDL and LDL from normolipidaemic and dyslipidaemic type 2 diabetic women and controls were isolated and quantified with HPLC and mass spectrometry. A detailed molecular characterisation of VLDL triacylglycerols (TAG) was also performed using the novel ozone-induced dissociation method, which allowed us to distinguish vaccenic acid (C18:1 n-7) from oleic acid (C18:1 n-9) in specific TAG species. Results Lipid class composition was very similar in VLDL and LDL from normolipidaemic type 2 diabetic and control participants. By contrast, dyslipidaemia was associated with significant changes in both lipid classes (e.g. increased diacylglycerols) and lipid species (e.g. increased C16:1 and C20:3 in phosphatidylcholine and cholesteryl ester and increased C16:0 [palmitic acid] and vaccenic acid in TAG). Levels of palmitic acid in VLDL and LDL TAG correlated with insulin resistance, and VLDL TAG enriched in palmitic acid promoted increased secretion of proinflammatory mediators from human smooth muscle cells. Conclusions We showed that dyslipidaemia is associated with major changes in both lipid class and lipid species composition in VLDL and LDL from women with type 2 diabetes. In addition, we identified specific molecular lipid species that both correlate with clinical variables and are proinflammatory. Our study thus shows the potential of advanced lipidomic methods to further understand the pathophysiology of type 2 diabetes.
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| 8. |
- Thurang, Anna, et al.
(författare)
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Women's experiences of caring when in treatment for alcohol dependency
- 2010
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Ingår i: Scandinavian Journal of Caring Sciences. - 0283-9318 .- 1471-6712. ; 24:4, s. 700-706
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Tidskriftsartikel (refereegranskat)abstract
- Despite the fact of increased levels of alcohol dependency in women and gender differences in how the disease affects men and women, the research on alcohol dependency continues to have a dominating perspective on men. The meaning of the phenomenon of caring in formal care for women with alcohol dependency is not well known. Thus, formal caregivers may find it problematic to know what is caring for women with alcohol dependency. The aim of the study was to illuminate the meaning of caring in formal care for women with alcohol dependency, as narrated by the women. The study was performed using a phenomenological-hermeneutic method. Data were collected in ten in-depth interviews with alcohol-dependent women. The themes presented are availability, being a patient and being a learner. The findings reveal that the women with alcohol dependency receiving a mandate from formal care, experience the relation between them and their caregiver as a mutual transformation. Within the mutual transformation, the participants experienced being respected as a responsible human being which renders possibilities for the women with alcohol dependency to continue in formal care even when the struggle against the disease became hard. Continual meetings with the caregiver allowed the women to gain structure in their daily life as well as allowing the women and their caregivers to develop mutual transformation, which both relieved the women's suffering and increased their experience of being involved in the care process.
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| 12. |
- Butler, L. M., et al.
(författare)
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Analysis of Body-wide Unfractionated Tissue Data to Identify a Core Human Endothelial Transcriptome
- 2016
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Ingår i: Cell Systems. - : Cell Press. - 2405-4712. ; 3:3, s. 287-301.e3
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Tidskriftsartikel (refereegranskat)abstract
- Endothelial cells line blood vessels and regulate hemostasis, inflammation, and blood pressure. Proteins critical for these specialized functions tend to be predominantly expressed in endothelial cells across vascular beds. Here, we present a systems approach to identify a panel of human endothelial-enriched genes using global, body-wide transcriptomics data from 124 tissue samples from 32 organs. We identified known and unknown endothelial-enriched gene transcripts and used antibody-based profiling to confirm expression across vascular beds. The majority of identified transcripts could be detected in cultured endothelial cells from various vascular beds, and we observed maintenance of relative expression in early passage cells. In summary, we describe a widely applicable method to determine cell-type-specific transcriptome profiles in a whole-organism context, based on differential abundance across tissues. We identify potential vascular drug targets or endothelial biomarkers and highlight candidates for functional studies to increase understanding of the endothelium in health and disease.
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| 13. |
- Dusart, Philip, et al.
(författare)
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A systems-approach reveals human nestin is an endothelial-enriched, angiogenesis-independent intermediate filament protein
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- The intermediate filament protein nestin is expressed during embryonic development, but considered largely restricted to areas of regeneration in the adult. Here, we perform a body-wide transcriptome and protein-profiling analysis to reveal that nestin is constitutively, and highly-selectively, expressed in adult human endothelial cells (EC), independent of proliferative status. Correspondingly, we demonstrate that it is not a marker for tumour EC in multiple malignancy types. Imaging of EC from different vascular beds reveals nestin subcellular distribution is shear-modulated. siRNA inhibition of nestin increases EC proliferation, and nestin expression is reduced in atherosclerotic plaque neovessels. eQTL analysis reveals an association between SNPs linked to cardiovascular disease and reduced aortic EC nestin mRNA expression. Our study challenges the dogma that nestin is a marker of proliferation, and provides insight into its regulation and function in EC. Furthermore, our systems-based approach can be applied to investigate body-wide expression profiles of any candidate protein.
