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Introduction: Overweight and obesity are associated with a more severe COronaVirus Disease 19 (COVID-19). Adipose tissue-related chronic inflammation could be a promoter for the occurrence of the cytokine storm that predicts aggravation of COVID-19. The primary aim was to investigate if this increased risk for more severe COVID-19 was associated with a higher inflammatory response. Methods: We enrolled patients <75 years old hospitalized in a medical COVID-19 ward with SARS-CoV-2-related pneumonia. Patients were classified according to BMI as normal weight, overweight, and obesity. Laboratory parameters were measured at admission and every second day during the hospital stay. Results: Ninety patients (64.4% males; median age 61 years) were enrolled. Invasive mechanical ventilation (IMV) was needed in 9% of the patients with normal weight, in 32.4% of the patients with overweight, and in 12.9% of the patients with obesity (p = 0.045). Maximal C-reactive protein (CRP) level during hospital stay was 92 (48–122) mg/L in patients with normal weight, 140 (82–265) mg/L in patients with overweight, and 117 (67–160) mg/L in patients with obesity (p = 0.037). Maximal ferritin values were 564 (403–1,379) μg/L in patients with a normal weight, 1,253 (754–2,532) μg/L in patients with overweight, and 828 (279–1,582) μg/L in patients with obesity (p = 0.015). Conclusion: Patients with overweight and obesity required more IMV and had higher peaks of CRP and ferritin than patients with normal weight during COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: The direct identification of SARS-CoV-2 RNA in nasopharyngeal swabs is recommended for diagnosing the novel COVID-19 disease. Pre-analytical determinants, such as sampling procedures, time and temperature storage conditions, might impact on the end result. Our aim was to evaluate the effects of sampling procedures, time and temperature of the primary nasopharyngeal swabs storage on real-time reverse-transcription polymerase chain reaction (rRT-PCR) results. Methods: Each nasopharyngeal swab obtained from 10 hospitalized patients for COVID-19 was subdivided in 15 aliquots: five were kept at room temperature; five were refrigerated (+4 °C); five were immediately mixed with the extraction buffer and refrigerated at +4 °C. Every day and for 5 days, one aliquot per condition was analyzed (rRT-PCR) for SARS-CoV-2 gene E and RNaseP and threshold cycles (Ct) compared. To evaluate manual sampling, 70 nasopharyngeal swabs were sampled twice by two different operators and analyzed separately one from the other. Results: A total of 6/10 swabs were SARS-CoV-2 positive. No significant time or storage-dependent variations were observed in SARS-CoV-2 Ct. Re-sampling of swabs with SARS-CoV-2 Ct lower than 33 resulted in highly reproducible results (CV=2.9%), while a high variability was observed when Ct values were higher than 33 (CV=10.3%). Conclusions: This study demonstrates that time and temperature of nasopharyngeal swabs storage do not significantly impact on results reproducibility. However, swabs sampling is a critical step, and especially in case of low viral load, might be a potential source of diagnostic errors. [ABSTRACT FROM AUTHOR]

In this work we present a framework for blood cholesterol levels prediction from genotype data. The predictor is based on an algorithm for cholesterol metabolism simulation available in literature, implemented and optimized by our group in the R language. The main weakness of the former simulation algorithm was the need of experimental data to simulate mutations in genes altering the cholesterol metabolism. This caveat strongly limited the application of the model in the clinical practice. In this work we present how this limitation could be bypassed thanks to an optimization of model parameters based on patient cholesterol levels retrieved from literature. Prediction performance has been assessed taking into consideration several scoring indices currently used for performance evaluation of machine learning methods. Our assessment shows how the optimization phase improved model performance, compared to the original version available in literature. [ABSTRACT FROM AUTHOR]

