Autoantibodies against myelin sheath and S100β are associated with cognitive dysfunction in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) has been associated with cognitive impairment and peripheral production of autoantibodies. Autoantibodies against central nervous system (CNS) proteins and S100 calcium-binding β (S100β) were found increased in diseases characterized by cognitive impairment like Alzheimer disease and Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). The aim of this study was to investigate the plasma levels of autoantibodies against myelin basic protein (anti-MBP), myelin oligodendrocyte glycoprotein (anti-MOG) and S100β, and their relationships with cognitive performance in RA patients. Twenty patients with active rheumatoid arthritis and 19 age-, sex-, and schooling-matched healthy controls were recruited. Multiple dimensions of cognitive function were evaluated by structured clinical questionnaires. Autoantibodies and S100β levels were assessed by ELISAs. Patients had significantly higher levels of anti-MBP IgG (17.51 ± 1.36 vs. 5.24 ± 0.53 ng/mL), anti-MOG IgG (5.68 ± 1.34 vs. 0.51 ± 0.49 ng/mL), and S100β protein (2.24 ± 0.50 vs. 0.47 ± 0.06) than controls (all p < 0.0001). After adjusting for potential confounders, RA group presented worse cognitive performance involving the working memory and executive functions such as inhibition, flexibility, and mental control in parallel to higher autoantibodies and S100β levels than healthy controls (all p < 0.001). Levels of anti-MBP were negatively associated with delayed verbal recall (DVR; r = ?0.42, p = 0.005), Stroop Color-Word (r = ?0.48, p = 0.004), and N-Back Total scores (r = ?0.59, p < 0.0001) and positively with Trail Making Test B (TMB, r = 0.53, p = 0.001). Negative correlation was found between levels of anti-MOG and DVR (r = ?0.64, p < 0.0001), N-Back Total scores (r = ?0.35, p = 0.03), Stroop Color-Word (r = ?0.51, p = 0.001), and positively with TMB (r = 0.50, p = 0.003). S100β levels were associated with DVR (r = ?0.51, p = 0.002), TMB (r = 0.46, p = 0.008), Stroop Color-Word (r = ?0.67, p < 0.0001), and N-Back Total (r = ?0.52, p = 0.003). RA is associated with impaired cognitive performance associated with higher levels of CNS-related autoantibodies and S100β levels. Given the importance of myelin integrity to cognition, our data indicate that these autoantibodies may be harmful to proper cognitive function.     

Evaluation of the Greek TranQol: a novel questionnaire for measuring quality of life in transfusion-dependent thalassemia patients

The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19–58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p < 0.001 and r = 0.5, p < 0.001, respectively). There was also a moderately strong correlation between the physical health scale of TranQol and the relevant SF-36v2 scales, including physical functioning (r = 0.4, p < 0.001), role-physical (r = 0.6, p < 0.001), and bodily pain (r = 0.5, p < 0.001). TranQol also exhibited good internal consistency (Cronbach’s alpha coefficient = 0.9) and excellent test-retest reliability (intra-class correlation coefficient = 0.9). The subgroup of patients that reported a better QoL 1 week after transfusion also demonstrated a significant improvement in their TranQol score. These are the first data regarding the administration of the Greek TranQol in a single thalassemia unit. The psychometric properties of the Greek TranQol confirmed it is a valid, reliable, and responsive to change questionnaire, which can be incorporated into future clinical trials.     

Esophageal intraluminal baseline impedance is associated with severity of acid reflux and epithelial structural abnormalities in patients with gastroesophageal reflux disease

Background

The esophageal intraluminal baseline impedance may be used to evaluate the status of mucosa integrity. Esophageal acid exposure decreases the baseline impedance. We aimed to compare baseline impedance in patients with various reflux events and with different acid-related parameters, and investigate the relationships between epithelial histopathologic abnormalities and baseline impedance.

Methods

A total of 229 GERD patients and 34 controls underwent 24-h multichannel intraluminal impedance and pH monitoring (MII–pH monitoring), gastroendoscopy, and completed a GERD questionnaire (GerdQ). We quantified epithelial intercellular spaces (ICSs) and expression of tight junction (TJ) proteins by histologic techniques.

