Role of Chemerin and Perivascular Adipose Tissue Characteristics on Cardiovascular Risk Assessment by Arterial Stiffness Markers in Patients with Morbid Obesity.

BACKGROUND AND OBJECTIVE: The development of arterial stiffness (AS) in obesity is a multifactorial and complex process. The pleomorphic actions of adipokines and their local activity in perivascular adipose tissue (PVAT) are potential modulators of AS appearance and progression. We aimed to assess the correlations between two adipokines (chemerin, adiponectin), PVAT morphological changes (adipocyte size, blood vessel wall thickness) and AS parameters in the special subgroup of patients with morbid obesity. MATERIAL AND METHODS: We enrolled 25 patients with morbid obesity and 25 non-obese patients, who were age- and gender-matched, untreated for cardiovascular risk factors, and admitted to hospital for laparoscopic surgical procedures (bariatric surgery for morbid obesity and non-inflammatory benign pathology surgery for non-obese patients). Before the surgical procedures, we evaluated demographic and anthropometric data and biochemical parameters including the studied adipokines. Arterial stiffness was evaluated using a Medexpert ArteriographTM TL2 device. In both groups, adipocyte size and vascular wall thickness as well as local adiponectin activity were analyzed in PVAT from intraoperative biopsies. RESULTS: In our study, adiponectin (p = 0.0003), chemerin (p = 0.0001) and their ratio (p = 0.005) had statistically significant higher mean values in patients with morbid obesity compared to normal-weight patients. In patients with morbid obesity there were significant correlations between chemerin and AS parameters such as aortic pulse wave velocity (p = 0.006) and subendocardial viability index (p = 0.009). In the same group adipocyte size was significantly correlated with another AS parameter, namely, aortic systolic blood pressure (p = 0.030). In normal-weight patients, blood vessel wall thickness positively correlated with AS parameters such as brachial (p = 0.023) and aortic augmentation index (p = 0.023). An important finding was the negative adipoR1 and adipoR2 immunoexpression in PVAT adipocytes of patients with morbid obesity. Additionally, we found significant correlations between blood vessel wall thickness and blood fasting glucose (p < 0.05) in both groups. CONCLUSIONS: Chemerin and adipocyte size could be predictive biomarkers for AS in patients with morbid obesity. Given the small number of patients included, our results need further validation.

Determinants of Arterial Stiffness in Patients with Morbid Obesity. The Role of Echocardiography and Carotid Ultrasound Imaging.

Background and objective: Morbid obesity is accompanied by an increased cardiovascular (CV) risk, which justifies a multidisciplinary, integrative approach. Arterial stiffness has a well-defined additional role in refining individual CV risk. Given that echocardiography and carotid ultrasound are usual methods for CV risk characterization, we aimed to identify the imaging parameters with a predictive value for early-onset arterial stiffness. Material and methods: We conducted a study in which 50 patients (divided into two equal groups with morbid obesity and without obesity), age and gender matched, untreated for cardiovascular risk factors, were addressed to bariatric surgery or non-inflammatory benign pathology surgery. Before the surgical procedures, we evaluated demographics, anthropometric data and biochemical parameters including adipokines (chemerin, adiponectin). Arterial stiffness was evaluated using the Medexpert ArteriographTM TL2 device. Transthoracic echocardiography and carotid ultrasound were also performed. We also analyzed adipocyte size and vascular wall thickness in intraoperative biopsies. Results: Left ventricle (LV) mass index (p = 0.2851), LV ejection fraction (LVEF) (p = 0.0073), epicardial adipose tissue thickness (p = 0.0001) as echocardiographic parameters and carotid intima-media thickness (p = 0.0033), relative wall thickness (p = 0.0295), wall to lumen thickness ratio (p = 0.0930) and carotid cross-sectional area (p = 0.0042) as ultrasound parameters were significant measures in our groups and were assessed in relation to adipocyte size, blood vessel wall thickness and adipokines serum levels. Statistical analysis revealed directly proportional relationships between LV mass index (p = 0.008), carotid systolic thickness of the media (p = 0.009), diastolic thickness of the media (p = 0.007), cross-sectional area (p = 0.001) and blood vessel wall thickness. Carotid relative wall thickness positively correlates with adipocyte size (p = 0.023). In patients with morbid obesity, chemerin and adiponectin/chemerin ratio positively correlates with carotid intima-media thickness (p = 0.050), systolic thickness of the media (p = 0.015) and diastolic thickness of the media (p = 0.001). The multiple linear regression models revealed the role of epicardial adipose tissue thickness and carotid cross-sectional area in predicting adipocyte size which in turn is an independent factor for arterial stiffness parameters such as pulse wave velocity, subendocardial viability ratio and aortic augmentation index. Conclusions: Our results suggest that epicardial adipose tissue thickness, carotid intima-media thickness, relative wall thickness and carotid cross-sectional area might be useful imaging parameters for early prediction of arterial stiffness in patients with morbid obesity.

