Pulmonary Involvement in Sjögren's Syndrome: Correlations with Biomarkers of Activity and High-Resolution Computer Tomography Findings.

(1) Background: Sjögren's syndrome (SS) represents a systemic autoimmune disease whose pathophysiology has yet to be elucidated, though it is known that the inflammatory process encountered in SS is of a systemic nature, with cytokines representing the main mediators for tissue damage. (2) Aim of the study: The aim of the present study is to further the understanding of the link between interleukin serum levels, cytokine serum levels, HRCT findings and the Warrick score (as tools for the evaluation of pulmonary involvement) in patients with pSS. (3) Methods: The present study is a retrospective, observational one aimed at ascertaining the link between SS activity and its clinical implications, as well as how interleukin and TNF-α levels correlate with systemic changes. The study enrolled 112 patients with pSS and 56 healthy subjects, matched for age and gender, as a control group. pSS activity was assessed using the ESSDAI. Cytokine levels and leukocyte and lymphocyte counts were measured in both groups. The focus score was calculated for each patient, HRCT was performed to assess lung function, and the Warrick score was calculated. (4) Conclusions: HRCT revealed NSIP in 13 patients (59.09%) and UIP in 9 patients. The strongest positive correlation was identified upon analyzing the relation between IL-8 and the Warrick score (r = 0.9156, p < 0.00001), followed by a positive correlation between the score and IL-6 levels (r = 0.5738, p < 0.0052). Unsurprisingly, the degree and severity of pulmonary involvement was also positively correlated with the degree of disease activity (r = 0.4345, p = 0.0433).

Endothelial Dysfunction in Primary Sjögren's Syndrome: Correlation with Serum Biomarkers of Disease Activity.

To assess the relationship between endothelial dysfunction and serum cytokines, anti-SSA and anti-SSB antibodies, beta-2 microglobulin levels, focus score and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) in primary Sjögren's syndrome (pSS) patients. The study included 90 patients with pSS and 45 healthy subjects, matched for age and gender, as controls. Serum beta-2 microglobulin, total cholesterol, HDL-cholesterol, triglycerides, TNF-α, and IL-6 were analyzed in both the groups. Patients with pSS were also tested for antinuclear antibodies, anti-SAA (anti-Sjögren's syndrome-related antigen A) antibodies, anti-SSB (anti-Sjögren syndrome related antigen B) antibodies, and focus score (the histopathologic one, based on minor salivary gland biopsy). Endothelial dysfunction was assessed by means of flow-mediated dilation (FMD) in the brachial artery. Data are presented as mean ± standard deviation. Statistical analysis was performed using the t-test and the Pearson's correlation. Differences were considered to be statistically significant if the value of p < 0.05. Endothelial dysfunction was identified in pSS patients (p < 0.00001). The serum levels of cytokines (TNF-α, respective IL-6) and beta-2 microglobulin were increased in pSS patients compared with controls (p < 0.00001). Endothelial dysfunction (expressed as FMD%) was correlated with focus score, ESSDAI, levels of anti-SSA and anti-SSB antibodies, beta-2 microglobulin, IL-6, and TNF-α, with statistical significance. Endothelial dysfunction is present in pSS patients and is associated with a high focus score and activity as well as increased concentrations of antibodies, pro-inflammatory cytokines, and beta 2-microglobulin.

Dyspepsia and Gut Microbiota in Female Patients with Postcholecystectomy Syndrome.

BACKGROUND: Gallstone disease (GSD) represents one of the most frequent digestive disorders, highly reported in female gender. The purpose of the study was to explore the clinical and gut microbiota particularities of female patients with postcholecystectomy syndrome (PCS) and the possible relationship between gut dysbiosis (DB) and abdominal complaints. PATIENTS AND METHODS: In total, 129 female participants: 104 outpatients divided into two equal groups, 52 PCS (+), 52 PCS (-) and 25 healthy controls were consecutively enrolled in this observational study. Patients underwent clinical examination with assessment of pain, bloating, transit disturbances, abdominal ultrasound/computer tomography/magnetic resonance imaging/endoscopic retrograde cholangiopancreatography, upper and lower digestive endoscopies. Laboratory work-ups and stool microbiology assessments were performed for all study participants (patients and controls). Stool microorganisms were identified by matrix-assisted laser desorption ionization - time-of-flight- mass spectrometry and in patients with DB also by next-generation sequencing. RESULTS: Older age, complicated gallstones disease, associated conditions like diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome were significantly present in PCS (+) group, as well as sedentary lifestyle and diets characterized by a low fiber intake (p<0.0001). PCS (+) patients displayed significant differences related to the incidence and severity of overall gut microbiota DB, decreased H index of biodiversity and the unbalanced Firmicutes/Bacteroidetes (F/B) ratios by comparison to the PCS (-) group (p<0.0001). Strong positive correlations of the severity of overall DB with bloating and the intestinal habit disorders, as well as of F/B ratios to all abdominal symptoms were noted. CONCLUSION: PCS in female patients was associated with older age, sedentary lifestyle, specific dietary habits, history of complicated gallstone disease, diabetes mellitus/impaired glucose tolerance and irritable bowel syndrome, as well as gut microbiota particularities. Overall DB and unbalanced F/B ratios were strongly correlated to abdominal complaints.