Results

Mean baseline values in reflux esophagitis (RE) (1752 ± 1018 Ω) and non-erosive reflux disease (NERD) (2640 ± 1143 Ω) were significantly lower than in controls (3360 ± 1258 Ω; p < 0.001 and p = 0.001, respectively). Among NERD subgroups, mean baselines in the acid reflux group (2510 ± 1239 Ω) and mixed acid/weakly acidic reflux group (2393 ± 1009 Ω) were much lower than in controls (3360 ± 1258 Ω; p = 0.020 and p < 0.001, respectively). The mean baseline in severe RE patients was significantly lower than in mild RE patients (LA-C/D vs. LA-A/B: 970 ± 505 Ω vs. 1921 ± 1024 Ω, p < 0.001). There was a significant negative correlation between baseline value and acid exposure time (AET) (r = ?0.41, p < 0.001), and a weak but significant correlation (r = ?0.20, p = 0.007) between baseline value and weakly AET. Negative correlations were observed between ICS and the baseline impedance (r = ?0.637, p < 0.001) and claudin-1 and the baseline impedance (r = ?0.648, p < 0.001).

Conclusions

Patients with dominant acid reflux events and with longer AET have low baseline impedance. Baseline values are correlated with esophageal mucosal histopathologic changes such as dilated ICS and TJ alteration.

     

The Value of the Electrocardiogram for Evaluating Prognosis in Patients with Idiopathic Pulmonary Arterial Hypertension

Background

Association between electrocardiography (ECG) features and right ventricular anatomy and physiology has been established. This study is aimed to identify the value of 12-lead ECG in evaluating prognosis of patients with idiopathic pulmonary arterial hypertension (IPAH).

Method

194 patients with newly diagnosed IPAH were included in this study. Correlations between electrocardiography variables and hemodynamics were assessed. Univariate and multivariable cox regression analysis were performed to identify ECG variables for predicting all-cause mortality in IPAH.

Results

Partial correlation analysis showed that P wave amplitude in lead II correlated with the mean pulmonary arterial pressure (mPAP, r = 0.349, p ≤ 0.001) and cardiac index (CI, r = ?0.224, p = 0.002); R wave amplitude in V1 correlated with mPAP (r = 0.359, p ≤ 0.001); S wave amplitude in V6 correlated with mPAP (r = 0.259, p = 0.030) and CI (r = ?0.220, p = 0.003). P wave amplitude in lead II (HR 1.555, p = 0.033) and R wave amplitude in lead aVR (HR 5.058, p < 0.001) were the independent predictors of all-cause mortality. Kaplan–Meier survival curves showed patients with a p ≥ 0.25 mv in lead II, and R ≥ 0.4 mv in lead aVR had lower 3-year survival (55 vs. 91%, p < 0.001).

Conclusion

Specific lead-12 ECG features could reflect right ventricular overload hemodynamics, and are useful to evaluate prognosis of patients with IPAH.

     

Association between gait characteristics and endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease

The aim of the study was to determine whether gait characteristics were associated with endothelial cell inflammation, oxidative stress, and apoptosis and with circulating biomarkers of inflammation and antioxidant capacity in older patients with symptomatic peripheral artery disease (PAD). Gait measurements of 231 symptomatic men and women with PAD were assessed during a 4-m walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells and on circulating inflammatory and vascular biomarkers. In a multivariate regression model for gait speed, the significant independent variables were age (p < 0.001), intercellular cell adhesion molecule-1 (ICAM-1) (p < 0.001), diabetes (p = 0.003), sex (p = 0.003), and history of cerebrovascular accidents (p = 0.021). In multivariate analyses for gait cadence, the significant independent predictors included high-sensitivity C-reactive protein (HsCRP) (p < 0.001), diabetes (p = 0.001), and hypertension (p = 0.001). In a multivariate regression model for gait stride length, the significant independent variables were HsCRP (p < 0.001), age (p < 0.001), ICAM-1 (p < 0.001), hypertension (p = 0.002), cellular reactive oxygen species production (p = 0.007), and sex (p = 0.008). Higher levels of circulating biomarkers of inflammation and endothelial cell oxidative stress were associated with slower gait speed, slower cadence, and shorter stride length in older symptomatic patients with PAD. Additionally, this profile of impaired gait was more evident in older patients, in women, and in those with diabetes, hypertension, and history of cerebrovascular accidents.     

