Lipid peroxidation as risk factor for endothelial dysfunction in antiphospholipid syndrome patients

The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616–0.837 and AUC 0.824, p?0.001, 95 % CI 0.690–0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.     

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.     

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.     

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.     

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.

     

The relationship of nitric oxide synthesis capacity,oxidative stress,and albumin-to-creatinine ratio in black and white men: the SABPA study

Inadequate substrate availability and increased nitric oxide synthase inhibitor levels attenuate nitric oxide (NO) synthesis, whereas increased vascular oxidative stress may lead to inactivation of NO. We compared markers of NO synthesis capacity and oxidative stress in a bi-ethnic male population. Inter-relationships of ambulatory blood pressure and urinary albumin-to-creatinine ratio with NO synthesis capacity and oxidative stress markers were investigated. NO synthesis capacity markers (L-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA)) and oxidative stress markers (serum peroxides, total glutathione, glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD), and catalase) were measured. Black men displayed higher blood pressure and albumin-to-creatinine ratio (all p < 0.001), while NO synthesis capacity was more favorable (higher L-arginine and lower ADMA (p ≤ 0.003)). Antioxidant enzyme activities were similar except for the redox status markers (GR activity and GR/GPx ratio), which were upregulated in black men (p < 0.001). In black men, ADMA was inversely related to GPx activity (R ² = 0.15; β = ?0.20; p = 0.050) and GPx/SOD ratio (R ² = 0.24; β = ?0.37; p < 0.001), but none of these markers related to blood pressure or albumin-to-creatinine ratio. In white men, albumin-to-creatinine ratio was positively associated with ADMA (R ² = 0.18; β = 0.39; p < 0.001) while ADMA was inversely related to GR activity (R ² = 0.26; β = ?0.29; p = 0.002) and GR/GPx ratio (R ² = 0.25; β = ?0.28; p = 0.003). Black men with elevated blood pressure and albumin-to-creatinine ratio displayed a favorable NO synthesis capacity. This may be counteracted by increased inactivation of NO, although it was not linked to vascular or renal phenotypes. In white men, reduced NO synthesis capacity may lower NO bio-availability, thereby influencing the albumin-to-creatinine ratio.     

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.     

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.

     

Clinical impact of galectin-3 in newly diagnosed t (15;17)(q22;q21)/PML-RARa acute promyelocytic leukemia treated with all-trans retinoic acid and arsenic trioxide-based regimens

Increased galectin-3 expression has been currently showed to be associated with poor prognosis in some hematological malignancies, such as acute myeloid leukemia, diffuse large B cell lymphoma. However, little is known about the clinical significance of galectin-3 in patients with acute promyelocytic leukemia (APL). We investigated the concentration of serum galectin-3 and characterized the relationship between galectin-3 and outcome in patients with APL. Higher galectin-3 levels were detected in patients with APL compared with the healthy controls (p < 0.001). Higher galectin-3 levels were closely associated with older ages (p < 0.001), the medical history of psoriasis (p = 0.036), coagulopathy (p = 0.042), and CD34 expression (p = 0.004). Compared with patients with lower galectin-3 levels, those with higher galectin-3 levels had significant shorter overall survival (p = 0.028) and relapse-free survival (p = 0.001). Multivariate analysis showed that serum galectin-3 was an independent unfavorable factor for relapse-free survival in patients with APL treated with all-trans retinoic acid and arsenic trioxide-based frontline therapy. Clinical impact of galectin-3 should be further investigated in patients with APL.     

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.     

A Moderated Mediation Model of HIV-Related Stigma,Depression, and Social Support on Health-Related Quality of Life among Incarcerated Malaysian Men with HIV and Opioid Dependence