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| 14. |
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| 15. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 16. |
- Fagerberg, Björn, 1943, et al.
(författare)
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Extremvärme ett ökande problem för globala folkhälsan
- 2016
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Ingår i: Läkartidningen. - 0023-7205. ; 113:31-33
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Tidskriftsartikel (refereegranskat)abstract
- High temperatures have a direct impact on body functions. Heat waves increase mortality risks due to myocardial infarction, stroke, and pulmonary disease. Cold temperatures also increase mortality, but with a longer latency. A recent study found only a small difference between the minimal mortality temperature (MMT) and the temperatures at which mortality rose steeply, although the majority of deaths occurred at temperatures below MMT. Global climate change with increasing temperatures seriously threatens health, work capacity, and generation of household incomes, particularly among poor people in hot countries. In Sweden, heat waves increase mortality in vulnerable groups of elderly people and patients with chronic heart and lung diseases, as well as those performing intensive physical work in hot environments. The medical profession can play an important role not only in prevention of climate change, but also in adaptation to climate change with the goal of minimizing health risks. © 2016, Swedish Medical Association. All rights reserved.
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| 17. |
- Fagerberg, Björn, 1943, et al.
(författare)
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Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population
- 2005
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 48:9, s. 1716-25
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Insulin resistance is associated with abnormalities in lipid and glucose metabolism, which are major components of metabolic syndrome and risk factors for vascular disease. This study examined the effect of tesaglitazar (Galida), a novel, dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, on lipid and glucose metabolism in patients with evidence of insulin resistance. METHODS: A 12-week, multicentre, randomised, double-blind, placebo-controlled, dose-finding study compared the efficacy and safety of oral tesaglitazar (0.1, 0.25, 0.5 and 1.0 mg/day) and placebo in 390 non-diabetic patients with hypertriglyceridaemia (plasma triglyceride concentration >1.7 mmol/l) and abdominal obesity (waist-to-hip ratio >0.90 for men and >0.85 for women). RESULTS: A 1.0-mg dose of tesaglitazar reduced fasting triglycerides (the primary endpoint) by 37% (95% CI: -43% to -30%; p<0.0001), non-HDL-cholesterol by 15% (95% CI: -20% to -10%; p<0.0001) and NEFA by 40% (95% CI: -51% to -27%; p<0.0001), and increased HDL-cholesterol by 16% (95% CI: 8 to -24%; p<0.0001). At the end of treatment there was a dose-dependent increase in patients with pattern A LDL particle diameter (40% at baseline vs 87% at 12 weeks for tesaglitazar 1.0 mg). Tesaglitazar produced significant reductions in fasting insulin concentration (-35%; p<0.0001) and plasma glucose concentration (-0.47 mmol/l; p<0.0001). Respiratory infection and gastrointestinal symptoms were the most common adverse events and were similarly frequent in all groups. CONCLUSIONS/INTERPRETATION: Tesaglitazar was well tolerated and produced significant, dose-dependent improvements in lipid and glucose metabolism and insulin sensitivity. Tesaglitazar may have the potential to prevent vascular complications and delay progression to diabetes in these patients.
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| 18. |
- Fagerberg, Nils, 1972-, et al.
(författare)
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Prediction of knot size in uneven-sized Norway spruce stands in Sweden
- 2023
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Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 544
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Tidskriftsartikel (refereegranskat)abstract
- The size of knots is negatively correlated with bending strength in sawn timber and it is therefore used as a quality grading criterion in national roundwood grading standards. Some standards even use the size of the largest knot as the sole estimate for individual log knottiness. The size of knots is determined by crown horizontal extension, which in turn is dependent on the impact of competing trees. Thus, with knot size models that are competition-dependent, roundwood quality due to knottiness can be simulated for different management al-ternatives. However, these types of models, calibrated on uneven-sized Norway spruce in Fennoscandia, are currently not available. Therefore, the objective of this study is to develop a competition-dependent model framework for prediction of the largest knot size per stem height section, for application within uneven-sized Norway spruce stands. Data from terrestrial laser scanning of an uneven-sized stand in southern Sweden are used to calibrate a modular prediction framework, consisting of interlinked allometric statistical models. Alternative framework sub-models are presented and the preferred model combination can be selected according to context and available input data. The flexible modular format enables further development of separate sub-components for adaptation to growing conditions not covered by the current calibration range.