Adipokines, and not vitamin D, associate with antibody immune responses following dual BNT162b2 vaccination within individuals younger than 60 years.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to a global health outbreak known as the COVID-19 pandemic which has been lasting since March 2020. Vaccine became accessible to people only at the beginning of 2021 which greatly helped reducing the mortality rate and severity of COVID-19 infection afterwards. The efficacy of vaccines was not fully known and studies documenting the immune responses following vaccination are continuing to emerge. Recent evidence indicate that natural infection prior vaccination may improve the antibody and cellular immune responses, while little is known about the factors influencing those processes. Here we investigated the antibody responses following BNT162b2 vaccination in relation to previous-infection status and age, and searched for possible biomarkers associated with the observed changes in immune responses. We found that the previous-infection status caused at least 8-times increase in the antibody titres, effect that was weaker in people over 60 years old and unaltered by the vitamin D serum levels. Furthermore, we identified adiponectin to positively associate with antibody responses and negatively correlate with pro-inflammatory molecules (MCP-1, factor D, CRP, PAI-1), especially in previously-infected individuals.

Biomarker Utility for Peripheral Artery Disease Diagnosis in Real Clinical Practice: A Prospective Study.

Peripheral arterial disease (PAD) is a common manifestation of generalized atherosclerosis, which affects more than 200 million patients worldwide. Currently, there is no ideal biomarker for PAD risk stratification and diagnosis. The goal of this research was to investigate the levels of inflammation biomarkers and cystatin C and to explore their utility for the diagnosis of PAD. The study included 296 participants, distributed in two groups: 216 patients diagnosed with PAD and 80 patients without PAD as controls. All studied biomarker levels (C-reactive protein, CRP; fibrinogen; erythrocyte sedimentation rate, ESR; neopterin; beta 2-microglobulin, B2-MG; and cystatin C) were significantly higher in the PAD group and indirectly correlated with the ankle-brachial index (ABI). The final logistic regression model included an association of neopterin, fibrinogen, and cystatin C as the most efficient markers for the prediction of PAD diagnosis. When comparing the area under the curve (AUC) for all biomarkers, the value for neopterin was significantly higher than those of all the other analyzed biomarkers. In agreement with previous studies, this research shows that markers such as fibrinogen, CRP, ESR, B2-MG, and cystatin C have significant value for the diagnosis of PAD, and also clearly underlines the accuracy of neopterin as a leading biomarker in PAD prediction.

Acute cardiac dyspnea in the emergency department: diagnostic value of N-terminal prohormone of brain natriuretic peptide and galectin-3.

OBJECTIVE: This study was performed to determine whether a dual-biomarker approach using N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and galectin-3 optimizes the diagnosis and risk stratification of acute cardiac dyspnea. Atypical clinical manifestations and overlapping pathologies require objective and effective diagnostic methods to avoid treatment delays. METHODS: This prospective observational study included 208 patients who presented to the emergency department for acute dyspnea. NT-proBNP and galectin-3 were measured upon admission. The patients were divided into two groups according to the etiology of their clinical manifestations: cardiac and non-cardiac dyspnea. The patients' New York Heart Association functional class, left ventricular ejection fraction, and discharge status were assessed. RESULTS: Diagnostic criteria for acute heart failure were fulfilled in 61.1% of the patients. NT-proBNP and galectin-3 were strongly and significantly correlated. Receiver operating characteristic analysis revealed similar areas under the curve for both markers in the entire group of patients as well as in the high-risk subsets of patients. CONCLUSIONS: The diagnostic performance of NT-proBNP and galectin-3 is comparable for both the total population and high-risk subsets. Galectin-3 adds diagnostic value to the conventional NT-proBNP in patients with acute cardiac dyspnea, and its utility is of major interest in uncertain clinical situations.