Although it is well established that HIV-related stigma, depression, and lack of social support are negatively associated with health-related quality of life (HRQoL) among people living with HIV (PLH), no studies to date have examined how these psychosocial factors interact with each other and affect HRQoL among incarcerated PLH. We, therefore, incorporated a moderated mediation model (MMM) to explore whether depression mediates the effect of HIV-related stigma on HRQoL as a function of the underlying level of social support. Incarcerated HIV-infected men with opioid dependence (N = 301) were recruited from the HIV units in Kajang prison in Malaysia. Participants completed surveys assessing demographic characteristics, HIV-related stigma, depression, social support, and HRQoL. Results showed that the effect of HIV-related stigma on HRQoL was mediated via depression (a1:β = 0.1463, p < 0.001; b1:β = ?0.8392, p < 0.001), as demonstrated by the two-tailed significance test (Sobel z = ?3.8762, p < 0.001). Furthermore, the association between social support and HRQoL was positive (β = 0.4352, p = 0.0433), whereas the interaction between HIV-related stigma and depression was negatively associated with HRQOL (β = ?0.0317, p = 0.0133). This indicated that the predicted influence of HIV-related stigma on HRQoL via depression had negative effect on HRQoL for individuals with low social support. The results suggest that social support can buffer the negative impact of depression on HRQoL and highlights the need for future interventions to target these psychosocial factors in order to improve HRQoL among incarcerated PLH.     

The Influence of Neurocognitive Impairment,Depression, and Alcohol Use Disorders on Health-Related Quality of Life among Incarcerated,HIV-Infected,Opioid Dependent Malaysian Men: A Moderated Mediation Analysis

Prior research has widely recognized neurocognitive impairment (NCI), depression, and alcohol use disorders (AUDs) as important negative predictors of health-related quality of life (HRQoL) among people living with HIV (PLWH). No studies to date, however, have explored how these neuropsychological factors operate together and affect HRQoL. Incarcerated male PLWH (N = 301) meeting criteria for opioid dependence were recruited from Malaysia’s largest prison. Standardized scales for NCI, depression, alcohol use disorders (AUDs) and HRQoL were used to conduct a moderated mediation model to explore the extent to which depression mediated the relationship between NCI, HRQoL, and AUDs using an ordinary least squares regression-based path analytic framework. Results showed that increasing levels of NCI (B = ?0.1773, p < 0.001) and depression (B = ?0.6147, p < 0.001) were negatively associated with HRQoL. The effect of NCI on HRQoL was significantly (Sobel z = ?3.5600, p < 0.001) mediated via depression (B = ?0.1230, p < 0.001). Furthermore, the conditional indirect effect of NCI on HRQoL via depression for individuals with AUDs was significant (B = ?0.9099, p = 0.0087), suggesting a moderated mediation effect. The findings disentangle the complex relationship using a moderated mediation model, demonstrating that increasing levels of NCI, which can be reduced with HIV treatment, negatively influenced HRQoL via depression for individuals with AUDs. This highlights the need for future interventions to target these complex interplay between neuropsychological factors in order to improve HRQoL among PLWH, particularly incarcerated PLWH with AUDs.     

Exercise training improves cardiopulmonary and endothelial function in women with breast cancer: findings from the Diana-5 dietary intervention study

To investigate whether exercise training (ET) improves cardiopulmonary and endothelial function in women with breast cancer (BC). Fifty-one female patients (aged between 39 and 72 years) with a history of primary invasive BC within the previous 5 years and enrolled in the Mediterranean diet-based DIANA (diet and androgens)-5 Trial were subdivided into 2 groups: an ET group (n = 25) followed a formal ET program of moderate intensity (3 session/week on a bicycle at 60–70 % VO₂peak for 3 months, followed by one session/week until 1-year follow-up), while a control group (n = 26) did not perform any formal ET. At baseline and at 1-year follow-up, all patients underwent cardiopulmonary exercise stress test (CPET) and measurements of vascular endothelial function by peripheral artery tonometry (Reactive Hyperemia Index, RHI). There were no significant differences between the groups in baseline anthropometrical, BC characteristics, and metabolic profile. No differences in baseline CPET and RHI parameters were found. Peak oxygen consumption (VO₂peak) significantly increased in ET group (from 12.4 ± 2.9 to 14.3 ± 3.3 mL/kg/min, p < 0.001) compared to the control group (from 12.8 ± 2.5 to 12.6 ± 2.8 mL/kg/min, p = 0.55; p < 0.001 between groups). Compared to the control group (from 2.0 ± 0.4 to 1.9 ± 0.4, p = 0.62), the ET group showed a significant improvement of RHI after 1 year (from 2.1 ± 0.7 to 2.5 ± 0.8, p < 0.001). Changes in VO₂peak were correlated with changes in RHI (ΔVO₂peak vs. ΔRHI: r = 0.47, p = 0.017). In BC survivors, ET program improves cardiopulmonary functional capacity and vascular endothelial function after 12 months. Whether these changes may favorably modulate some of the pathophysiological mechanisms implied in cancer evolution should be investigated.     

