Interleukin-23 serum level in systemic lupus erythematosus patients: Relation to disease activity and different disease parameters

Aim of the workTo assess serum level of interleukin 23 (IL-23) in systemic lupus erythematosus (SLE) patients and to evaluate its association with disease parameters and activity.Patients and methodsThe study involved 40 SLE patients and 40 controls. The SLE disease activity index (SLEDAI) and damage index (SDI) were assessed. Serum level of IL-23 was measured by enzyme linked immunosorbant assay (ELISA).ResultsPatients were 38 females and 2 males (F:M 19:1),with a mean age of 31.3 ± 7.5 years (17–50 years) and disease duration 4.8 ± 2.9 years (1–13 years). Their mean SLEDAI was 14.3 ± 6.8 (3–32) and SDI 0.4 ± 0.5 (0–2). 85% of patients had photosensitivity, alopecia in 60%, malar rash in 57.5%, oral ulcers 52.5%, arthralgia/arthritis 47.5%, serositis and lupus nephritis in 27.5%, discoid rash in 22.5% and neuropsychiatric in 2.5%. Mean serum level of IL-23 was significantly elevated in patients (107.9 ± 17.3 ng/L; 72.7–165.5 ng/mL) compared to controls (91.6 ± 19.1 ng/L; 57.6–140.3 ng/mL; p < 0.001). IL-23 was significantly elevated in patients with oral ulcers (p = 0.03), arthritis (p < 0.001), lupus nephritis (p = 0.01), alopecia (p = 0.02) and positive anti-dsDNA (p < 0.001). IL-23 significantly correlated with SLEDAI (r = 0.89, p < 0.001), complement C3 (r = -0.55, p < 0.001) and C4 (r = -0.5, p = 0.001). IL-23 could significantly predict SLE at a cut-off 93.1 ng/L (sensitivity 80% and specificity 55%).ConclusionIL-23 may be involved in the pathogenesis of SLE; especially in renal, mucocutaneous and musculoskeletal manifestations and it can be used as a disease activity biomarker. These findings support the possibility of its use as a therapeutic target in SLE.     

Serum resistin,insulin resistance and carotid intima-media thickness as an indication of subclinical atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo evaluate resistin level in systemic lupus erythematosus (SLE) patients and to assess the relationship with insulin resistance, disease characteristics, inflammatory markers and carotid intima-media thickness (CIMT) as a marker of subclinical atherosclerosis.Patients and methodsThirty adult SLE patients and twenty age and sex-matched control were enrolled. All patients were subjected to history taking, clinical examination and assessment of anthropometric measurements. Laboratory investigations included serum resistin, measures of insulin resistance, highly sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR) and lipid profile. Carotid duplex was performed for measurement of CIMT. SLE disease activity index (SLEDAI-2k) and damage index were evaluated.ResultsThe 30 patients were 23 (76.7%) females and 7 (23.3%) males (F:M 3.3:1) with a mean age of 30.9 ± 7.9 years. The disease duration was 4.8 ± 1.8 years. The mean serum resistin in patients was 7.7 ± 2.9 ng/dl and in control was 8.5 ± 5.1 ng/dl (p = 0.8). The ESR and hs-CRP were significantly increased (p < 0.001) and the high-density lipoprotein (HDL) decreased (p < 0.001). The mean CIMT was significantly increased in cases (0.62 ± 0.16 mm) compared to control (0.51 ± 0.11 mm)(p = 0.006). Serum resistin significantly correlated with hs-CRP, HDL and anti-nuclear antibody (p = 0.027, p < 0.001,p = 0.013 respectively). There was no significant correlation between resistin and markers of insulin resistance, SLEDAI-2 k and CIMT.ConclusionResistin expression in the serum of patients with SLE was not significantly higher than controls. Although resistin was correlated with two cardiovascular risk factors (HDL-C, hs-CRP), it did not correlate significantly with insulin resistance, disease activity, damage index and CIMT in SLE patients.     

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p < 0.001). There were significant correlations between IL-18 and SLEDAI (p = 0.002), proteinuria (p = 0.027), renal activity score (p = 0.003) and activity index (p = 0.039) in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN.ConclusionIL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE.     