Autoantibodies against interleukin-21 correlate with disease activity in patients with rheumatoid arthritis

The objective of this study is to investigate the levels of interleukin (IL)-21 and autoantibodies (AAbs) against IL-21 and their association with clinical characteristics and laboratory parameters in patients with rheumatoid arthritis (RA). One hundred twenty-six patients with RA, 69 patients with osteoarthritis (OA), and 88 healthy controls (HC) were included in this study. The levels of IL-21 and AAbs against IL-21 in the serum were measured using enzyme-linked immunosorbent assay (ELISA). The correlation between the levels of IL-21 and anti-IL-21 AAbs with clinical and laboratory parameters was evaluated. The results showed that the concentration of IL-21 was significantly higher in the serum of patients with RA (15.58 ± 3.22 ng/ml) than OA (1.80 ± 0.99 ng/ml) and HC (0.07 ± 0.03 ng/ml, p < 0.01). The levels of IL-21 in the serum correlated with erythrocyte sedimentation rate (ESR) in patients with RA (r = 0.435, p < 0.01). Anti-IL-21 AAbs could be detected in RA patients. The median AU value of AAbs against IL-21 was significantly higher in serum of RA (47.90) than in that of OA (15.17) and HC (8.19, p < 0.01). The titers of AAbs against IL-21 correlated with Disease Activity Score-28 (DAS28) (r = 0.449, p < 0.001), ESR (r = 0.386, p < 0.001), and CRP (r = 0.241, p = 0.03). Both IL-21 and AAbs against IL-21 are elevated in RA. The levels of AAbs against IL-21 correlate with disease activity, which suggests that anti-IL-21 AAbs may play a role in the pathogenesis of RA.     

Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity,damage, and functional status

The study aims to evaluate the clinical significance of serum levels of tumor necrosis factor alpha (TNF-α) and -308 A/G promoter polymorphism in juvenile idiopathic arthritis (JIA) patients and find any association to the subsets, clinical and laboratory features, disease activity, and damage as well as functional disability. Forty-eight JIA children and 30 controls were included in the present study. Juvenile arthritis disease activity score in 27 joints (JADAS-27) was calculated, juvenile arthritis damage index (JADI) was assessed, and Childhood Health Assessment Questionnaire (CHAQ) measured the functional status. Serum TNF-α was assayed by ELISA and gene (-308) promoter polymorphism was determined by polymerase chain reaction. The 48 JIA children (mean age 11.5 ± 2.8 years) were 13 systemic, 17 oligoarticular, and 18 polyarticular onset. The serum TNF-α was significantly higher in patients (90.4 ± 6.3 ng/ml) compared to control (3.5 ± 2.6 ng/ml) (p < 0.0001) with a tendency to be higher in the polyarticular subtype. All controls had TNF-α -308 GG alleles. The frequency of GG genotype tended to be higher in systemic onset compared to oligoarticular and polyarticular subtypes. The serum TNF-α significantly correlated with JADAS-27 (r = 0.32, p = 0.03) and CHAQ (r = 0.37, p = 0.01) and negatively with the presence of GG alleles (r = ?0.48, p = 0.001). The GG alleles were significantly negatively associated with C-reactive protein (r = ?0.32, p = 0.03) with a tendency to negatively correlate with JADAS-27, CHAQ, and JADI-extrarticular (r = ?0.28, p = 0.06; r = ?0.25, p = 0.09 and r = ?0.25, p = 0.09, respectively). There is evidence of a possible influence of the ?308 SNP promoter position on the production of TNF-α, the severity of JIA which may consequently influence the response to anti-TNF-α treatment.     