Modifications in the spectrum of bone mass predictive factors with menopausal status.

PURPOSE: Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women. METHODOLOGY: This cross-sectional study included 93 women (38 premenopausal and 55 postmenopausal). Bone mineral density (BMD) and body composition were assessed by dual-energy X-ray absorptiometry. Serum levels of leptin, adiponectin, resistin, and also of the phosphocalcic markers parathormone and vitamin D were measured. RESULTS: Only lean mass (LM) was an independent predictor of BMD in premenopausal women (r2 = 0.381, p < 0.001 for femoral neck BMD, r2 = 0.2, p < 0.01 for whole-body BMD) in both unadjusted and age-adjusted models. The effect of total FM upon BMD became nonsignificant when LM was added to the models assessed. In postmenopausal women, although LM, trunk-to-leg fat ratio, and resistin were initially associated with BMD in unadjusted models, only the trunk-to-leg fat ratio independently predicted BMD at various sites (r2 = 0.171, p < 0.01 for lumbar BMD, r2 = 0.078, p < 0.05 for radius BMD, r2 = 0.094, p < 0.05 for whole-body BMD) after adjusting for age. CONCLUSIONS: While in premenopausal women the effect of LM upon bone is prevalent, after menopause, the fat distribution reflected by trunk-to-leg fat ratio is a major determinant of bone mass at different sites. Our study also stresses that the relationship between total FM and BMD is not mediated by adipokines in women irrespective of menopausal status and body composition, but it is largely mediated by LM only in young premenopausal women.

LOW LEVELS OF SERUM CYANOCOBALAMIN IN A METFORMIN-TREATED PATIENT. CASE REPORT AND COMPARISON WITH LITERATURE DATA.

Metformin is a widely used oral antidiabetic biguanide compound. According to the literature, metformin may lower the serum cyanocobalamin levels. We present the case of a 71-old-male treated with metformin for 15 years. When presenting to a periodic checkup, low serum cyanocobalamin levels where found. Laboratory tests showed levels below normal range for hemoglobin (12.7 g/dL) and hematocrit (37.8%). After patient reevaluation, a change in antidiabetic treatment will be considered if metformin will be found the cause of low serum cyanocobalamin levels. Other cases reported in the literature support this hypothesis, justifying the study of the influence of metformin therapy on serum vitamin B12 levels in patients diagnosed with diabetes. The influence of patient age, metformin dosage, duration of treatment and time since diabetes diagnosis on serum levels of vitamin B12 also need to be determined.

Impact of fatigue in patients with chronic obstructive pulmonary disease: results from an exploratory study.

INTRODUCTION: Fatigue, which is also present in the healthy population, is a common but understudied symptom in chronic obstructive pulmonary disease (COPD). We hypothesized that clinically significant fatigue is also frequent in COPD and can be associated with an increased disease burden. METHODS: An exploratory analysis derived from an ongoing cross-sectional study was carried out to evaluate levels of fatigue and impact on health-related quality of life/health status in patients with COPD (COPD group; n = 20) and healthy subjects (control group; n = 5). Health-related quality of life was measured using the Short Form Health Survey 36 (SF-36), health status with the Clinical COPD Questionnaire (CCQ), and airways obstruction with postbronchodilator forced expiratory volume in 1 s (FEV1 %predicted). Fatigue was measured with the vitality score of the SF-36, its clinical significance being defined by values of 50 or less. Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy scale for fatigue (FACIT-F). RESULTS: Vitality scores were significantly worse in the COPD group (45.60 versus 76.25; p = 0.004). FACIT-F scores were significantly lower in the COPD group versus the control group (74.5 versus 95.0; p = 0.03). Clinically significant fatigue was detected in 60% of the COPD group, and was associated with a worse FEV1 %predicted (47.71 versus 65.82%; p = 0.016), worse symptoms burden (CCQ symptoms score 3.75 versus 2.43; p = 0.019), and worse overall health status (CCQ total score 3.30 versus 2.11; p = 0.011). Its link with systemic inflammation remains to be clarified further. CONCLUSIONS: Clinically significant fatigue is common among patients with COPD and is associated with an increased disease burden. It should therefore be integrated as a measure of disease prognosis and control in patients with COPD.