Hyponatremia and Renal Venous Congestion in Heart Failure Patients.

OBJECTIVE: The interrelationship between the heart and kidneys has a great importance in the homeostasis of the cardiovascular system. Heart failure patients present intrarenal arterial hypoperfusion and intrarenal venous congestion due to reduced left ventricle ejection fraction, which triggers numerous neurohormonal factors. The aim of this study was to investigate intrarenal vascularization (arterial and venous), as well as the links between it and systemic congestion and, on the other side, with the mortality in patients with heart failure. Material and Methods. This cross-sectional study was performed on a group of 44 patients with heart failure in different stages of evolution and 44 healthy subjects, matched for age and gender, as controls. Serum natremia, NT-proBNP, and creatinine analyses were performed in all patients and controls. Renal and cardiac ultrasonography was done in all patients and controls, recording intrarenal arterial resistive index (RRI), intrarenal venous flow (IRVF) pattern, renal venous stasis index (RVSI), and left ventricular ejection fraction (LVEF). Data are recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student t-test, ANOVA test, and the Pearson correlation. Differences were considered statistically significant at the value of p < 0.05. RESULTS: Hyponatremia was identified in 47.72% of the HF patients. This study revealed correlations between serum natremia and LVEF, NT-proBNP, serum creatinine, interlobar venous RVSI (p < 0.00001), and interlobar artery RRI (p ≤ 0.002). Hyponatremia and renal venous congestion represent negative prognostic factors in HF patients. CONCLUSION: In HF patients, hyponatremia was correlated with cardiac dysfunction and intrarenal venous congestion. Hyponatremia and renal venous congestion represented negative prognostic factors in HF patients.

Correlations between Vascular Stiffness Indicators, OPG, and 25-OH Vitamin D3 Status in Heart Failure Patients.

Background and objectives: The purpose of the study is to correlate vascular calcification biomarkers osteoprotegerin (OPG) and 25-hydroxyvitamin D3 (25-OH-D3), indicators of arterial stiffness carotid-femoral pulse wave velocity (c-f PWV) and renal resistive index (RRI), with parameters of left ventricular function in heart failure patients versus control. Materials and methods: Our case-control study compared 60 patients with ischemic heart failure and reduced left ventricular ejection fraction (LVEF) (<40%) with a control group of 60 healthy age-matched subjects (CON). Serum levels of OPG and 25-OH-D3 were determined by ELISA. Left ventricular volumes (LVESV, LVEDV) and LVEF were measured by echocardiography. C-f PWV was determined using the arteriograph device. RRI was measured by duplex Doppler. Peak systolic velocity (PSV) and minimum end-diastolic velocity (EDV) were determined using angle correction. The estimated glomerular filtration rate (eGFR) was calculated using the MDRD equation. The Pearson's correlation coefficient was used for interpretation of results. Results: OPG values were significantly higher in heart failure (HF) patients vs. CON (4.7 ± 0.25 vs. 1.3 ± 0.67 ng/mL, p < 0.001). 25-OH vitamin D3 levels were significantly lower in HF patients vs. CON (20.49 ± 7.31 vs. 37.09 ± 4.59 ng/mL, p < 0.001). Multiple regression analysis considering 25-OH D3 as a dependent variable demonstrated indicators of vascular stiffness RRI, c-f PWV and vascular calcification biomarker OPG as predictors. OPG values were significantly correlated with cardiac parameters LVEDV (r = 0.862, p < 0.001), LVEF (r = -0.832, p < 0.001), and c-f PWV(r = 0.833, p < 0.001), and also with 25-OH-D3 (r = -0.636, p < 0.001). RRI values were significantly correlated with cardiac parameters LVEDV (r = 0.586, p < 0.001) and LVEF (r = -0.587, p < 0.001), and with eGFR (r = -0.488, p < 0.001), c-f PWV(r = 0.640, p < 0.001), and 25-OH-D3 (r = -0.732, p < 0.001). Conclusions: This study showed significant correlations between vitamin D deficit and vascular stiffness indicators in heart failure patients with reduced ejection fraction, demonstrating the importance of these examinations for a better evaluation of these patients. Together with the evaluation of renal function, the measurement of vascular stiffness indicators and biomarkers might play a key role in identifying patients at greater risk for worsening disease prognosis and for shorter life expectancy, who could benefit from vitamin D supplementation. The abstract was accepted for presentation at the Congress of the European Society of Cardiology, Munich, 2018.