Predictors of changes in disease activity among children with juvenile dermatomyositis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry

Determinants of changes in disease activity among patients with juvenile dermatomyositis (JDM) are unknown. Our objective was to develop predictive models to predict changes in disease activity using the CARRA Legacy Registry. The CARRA Legacy Registry included 658 subjects with definite or probably JDM with 297 subjects with a one follow-up visit after baseline, and we studied the 65 subjects with active disease at baseline. Linear regression models were used to build risk scores for changes in disease activity adjusted for baseline disease activity, age, sex, and disease duration. Disease activity improved from baseline to 6-month follow-up as measured by patient/parent global health score (median 4; p = 0.008), patient pain score (median 2; p = 0.014), physician global (median 4; p < 0.001), and Childhood Myositis Assessment Scale (CMAS) (median 41, p < 0.001). Anti-nuclear antibodies (p = 0.013) and hydroxychloroquine use (p = 0.045) were significant predictors of less improvement in patient/parent global and baseline patient/parent global. Anti-nuclear antibodies (p = 0.001) and V/shawl sign (p = 0.005) were significant predictors of less improvement in patient pain (R-square improved from 0.29 for adjustors alone to 0.46 for the full model). Small joint arthritis (p < 0.01) predicted less improvement and dysphagia/dysphonia (p = 0.033) predicted greater improvement in CMAS and baseline CMAS (R-square improved from 0.73 for adjustors alone to 0.86 for the full model). Disease characteristics can help identify patients who are less likely to improve over time. Risk scores to predict future changes in disease activity could be used to trigger more aggressive treatment earlier in the disease course.     

The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis

The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median 76.6 pg/ml [interquartile range (IQR) 57.9–136.2] vs. 29.9 pg/ml (IQR 21.9–65.5), P < 0.001) and disease controls. Serum IL-35 in IIM patients negatively correlated with disease duration moderately (r = ?0.35, P < 0.01). Patients with dysphagia had higher IL-35 than those without (median149.35 pg/ml (IQR 87.97–267.32) vs. 70.72 pg/ml (IQR 54.49–123.42), P = 0.001). Cross-sectional correlation analysis showed a weak positive correlation between serum IL-35 and CK (r = 0.293, P = 0.003), moderate positive correlation with erythrocyte sedimentation rate (ESR) (r = 0.304, P = 0.002), serum ferritin (SF) (r = 0.467, P = 0.001) and LDH levels (r = 0.401, P < 0.001). Additionally, serum IL-35 was higher in patients who were positive for anti-HMGCR (median 292.04 pg/ml (IQR 67.9–442.86) vs. 74.66 pg/ml (IQR 57.24–131.32), P = 0.038) and anti-SRP antibody (median 130.33 pg/ml (IQR 88.04–481.28) vs. 73.06 pg/ml (IQR 56.78–134.28), P = 0.009) than in negative patients, respectively. Follow-up study showed that changes in IL-35 levels after treatment correlated with changes in MYOACT scores moderately (r = 0.375, P = 0.029). These data indicate that increased serum IL-35 could act as a disease activity marker and as a risk factor for esophageal involvement in IIM. IL-35 may participate in the pathophysiological processes of IIM, but it still needs further study to confirm.     

Relationship between HRV measurements and demographic and clinical variables in a population of patients with atrial fibrillation

Little is known about the role of HRV in atrial fibrillation (AF) patients. Aim of our study was to assess the relationship between HRV measurements and demographic and clinical variables in a population of 274 AF patients. We selected all consecutive patients with persistent/permanent AF among whom had performed a Holter ECG in our Department from April 2010 to April 2015. Time-domain analysis of HRV was evaluated. Demographic and clinical variables were collected for each patient. At multivariable logistic regression, a higher pNN50 was associated with ACE inhibitors/ARBs (p = 0.016) and a lower pNN50 with obesity (p = 0.037) and higher heart rate (HR) (p < 0.0005). A higher RMSSD was associated with ACE inhibitors/ARBs (p = 0.001), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower RMSSD with a higher HR (p < 0.0005). A higher SDNN_i was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.002) and a lower SDNN_i with dysthyroidism (p = 0.048) and higher HR (p < 0.0005). A higher SDANN was associated with non-dihydropyiridine calcium-channel-blockers (p = 0.002) and ACE inhibitors/ARBs (p = 0.002) and a lower SDANN with hypertension (p = 0.034), obesity (p = 0.011), stroke (p = 0.031), pneumonia (p = 0.005) and higher HR (p < 0.0005). A higher SDNN was associated with ACE inhibitors/ARBs (p < 0.0005), digitalis (p < 0.0005) and beta-blockers (p = 0.022) and a lower SDNN with obesity (p = 0.012), pneumonia (p = 0.049) and higher HR (p < 0.0005). Our study showed that, in AF patients, there is a direct relationship between some clinical variables and HRV measurements; as for patients with sinus rhythm, even in AF patients this relationship seemed to reflect the autonomic nervous system activity.     