Correlations of the changes in bioptic findings with echocardiographic,clinical and laboratory parameters in patients with inflammatory cardiomyopathy

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction—LVEF <40 %) with heart failure symptoms ≤6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm² and/or >7 T-lymphocytes/mm² in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm² and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm² (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = ?0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = ?0.33; p = 0.038 and R = ?0.45; p = 0.003) and with the change in LVEDV (R = ?0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment option in patients with recent onset biopsy-proven inflammatory cardiomyopathy.     

The significance and predictive value of free light chains in the urine of patients with chronic inflammatory rheumatic disease

In patients with rheumatic diseases, reliable markers for determining disease activity are scarce. One potential parameter is the level of immunoglobulin free light chains (FLCs), which is known to be elevated in the blood of patients with certain rheumatic diseases. Few studies have quantified FLCs in urine, a convenient source of test sample, in patients with different rheumatic diseases. We carried out a retrospective analysis of patients with rheumatic disease attending the University hospital of Goettingen, Germany. Subjects were included if they had urine levels of both κ and λ FLCs available and did not have myeloma. Data regarding systemic inflammation and kidney function were recorded, and FLC levels were correlated with inflammatory markers. Of the 382 patients with rheumatic disease, 40.1 % had chronic polyarthritis, 21.2 % connective tissue disease, 18.6 % spondyloarthritis and 15.7 % vasculitis. Elevated levels of κ FLCs were found for 84 % of patients and elevated λ for 52.7 %. For the patients with rheumatoid arthritis, FLCs correlated with C-reactive protein (κ, r = 0.368, p < 0.001; λ, r = 0.398, p < 0.001) and erythrocyte sedimentation rate (κ, r = 0.692, p < 0.001; λ, r = 0.612, p < 0.001). Patients being treated with rituximab displayed FLC levels similar to those of the reference group. There were clear elevations in both κ and λ FLCs in patients with rheumatic disease, but not in κ/λ ratio. The correlation between FLCs and inflammatory markers in patients with rheumatoid arthritis demonstrates their potential for predicting disease activity.     

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.

     

Early Trends in Bronchoscopic Lung Volume Reduction: A Systematic Review and Meta-analysis of Efficacy Parameters

Introduction

The goal of our systematic review and meta-analysis is to examine the therapeutic effectiveness of bronchoscopic lung volume reduction (BLVR), and to compare it with medical management and lung volume reduction surgery.

Methods

Variables of interest were absolute change in FEV1, 6MWT, and SGRQ. Meta-analysis was performed for the BLVR modalities with ≥3 trials. Of the 18 shortlisted publications, only valves (four trials; n = 159) and coils (six trials; n = 194) qualified for meta-analysis. To avoid redundant reporting for valves, only the data for intact fissure subjects were analyzed. Outcome data are presented as the mean difference from baseline with 95% confidence interval at 6-months follow-up.

Results

For BLVR using valves, the pooled mean difference (PMD) for FEV1 was 0.146 L (95% CI 0.111–0.181; p < 0.001), 6MWT was 45.225 meters (95% CI 26.954–63.495; p < 0.001), and SGRQ was ?8.825 points (95% CI ?14.824 to ?2.825; p = 0.004). All the PMDs were statistically significant and higher than their respective minimal clinically important difference (MCID). For BLVR using coils, the PMD for FEV1 was 0.080 L (95% CI 0.057–0.104; p < 0.001), 6MWT was 45.320 meters (95% CI 28.040–62.600; p < 0.001), and SGRQ was ?10.570 points (95% CI ?13.299 to ?7.841; p < 0.001). All three variables showed statistically significant PMDs but that for FEV1 was smaller than the MCID. Data from BLVR modalities with <3 major publications are reviewed in the discussion section.