Methylmalonic acid and vitamin B12 in patients with heart failure

ObjectiveVitamin B12 deficiency among patients with heart failure (HF) may have been underestimated. High serum levels of methylmalonic acid (MMA) have been identified in several studies as an early indicator of vitamin B12 deficiency. Furthermore, MMA seems to constitute a biomarker of oxidative stress and mitochondrial dysfunction. There are scarce data regarding vitamin B12 and MMA in patients with HF. The aim of this study was to investigate vitamin B12 and MMA serum levels in patients with HF.MethodsOne hundred five consecutive patients admitted to our hospital with symptoms and signs of acute decompensated HF were included in the study. Demographic and clinical characteristics as well as comorbidities and medical treatment before hospital admission were recorded. Transthoracic echocardiography was performed in all patients. Blood samples were collected during the first 24 hours of hospitalization and measured for complete blood count, biochemical profile, vitamin B12, N-terminal prohormone of brain natriuretic peptide, and MMA levels. Finally, 51 healthy individuals constituted the control group.ResultsA total of 43.8% of patients with HF had elevated MMA levels, but only 10.5% had overt vitamin B12 deficiency, defined as serum cobalamin levels below 189 pg/ml. Mean MMA level was higher in patients with HF than in controls (33.0 ± 9.6 vs. 19.3 ± 6.3 ng/ml; p < 0.001). This difference remained significant when adjusted for age, sex, vitamin B12, and folate serum levels and kidney function (B = 14.7 (9.6–19.7); p < 0.001). MMA levels were higher in patients with acutely decompensated chronic HF than in those with newly diagnosed acute HF (34.7 ± 10.5 vs. 30.7 ± 7.8 ng/ml; p = 0.036). Correlation analysis revealed significantly negative correlation between MMA and vitamin B12 levels only in patients without comorbidities.ConclusionPatients with HF have elevated MMA levels, independent of age, gender, HF category, or comorbidities, possibly indicating subclinical vitamin B12 deficiency. Further research is needed to investigate subclinical vitamin B12 deficiency in patients with HF and/or to clarify whether MMA constitutes a biomarker of oxidative stress.     

Serum level of galectin-9 in systemic lupus erythematosus patients with lupus nephritis: Relation to clinical characteristics and disease activity

Aim of the workTo assess galectin-9 (Gal-9) level in the serum of systemic lupus erythematosus (SLE) patients with and without renal involvement and clarify its relation with disease activity.Patients and methods50 SLE patients; 25 with lupus nephritis (LN) and 25 without as well as 25 controls were studied. Systemic Lupus International Collaborating Clinics (SLICC) renal activity score and SLE disease activity index 2000 (SLEDAI-2 K) were determined. Serum Gal-9 was measured in all participants.ResultsGal-9 level was significantly elevated in SLE patients with (16.7; 11.6–33.7 ng/ml) and without (15.9; 11.8–25 ng/ml) compared to controls (3.9; 2.8–5.4 ng/ml) (p < 0.001) but was comparable between the patients groups (p = 0.83). In LN patients, serum Gal-9 and SLICC renal activity score significantly correlated (r = 0.48, p = 0.016). Serum Gal-9 significantly correlated with SLEDAI-2 K in patients with (r = 0.71, p < 0.001) and without (r = 0.95, p < 0.001) LN, with anti-double stranded deoxyribonucleic acid (anti-ds-DNA) titers (with r = 0.57, p < 0.001 and without r = 0.79, p < 0.001) and inversely with C3 (with r = -0.44, p = 0.027 and without r = -0.63, p < 0.001) and C4 (with r = -0.47, p = 0.018 and without r = -0.43, p = 0.03). Gal-9 had an area under the curve (AUC) of 0.96 to distinguish SLE cases from control. However, AUC between LN group and non-nephritic SLE was 0.48. On regression, SLEDAI-2 K was the only significant factor associated with serum Gal-9 (p < 0.001).ConclusionIn SLE patients, significantly raised Gal-9 levels and relation with disease activity were detected indicating its clinical relevance as biomarker of disease activity and its potential value in the disease diagnosis. Its value in discriminating LN from non-nephritic SLE is limited.     