Cross-cultural adaptation and validation of the Chinese version of the Health Assessment Questionnaire for the Spondyloarthropathies (HAQ-S)

The Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) is a commonly used questionnaire to evaluate function and health status of patients with ankylosing spondylitis (AS). The objective of this study was to cross-culturally adapt the HAQ-S into Chinese and then to evaluate its reliability and validity. The Chinese version of the HAQ-S was obtained with a five-step procedure of translation and cross-cultural adaptation. All invited patients met the New York criteria for AS, and a total of 103 patients finally participated in this study. Intraclass correlation coefficient (ICC) was used to evaluate the test-retest and inter-rater reliability of the HAQ-S. Internal consistency of the questionnaire was evaluated by Cronbach’s alpha coefficient. Spearman’s correlation coefficient was calculated to assess the construct validity between the HAQ-S and Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Bath AS Metrology Index (BASMI), and the laboratory parameters (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP). Test-retest and inter-rater reliability were excellent with intraclass correlation coefficients of 0.987 (p < 0.05) and 0.982 (p < 0.05), respectively. The overall internal consistency of the HAQ-S was found satisfactory (Cronbach’s alpha = 0.914). The Chinese version of the HAQ-S correlated good with the BASFI (r = 0.749, p < 0.01), and moderate with the BASDAI (r = 0.581, p < 0.01) and the BASMI (r = 0.425, p < 0.01). But, the adapted questionnaire correlated poorly with ESR (r = 0.298, p < 0.01) or CRP (r = 0.283, p < 0.01). The Chinese version of the HAQ-S is reliable and valid for the evaluation of Chinese-speaking patients with AS.     

Association of RBC count and Hct with MS and its components in China rural population

Due to the abnormal hemorheology in patients with metabolic syndrome (MS), some differences may exhibit in erythrocyte parameters. This cross-sectional study was to determine whether the red blood cell (RBC) count and hematocrit (Hct) were associated with MS in China rural area. We selected 11,191 (5170 males and 6021 females) subjects over 35 years. MS was defined according to the revised ATPIII criteria. We used Student’s t test to compare the erythrocyte parameters between normal and MS groups. We also assessed the erythrocyte parameters for different MS component numbers. A partial correlation coefficient was used to evaluate the relationship between erythrocyte parameters and each MS component. The RBC counts and Hct were generally higher in MS/component groups than normal groups for both genders. The RBC counts and Hct increased with the increasing MS component numbers. The partial correlation coefficients between erythrocyte parameters and waist circumference (WC) were bigger than other components (RBC count: r = 0.258 for male and r = 0.218 for female, p < 0.001; Hct: r = 0.209 for male and r = 0.149 for female, p < 0.001). RBC count and Hct were positively related with MS/component for both genders. They were more associated with WC and diastolic blood pressure (DBP) than with other MS components.     

Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from <Emphasis Type="Italic">Proteus mirabilis</Emphasis>

Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis—hemolysin (HpmB), urease C (UreC), and urease F (UreF)—were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p = 0.005, p < 0.001, and p = 0.003 and p = 0.007, p = 0.002, and p < 0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide—which are non-cross-reactive with human tissue antigens—were observed and their significant difference compared to healthy controls (p = 0.007, p < 0.001, p < 0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.     

