Comparison between hospitalized patients affected or not by COVID-19 (RESILIENCY study)

Dear Editor, in the recent report of Munblit and coworkers [1], authors observed that the combination of clinical features was sufficient to diagnose COVID-19 indicating that laboratory testing is not critical in real-life clinical practice. To date, all patients admitted to Emergency Department with acute respiratory failure and/or fever should be considered as a suspected SARS-CoV-2 infection [2-3], and an early recognition of etiology and the prompt therapeutic management are crucial to improve survival [4-5]. From March to July 2020, we performed a prospective, multicenter study (RESILIENCY study). During the study period, all patients hospitalized for suspected or confirmed COVID-19 were prospectively recruited in 3 large hospitals in Rome, Italy. All patients with suspected SARS-CoV-2 infection, admitted to the hospital in case of fever and/or hypoxemic respiratory failure (PaO2 <60 mmHg at rest in ambient air) or of exacerbation of underlying diseases or severe symptoms not manageable outside the hospital, were evaluated according to a predefined protocol (see Figure 1). Overall, 653 patients were included in the study: 309 (47.3%) patients with confirmed COVID-19 and 344 (52.7%) without COVID-19, hospitalized for other causes. Baseline characteristics and outcomes of the study population showed that the main causes of hospitalization among patients without COVID-19 were: acute heart failure (47%), bacterial pneumonia (38.5%), and pulmonary embolism (9.2%). Overall, 67 (21.7%) patients of COVID-19 group and 45 (13.1%) hospitalized for other causes were admitted to intensive care unit; 30-day mortality was observed in 59 (19%) patients of COVID-19 group and 62 (18%) of non-COVID-19 group. The multivariate analysis about risk factors for COVID-19 etiology at time of hospitalization showed that dry cough (OR 3.76, CI 95% 1.98-7.92, P<0.001), duration of fever>3 days (OR 5.21, CI 95% 2.34-9.21, P<0.001), lymphocytopenia (OR 1.98, CI 95% Downloaded from https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1745/5989494 by Sapienza Università di Roma user on 01 December 2020 Accepted Manuscript 3 1.27-4.22, P=0.002) and PaO2/FiO2 ratio<250 (OR 4.98, CI 95% 2.22-9.71, P<0.001) were independently associated with COVID-19 etiology, while procalcitonin value>1 ng/ mL (OR 0.21, CI 95% 0.08-0.82, p<0.001), and lactate>2 mmol/L (OR 0.41, CI 95% 0.15-0.77, p<0.001) were associated with non-COVID-19 etiology. Finally, analysis about predictors of 30-day mortality showed that age (per-year increase OR 1.33; CI 95% 1.11-2.10; p<0.001), cardiovascular disease (OR 4.58; CI 95% 2.07-8.25; p<0.001), and ICU admission (OR 2.1; CI 95% 1.48-4.4; p<0.001) were independently associated with all-cause 30-day mortality, while the use of low-molecularweight heparin (OR 0.22, CI 95% 0.03-0.45, p=0.002) was associated with survival. The findings of the present study can be summarized as follows:1) the prompt identification of specific clinical characteristics (like dry cough or duration of fever>3 days), and laboratory findings (like lymphocytopenia, PaO2/FiO2 ratio<250, procalcitonin value>1 ng/ mL, and lactate>2 mmol/L) can help physicians to distinguish rapidly between COVID19 or other etiologies [6]; 2) the application of a standard approach to management of patients with acute respiratory failure and/or fever associated with the knowledge of clinical and laboratory characteristics of COVID-19 can early drive physicians to therapeutic choices; and 3) age, cardiovascular disease, and ICU admission show an independent association with all-cause 30-day mortality [7], while the use of low-molecular-weight heparin was associated with survival [8]. In conclusion, COVID-19 syndrome is characterized by a heterogeneous clinical, laboratoristic, and radiological presentation, especially at its onset [9]. However, the application of a standard approach to management of patients with acute respiratory failure and/or fever and the knowledge of clinical and laboratory characteristics of COVID-19 can early drive therapeutic choic

