Special Issue “Micro and Nano Flows 2016 (MNF2016) – Biomedical Stream”

Editorial - Special Issue “Micro and Nano Flows 2016 (MNF2016) –Biomedical Stream

Semaglutide therapy decreases epicardial fat inflammation and improves psoriasis severity in patients affected by abdominal obesity and type-2 diabetes

Psoriasis is often associated with abdominal obesity and type-2 diabetes (T2D). The inflammatory process in psoriasis can target adipose tissue depots, especially those surrounding the heart and coronary arteries, exposing to an increased risk of cardiovascular diseases. A 50-year-old female patient referred to us for abdominal obesity and T2D, which were not controlled with lifestyle modifications. She had suffered from psoriasis for some years and was treated with guselkumab, without success. Epicardial adipose tissue (EAT) attenuation and pericoronary adipose tissue (PCAT) attenuation for each coronary, defined as mean attenuation expressed in Hounsfield unit (HU), were assessed by routine coronary computed tomography angiography. At baseline, EAT attenuation was −80 HU and PCAT attenuation of the right coronary artery (RCA) was −68 HU, values associated with an increased cardiac mortality risk. Psoriasis area and severity index (PASI) was 12.0, indicating severe psoriasis, while dermatology life quality index (DLQI) was 20, indicating a negative effect on the patient’s life. Semaglutide (starting with 0.25 mg/week for 4 weeks, increased to 0.50 mg/week for 16 weeks, and then to 1 mg/week) was started. After 10 months, semaglutide treatment normalized glycated hemoglobin and induced weight loss, particularly at abdominal level, also followed by a reduction in computed tomography-measured EAT volume. EAT attenuation and PCAT attenuation of RCA decreased, showing an important reduction of 17.5 and 5.9% respectively, compared with baseline. PASI and DLQI decreased by 98.3 and 95% respectively, indicating an improvement in psoriasis skin lesions and an important amelioration of the patient’s quality of life, compared with baseline

The density of crown-like structures in epicardial adipose tissue could play a role in cardiovascular diseases

The visceral fat of patients affected by abdominal obesity is inflamed, and the main histopathologic feature is the high density of crown-like structures (CLS). Epicardial adipose tissue (EAT) is a visceral fat of paramount importance for its relationships with coronary vessels and myocardium. Its inflammation in patients with abdominal obesity could be of clinical relevance, but histopathological studies on CLS density in EAT are lacking. This study aimed to assess the histopathology of EAT biopsies obtained from patients undergoing open-heart surgery. We collected EAT biopsies from 10 patients undergoing open-heart surgery for elective coronary artery bypass grafting (CABG) (n = 5) or valvular replacement (VR) (n = 5). Biopsies were treated for light microscopy and immunohistochemistry. We quantify the CLS density in each EAT sample. Despite all patients having abdominal obesity, in EAT samples, no CLS were detected in the VR group; in contrast, CLS were detected in the CABG group (about 17 CLS/10 adipocytes vs. 0.0 CLS/10 adipocytes, CABG vs. VR group, respectively). An impressive density of CLS (100 times that of other patients) was found in one patient (LS) in the CABG group that had a relevant anamnestic aspect: relatively rapid increase of weight gain, especially in abdominal adipose tissue, coincident with myocardial infarction. CLS density could be an important predictive tool for cardiovascular diseases. Furthermore, the LS case implies a role for timing in weight gain. No level of evidence; this is a basic science study

Impact of BNT162b2 Booster Dose on SARS-CoV-2 Anti-Trimeric Spike Antibody Dynamics in a Large Cohort of Italian Health Care Workers

Accurate studies on the dynamics of Pfizer-Biontech BNT162b2-induced antibodies are crucial to better tailor booster dose administration depending on age, comorbidities, and previous natural infection with SARS-CoV-2. To date, little is known about the durability and kinetics of antibody titers months after receiving a booster dose. In this work, we studied the dynamic of anti-Trimeric Spike (anti-TrimericS) IgG titer in the healthcare worker population of a large academic hospital in Northern Italy, in those who had received two vaccine doses plus a booster dose. Blood samples were collected on the day of dose 1, dose 2, then 1 month, 3 months, and 6 months after dose 2, the day of the administration of the booster dose, then 1 month and 3 months after the booster dose. The vaccination immunogenicity was evaluated by dosing anti-TrimericS IgG titer, which was further studied in relation to SARS-CoV-2 infection status, age, and sex. Our results suggest that after the booster dose, the anti-TrimericS IgG production was higher in the subjects that were infected only after the completion of the vaccination cycle, compared to those that were infected both before and after the vaccination campaign. Moreover, the booster dose administration exerts a leveling effect, mitigating the differences in the immunogenicity dependent on sex and age