Conclusions

BLVR offers early promise in the palliation of advanced emphysema. Better characterization of patients to identify phenotypes that will derive sustained benefit is needed.

     

Association between self-reported snoring and arterial stiffness: data from the Brisighella Heart Study

The correlation of both obstructive sleep apnoea syndrome (OSAS) and snoring with cardiovascular risk is well known, but its investigation is complex and not suitable for studying large cohorts of subjects. Thus, we prospectively evaluated 1476 non-pharmacologically treated subjects selected from the last survey of the Brisighella Heart Study. Snoring and sleep apnoea were investigated asking the subjects if they were aware of snoring during the night, and if this was associated with episodes of apnoea. A full set of clinical and laboratory parameters were evaluated, while augmentation index (AIx), and pulse wave velocity (PWV) were recorded with the Vicorder^® apparatus. A logistic regression analysis identifies as main independent predictors of AIx age (OR 1.058, 95 % CI 1.043–1.065, p < 0.001), Body Mass Index (OR 1.046, 95 % CI 1.014–1.079, p = 0.005), and apolipoprotein B (OR 1.014, 95 % CI 1.004–1.023, p = 0.001). The main independent predictors of PWV are snoring (OR 1.215, 95 % CI 1.083–1.390, p < 0.001), and snoring with apnoea (OR 1.351, 95 % CI 1.135–1.598, p = 0.014), age (OR 1.078, 95 % CI 1.052–1.089, p < 0.001), serum uric acid [SUA] (OR 1.093, 95 % CI 1.026–1.151, p < 0.001) and mean arterial pressure (OR 1.042, 95 % CI 1.024–1.056, p < 0.001). In conclusion, in our cohort of overall healthy subjects, self-reported snoring and sleep apnoea are independently associated with a higher PVW, and AIx is statistically significantly higher in snorers with or without sleep apnoea than in non-snorers. Body Mass Index and apolipoprotein B are associated with AIx, while SUA and mean arterial pressure are related to PWV.     

Subendocardial viability ratio in patients with rheumatoid arthritis: comparison with healthy controls and identification of prognostic factors

Cardiac involvement is common in rheumatoid arthritis. Subendocardial viability ratio (SEVR) is a non-invasive measure of microvascular coronary perfusion, yet it remains unclear whether it is affected in rheumatoid arthritis patients. We additionally sought predictors of SEVR in rheumatoid arthritis among a wide range of disease-related parameters, cardiac and hemodynamic factors, and markers of atherosclerosis, arteriosclerosis, and endothelial dysfunction. SEVR was estimated in rheumatoid arthritis patients and healthy controls by applanation tonometry, which was also used to evaluate arterial stiffness (pulse wave velocity and augmentation index). In the rheumatoid arthritis group, carotid intima–media thickness (cIMT) was additionally estimated by ultrasound, cardiac and hemodynamic parameters by impedance cardiography, and endothelial dysfunction by measurement of asymmetric dimethylarginine (ADMA). In a total of 122 participants, SEVR was lower among 91 patients with rheumatoid arthritis compared to 31 controls (141.4 ± 21.9 vs 153.1 ± 18.7%, p = 0.009) and remained so among 29 rheumatoid arthritis patients without hypertension, diabetes, or cardiovascular diseases, compared to the control group (139.7 ± 21.7 vs 153.1 ± 18.7%, p = 0.013). SEVR did not significantly correlate with arterial stiffness, cIMT, ADMA, or disease-related parameters. Multivariate analysis revealed gender (p = 0.007), blood pressure (p = 0.028), heart rate (p = 0.025), cholesterol levels (p = 0.008), cardiac index (p < 0.001) and left ventricular ejection time (p = 0.004) as independent predictors of SEVR among patients with rheumatoid arthritis. Patients with rheumatoid arthritis exhibit lower values of SEVR compared to healthy individuals. Cardiac and hemodynamic parameters, rather than functional indices of endothelial and macrovascular dysfunction, may be useful as predictors of myocardial perfusion in rheumatoid arthritis.