The role of neuromedin U in adiposity regulation. Haplotype analysis in European children from the IDEFICS Cohort

Background and aims: Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children. Methods and results: From a large European multi-center study on childhood obesity, 4,528 children (2.0–9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years’ time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05). Conclusions: This study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation

Growth Hormone Is Necessary for the p53-Mediated, Obesity-Induced Insulin Resistance in Male C57BL/6J × CBA Mice

Insulin resistance is a key marker of both obesity and GH excess. The purpose of the study was to assess the role of GH on p53-mediated insulin resistance of male mice with obesity due to a high-fat diet. C57BL/6J CBA male mice fed on a high-fat diet (Obe) were studied; male mice fed a normal diet (Lean) or transgenic mice for bovine GH under the same genetic background (Acro) served as controls. The convergence of p53 and GH pathways was evaluated by Western blot. Obe mice had insulin resistance, which was sustained by a selective increased expression of p53 in adipose tissue. Normal insulin sensitivity was restored, and adipose p53 expression normalized when the GH pathway was blocked. Only the adipose p53 expression was sensitive to the GH blockage, which occurred through the p38 pathway. Adipose tissue of Obe mice had a coordinate overexpres- sion of suppressors of cytokine signal 1–3 and signal transducers and activators of transcrip- tion-1, -3, and -5b, not different from that of Acro mice, suggesting an increased sensitivity of adipose tissue to GH. On the contrary, Lean mice were unaffected by changes of GH action. GH seems to be necessary for the increased adipose p53 expression and for insulin resistance of obese mice

Incidence and Risk Factors for Tractional Macular Detachment after Anti-Vascular Endothelial Growth Factor Agent Pretreatment before Vitrectomy for Complicated Proliferative Diabetic Retinopathy

The study's purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65-0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11-0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02-1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age

Dialkyl carbonates: scale-up synthesis and application as green solvents for PVDF membranes preparation

Dialkyl carbonates (DACs) are well-known green solvents and reagents that have been extensively investigated as safe alternatives to chlorine-based compounds. In fact, they can replace alkyl halides and dimethyl sulfate in alkylation and carbonylation reactions as well as phosgene and its derivatives in alkoxycarbonylation ones. Recently we have developed a high yielding scale-up synthesis of non-commercially available or expensive DACs via transcarbonylation reactions of an alcohol with dimethyl carbonate (DMC) promoted by the nitrogen-based organocatalyst 1,5,7-triazabicyclo[4.4.0]dec-5-ene TBD. Compared to previously published works, the proposed procedure has been customized for DACs large scale production (up to 100 mL of product obtained). Purification of these compounds has been achieved by fractional distillation and the exceeding reagents have been recovered and recycled. Selected DACs for this study include both symmetrical and unsymmetrical compounds, incorporating several alkyl, alkoxyalkyl, alkylamino and alkylthio functional groups. Chemical-physical properties of the new DACs have been also evaluated, as well as their water solubility. Furthermore, biodegradability and cytotoxicity tests have been carried out to investigate the effects of the different substituents on the greenness of these potential solvents and reagents. DACs application as green solvents for membrane preparation was next investigated, using non-solvent induced phase separation (NIPS) and vapor induced phase separation (VIPS) techniques, achieving both porous and plain membranes [4]. Morphology, additives effect, physical-chemical and mechanical proprieties as well as their performances in terms of water permeability and rejection were evaluated and compared to membranes obtained using commercially available cyclic carbonates (namely ethylene carbonate – EC and propylene carbonate – PC)

Direct Aortic CoreValve Implantation via Right Anterior Thoracotomy in a Patient with Patent Bilateral Mammary Artery Grafts and Aortic Arch Chronic Dissection

Direct aortic trans-catheter aortic valve implantation is an alternative approach to treat high risk for surgery patients affected by severe aortic stenosis and concomitant peripheral vascular disease. We describe a case of direct aortic CoreValve implantation made via a right anterior thoracotomy in a 78-year-old male affected by severe aortic stenosis and severe peripheral vasculopathy, who previously underwent coronary artery bypass grafting, with patent bilateral mammary artery grafts and chronic aortic arch dissection