Nivolumab for advanced non-small cell lung cancer: an evaluation of a phase III study.

Lung cancer still remains associated with a high mortality rate and more efficacious therapies are needed in order to improve the disease outcome. Nivolumab is a monoclonal antibody which blocks the programmed death-1 receptor which is currently evaluated in phase III clinical trials in advanced lung cancer. Here, we evaluate the results of a phase III study in which nivolumab efficacy and safety were compared to those of docetaxel. Nivolumab was able to improve survival and progression-free survival and exhibited a very good safety profile. Further clinical data are needed in order to better position this therapy among the existing methods. The promising results support the use of this therapy as a stand-alone approach.

Th1 and Th2 cytokine response in patients with pulmonary tuberculosis and health care workers occupationally exposed to M. tuberculosis.

UNLABELLED: Aiming to detect reliable markers indicating protection from or susceptibility to tuberculosis infection, we investigated both Th1/Th2 cytokines and total IgE plasma levels in health care workers occupationally exposed to M. tuberculosis, in patients with pulmonary tuberculosis and in healthy persons. MATERIAL AND METHOD: The study groups have included 15 health care workers in close contact with TB patients, patients with active pulmonary tuberculosis at diagnosis and after treatment (12 advanced and 10 moderate TB, of which 6 had also pleurisy) and 20 healthy volunteers. Peripheral blood mononuclear cells (PBMC) were stimulated with PPD for 7 days and the release of six cytokines (IL-2, IFN-gamma, TNFalpha, IL-4, IL-5, IL-10) was simultaneously quantified by cytometric bead array (CBA) in culture supernatants. The same method was used to determine the cytokine level in plasma and pleural effusions from TB patients. Six neoplastic pleurisies were included in this investigation as a control group. Total plasma IgE level was measured by chemiluminescence technique. RESULTS: Plasma and pleural fluid cytokine analysis at the outset of tuberculosis disease reflect the same Th1 response dominated by IFN-gamma. In opposition, very low IFN-gamma levels were recorded in neoplastic pleural fluids. Both types of cytokines (Th1 and Th2) were secreted in response to in vitro PPD stimulation of PBMCs and had different evolution in moderate and advanced TB. Thus, IFN-gamma, TNFalpha, IL-4, and IL5 production after 6 months-treatment decreased in moderate TB and increased in severe disease (p < 0.05). Moreover, total IgE plasma levels were higher than the normal value (87 IU/ml) in health care workers and significant amounts were recorded in patients, especially in advanced TB after 6 months of treatment (p = 0.00). CONCLUSIONS: Our results confirm that the quantification of IFNa could be a good marker for the diagnosis of TB pleural effusions but raised the question whether plasma IgE levels might be a reliable marker indicating the transition to disease. Further studies are needed to understand the complex interaction between pro- and anti-inflammatory cytokines that might play an Key words: TUBERCULOSIS, CYTOKINES,

[High values of soluble cytokeratin 18 in breast carcinomas may have different meanings]. / Valorile crescute ale citokeratinei 18 serice in neoplasmele mamare pot avea semnificatii diferite.

We have investigated the cellular and serum CK18 in 26 non-treated primary ductal invasive breast carcinomas. The soluble CK18 (TPS) was detected by chemiluminescent assay, and the cellular CK18 and PCNA expression by immunocytochemistry. Flow-cytometry was used to estimate the amount of DNA in malignant cells. There was a significant correlation between soluble CK18 and the pre-menopausal status (p < 0.05), characterized in our group by a PCNA estimated low proliferation index. We have also found a significant correlation between soluble CK18 and the DNA index (p < 0.01). The intracellular CK18 has correlated with the PCNA expression (p < 0.05), while no correlation could be found between cellular and serum CK18. The values of soluble CK18 may offer information about the treatment-induced cell death, if monitored, while isolated measurements should be interpreted cautiously. Elevated levels of serum CK18 in non-treated carcinomas may rather reflect a high tumor turn-over or perhaps a more intensive tumor cell killing.