Elevated interleukin levels are associated with higher severity and mortality in COVID 19 – A systematic review,meta-analysis,and meta-regression

Background and aimsCOVID 19 pneumonia commonly leads to ARDS. The occurrence of ARDS in COVID 19 patients is thought to occur secondary to an exaggerated immunologic response. In this meta-analysis, we aim to comprehensively study the various levels of immunological parameters in patients with COVID 19.Materials and methodsWe performed a systematic literature search from PubMed, EuropePMC, SCOPUS, Cochrane Central Database, and medRxiv with the search terms, “COVID-19” and “Interleukin”. The outcome of interest was prognosis in COVID 19 patients.ResultsWe performed meta analysis of 16 studies. Higher counts of CD4 and CD8 with Lower Levels of TNF-a, IL2R, IL6, IL8 were observed on patients with good prognosis compared to patients with poor prognosis; −0.57 (pg/mL) (−1.10, −0.04, p = 0.04), (I² 91%, p < 0.001); −579.84 (U/mL) (−930.11, −229.57, p < 0.001), (I² 96%, p < 0.001); −1.49 (pg/mL) (−1.97, −1.01, p < 0.001), (I² 94%, p < 0.001); −0.80 (pg/mL) (−1.21, −0.40, p < 0.001), (I2 79%, p < 0.001); −2.51 (pg/mL) (−3.64, −1.38, p < 0.00001), (I² 98%, p < 0.001) respectively. Meta-regression showed age and hypertension (coefficient: 1.99, and −1.57, p = 0.005, and 0.006) significantly influenced association between IL-6 and poor outcome.ConclusionElevated immune response to coronavirus occurs in COVID 19 patients. Higher counts of CD4 and CD8 were seen in patients with good prognosis compared to patients with poor prognosis, with Lower levels of TNF-a, IL2R, IL6, IL8, were observed in patients with good prognosis compared to patients with poor prognosis.     

Sexual dysfunction and physical performance in female systemic lupus erythematosus patients

Aim of the workTo investigate the sexual dysfunction in systemic lupus erythematosus (SLE) patients and its relation to physical fitness and other disease parameters.Patients and methodsThe study included 47 SLE females and 47 matched healthy controls. SLE disease activity index (SLEDAI) and systemic lupus international collaborative clinics damage index (SLICC DI) were assessed. Physical performance of the patients was assessed by the grip ability test (GAT), gait velocity test, Jebsen hand function test, fatigue severity scale (FSS) and the modified health assessment questionnaire (mHAQ). Sexual dysfunction of the patients was assessed by the sexual function index (FSFI). Depressive disorders of the patients were assessed by Beck depression inventory.ResultsThe mean age of the patients was 28.7 ± 7.2 years and disease duration 4.4 ± 2.9 years. GAT was significantly lower (43.65 vs 70.00; p = 0.001), and FSS higher (6.5 vs 1; p = 0.001) in patients compared to control. The total FSFI was significantly lower (23.41 vs 29.60; p = 0.001) and all domains scores were significantly lower except the pain domain (p = 0.001). Beck depression inventory score was higher in patients (13.29 vs 12.74; p = 0.365). SLE females with prescribed corticosteroids and azathioprine had significantly lower FSFI as compared to those without while FSFI score was higher in those receiving hydroxychloroquine. The FSFI significantly correlated with C4 level (r = 0.328, p = 0.024 and inversely with, SLEDAI (r = ?0.07, p = 0.001), FSS (r = ?0.54, p = 0.001), mHAQ (?0.37, p = 0.01) and with Beck depression inventory (r = ?0.57, p = 0.001).ConclusionMarried female patients with SLE revealed a higher degree of sexual dysfunction of all domains except pain.     

Right-to-Left Shunt Through Iatrogenic Atrial Septal Defect After MitraClip Procedure

ObjectivesThe aim of this study was to investigate the incidence, characteristics, hemodynamic conditions, and clinical significance of right-to-left (R-L) shunt through an iatrogenic atrial septal defect (iASD) after the MitraClip procedure.BackgroundR-L shunt through an iASD after the MitraClip procedure has not been well investigated.MethodsFrom 2014 to 2017, 385 consecutive patients with mitral regurgitation underwent the MitraClip procedure. iASD was assessed using intraprocedural transesophageal echocardiography. Right and left heart catheterization was used to assess the hemodynamic status of patients. All patients provided written informed consent for the procedure. All data for this study were collected from an established interventional cardiology laboratory database approved by the Cedars-Sinai Medical Center Institutional Review Board.ResultsR-L shunt was observed in 20 patients (5%). In 7 of these patients (35%), R-L shunt was accompanied by acute deoxygenation. Prevalence of severe tricuspid regurgitation (55% vs. 20%; p = 0.001), serum B-type natriuretic peptide (664 pg/ml [434 to 1,169 pg/ml] vs. 400 pg/ml [195 to 699 pg/ml]; p = 0.006), mean pulmonary artery pressure (38 mm Hg [34 to 45 mm Hg] vs. 29 mm Hg [22 to 37 mm Hg]; p < 0.001), and right atrial pressure (19 mm Hg [13 to 20 mm Hg] vs. 10 mm Hg [7 to 14 mm Hg]; p < 0.001) were significantly higher in patients with R-L shunt than in those with left-to-right shunt. Patients with R-L shunt also showed a more prominent reduction in the left atrial V-wave and mean pressure from baseline to post-procedure compared with those with left-to-right shunt (−22.8 ± 2.6 mm Hg vs. −11.8 ± 0.9 mm Hg [p = 0.002] and −7.9 ± 0.8 mm Hg vs. −4.0 ± 0.4 mm Hg [p = 0.003], respectively).ConclusionsR-L shunt through an iASD was observed in 5% of patients who underwent the MitraClip procedure and in one-third of patients with R-L shunt presented acute deoxygenation. Elevated right atrial pressure concomitant with pulmonary hypertension and significant reduction in left atrial pressure after MitraClip deployment were associated with R-L shunt.     

Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI)

ObjectivesThe aim of this study was to evaluate the effect of ticagrelor versus clopidogrel on left ventricular (LV) remodeling after reperfusion of ST-segment elevation myocardial infarction (STEMI) in humans.BackgroundAnimal studies have demonstrated that ticagrelor compared with clopidogrel better protects myocardium against reperfusion injury and improves remodeling after myocardial infarction.MethodsIn this investigator-initiated, randomized, open-label, assessor-blinded trial performed at 10 centers in Korea, patients were enrolled if they had naive STEMI successfully treated with primary percutaneous coronary intervention (PCI) and at least 6-month planned duration of dual-antiplatelet treatment. The coprimary endpoints were LV remodeling index (LVRI) (a relative change of LV end-diastolic volume) measured on 3-dimensional echocardiography and N-terminal pro–B-type natriuretic peptide level at 6 months.ResultsAmong initially enrolled patients with STEMI (n = 336), 139 in each group completed the study. LVRI at 6 months was numerically lower with ticagrelor versus clopidogrel (0.6 ± 18.6% vs. 4.5 ± 16.5%; p = 0.095). Ticagrelor significantly reduced the 6-month level of N-terminal pro–B-type natriuretic peptide (173 ± 141 pg/ml vs. 289 ± 585 pg/ml; p = 0.028). These differences were prominent in patients with pre-PCI TIMI (Thrombolysis In Myocardial Infarction) flow grade 0. By multivariate analysis, ticagrelor versus clopidogrel reduced the risk for positive LV remodeling (LVRI >0%) (odds ratio: 0.56; 95% confidence interval: 0.33 to 0.95; p = 0.030). The LV end-diastolic volume index remained unchanged during ticagrelor treatment (from 54.7 ± 12.2 to 54.2 ± 12.2 ml/m²; p = 0.629), but this value increased over time during clopidogrel treatment (from 54.6 ± 11.3 to 56.4 ± 13.9 ml/m²; p = 0.056) (difference −2.3 ml/m²; 95% confidence interval: −4.8 to 0.2 ml/m²; p = 0.073). Ticagrelor reduced LV end-systolic volume index (from 27.0 ± 8.5 to 24.7 ± 8.4 ml/m²; p < 0.001), whereas no reduction was seen with clopidogrel (from 26.2 ± 8.9 to 25.6 ± 11.0 ml/m²; p = 0.366) (difference −1.8 ml/m²; 95% confidence interval: −3.5 to −0.1 ml/m²; p = 0.040).ConclusionsTicagrelor was superior to clopidogrel for LV remodeling after reperfusion of STEMI with primary PCI. (High Platelet Inhibition With Ticagrelor to Improve Left Ventricular Remodeling in Patients With ST Segment Elevation Myocardial Infarction [HEALING-AMI]; NCT02224534)     

Triglycerides and Residual Atherosclerotic Risk

BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318)     

Programmed death 1 (PD-1) serum level and gene expression in recent onset systemic lupus erythematosus patients