Epicardial fat inflammation response to COVID‐19 therapies

OBJECTIVE: Adipose tissue plays a role in the novel coronavirus disease 2019 (COVID‐19). Epicardial adipose tissue (EAT), a unique visceral fat, presents with high degree of inflammation in severe COVID‐19 disease. Whether and how adipose tissue may respond to the COVID‐19 therapies is unknown. METHODS: We retrospectively analyzed the difference in computed tomography (CT) measured EAT and subcutaneous (SAT) attenuation, defined as mean attenuation expressed in Hounsfield units (HU), in 72 patients [mean±SD age was 59.6±12.4 years, 50 (69%) were men] at the hospital admission for COVID‐19 and 99 days [IQR (71‐129)] after discharge. RESULTS: At the admission, EAT HU was significantly correlated with blood glucose levels, interleukin 6 , troponin T levels and waist circumference. EAT HU decreased from ‐87.21±16.18 to ‐100.0±11 (p<0.001) whereas SAT HU did not change (‐110.21±12.1 to ‐111.11±27.82, p=0.78) after therapy. Changes in EAT HU (expressed as ∆) significantly correlated with dexamethasone therapy (r= ‐ 0.46, p= 0.006), and when dexamethasone was combined with tocilizumab (r= ‐0.24, p=0.04). CONCLUSIONS: Dexamethasone therapy was associated with significant reduction of EAT inflammation in COVID‐19 patients, whereas SAT showed no changes. Anti‐inflammatory therapies targeting visceral fat may be helpful in COVID‐19 diseases

Abdominal obesity phenotype is associated with COVID-19 chest X-ray severity score better than BMI-based obesity

Chest X-ray (CXR) severity score and BMI-based obesity are predictive risk factors for COVID-19 hospital admission. However, the relationship between abdominal obesity and CXR severity score has not yet been fully explored. This retrospective cohort study analyzed the association of different adiposity indexes, including waist circumference and body mass index (BMI), with CXR severity score in 215 hospitalized patients with COVID-19. Patients with abdominal obesity showed significantly higher CXR severity scores and had higher rates of CXR severity scores ≥ 8 compared to those without abdominal obesity (P < 0.001; P = 0.001, respectively). By contrast, patients with normal weight, with overweight and those with BMI-based obesity showed no significant differences in either CXR severity scores or in the rates of CXR severity scores ≥ 8 (P = 0.104; P = 0.271, respectively). Waist circumference and waist-to-height ratio (WHtR) correlated more closely with CXR severity scores than BMI (r = 0.43, P < 0.001; r = 0.41, P < 0.001; r = 0.17, P = 0.012, respectively). The area under the curves (AUCs) for waist circumference and WHtR were significantly higher than that for BMI in identifying a high CXR severity score (≥ 8) (0.68 [0.60-0.75] and 0.67 [0.60-0.74] vs 0.58 [0.51-0.66], P = 0.001). A multivariate analysis indicated abdominal obesity (risk ratio: 1.75, 95% CI: 1.25-2.45, P < 0.001), bronchial asthma (risk ratio: 1.73, 95% CI: 1.07-2.81, P = 0.026) and oxygen saturation at admission (risk ratio: 0.96, 95% CI: 0.94-0.97, P < 0.001) as the only independent factors associated with high CXR severity scores. Abdominal obesity phenotype is associated with a high CXR severity score better than BMI-based obesity in hospitalized patients with COVID-19. Therefore, when visiting the patient in a hospital setting, waist circumference should be measured, and patients with abdominal obesity should be monitored closely. Level of evidence Cross-sectional descriptive study, Level V