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| 19. |
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| 23. |
- Fagerberg, T, et al.
(författare)
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Swedish Universities Scales of Personality: Relation to Other Personality Instruments
- 2021
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Ingår i: Psychiatry investigation. - : Korean Neuropsychiatric Association. - 1738-3684 .- 1976-3026. ; 18:5, s. 373-384
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate associations between Swedish universities Scales of Personality (SSP) and scales of the following personality instruments: Structured Clinical Interview for DSM-III-R axis II screening questionnaire (SCID-II screen), revised NEO personality inventory (NEO-PI-R), revised Chapman scales (Chapman) and the psychotic traits questionnaire (STQ).Methods Healthy individuals (n=406) completed self-report personality questionnaires including SSP and at least one more personality inventory. Correlations were calculated between the 13 different SSP subscales as well as SSP’s three factors and factors and scales/subscales in SCID-II screen, NEO-PI-R, Chapman and STQ. The main factors of the various instruments were factor analysed. ICC were calculated.Results SSP Neuroticism factor correlated with SCID-II cluster C (r=0.71), NEO Neuroticism (r=0.80) and Chapman Social anhedonia (r=0.62). SSP Extraversion factor correlated with NEO Extraversion (r=0.63) and SSP Aggressiveness factor with NEO Agreeableness (r=-0.62). Strong correlations between SSP factors and scales and scales of the other instruments were sparse, although weaker correlations were common.Conclusion SSP is a useful investigation tool when measuring personality traits related to temperament-like features. SSP partly correlates well to especially three of the NEO-PI-R factors. The different personality inventories are not completely comparable to each other. Instead, they measure personality aspects in partly different ways.
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| 24. |
- Fagerberg, T, et al.
(författare)
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Thirteen year follow up of long term treated psychotic disorder: Personality aspects
- 2021
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Ingår i: EUROPEAN PSYCHIATRY. - : Royal College of Psychiatrists. - 0924-9338 .- 1778-3585. ; 64, s. S512-S512
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Psychotic disorders often cause a drastic change in the life situation of the affected individual. Personality is an aspect that can affect the symptoms and social function in psychotic disorders.ObjectivesNo study has examined stability of personality traits exceeding five years in patients with schizophrenia. The aim of this study was to investigate the stability of personality traits over a 13-year period among patients with psychotic disorder and healthy individuals and to evaluate case-control differences.MethodsAt three occasions during a 13-year period patients with psychotic disorders (n=28) and non-psychotic individuals (n=57) completed Swedish universities Scales of Personality (SSP). For all the individuals within- and between-subject analyses were performed at three occasions for all 13 subscales and the three overall factors of SSP. Correlations, means and SDs were calculated.ResultsTests of within-subject correlations showed differences in two subscales: Lack of Assertiveness, which were influenced by age and Physical Trait Aggression, where patients ratings were stable, whereas controls rated themselves less aggressive at higher age. Between-subjects correlations showed differences regarding any of the parameters diagnosis, time, age, gender or age x gender in nine of the 13 subscales as well as in factor Neuroticism.ConclusionsLong term follow-up showed a generally high stability of personality traits measured with SSP, especially among patients. Between-subject analyses over the 13 years showed that patients differed compared to controls for the SSP factor Neuroticism as well as the subscale Detachment, which is in accordance with previous studies.
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| 25. |
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| 26. |
- Groenning, Minna, et al.
(författare)
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Thermodynamic stability and denaturation kinetics of a benign natural transthyretin mutant identified in a Danish kindred
- 2011
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Ingår i: AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS. - : Informa Healthcare. - 1350-6129. ; 18:2, s. 35-46
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Tidskriftsartikel (refereegranskat)abstract
- The disease phenotype of transthyretin (TTR) is dramatically influenced by single point mutations in the TTR gene. Herein, we report on a novel mutation D99N (Asp99Asn) in TTR found in a Danish kindred. None of the family members carrying this mutation have so far shown any clinical signs of amyloidosis. One carrier found compound heterozygous for TTR D99N and L111M (Leu111Met) associated with cardiac amyloid is asymptomatic (42 years). Disease severity can often be linked to both the kinetics of fibril formation and the degree of destabilisation of the native state. In this study, we show that the thermodynamic stability and rate of tetramer dissociation of the variant TTR D99N is unchanged or slightly more stable than wild type (WT) TTR. Furthermore, the in vitro fibrillation kinetics of the variant reveals an unchanged or slightly suppressed tendency to form fibrils compared to WT. Thus, the in vitro experiments support the lack of clinical symptoms observed so far for the TTR D99N carriers. In line with this, studies on kinetic stability and fibrillation kinetics reveal indistinguishable stability of TTR heterotetramers D99N/L111M compared to the heterotetramers WT/L111M. In conclusion, TTR D99N is predicted to be a non-pathogenic benign mutation with WT properties.andlt;/.