Association Between Small Intestinal Bacterial Overgrowth by Glucose Breath Test and Coronary Artery Disease

Background

A possible role of gut bacteria and their metabolic by-products in the development of coronary artery disease (CAD) is suspected. There is a lack of studies evaluating the association of small intestinal bacterial overgrowth (SIBO) with the development of CAD.

Aim

To evaluate the frequency and risk factors for angiography-confirmed CAD in patients with or without SIBO.

Methods

A total of 1059 patients tested for SIBO using the glucose hydrogen/methane breath test from 2006 to 2014 were evaluated. In total, 160 had coronary artery angiography and were included in the study. SIBO-positive patients were compared to SIBO-negative patients. Demographic, clinical, and laboratory variables and the presence of CAD on coronary angiography were analyzed.

Results

Patients with SIBO had a higher frequency of CAD (78.9 vs. 38.6%, p < 0.001), diabetes mellitus (40.0 vs. 22.9%, p = 0.016), chronic kidney disease (26.7 vs. 12.9%, p = 0.025), use of angiotensin conversion enzyme inhibitor/blocker (45.5 vs. 32.9%, p = 0.008), and statins (75.6 vs. 61.4%, p = 0.004). Patients with SIBO had an increased number of coronary arteries affected compared to SIBO-negative patients (1-vessel disease 67.2 vs. 32.8%, p < 0.001; 2-vessel disease 85.7 vs. 14.3%, p < 0.001; and 3-vessel disease 82.4 vs. 17.6%, p < 0.001, respectively). In the stepwise multivariate logistic regression analysis, SIBO remained an independent risk factor for CAD (odds ratio 7.18, 95% confidence interval 3.09–16.67; p < 0.001).

Conclusion

SIBO was found to be associated with CAD and with the number of coronary arteries involved in this study from a single tertiary center. Further studies are necessary to confirm the association of SIBO with CAD. In the presence of risk factors, patients with SIBO may benefit from assessment for CAD.

     

Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy

Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were <20 ng/mL and 21–29 ng/ml, respectively. Patients were sub-grouped according to biologic therapy. A multivariate analysis was performed. Two-hundred patients, including 136 with a rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p < 0.0001), in either rheumatic diseases (78.7 vs 41 %; p < 0.0001) or IBD (75 vs 50 %; p = 0.03) group. At multivariate analysis, only biologic therapy was independently associated with vitamin D deficit (OR 4.61; p = 0.001). Patients with vitamin D deficiency/insufficiency had hypocalcemia more frequently than controls (22.8 vs 10.9 %; p = 0.03), while PTH values did not differ significantly. This study finds that the prevalence of vitamin D deficiency/insufficiency was very high in patients with either rheumatic diseases or IBD receiving a biologic therapy.     

Cardiovascular risk assessment in patients with rheumatoid arthritis: a correlative study of noninvasive arterial health testing

This study aimed to determine the relationship between noninvasive measures of arterial health and both estimated 10-year cardiovascular risk and measures of disease activity over time in established rheumatoid arthritis. Fifty rheumatoid arthritis patients underwent noninvasive arterial health testing (brachial artery reactivity, aortic augmentation index [AIx], pulse wave velocity, carotid artery intima-media thickness, and carotid artery plaque presence) and assessment of clinical disease activity (tender or swollen joint counts, Clinical Disease Activity Index [CDAI], and Health Assessment Questionnaire II [HAQ-II]). Clinical measures during 3 years before the study visit were averaged. Arterial health testing was compared with the American Heart Association/American College of Cardiology (AHA/ACC) Pooled Cohort Equation. Spearman methods identified correlations between disease activity measures, cardiac biomarkers, and arterial health parameters. Among the patients (mean age, 57.5 years), disease activity was moderate (mean [SD] CDAI, 16.9 [15.3]). At the study visit, corrected aortic augmentation index correlated with CDAI (r = 0.37, P = .009) and HAQ-II (r = 0.33, P = .02). AIx correlated with time-averaged tender joint count (r = 0.37, P = .008), CDAI (r = 0.36, P = .01), HAQ-II (r = 0.36, P = .01), swollen joint count (r = 0.36, P = .10), patient global assessment (r = 0.33, P = .02), physician global assessment (r = 0.35, P = .01), and pain score (r = 0.38, P = .007). The AHA/ACC low-risk group (<5% 10-year risk) had highest prevalence of carotid plaques. Arterial health testing may identify increased risk of cardiovascular disease compared with risk obtained through AHA/ACC Pooled Cohort Equation. Measures of arterial stiffness correlate with the burden of disease activity over time.     

