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- Samuelsson, I, et al.
(author)
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Myocardial infarctions, subtypes and coronary atherosclerosis in SLE: a case-control study
- 2021
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In: Lupus science & medicine. - : BMJ. - 2053-8790. ; 8:1
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Journal article (peer-reviewed)abstract
- Patients with SLE have increased risk of myocardial infarction (MI). Few studies have investigated the characteristics of SLE-related MIs. We compared characteristics of and risk factors for MI between SLE patients with MI (MI-SLE), MI patients without SLE (MI-non-SLE) and SLE patients without MI (non-MI-SLE) to understand underlying mechanisms.MethodsWe identified patients with a first-time MI in the Karolinska SLE cohort. These patients were individually matched for age and gender with MI-non-SLE and non-MI-SLE controls in a ratio of 1:1:1. Retrospective medical file review was performed. Paired statistics were used as appropriate.ResultsThirty-four MI-SLE patients (88% females) with a median age of 61 years were included. These patients had increased number of coronary arteries involved (p=0.04), and ≥50% coronary atherosclerosis/occlusion was numerically more common compared with MI-non-SLE controls (88% vs 66%; p=0.07). The left anterior descending artery was most commonly involved (73% vs 59%; p=0.11) and decreased (<50%) left ventricular ejection fraction occurred with similar frequency in MI-SLE and MI-non-SLE patients (45% vs 36%; p=0.79). Cardiovascular disease (44%, 5.9%, 12%; p<0.001) and coronary artery disease (32%, 2.9%, 0%; p<0.001), excluding MI, preceded MI/inclusion more commonly in MI-SLE than in MI-non-SLE and non-MI-SLE patients, respectively. MI-SLE patients had lower plasma albumin levels than non-MI-SLE patients (35 (29–37) vs 40 (37–42) g/L; p=0.002).ConclusionIn the great majority of cases, MIs in SLE are associated with coronary atherosclerosis. Furthermore, MIs in SLE are commonly preceded by symptomatic vascular disease, calling for attentive surveillance of cardiovascular disease and its risk factors and early atheroprotective treatment.
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| 2. |
- Samuelsson, I, et al.
(author)
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MYOCARDIAL INFARCTIONS, SUBTYPES, LOCATIONS AND CORONARY ATHEROSCLEROSIS IN SLE - A COMPARATIVE STUDY WITH MATCHED CONTROLS
- 2021
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In: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 643-643
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Conference paper (other academic/artistic)abstract
- Myocardial infarction (MI) is estimated to be 2- to 3-fold elevated in systemic lupus erythematosus (SLE) as compared to gender- and age-matched controls (1-2). Even though some risk factors have been purposed, mechanisms of increased MI incidence remains to be determined.Objectives:To explore underlying mechanisms, we compared MI characteristics and risk factors between SLE patients with MI (MI-SLE), MI patients without SLE (MI-nonSLE) and SLE patients without MI (nonMI-SLE).Methods:We performed retrospective medical file review including angiography and echocardiography reports in 34 MI-SLE patients, 34 MI-nonSLE patients and 34 nonMI-SLE patients – all individually matched for gender and age in a ratio of 1:1:1.Results:Median age was 61 years and 88% were females. MI-SLE patients had more coronary arteries involved (table 1; p=0.038), and ≥50% coronary atherosclerosis/occlusion at MI was numerically more common compared to MI-nonSLE controls (88% versus 66%; p=0.065). The left anterior descending artery was most frequently involved in both MI groups (73% versus 59%; p=0.11). Decreased (<50%) left ventricular ejection fraction occurred with similar frequency (45% versus 36%; p=0.79) in MI-SLE patients compared to MI-nonSLE patients. Cardiovascular disease (CVD) (44%, 5.9%, 12%; p<0.001) and coronary artery disease excluding MI (CAD, 32%, 2.9%, 0%; p<0.001) preceded MI/inclusion more commonly in MI-SLE than in MI-nonSLE and nonMI-SLE patients, respectively. MI-SLE patients differed from nonMI-SLE patients through lower plasma albumin levels (35 (29-37) versus 40 (37-42) g/L; p=0.002) and longer disease duration (22 (14-32) versus 14 (6.3-24) years; p=0.038).Conclusion:We demonstrate that non-procedural MIs in SLE are in 88% of cases associated with significant coronary atherosclerosis. Increased prevalence of CAD prior MI and higher number of coronary arteries involved at MI, suggest accelerated coronary atherosclerosis in SLE patients. This calls for attentive surveillance of CVD and early atheroprotective treatment in this patients group.References:[1]Hak AE et al. Systemic lupus erythematosus and the risk of cardiovascular disease: Results from the nurses’ health study. Arthritis and rheumatism 2009;61:1396-402.