[HDL-cholesterol-- active or passive participant in the pathogenesis of atherosclerosis]. / HDL-colesterolul--participant activ sau pasiv în patogenia aterosclerozei?

It is known that high sanguin levels of cholesterol and LDL-cholesterol (LDLc) have an important role in the pathogenesis of atherosclerosis. The treatment of hypercholesterolemia with statins and/or with fibrates have had beneficial effects on coronary heart disease and on other localization of atherosclerosis. The decreased of cholesterol and LDL-cholesterol is the most important effect of this treatment. The epidemiological studies have revealed that the treatment with statins and/or with fibrates produce an increase of HDL-cholesterol (HDLc), which is also very important in the regression of atherosclerosis. We tried in this review to explain the mechanisms of the increase of HDL-cholesterol, in concordance with the data from literature.

[Evaluation of the systolic and diastolic function of the left ventricle in patients with diabetes mellitus and microalbuminuria]. / Evaluarea functiei sistolice si diastolice a ventriculului stâng la pacientii cu diabet zaharat cu microalbuminurie.

UNLABELLED: The objective of this study is to reveal the deterioration of the systolic and diastolic function of the left ventricle (LV) in patients with diabetes mellitus (DM), in correlation with type of DM, the edge and the complications of DM and the associated diagnosis. METHODS: The study included 43 patients with DM (29 patients with DM type 1 or 2 insulinodependent--DMID and 14 patients with DM type 2 nonisulinodependent--DMNID). The age of patients was between 21 years and 57 years, with a duration of DM between 1 year and 22 years. The ecocardiographic evaluation have determined 38 parameters (B mod, M mod, CWD, PWD, colour Doppler). From these parameters, 12 was used for the measurement of the systolic function of the LV and 18 was used for the determination of the diastolic function of the left ventricle. The clinical and biological exam have performed: glycaemia, proteinuria, dyslipidemic syndrome, complications of DM and ischaemic heart disease (ECG). RESULTS: The ejection fraction (EF) of the LV was ?60% in 23 patients, between 50% and 60% in 17 patients and between 40% and 50% in 3 patients. The values of MSER (mean systolic ejection rate) was between 221 ml/s si 515 ml/s and the values of MVCF (mean velocity of circumferential shortening) was between 0.9 circ/s si 1, 8 circ/s. The ratio of the E and A waves at the mitral valve was > 1 in 22 patients and < 1 in 21 patients. The LV isovolumic relaxation time (IVRT) was < 70 ms in 13 patients, > 100 ms in 14 patients and had normal values in 16 patients. The E wave deceleration time (EDT) was < 150 ms in 24 patients and had normal values in 19 patients. There is no connection between the systolic/diastolic function and the other determined parameters. CONCLUSIONS: The alteration of the LV systolic function was present in 20 patients from 43 patients. The LV diastolic dysfunction through relaxation troubles was present in 14 patients and the LV diastolic dysfunction through compliance trouble was present in 13 patients. A number of 16 patients had preserved (for the moment) a normal LV diastolic function. The number of patients with these two types of LV diastolic dysfunction was equal in our study. Other studies had found a predominance of LV diastolic dysfunction through compliance troubles in DM.

[Early detection of diabetic nephropathy in children and teenagers with type I diabetes]. / Depistarea precoce a nefropatiei diabetice la copilul si adolescentul cu diabet de tip.

Microalbuminuria (MA) is a noninvasive marker which has to be effected for all the patients in order to watch the appearance of the kidney disease. The aim of this study was the identification of the MA and of its associated factors within a lot of 110 children and teenagers suffering from type 1 diabetes mellitus. Persistent MA (the incipient diabetic nephropathy) was detected in the case of 10 patients (9%) and the intermittent one at 13 of them (11.8%). In all the cases, a poor glycemic control was associated, the average of the Hb A1c being higher than 10%. The progression of MA was associated with high blood-pressure values in the case of 2 patients and other chronic complications were present at 15 of them. In conclusion, we detected MA in 20.8% of the patients and its prevalence was significantly associated with poor glycemic control.