Heart Involvement in Inflammatory Rheumatic Diseases: A Systematic Literature Review.

Introduction: Patients with inflammatory rheumatic diseases have an increased risk of developing cardiovascular manifestations. The high risk of cardiovascular pathology in these patients is not only due to traditional cardiovascular risk factors (age, gender, family history, smoking, sedentary lifestyle, cholesterol), but also to chronic inflammation and autoimmunity. Aim: In this review, we present the mechanisms of cardiovascular comorbidities associated with inflammatory rheumatic diseases, as they have recently been reported by different authors, grouped in electrical abnormalities, valvular, myocardial and pericardial modifications and vascular involvement. Methods: We conducted a systematic search of published literature on the following online databases: EBSCO, ScienceDirect, Scopus and PubMed. Searches were limited to full-text English-language journal articles published between 2010 and 2017 using the following key words: heart, systemic inflammation, autoimmunity, rheumatic diseases and disease activity. After the primary analysis we included 50 scientific articles in this review. Results: The results showed that cardiac manifestations of systemic inflammation can occur frequently with different prevalence in rheumatoid arthritis (RA), systemic lupus erythematosus(SLE), systemic sclerosis(SSc) and ankylosing spondylitis(AS). Rheumatologic diseases can affect the myocardium, cardiac valves, pericardium, conduction system and arterial vasculature. Conclusions: Early detection, adequate management and therapy of specific cardiac involvement are essential in rheumatic disease. Electrocardiographic and echocardiographic evaluation should be performed as routine investigations in patients with inflammatory rheumatic diseases.

The Utility of Major Salivary Gland Ultrasonographic Parameters in the Diagnosis of Sjögren Syndrome.

OBJECTIVE: To investigate ultrasonographically the salivary glands and to correlate ultrasonographic parameters with focus score, serum beta-2-microglobulin, and stimulated salivary flow rate. MATERIAL AND METHODS: 32 patients with primary Sjögren's syndrome (pSS) and 32 healthy controls were enrolled in this case-control study, performed in the Department of Internal Medicine, Division of Rheumatology, "Victor Babeș" University of Medicine and Pharmacy, Timișoara, Romania. All the patients and controls were examined by salivary gland ultrasonography (B-mode, color and spectral Doppler, and sonoelastography), determining the following parameters: salivary gland ultrasonography (SGUS) score, resistive index (RI) of transverse facial artery, and shear wave velocity (SWV). Serum beta-2-microglobulin and stimulated saliva amount were determined in all the patients and controls. Minor salivary gland biopsy with focus score assessment was done in pSS patients. RESULTS: Patients with pSS presented higher SGUS score and parotid and submandibular SWV and reduced RI of transverse facial artery than controls (p < 0.0001). In pSS patients, statistically significant correlations were identified between assessed ultrasonographic parameters and focus score, serum beta-2-microglobulin, and respective stimulated saliva flow (p < 0.0001). CONCLUSIONS: This study highlighted statistically significant correlations between salivary gland ultrasonographic parameters and focus score, serum beta-2-microglobulin, and stimulated saliva flow.

Bone turnover markers in postmenopausal osteoporosis and their correlation with bone mineral density and menopause duration.

BACKGROUND: Biochemical bone turnover markers (BTMs) estimates the bone remodeling process, being valuable in the personalized approach of osteoporotic patients. AIM: The aim of the study was to evaluate the correlation between biochemical BTMs and bone mineral density (BMD), depending on menopause period, in postmenopausal osteoporotic women, compared to postmenopausal women without osteoporosis. PATIENTS, MATERIALS AND METHODS: The study included 149 untreated postmenopausal women, divided into three groups: group 1 (65 osteoporotic women with less than 10 years of menopause), group 2 (44 osteoporotic patients, with over 10 years of menopause), and the control group with 40 postmenopausal women without osteoporosis. RESULTS: All BTMs levels were higher in the groups with osteoporosis, than in the control group. Lumbar BMD values correlated positively with deoxypyridinoline (DPD) and negatively with bone-specific isoform of alkaline phosphatase (BAP), tartrate-resistant acid phosphatase band 5b (TRAP 5b), osteocalcin (OC) and cross-linked N-telopeptides of type I collagen (NTX). Serum estradiol levels correlated positively with spine BMD in the whole study group (r=0.508, p=0.001). BTMs correlated positively with each other. Osteoporotic women with longer period of menopause presented significantly higher values of resorption markers (NTX and TRAP 5b), compared to the group with menopause duration less than 10 years. At a cutoff value of 12 µg∕L, BAP presented 82.4% sensitivity and 62.5% specificity. CONCLUSIONS: Our study showed that BTMs correlated negatively with lumbar BMD and positively with each other. Resorption markers levels increase with duration of estradiol deprivation period.