Determinants of resting energy expenditure (REE) in humans are still under investigation, especially the association with insulin resistance. Brown adipose tissue (AT) regulates energy expenditure through the activity of the uncoupling protein 1 (UCP1). White AT browning is the process by which some adipocytes within AT depots acquire properties of brown adipocytes ("brite" adipocytes) and it correlates with metabolic improvement. We analyzed determinants of REE in patients with obesity and assessed UCP1 expression as a "brite" marker in abdominal subcutaneous AT (SAT) and visceral omental AT (VAT). Clinical data, REE, free fat mass (FFM), and fat mass (FM) were determined in 209 patients with obesity. UCP1 , PPARG coactivator 1 alpha (PPARGC1A), transcription factor A, mitochondrial (TFAM), T-box transcription factor 1 (TBX1), and solute carrier family 27 member 1 (SLC27A1) expression was assayed in SAT and VAT samples, obtained during sleeve gastrectomy from 62 patients with obesity. REE and body composition data were also available for a subgroup of 35 of whom. In 209 patients with obesity a multiple regression model was computed with REE as the dependent variable and sex, waist, FFM, FM, homeostasis model assessment-insulin resistance (HOMA), interleukin-6 and High Density Lipoprotein-cholesterol as the independent variables. Only FFM, FM and HOMA were independently correlated with REE (r = 0.787, AdjRsqr = 0.602). In each patient VAT displayed a higher UCP1, PPARGC1A, TFAM, TBX1 , and SLC27A1 expression than SAT and UCP1 expression in VAT (UCP1 -VAT) correlated with Body Mass Index (BMI) (r = 0.287, p < 0.05). Introducing UCP1 -VAT in the multivariate model, we showed that FFM, HOMA, interleukin-6, High Density Lipoprotein-cholesterol, and UCP1 -VAT were independent factors correlated with REE (r = 0.736, AdjRsqr = 0.612). We confirmed that REE correlates with FFM, FM and HOMA in a large cohort of patients. Our results clearly showed that UCP1 -VAT expression was significantly increased in severe human obesity (BMI > 50 kg/m2) and that it behaved as an independent predictor of REE. Lastly, we suggest that an increased REE and browning in metabolically complicated severe obesity could represent an effort to counteract further weight gain. [ABSTRACT FROM AUTHOR]

Eur J Clin Invest 2012; 42 (11): 1197-1204 Abstract Background The low-grade chronic inflammation present in obesity has been recognized as a risk factor for thrombosis, atherosclerosis and cardiovascular complications. In this context, production by adipose organ of a number of inflammatory adipokines could play a crucial role. It has been reported that obesity represents a risk factor for acquired thrombotic thrombocytopenic purpura (TTP), a disease caused by ADAMTS13 deficiency because of anti-ADAMTS13 antibodies, but the pathophysiological link between obesity and TTP is still unknown. We aimed to investigate mechanisms linking obesity to risk of TTP. Materials and methods Eighty obese patients consecutively admitted to Bariatric Unit of Padua between 2006 and 2009, and 39 lean subjects were characterized by anthropometric, metabolic and inflammatory parameters. ADAMTS13 autoantibodies, activity and antigen levels, and several cytokines including thrombospondin-1 were measured. Results 21·3% of obese patients were positive for noninhibitory ADAMTS13 autoantibodies, while all lean subjects were negative ( P < 0·01). No differences in ADAMTS13 activity and antigen levels were found. Thrombospondin-1 levels were significantly higher in obese than in lean subjects (974·4 ± 592·7 vs. 318·9 ± 202·1 ng/mL; P < 0·001) and were inversely correlated with ADAMTS13 activity ( R = −0·4853; P < 0·001). Dot blot suggests that anti-ADAMTS13 antibodies in obese patients bind recombinant thrombospondin-1. Conclusions We suggest that anti-ADAMTS13 antibodies are directed against thrombospondin domains shared between ADAMTS13 and thrombospondin-1 and that their generation may be sustained by high levels of thrombospondin-1. This phenomenon could be of relevance, because little is known on the pathogenesis of TTP and its possible link with obesity. [ABSTRACT FROM AUTHOR]

Although obesity represents a risk factor for the development of type 2 diabetes mellitus (T2DM), the link between these pathological conditions is not so clear. The manner in which the different elements of adipose tissue (AT) interplay in order to grow has been suggested to have a role in the genesis of metabolic complications, but this has not yet been fully addressed in humans. Through IHC, transmission electron microscopy, cytometry, and in vitro cultures, we described the morphological and functional changes of subcutaneous and visceral AT (SAT and VAT) in normoglycemic, prediabetic and T2DM patients with obesity compared to lean subjects. In both SAT and VAT we measured a hypertrophic and hyperplastic expansion, causing similar vascular rarefaction in obese patients with different degrees of metabolic complications. Capillaries display dysfunctional basement membrane thickening only in T2DM patients evidencing VAT as a new target of T2DM microangiopathy. The largest increase in adipocyte size and decrease in adipose stem cell number and adipogenic potential occur both in T2DM and in prediabetes. We showed that SAT and VAT remodeling with stemness deficit is associated with early glucose metabolism impairment suggesting the benefit of an AT-target therapy controlling hypertrophy and hyperplasia already in prediabetic obese patients. [ABSTRACT FROM AUTHOR]