Aim of the workTo investigate the potential association of protein programmed death 1 (PD-1) serum level and its gene expression inrecent onset systemic lupus erythematosus (SLE) patients and study its association with the disease activity.Patients and methodsThe study included 80 recently diagnosed SLE patients and 80 healthy controls. SLE disease activity index (SLEDAI) was assessed. The serum level of soluble (sPD-1) was assessed by enzyme linked immunosorbent assay (ELISA) and its gene expression level was evaluated by real time-polymerase chain reaction (RT-PCR).ResultsThey were 68 females and 12 males (F: M 5.7:1) with age 30.8 ± 8.7 years and disease duration of 3.2 ± 1.7 months. The sPD-1 and PD-1 gene expression level (folds) were significantly elevated in patients (1280.6 ± 1448.1 pg/ml and 0.3 ± 0.06 folds) than controls (109.1 ± 11.9 pg/ml and 0.03 ± 0.008 folds) (p < 0.001). A significant correlation was found between sPD-1 and hematuria, pyuria, fever and C3 level (p = 0.01, p = 0.001, p = 0.02, and p = 0.03 respectively), and between PD-1gene expression and psychosis and fever (p = 0.03, p = 0.014). No significant correlation was found between SLEDAI and PD-1 gene expression or sPD-1 level (p = 0.1, p = 0.23 respectively). No significant correlation was found between sPD-1 and PD-1 gene expression levels and the autoantibodies.ConclusionPD-1 gene expression as well as the serum level of sPD-1 are elevated significantly in recent onset SLE patients denoting that they may have a role in the pathogenesis of the disease while there was no relation to the disease activity. This biomarker may be potentially promising for the development of a novel lupus immunotherapy by targeting the PD-1 pathway.     

Serum interleukin-6 in primary fibromyalgia syndrome patients: Impact on disease burden,severity, quality of life and sleep

Aim of the workTo assess serum interleukin-6 (IL-6) level in primary fibromyalgia syndrome (FMS) patients and to study its relation to disease burden parametersPatients and methodsForty primary FMS patients and 40 age and sex matched controls were studied. Patients answered multiple questionnaires. Fatigue was assessed by multidimensional fatigue inventory (MFI-20), pain severity by visual analogue scale (VAS-pain) and sleep quality by sleep quality numerical rating scale (NRS). The 36-Item Short Form (SF-36) was used to assess quality of life and fibromyalgia Impact Questionnaire (FIQ) was used to evaluate patient status, progress and outcomes.ResultsThe patients mean age was 36.5 ± 7.1 years and disease duration 5.3 ± 2.95 years and they were 38 females and 2 males. The mean serum IL-6 level was significantly higher in patients (134.9 ± 67.3 pg/ml) than control (41.1 ± 8.5 pg/ml)(p = 0.001). The mean VAS-pain was 6.2 ± 1.3 (4–8), FIQ was 58 ± 6.1 (50–70), SF-36 47 ± 10.2 (30–60), MFI20 was 76.5 ± 10.6 (60–95) and sleep quality NRS was 6.9 ± 1.2 (5–9). The values of the studied parameters and scores were significantly different from the control 1.4 ± 0.5; 14.4 ± 6.5; 93.9 ± 3.5 10 ± 5.2 and 0.9 ± 0.8 respectively; p = 0.001 for all). There was a significant correlation between serum IL-6 levels and VAS-pain (r = 0.72, p = 0.001), FIQ (r = 0.58, p = 0.001), SF-36 (r = 0.78, p = 0.001), MFI-20 (r = 0.74, p = 0.001) and sleep NRS (r = 0.78,p = 0.001). On regression, IL-6 level had a greater impact on sleep NRS (p = 0.001), SF-36 (p = 0.005) and MFI20 (p = 0.01).ConclusionsSerum IL-6 level is high in primary FMS patients. Also, serum IL-6 is significantly related to the parameters of fatigue, functional status, sleep quality and pain.     