Physical inactivity increases endostatin and osteopontin in patients with coronary artery disease

The balance between the angiostatic factor endostatin (ES) and angiogenic factor osteopontin (OPN) is essential in physiological and pathological angiogenesis. Several circumstances might influence this equilibrium and are of distinct interest when investigating mechanisms in coronary artery disease (CAD). The present explorative cross-sectional study was to investigate the influence of physical inactivity on ES and OPN levels in 181 male and 71 female patients with angiographycally verified CAD. Anamnestic and laboratory data were collected; ES was measured in serum and OPN in plasma by ELISA. Univariate analysis of variance was used to test for the influence of physical activity on ES and OPN levels and age, BMI, sex and diabetes status were included as covariates. ES and OPN intercorrelated significantly (r = 0.42; p < 0.001). ES and OPN decreased significantly in response to increasing activity level of patients suffering CAD (F = 5.5; p < 0.001 and F = 3.6; p < 0.01 resp.). This study is the first to show a linear decrease in ES and OPN levels in CAD patients depending on the degree of physical activity undergone. Lower levels of ES and OPN in physically active patients might be a sign of increased angiogenesis and decreased inflammation and calcifying activity and therefore contribute to the understanding of the damaging effect of physical inactivity in cardiovascular disease.     

Paced QRS duration and myocardial scar amount: predictors of long-term outcome of right ventricular apical pacing

Long-term right ventricular apical pacing (RVAP) is reportedly associated with heart failure (HF) development. However, the predictors of pacing-induced HF (PHF) remained unclear. We retrospectively enrolled 234 patients without structural heart disease who underwent a permanent pacemaker implantation with RVAP between 1982 and 2004. RVAP-induced HF was defined as left ventricular ejection fraction decrease >5 % with HF symptom without other HF development etiology. The QRS duration of a paced beat (pQRSd) and myocardial scar score were analyzed from each patient’s 12-lead ECG. During a mean 15.6 years (range 3.3–30.0 years), 48 patients (20.5 %) patients developed RVAP-induced HF. The PHF group patients had a longer pQRSd (192.4 ± 13.5 vs. 175.7 ± 14.7 ms in non-PHF patients, p < 0.001) and a higher myocardial scar score (5.2 ± 1.9 vs. 2.7 ± 1.9, respectively p < 0.001). In multivariate Cox regression analysis, old age at implantation [Hazard ratio (HR) 1.62, 95 % confidential interval (CI) 1.22–2.16, p = 0.001], a longer pQRSd (HR 1.54, 95 % CI 1.15–2.05, p = 0.003), a higher myocardial scar score (HR 1.23, 95 % CI 1.03–1.49, p = 0.037), and a higher percentage of ventricular pacing (HR 1.31, 95 % CI 1.01–1.49, p = 0.010) were independent predictors of PHF. Based on the results of the receiver-operating characteristic (ROC) curve, the pQRSd cutoff was 185 ms (AUC 0.79, sensitivity 66.7 %, specificity 76.3 %) and myocardial scar score cutoff value was 4 (AUC 0.81, sensitivity 81.3 %, specificity 66.1 %). The pQRSd was positively correlated with scar score (r = 0.70, p < 0.001). pQRSd ≥185 ms and/or myocardial scar score ≥4 might be independent long-term prognostic markers of PHF.     

