| 61. |
- Little, Jayne, et al.
(författare)
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Glucocorticoid use and factors associated with variability in this use in the Systemic Lupus International Collaborating Clinics Inception Cohort
- 2018
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 57:4, s. 677-687
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To describe glucocorticoid (GC) use in the SLICC inception cohort and to explore factors associated with GC use. In particular we aimed to assess temporal trends in GC use and to what extent physician-related factors may influence use. Methods. Patients were recruited within 15 months of diagnosis of SLE from 33 centres between 1999 and 2011 and continue to be reviewed annually. Descriptive statistics were used to detail oral and parenteral GC use. Cross sectional and longitudinal analyses were performed to explore factors associated with GC use at enrolment and over time. Results. We studied 1700 patients with a mean (S.D.) follow-up duration of 7.26 (3.82) years. Over the entire study period, 1365 (81.3%) patients received oral GCs and 447 (26.3%) received parenteral GCs at some point. GC use was strongly associated with treatment centre, age, race/ethnicity, sex, disease duration and disease activity. There was no change in the proportion of patients on GCs or the average doses of GC used over time according to year of diagnosis. Conclusion. GCs remain a cornerstone in SLE management and there have been no significant changes in their use over the past 10-15 years. While patient and disease factors contribute to the variation in GC use, between-centre differences suggest that physician-related factors also contribute. Evidence-based treatment algorithms are needed to inform a more standardized approach to GC use in SLE.
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| 62. |
- Lu, Mary, et al.
(författare)
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Non-Lymphoma Hematological Malignancies in Systemic Lupus Erythematosus
- 2013
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Ingår i: Oncology. - : S. Karger AG. - 1423-0232 .- 0030-2414. ; 85:4, s. 235-240
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe non-lymphoma hematological malignancies in systemic lupus erythematosus (SLE). Methods: A large SLE cohort was linked to cancer registries. We examined the types of non-lymphoma hematological cancers. Results: In 16,409 patients, 115 hematological cancers [including myelodysplastic syndrome (MDS)] occurred. Among these, 33 were non-lymphoma. Of the 33 non-lymphoma cases, 13 were of lymphoid lineage: multiple myeloma (n = 5), plasmacytoma (n = 3), B cell chronic lymphocytic leukemia (B-CLL; n = 3), precursor cell lymphoblastic leukemia (n = 1) and unspecified lymphoid leukemia (n = 1). The remaining 20 cases were of myeloid lineage: MDS (n = 7), acute myeloid leukemia (AML; n = 7), chronic myeloid leukemia (CML; n = 2) and 4 unspecified leukemias. Most of these malignancies occurred in female Caucasians, except for plasma cell neoplasms (4/5 multiple myeloma and 1/3 plasmacytoma cases occurred in blacks). Conclusions: In this large SLE cohort, the most common non-lymphoma hematological malignancies were myeloid types (MDS and AML). This is in contrast to the general population, where lymphoid types are 1.7 times more common than myeloid non-lymphoma hematological malignancies. Most (80%) multiple myeloma cases occurred in blacks; this requires further investigation. (C) 2013 S. Karger AG, Basel
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| 63. |
- Markmann, James F., et al.
(författare)
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Phase 3 trial of human islet-after-kidney transplantation in type 1 diabetes
- 2021
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 21:4, s. 1477-1492
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic islet transplant offers a minimally invasive option for beta cell replacement in the treatment of type 1 diabetes (T1D). The CIT consortium trial of purified human pancreatic islets (PHPI) in patients with T1D after kidney transplant (CIT06), a National Institutes of Health-sponsored phase 3, prospective, open-label, single-arm pivotal trial of PHPI, was conducted in 24 patients with impaired awareness of hypoglycemia while receiving intensive insulin therapy. PHPI were manufactured using standardized processes. PHPI transplantation was effective with 62.5% of patients achieving the primary endpoint of freedom from severe hypoglycemic events and HbA(1c) <= 6.5% or reduced by >= 1 percentage point at 1 year posttransplant. Median HbA(1c)declined from 8.1% before to 6.0% at 1 year and 6.3% at 2 and 3 years following transplant (P < .001 for all vs baseline), with related improvements in hypoglycemia awareness and glucose variability. The improved metabolic control was associated with better health-related and diabetes-related quality of life. The procedure was safe and kidney allograft function remained stable after 3 years. These results add to evidence establishing allogeneic islet transplant as a safe and effective treatment for patients with T1D and unstable glucose control despite intensive insulin treatment, supporting the indication for PHPI in the post-renal transplant setting.
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| 64. |
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| 65. |
- Mendel, Arielle, et al.