Clinical and electrophysiological assessment of cranial and peripheral neuropathies in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo study the frequency of cranial and peripheral neuropathies in systemic lupus erythematosus (SLE), their clinical characteristics, electrophysiological pattern and relation to disease activity.Patients and methodsThe study included 30 SLE patients and 20 matched healthy controls. Electrophysiological assessment included routine nerve conduction studies for assessment of peripheral nerves and visual evoked potential, blink reflex, and brain stem auditory evoked potential for assessment of the second, fifth, seventh, and eighth cranial nerves, respectively. Safety of Estrogens in Lupus Erythematosus National Assessment–SLE Disease Activity Index (SELENA–SLEDAI) was assessed.ResultsThe mean age of the patients was 35.8 ± 8.6 years, 27 females and 3 males (9:1) with median disease duration 4.5(1.2–8) years and SELENA-SLEDAI of 12.09 ± 4.94. The mean complement-3 (C3) level was 81.2 ± 26.9 mg/dl and C4 was 11.5 ± 4.4 mg/dl. Peripheral neuropathy was detected electrophysiologically in 66.7% and clinically in 53.3% of the patients and was sensory more than motor. Sensory neuropathy was found in 9(30%), sensorimotor in 11(36.7%), demyelinating in 9(30%), axonal in 6(20%) and both axonal and demyelinating in 5(16.7%) patients. 13.3% had subclinical neuropathy. Sensorimotor and sensory neuropathies were detected in 36.7% and 30% of patients, respectively. Cranial neuropathy was not detected in any patient or control clinically or electrophysiologically. Peripheral neuropathy significantly correlated with SELENA-SLEDAI (r = 0.55, p = 0.002) and negatively with C3 and C4 (r = ?0.65, p = 0.012 and r = ?0.63, p = 0.015 respectively).ConclusionPeripheral neuropathy is a well-recognized but underestimated manifestation of neuropsychiatric SLE with predominance of sensorimotor variant. Peripheral neuropathy is associated with disease activity and complement consumption.     

Elevated interleukin-18 levels correlated with disease activity in systemic lupus erythematosus

The aim of this study was to determine the serum interleukin-18 (IL-18) levels in patients with systemic lupus erythematosus (SLE) and to assess their relationship with disease activity. Thirty-five patients with SLE and 35 age- and sex-matched controls were enrolled in this study. Paired serum samples were collected from all the patients with SLE, both at active stage before treatment and at the stable stage after treatment. The serum IL-18 levels were determined using ELISA and their correlations with the disease activity, measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as anti-dsDNA antibody, CH50, C3, C4, and circulating immune complex levels, were analyzed. The serum IL-18 levels in patients with SLE were significantly higher than those in the controls, particularly when the disease status was active (mean±SD: active stage, 721.23±360.15 pg/ml; inactive stage, 343.68±317.78 pg/ml; controls, 113.98±13.22 pg/ml, p<0.05). The IL-18 levels measured at the active stage before treatment correlated well with SLEDAI (r=0.41, p<0.05) and anti-dsDNA antibody titer (r=0.35, p<0.05). When we compared the changes of the IL-18 level and those of parameters reflecting the disease activity between the active stage and the stable stage of the disease, it was found that the changes in IL-18 level correlated well with the changes of SLEDAI score during the patients disease course (r=0.39, p<0.05). In conclusion, the serum IL-18 levels were elevated in patients with SLE, and these increased levels correlated well with SLE disease activity.Abbreviations CIC Circulating immune complex - IFN Interferon - IL Interleukin - SLE Systemic lupus erythematosus - TNF Tumor necrosis factor     

Watchman Occlusion in Long-Standing Persistent Atrial Fibrillation: Larger Left Atrial Appendages With Greater Residual Leak

ObjectivesThis study sought to compare patients with and without long-standing persistent atrial fibrillation (LSPAF) undergoing Watchman left atrial appendage (LAA) occlusion.BackgroundAn increased burden of atrial fibrillation is associated with progressive left atrial remodeling and enlargement.MethodsTransesophageal echocardiography (TEE) measures of LAA ostial diameter and depth, device compression, and residual leak were evaluated in 101 consecutive Watchman cases. The patients were categorized into LSPAF (n = 48) or non-LSPAF (n = 53) groups and compared.ResultsThe average LAA ostial diameter for LSPAF versus non-LSPAF by TEE omniplane at 0° was 21.1 ± 4.1 mm versus 18.2 ± 3.6 mm (p = 0.0002); at 45° was 18.7 ± 3.4 mm versus 16.3 ± 3.1 mm (p = 0.0004); at 90° was 19.6 ± 3.8 mm versus 16.2 ± 3.4 mm (p = 0.00001); and at 135° was 21.0 ± 4.1 mm versus 18.0 ± 4.1 mm (p = 0.0005). The average LAA depth for LSPAF versus non-LSPAF by TEE at 0° was 28.1 ± 6.4 mm versus 25.2 ± 4.9 mm (p = 0.02); at 45° was 27.9 ± 5.8 mm versus 25.1 ± 4.3 mm (p = 0.007); at 90° was 27.2 ± 5.2 mm versus 22.8 ± 3.7 mm (p = 0.0001); and at 135° was 25.6 ± 5.4 mm versus 21.5 ± 3.8 mm (p = 0.0001). In successfully treated patients, 77% of the LSPAF group received larger device (27, 30, or 33 mm) implants versus only 46% in the non-LSPAF group (p = 0.003). While both groups had similar rates of moderate (3 to 5 mm) leaks at implant (2% vs. 0%; p = 0.14), 27% of the LSPAF vs. 4% of the non-LSPAF group had moderate leaks (p = 0.04) on 6-week follow-up TEE.ConclusionsPatients with LSPAF have significantly larger LAA sizes, require larger devices, and have more residual leak on follow-up TEE. LSPAF may represent a higher risk group that warrants more stringent long-term follow-up.     