Human Epicardial Adipose Tissue Expresses Glucose-dependent Insulinotropic Polypeptide, Glucagon and Glucagon-Like Peptide 1 Receptors as Potential Targets of Pleiotropic Therapies

Human Epicardial Adipose Tissue (EAT) plays a crucial role in the development and progression of coronary artery disease, atrial fibrillation and heart failure. Microscopically, EAT is composed of adipocytes, nerve tissues, inflammatory, stromovascular and immune cells. EAT is a white adipose tissue, albeit it also has brown-fat like or beige fat features. No muscle fascia divides EAT and myocardium; this allows a direct interaction and cross talk between the epicardial fat and the myocardium. Thus, it might be a therapeutic target for pharmaceutical compounds acting on G-Protein-Coupled Receptors, such as those for Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon (GCG) and Glucagon-Like Peptide-1 (GLP-1), whose selective stimulation with innovative drugs has demonstrated beneficial cardiovascular effects. The precise mechanism of these novel drugs and their tissue and cellular target(s) need to be better understood. We evaluate whether human EAT expresses GIP, GCG and GLP-1 receptors and whether their presence is related to EAT transcriptome. We also investigated protein expression and cell type localization specifically for GIPR and GCGR. EAT samples were collected from 33 patients affected by cardiovascular diseases undergoing open heart surgery (90.9% males, age 67.2±10.5 years mean ± SD). Microarray and immunohistochemistry analysis were performed. Microarray analysis showed that GIPR and GCGR messenger Ribonucleic Acids (mRNAs) are expressed in EAT, beyond confirming the previously found GLP-1(3776±1377 arbitrary unit (A.U.), 17.77±14.91 A.U., and 3.41±2.27 A.U., respectively). The immunohistochemical analysis consistently indicates that GIPR and GCGR are expressed in EAT, mainly in macrophages, isolated and in crown-like structures. In contrast, only some mature adipocytes of different sizes showed cytoplasmic immunostaining, similar to endothelial cells and pericytes in the capillaries and pre-capillary vascular structures. Notably, EAT GIPR is statistically associated with the low expression of genes involved in Free Fatty Acid (FFA) oxidation and transport and those promoting FFA biosynthesis and adipogenesis (p<0.01). EAT GCGR, in turn, is related to genes involved in FFA transport, mitochondrial fatty acid oxidation, and white-to-brown adipocyte differentiation, in addition to genes involved in the reduction of fatty acid biosynthesis and adipogenesis (p<0.01). Having reported the expression of the GLP-1 receptor previously, here, we showed that GIPR and GCGR similarly present at mRNA and protein levels in human EAT, particularly in macrophages and partially adipocytes, suggesting these G-protein-coupled receptors as pharmacological targets on the ongoing innovative drugs, which seem cardiometabolically healthy well beyond their effects on glucose and body weight.

Antibody responses to BNT162b2 mRNA vaccine: Infection-naive individuals with abdominal obesity warrant attention

Objective The excess of visceral adipose tissue might hinder and delay immune response. How people with abdominal obesity (AO) will respond to mRNA vaccines against SARS-CoV-2 is yet to be established. SARS-CoV-2-specific antibody responses were evaluated after the first and second dose of the BNT162b2 mRNA vaccine, comparing the response of individuals with AO with the response of those without, and discerning between individuals with or without prior infection. Methods Immunoglobulin G (IgG)-neutralizing antibodies against the Trimeric complex (IgG-TrimericS) were measured at four time points: at baseline, at day 21 after vaccine dose 1, and at 1 and 3 months after dose 2. Nucleocapsid antibodies were assessed to detect prior SARS-CoV-2 infection. Waist circumference was measured to determine AO. Results Between the first and third month after vaccine dose 2, the drop in IgG-TrimericS levels was more remarkable in individuals with AO compared with those without AO (2.44-fold [95% CI: 2.22-2.63] vs. 1.82-fold [95% CI: 1.69-1.92], respectively, p < 0.001). Multivariable linear regression confirmed this result after inclusion of assessed confounders (p < 0.001). Conclusions The waning antibody levels in individuals with AO may further support recent recommendations to offer booster vaccines to adults with high-risk medical conditions, including obesity, and particularly to those with a more prevalent AO phenotype