[2]Fischer LM et. Effect of rheumatoid arthritis or systemic lupus erythematosus on the risk of first-time acute myocardial infarction. The American journal of cardiology 2004;93:198-200.Table 1.MI characteristicsMI-SLENtotalMI-nonSLENtotalP-valueECG findingsNSTEMI23 (72%)3221 (66%)321.0 STEMIPresence of atherosclerosis9 (28%)3211 (34%)32 0-VD3 (12%)2610 (35%)290.065 MI-CAD (≥1-VD)Number of involved arteries23 (88%)2619 (66%)29 0-VD3 (12%)2610 (35%)290.038 1-VD13 (50%)269 (31%)29 ≥2-VD10 (39%)2610 (35%)29Involvement of specific arteriesLMCA3 (12%)260 (0%)290.50 LAD19 (73%)2617 (59%)290.11 RCA7 (27%)269 (31%)290.75 Cx6 (23%)266 (21%)291.0Left ventricular ejection fraction <50%13 (45%)2912 (36%)330.79 ≥50%16 (55%)2921 (64%)330-VD = 0-Vessel disease. 1-VD = 1-Vessel disease. 2-VD = 2-Vessel disease. Cx = Circumflex artery. LAD = Left anterior descending artery. LMCA = Left main coronary artery. MI-CAD = MI with coronary artery disease. NSTEMI = Non-ST-elevation MI. RCA = Right coronary artery. STEMI = ST-elevation MI.Disclosure of Interests:Isak Samuelsson: None declared, Ioannis Parodis Grant/research support from: The author declare that he has no conflict of interest related to this work, Iva Gunnarsson Grant/research support from: The author declare that she has no conflict of interest related to this work, Agneta Zickert: None declared, Claes Hofman-Bang: None declared, Håkan Wallén Grant/research support from: The author declare that he has no conflict of interest related to this work, Elisabet Svenungsson Grant/research support from: The author declare that she has no conflict of interest related to this work
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| 7. |
- Johnson, Mats, 1956, et al.
(author)
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A randomized controlled trial of a new intervention in early symptomatic syndromes eliciting neurodevelopmental clinical examinations: PR-ESSENCE
- 2021
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In: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 32:1, s. 63-74
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Journal article (peer-reviewed)abstract
- The need for effective intervention programs for youth with neurodevelopmental problems (ESSENCE) and challenging behaviour is great. This study examines Problem Resolution in ESSENCE (PR-ESSENCE), a newly developed model in which children and parents develop mutual problem resolution strategies. Ten-week randomized controlled trial of PR-ESSENCE for children and adolescents aged 5-18 years, compared to treatment as usual. Outcomes were assessed at baseline and randomized period endpoint. Primary outcome was the Clinical Global Impression-Improvement scale (CGI-I) rated by blinded assessors. Secondary outcomes were rated by parents-SNAP-IV, Eyberg Child Behavior Inventory (ECBI), Relationship Problems Questionnaire, Family Burden of Illness Module, and children-Beck Youth Inventories (BYI). ClinicalTrials.gov identifier: NCT03780413. The study enrolled 108 participants (active n = 72; controls n = 36, randomized 2:1), of whom 95 completed the randomized period. No clinically significant group differences were found in baseline characteristics. More than half had autism and 80% had ADD or ADHD. Large treatment effects were seen on CGI-I (ITT analysis, Effect Size 1.48). Treatment responders, much/very much improved on CGI-I, were 51.4% in active group and 5.6% of controls. Effect sizes were medium to large in parent ratings on SNAP-IV (ODD and ADHD symptoms), ECBI (behaviour problems), and in BYI child self-ratings of disruptive behaviour. PR-ESSENCE treatment improved global symptoms and functioning (CGI-I), behaviour problems, ADHD and ODD symptoms, and disruptive behaviour. Treatment effects were at least equivalent to those in previous studies of well-established Parent Management Training and Collaborative Problem Solving programs.
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| 8. |
- Kmezic, I., et al.