Galectin-3 and interleukin-7 as potential serologic markers in rheumatoid arthritis patients

Aim of the workTo assess the level of serum galectin-3 and interleukin-7 (Il-7) in rheumatoid arthritis (RA) patients and to study their association with disease activity as well as other disease parameters.Patients and methodsSerum samples from 66 RA patients and 20 matched controls were tested for galectin-3 and IL-7 using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using disease activity score (DAS28).ResultsThe mean age of the patients was 46.6 ± 12.02 years, mean disease duration was 7.5 ± 7.6 years and they were 61 females and 5 males. The mean DAS28 of the patients was 4.72 ± 1.77. Serum galectin-3 and IL-7 were higher in RA patients (7.7 ± 5.7 ng/ml and 9.03 ± 5.97 pg/ml) than the control (1.5 ± 0.8 ng/ml and 1.6 ± 1.1 pg/ml) (p < 0.001). Serum galectin-3 and IL-7 significantly correlated with age (r = 0.27, p = 0.03 and r = 25, p = 0.04), DAS28 (r = 0.64, p < 0.001 and r = 39, p = 0.001), as well as to each other (r = 0.48, p < 0.001). Serum galectin-3 significantly correlated with ESR (r = 0.29, p = 0.018) and significantly higher in those with fever (p = 0.017). At a cutoff of 2.94 ng/ml, serum galectin-3 showed 84.8% sensitivity and 100% specificity (p < 0.001) and at 2.71 pg/ml, serum IL7 showed a sensitivity of 92.4% and a specificity of 95% (p < 0.001) to diagnose RA.ConclusionSerum galectin-3 and IL-7 were higher in patients than in controls and were increased with high disease activity making them promising biomarkers for RA. Both of them showed high diagnostic power for RA. This may provide further understanding of RA pathogenesis and suggest new therapeutic interventions.     

Assessment of serum interleukin-20 level in rheumatoid arthritis patients: Relation to disease activity and ultrasound measures

Aim of the workTo investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings.Patients and methods45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score (DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay.ResultsMean age of patients was 34.5 ± 11 years; 39 females and 6 males and disease duration 15.8 ± 8.3 years. Their mean DAS-28 was 4.1 ± 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1–58.5 ng/l) than in controls 13.1; 11–15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL- 20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001).ConclusionPatients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA.     

Randomized Trial of Ivabradine in Patients With Hyperadrenergic Postural Orthostatic Tachycardia Syndrome

BackgroundPostural orthostatic tachycardia syndrome (POTS) is a complex, multifaceted disorder that impairs functional status and quality of life. Current pharmacological treatments are limited.ObjectivesThis study investigated the effect of ivabradine (selective blocker of the I_funny channel in the sinoatrial node) on heart rate, quality of life (QOL), and plasma norepinephrine (NE) levels in patients with hyperadrenergic POTS defined by plasma NE >600 pg/ml and abnormal tilt table test.MethodsIn total, 22 patients with hyperadrenergic POTS as the predominant subtype completed a randomized, double-blinded, placebo-controlled, crossover trial with ivabradine. Patients were randomized to start either ivabradine or placebo for 1 month, and then were crossed over to the other treatment for 1 month. Heart rate, QOL, and plasma NE levels were measured at baseline and at the end of each treatment month.ResultsThe average age was 33.9 ± 11.7 years, 95.5% were women (n = 21), and 86.4% were White (n = 23). There was a significant reduction in heart rate between placebo and ivabradine (p < 0.001). Patients reported significant improvements in QOL with RAND 36-Item Health Survey 1.0 for physical functioning (p = 0.008) and social functioning (p = 0.021). There was a strong trend in reduction of NE levels upon standing with ivabradine (p = 0.056). Patients did not experience any significant side-effects, such as bradycardia or hypotension, with ivabradine.ConclusionIvabradine is safe and effective in significantly improving heart rate and QOL in patients with hyperadrenergic POTS as the predominant subtype.     