Lycopene and Vascular Health.

Lycopene is a lipophilic, unsaturated carotenoid, found in red-colored fruits and vegetables, including tomatoes, watermelon, papaya, red grapefruits, and guava. The present work provides an up to date overview of mechanisms linking lycopene in the human diet and vascular changes, considering epidemiological data, clinical studies, and experimental data. Lycopene may improve vascular function and contributes to the primary and secondary prevention of cardiovascular disorders. The main activity profile of lycopene includes antiatherosclerotic, antioxidant, anti-inflammatory, antihypertensive, antiplatelet, anti-apoptotic, and protective endothelial effects, the ability to improve the metabolic profile, and reduce arterial stiffness. In this context, lycopene has been shown in numerous studies to exert a favorable effect in patients with subclinical atherosclerosis, metabolic syndrome, hypertension, peripheral vascular disease, stroke and several other cardiovascular disorders, although the obtained results are sometimes inconsistent, which warrants further studies focusing on its bioactivity.

Vitamin D Status, Disease Activity, and Endothelial Dysfunction in Early Rheumatoid Arthritis Patients.

Cardiovascular diseases represent important complications in rheumatoid arthritis (RA) patients, generated by an accelerated atherosclerosis. The aim of this study is represented by the assessment of the correlations between serum levels of vitamin D, disease activity, and endothelial dysfunction in patients with early RA. Material and Methods. The study was performed on a group of 35 patients with early RA and 35 healthy subjects matched for age and gender, as controls. In all studied subjects, the following were determined: inflammatory markers, insulin resistance, vitamin D levels, and endothelial dysfunction. Statistical analysis were performed using the Student's t-test and the Pearson's test. p values of less than 0.05 were considered statistically significant. Results. The group of patients with RA patients presented inflammation, low levels of vitamin D, elevated insulin resistance, and reduced flow-mediated vasodilation, statistically significant compared to the control group (p < 0.00001). Significant inverse correlations between the levels of 25(OH) vitamin D and DAS28, respective insulin resistance, and significant positive correlation between 25(OH) vitamin D and endothelial function were demonstrated. Conclusion. In early RA patients with moderate and high disease activity, low serum levels of vitamin D were associated with disease activity, increased insulin resistance, and endothelial dysfunction.

Arterial stiffness in hematologic malignancies.

Malignant and cardiovascular disorders are the top causes of mortality worldwide. This article reviews the main literature data and mechanisms linking hematologic malignancies and arterial stiffness, focusing on recent experimental and clinical results. Several links were found in hematologic malignancies between complete blood count and arterial stiffness. Chemotherapy, especially anthracyclines, cyclophosphamide and tyrosine kinase inhibitors, as well as radiotherapy and hematopoietic stem cell transplantation are the main known causes of arterial stiffness increase in hematologic malignancies. The mechanisms of arterial stiffness elevation in hematologic malignancies include an increased oxidative stress, impaired vascular wall homeostasis, endothelial dysfunction and apoptosis of endothelial cells, overexpression of inflammatory cytokines, accelerated atherosclerosis, increased blood viscosity and unstable platelet aggregates. Guidelines regarding cardiovascular health screening and cardiovascular risk scores are necessary for hematologic cancer survivors in order to improve prognosis and quality of life of the patients.

Electrocardiographic Predictors of Cardiovascular Mortality.

Cardiovascular diseases are the main causes of mortality. Sudden cardiac death may also appear in athletes, due to underlying congenital or inherited cardiac abnormalities. The electrocardiogram is used in clinical practice and clinical trials, as a valid, reliable, accessible, inexpensive method. The aim of the present paper was to review electrocardiographic (ECG) signs associated with cardiovascular mortality and the mechanisms underlying those associations, providing a brief description of the main studies in this area, and consider their implication for clinical practice in the general population and athletes. The main ECG parameters associated with cardiovascular mortality in the present paper are the P wave (duration, interatrial block, and deep terminal negativity of the P wave in V1), prolonged QT and Tpeak-Tend intervals, QRS duration and fragmentation, bundle branch block, ST segment depression and elevation, T waves (inverted, T wave axes), spatial angles between QRS and T vectors, premature ventricular contractions, and ECG hypertrophy criteria.