(author)
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Neurofilament light chain and total tau in the differential diagnosis and prognostic evaluation of acute and chronic inflammatory polyneuropathies
- 2022
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 29:9, s. 2810-2822
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Journal article (peer-reviewed)abstract
- Background and Purpose: To investigate the diagnostic and prognostic value of axonal injury biomarkers in patients with inflammatory polyneuropathies. Methods: Neurofilament light chain (NfL) and total tau (T-tau) were measured in the cerebrospinal fluid (CSF) and plasma in 41 patients with Guillain–Barré syndrome (GBS), 32 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), 10 with paraproteinemia-related demyelinating polyneuropathy (PDN), and 8 with multifocal motor neuropathy (MMN), in comparison with 39 disease-free controls and 59 other controls. Outcome was measured with the GBS-disability score (GBS-ds) or Inflammatory Neuropathy Cause and Treatment (INCAT) disability score. Results: Neurofilament light chain levels in CSF and plasma were higher in GBS, CIDP, and PDN vs. disease-free controls. Patients with MMN had higher NfL levels in plasma vs. disease-free controls, but lower levels in CSF and plasma vs. patients with amyotrophic lateral sclerosis (ALS). T-tau levels in plasma were higher in GBS, CIDP, PDN, and MMN vs. all control groups. Neurofilament light chain levels in CSF and plasma in patients with GBS correlated with GBS-ds, as higher levels were associated with inability to run after 6 and 12 months. NfL levels in CSF and plasma in CIDP did not correlate significantly with outcome. Conclusions: Acute and chronic inflammatory neuropathies are associated with an increase in levels of NfL in CSF and plasma, but NfL is validated as a prognostic biomarker only in GBS. NfL could be used in differentiating patients with MMN from ALS. T-tau in plasma is a novel biomarker that could be used in a diagnostic assessment of patients with acute and chronic inflammatory polyneuropathies.
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| 9. |
- Ludvigsson, Johnny, et al.
(author)
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Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial
- 2021
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 44:7, s. 1604-1612
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Journal article (peer-reviewed)abstract
- OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean +/- SD 16.4 +/- 4.1) with a diabetes duration of 7-193 days (88.8 +/- 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 mu g GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA(1c) <= 9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
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| 10. |
- Piehl, F., et al.
(author)
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Efficacy and Safety of Rituximab for New-Onset Generalized Myasthenia Gravis The RINOMAX Randomized Clinical Trial
- 2022
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In: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157.
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Journal article (peer-reviewed)abstract
- IMPORTANCE Rituximab is a third-line option for refractory generalized myasthenia gravis (MG) based on empirical evidence, but its effect in new-onset disease is unknown. OBJECTIVE To investigate the efficacy and safety of rituximab compared with placebo as an add-on to standard of care for MG. DESIGN, SETTING, AND PARTICIPANTS This randomized, double-blind, placebo-controlled study took place throughout 48 weeks at 7 regional clinics in Sweden. Key inclusion criteria were age older than 18 years, onset of generalized symptoms within 12 months or less, and a Quantitative Myasthenia Gravis (QMG) score of 6 or more. Patients were screened from October 20, 2016, to March 2, 2020. Key exclusion criteria included pure ocular MG, suspected thymoma, previous thymectomy, and prior noncorticosteroid immunosuppressants or high doses of corticosteroids. INTERVENTIONS Participants were randomized 1:1 without stratification to a single intravenous infusion of 500 mg of rituximab or matching placebo. MAIN OUTCOMES AND MEASURES Minimal disease manifestations at 16 weeks defined as a QMG score of 4 or less with prednisolone, 10 mg or less daily, and no rescue treatment. RESULTS Of 87 potentially eligible patients, 25 were randomized to rituximab (mean [SD] age, 67.4 [13.4] years; 7 [28%] female) and 22 to placebo (mean [SD] age, 58 [18.6] years; 7 [32%] female). Compared with placebo, a greater proportion with rituximab met the primary end point; 71% (17 of 24) in the rituximab group vs 29% (6 of 21) in the placebo group (Fisher exact test P = .007; probability ratio, 2.48 [95% CI, 1.20-5.11]). Secondary end points, comparing changes in Myasthenia Gravis Activities of Daily Living and Myasthenia Gravis Quality of Life at 16 weeks with QMG at 24 weeks did not differ between groups with censoring for rescue treatment (per-protocol analysis) but were in favor of active treatment when rescue treatment was taken into account by worst rank imputation (post hoc analysis). Rescue treatments were also more frequent in the placebo arm (rituximab: 1 [4%]; placebo, 8 [36%]). One patient in the placebo arm had a myocardial infarction with cardiac arrest and 1 patient in the active arm experienced a fatal cardiac event. CONCLUSIONS AND RELEVANCE A single dose of 500 mg of rituximab was associated with greater probability of minimal MG manifestations and reduced need of rescue medications compared with placebo. Further studies are needed to address long-term benefit-risk balance with this treatment.
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