Changes in Plasma Renin Activity After Renal Artery Sympathetic Denervation

BackgroundThe renin-angiotensin-aldosterone system plays a key role in blood pressure (BP) regulation and is the target of several antihypertensive medications. Renal denervation (RDN) is thought to interrupt the sympathetic-mediated neurohormonal pathway as part of its mechanism of action to reduce BP.ObjectivesThe purpose of this study was to evaluate plasma renin activity (PRA) and aldosterone before and after RDN and to assess whether these baseline neuroendocrine markers predict response to RDN.MethodsAnalyses were conducted in patients with confirmed absence of antihypertensive medication. Aldosterone and PRA levels were compared at baseline and 3 months post-procedure for RDN and sham control groups. Patients in the SPYRAL HTN-OFF MED Pivotal trial were separated into 2 groups, those with baseline PRA ≥0.65 ng/ml/h (n = 110) versus <0.65 ng/ml/h (n = 116). Follow-up treatment differences between RDN and sham control groups were adjusted for baseline values using multivariable linear regression models.ResultsBaseline PRA was similar between RDN and control groups (1.0 ± 1.1 ng/ml/h vs. 1.1 ± 1.1 ng/ml/h; p = 0.37). Change in PRA at 3 months from baseline was significantly greater for RDN compared with control subjects (?0.2 ± 1.0 ng/ml/h; p = 0.019 vs. 0.1 ± 0.9 ng/ml/h; p = 0.14), p = 0.001 for RDN versus control subjects, and similar differences were seen for aldosterone: RDN compared with control subjects (?1.2 ± 6.4 ng/dl; p = 0.04 vs. 0.4 ± 5.4 ng/dl; p = 0.40), p = 0.011. Treatment differences at 3 months in 24-h and office systolic blood pressure (SBP) for RDN versus control patients were significantly greater for patients with baseline PRA ≥0.65 ng/ml/h versus <0.65 ng/ml/h, despite similar baseline BP. Differences in office SBP changes according to baseline PRA were also observed earlier at 2 weeks post-RDN.ConclusionsPlasma renin activity and aldosterone levels for RDN patients were significantly reduced at 3 months when compared with baseline as well as when compared with sham control. Higher baseline PRA levels were associated with a significantly greater reduction in office and 24-h SBP. (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED Study; NCT02439749)     

Superiority of cardiac magnetic resonance imaging over echocardiography in early detection of subclinical cardiac abnormalities in systemic lupus erythematosus patients

BackgroundCardiovascular disease (CVD) has become increasingly recognized as a cause of mortality, especially in patients with long-standing systemic lupus erythematosus (SLE).Aim of the workTo detect subclinical cardiac involvement and its relation to clinical characteristics, disease activity and damage.Patients and methodsTransthoracic echocardiography (TTE) was performed in 36 SLE patients. Cardiac magnetic resonance (CMR) sections were obtained. T1-weighted inversion recovery scout images were obtained after injection of gadolinium.ResultsThirty-six patients were included with a mean age of 32.4 ± 8.5 years; 35 females and 1 male; with disease duration of 7.9 ± 5 years. The frequent cardiac presentations on TTE were tricuspid regurgitation (TR) (41.6%), mitral regurgitation (MR) (36.1%), mitral thickening (25%), early diastolic mitral flow/mitral flow during atrial contraction (E/A) < 1 (19.4%). The most frequent cardiac presentations by CMR were MR (25%), pericarditis (25%), mitral thickening (13.9%), TR (13.9%), myocarditis (8.3). Neither SLE Disease Activity Index (SLEDAI) nor Systemic Lupus International Collaborating Clinics (SLICC) damage index, high- sensitivity-C reactive protein (hsCRP), C3 and C4 levels were significantly correlated with the ejection fraction (EF) by CMR. There was significant negative correlation between disease duration and EF by CMR (r = ?0.36, p = 0.03). Using multiple regression, EF by CMR was strongly predicted by disease duration (p = 0.025). The analysis of EF and MR fraction by CMR and TTE showed acceptable moderate agreement. CMR and TTE showed 83.3% agreement in the detection of pericarditis.ConclusionCMR is superior to echocardiography in detection of subclinical abnormalities in SLE.