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| 27. |
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| 28. |
- Johannesson, M, et al.
(författare)
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The cost-effectiveness of a cardiovascular multiple-risk-factor intervention programme in treated hypertensive men
- 1995
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Ingår i: Journal of internal medicine. - : Blackwell Science. - 1365-2796 .- 0954-6820. ; 237:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to carry out a cost‐effectiveness analysis of a multifactorial intervention programme in treated hypertensive patients. Design. A cost‐effectiveness analysis based on 3 years of follow‐up in an open, randomized, parallel‐group study with allocation either to a comprehensive, multiple‐risk‐factor modification programme or to conventional treatment. Setting. An outpatient clinic of a city hospital. Subjects. Inclusion criteria were: male sex, age 50–72 (mean 66.4) years, treated hypertension and at least one of the following: serum cholesterol ≥ 6.5 mmol L‐1, and/or smoking and/or diabetes mellitus. A total of 508 patients were included in the study. Interventions. Advice given to individuals, and group meetings based on nutritional advice and behavioural treatment principles. If necessary, drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol of < 6.0 mmol L−1, no smoking, HbAlc < 6.0% and diastolic blood pressure < 90 mmHg in both groups. Main outcome measure. Incremental cost per life‐year gained of the intervention programme. Results. The cost per life‐year gained was SEK 4000 in an estimation based on the observed risk reduction and ranged between SEK 62 000 and SEK 163 000 in three estimations based on the risk factor changes. Conclusions. The analysis indicates that the intervention programme is cost‐effective in the studied patient population.
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| 29. |
- Lakshmikanth, T., et al.
(författare)
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Human Immune System Variation during 1 Year
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 32:3
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Tidskriftsartikel (refereegranskat)abstract
- The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal cum. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.
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| 33. |
- Olén, Ola, et al.
(författare)
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Increasing Risk of Lymphoma Over Time in Crohn's Disease but Not in Ulcerative Colitis : A Scandinavian Cohort Study
- 2023
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier. - 1542-3565 .- 1542-7714. ; 21:12, s. 3132-3142
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Earlier studies have provided varying risk estimates for lymphoma in patients with inflammatory bowel disease (IBD), but often have been limited by detection biases (especially during the first year of follow-up evaluation), misclassification, and small sample size; and rarely reflect modern-day management of IBD.Methods: We performed a binational register-based cohort study (Sweden and Denmark) from 1969 to 2019. We compared 164,716 patients with IBD with 1,639,027 matched general population reference individuals. Cox regression estimated hazard ratios (HRs) for incident lymphoma by lymphoma subtype, excluding the first year of follow-up evaluation.Results: From 1969 to 2019, 258 patients with Crohn's disease (CD), 479 patients with ulcerative colitis (UC), and 6675 matched reference individuals developed lymphoma. This corresponded to incidence rates of 35 (CD) and 34 (UC) per 100,000 person-years in IBD patients, compared with 28 and 33 per 100,000 person-years in their matched reference individuals. Although both CD (HR, 1.32; 95% CI, 1.16–1.50) and UC (HR, 1.09; 95% CI, 1.00–1.20) were associated with an increase in lymphoma, the 10-year cumulative incidence difference was low even in CD patients (0.08%; 95% CI, 0.02–0.13). HRs have increased in the past 2 decades, corresponding to increasing use of immunomodulators and biologics during the same time period. HRs were increased for aggressive B-cell non-Hodgkin lymphoma in CD and UC patients, and for T-cell non-Hodgkin lymphoma in CD patients. Although the highest HRs were observed in patients exposed to combination therapy (immunomodulators and biologics) or second-line biologics, we also found increased HRs in patients naïve to such drugs.Conclusions: During the past 20 years, the risk of lymphomas have increased in CD, but not in UC, and were driven mainly by T-cell lymphomas and aggressive B-cell lymphomas.
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| 34. |
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