Defining Swallowing-Related Quality of Life Profiles in Individuals with Amyotrophic Lateral Sclerosis

Although it is known that dysphagia contributes to significant malnutrition, pneumonia, and mortality in amyotrophic lateral sclerosis (ALS), it remains unclear how swallowing impairment impacts quality of life in this vulnerable patient population. The aim of the current study was to (1) delineate swallow-related quality of life (SR-QOL) profiles in individuals with ALS and (2) evaluate relationships between SR-QOL, degree of swallowing impairment, and ALS global disease progression. Eighty-one ALS patients underwent a standardized videofluoroscopic swallow study and completed the swallowing quality of life (SWAL-QOL) instrument and ALS functional rating scale-revised (ALSFRS-R). Penetration Aspiration Scale (PAS) scores were derived by a blinded rater. Correlation analyses and a between groups ANOVA (safe vs. penetrators vs. aspirators) were performed. Mean SWAL-QOL score for this cohort was 75.94 indicating a moderate degree of SR-QOL impairment with fatigue, eating duration, and communication representing the most affected domains. Correlations were revealed between the SWAL-QOL and (1) PAS (r = ?0.39, p < 0.001) and (2) ALSFRS-R (r = 0.23, p < 0.05). Mean (SD) SWAL-QOL scores for safe versus penetrator versus aspirator groups were 81.2 (2.3) versus 77 (3.4) versus 58.7 (5.9), respectively, with a main effect observed [F(2,78) = 9.71, p < 0.001]. Post hoc testing revealed lower SWAL-QOL scores for aspirators versus safe swallowers (p < 0.001) and aspirators versus penetrators (p < 0.001). Overall, SR-QOL was moderately reduced in this cohort of ALS patients and profoundly impacted in ALS aspirators and individuals with advanced disease. These findings highlight the importance of early multidisciplinary intervention to not only avoid malnutrition, weight loss, and pulmonary sequelae but also the associated reduced QOL seen in these individuals.     

Gender Differences in Platelet Reactivity in Patients Receiving Dual Antiplatelet Therapy

Background

Cardiovascular risk is still underestimated in women, experiencing higher mortality and worse prognosis after acute cardiovascular events. Gender differences have been reported in thrombotic and hemorrhagic risk during dual antiplatelet therapy (DAPT), thus suggesting a potential variability in platelet reactivity according to sex. The aim of the present study was to assess the role of gender on platelet function and the prevalence of high-on treatment residual platelet reactivity (HRPR) during DAPT in patients with recent acute coronary syndrome or percutaneous coronary revascularization.

Methods

Patients treated with DAPT (ASA and clopidogrel or ticagrelor) were scheduled for platelet function assessment at 30–90 days post-discharge. By whole blood impedance aggregometry, HRPR was considered for ASPI test >862 AU*min (for ASA) and ADP test values ≥417 AU*min (for ADP-antagonists).

Results

We included 541 patients on DAPT, 122 (22.6 %) of whom were females. Females were older (p < 0.001), displayed more frequently hypercholesterolemia (p = 0.003), renal failure (p = 0.04), acute presentation (p < 0.001), higher cholesterol levels and platelets count (p < 0.001). Inverse association was demonstrated with smoking (p < 0.001), previous PCI (p = 0.04) and statin use (p = 0.03), creatinine and haemoglobin (p < 0.001). Female gender did not influence mean platelet reactivity or the prevalence of HRPR for ASA (1.7 % vs 1.4 %, OR[95%CI] = 1.14[0.17–4.36], p = 0.99, adjusted OR[95%CI] = 1.54[0.20–11.6], p = 0.68) or ADP-antagonists (26.3 % vs 22.8 %, OR[95%CI] = 1.17[0.52–1.34], p = 0.45, adjusted OR[95%CI] = 1.05[0.59–1.86], p = 0.87). Results did not change when considering separately the 309 patients treated with clopidogrel (34 % vs 31.3 %, OR[95%CI] = 1.13[0.62–2.07], p = 0.76, adjusted OR[95%CI] = 1.35[0.63–2.9], p = 0.44 for females vs males), or patients (n = 232) on ticagrelor (20.4 % vs 11.1 %, OR[95%CI] = 2.27[0.99–5.17], p = 0.06 for females vs males), confirmed after correction for baseline differences (adjusted OR[95%CI] = 1.21[0.28–2.29], p = 0.68).

Conclusion

In patients receiving dual antiplatelet therapy, gender does not impact on the prevalence of high-on treatment residual platelet reactivity (HRPR) with the major antiplatelet agents ASA, clopidogrel or ticagrelor.