(författare)
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Use of combined hormonal contraceptives among women with systemic lupus erythematosus with and without medical contraindications to oestrogen
- 2019
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Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:7, s. 1259-1267
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. To assess the prevalence of combined hormonal contraceptives (CHCs) in reproductive-age women with SLE with and without possible contraindications and to determine factors associated with their use in the presence of possible contraindications. Methods. This observational cohort study included premenopausal women ages 18-45 years enrolled in the SLICC Registry ≤15 months after SLE onset, with annual assessments spanning 2000-2017. World Health Organization Category 3 or 4 contraindications to CHCs (e.g. hypertension, aPL) were assessed at each study visit. High disease activity (SLEDAI score >12 or use of >0.5 mg/kg/day of prednisone) was considered a relative contraindication. Results. A total of 927 SLE women contributed 6315 visits, of which 3811 (60%) occurred in the presence of one or more possible contraindication to CHCs. Women used CHCs during 512 (8%) visits, of which 281 (55%) took place in the setting of one or more possible contraindication. The most frequently observed contraindications were aPL (52%), hypertension (34%) and migraine with aura (22%). Women with one or more contraindication were slightly less likely to be taking CHCs [7% of visits (95% CI 7, 8)] than women with no contraindications [9% (95% CI 8, 10)]. Conclusion. CHC use was low compared with general population estimates (>35%) and more than half of CHC users had at least one possible contraindication. Many yet unmeasured factors, including patient preferences, may have contributed to these observations. Further work should also aim to clarify outcomes associated with this exposure.
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| 66. |
- Nguyen, Yann, et al.
(författare)
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Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort
- 2023
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Ingår i: Arthritis and Rheumatology. - 2326-5191. ; 75:12, s. 2195-2206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality. (Figure presented.).
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| 67. |
- Parker, Ben, et al.
(författare)
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Clinical associations of the metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:8, s. 1308-1314
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Tidskriftsartikel (refereegranskat)abstract
- Background The metabolic syndrome (MetS) may contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, lupus phenotype and therapy exposure with the presence of MetS. Methods The Systemic Lupus International Collaborating Clinics Registry for Atherosclerosis inception cohort enrolled recently diagnosed (<15months) SLE patients from 30 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected according to a standardised protocol. MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Univariate and backward stepwise multivariate logistic regression were used to assess the relationship of individual variables with MetS. Results We studied 1686 patients, of whom 1494 (86.6%) had sufficient data to determine their MetS status. The mean (SD) age at enrolment and disease duration was 35.2years (13.4) and 24.1weeks (18.0), respectively. MetS was present at the enrolment visit in 239 (16%). In backward stepwise multivariable regression analysis, higher daily average prednisolone dose (mg) (OR 1.02, 95% CI 1.00 to 1.03), older age (years) (OR 1.04, 95% CI 1.03 to 1.06), Korean (OR 6.33, 95% CI 3.68 to 10.86) and Hispanic (OR 6.2, 95% CI 3.78 to 10.12) ethnicity, current renal disease (OR 1.79, 95% CI 1.14 to 2.80) and immunosuppressant use (OR 1.81, 95% CI 1.18 to 2.78) were associated with MetS. Conclusions Renal lupus, higher corticosteroid doses, Korean and Hispanic ethnicity are associated with MetS in SLE patients. Balancing disease control and minimising corticosteroid exposure should therefore be at the forefront of personalised treatment decisions in SLE patients.
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| 68. |
- Parker, Ben, et al.
(författare)
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Impact of early disease factors on metabolic syndrome in systemic lupus erythematosus: data from an international inception cohort
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 74:8, s. 1530-1536
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Tidskriftsartikel (refereegranskat)abstract
- Background The metabolic syndrome (MetS) may contribute to the increased cardiovascular risk in systemic lupus erythematosus (SLE). We examined the association between MetS and disease activity, disease phenotype and corticosteroid exposure over time in patients with SLE. Methods Recently diagnosed (< 15 months) patients with SLE from 30 centres across 11 countries were enrolled into the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort from 2000 onwards. Baseline and annual assessments recorded clinical, laboratory and therapeutic data. A longitudinal analysis of factors associated with MetS in the first 2 years of follow-up was performed using random effects logistic regression. Results We studied 1150 patients with a mean (SD) age of 34.9 (13.6) years and disease duration at enrolment of 24.2 (18.0) weeks. In those with complete data, MetS prevalence was 38.2% at enrolment, 34.8% at year 1 and 35.4% at year 2. In a multivariable random effects model that included data from all visits, prior MetS status, baseline renal disease, SLICC Damage Index > 1, higher disease activity, increasing age and Hispanic or Black African race/ethnicity were independently associated with MetS over the first 2 years of follow-up in the cohort. Conclusions MetS is a persistent phenotype in a significant proportion of patients with SLE. Renal lupus, active inflammatory disease and damage are SLE-related factors that drive MetS development while antimalarial agents appear to be protective from early in the disease course.
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| 69. |
- Poch, Christine M, et al.
(författare)
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Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors
- 2022
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Ingår i: Nature Cell Biology. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 1465-7392 .- 1476-4679.
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Tidskriftsartikel (refereegranskat)abstract
- Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host–graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.
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| 70. |
- Schumann, Gunter, et al.
(författare)
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Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:17, s. 7119-7124
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of similar to 2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene (AUTS2) was associated with alcohol consumption at genome-wide significance (P = 4 x 10(-8) to P = 4 x 10(-9)). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples (P = 0.026) and significant (P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Downregulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila (P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.
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