The broad spectrum of COVID-like patients initially negative at RT-PCR testing: a cohort study

Background: Patients that arrive in the emergency department (ED) with COVID-19-like syndromes testing negative at the first RT-PCR represent a clinical challenge because of the lack of evidence about their management available in the literature. Our first aim was to quantify the proportion of patients testing negative at the first RT-PCR performed in our Emergency Department (ED) that were confirmed as having COVID-19 at the end of hospitalization by clinical judgment or by any subsequent microbiological testing. Secondly, we wanted to identify which variables that were available in the first assessment (ED variables) would have been useful in predicting patients, who at the end of the hospital stay were confirmed as having COVID-19 (false-negative at the first RT-PCR). Methods: We retrospectively collected data of 115 negative patients from2020, March 1st to 2020, May 15th. Three experts revised patients’ charts collecting information on the whole hospital stay and defining patients as COVID-19 or NOT-COVID-19. We compared ED variables in the two groups by univariate analysis and logistic regression. Results: We classified 66 patients as COVID-19 and identified the other 49 as having a differential diagnosis (NOT-COVID), with a concordance between the three experts of 0.77 (95% confidence interval (95%CI) 0.66- 0.73). Only 15% of patients tested positive to a subsequent RT-PCR test, accounting for 25% of the clinically suspected. Having fever (odds ratio (OR) 3.32, (95%CI 0.97-12.31), p = 0.06), showing a typical pattern at the first lung ultrasound (OR 6.09, (95%CI 0.87-54.65), p = 0.08) or computed tomography scan (OR 4.18, (95%CI 1.11-17.86), p = 0.04) were associated with a higher probability of having COVID-19. Conclusions: In patients admitted to ED with COVID-19 symptoms and negative RT-PCR a comprehensive clinical evaluation integrated with lung ultrasound and computed tomography could help to detect COVID-19 patients with a false negative RT-PCR result

False-negative real-time polymerase chain reaction tests in COVID-19 patients: an epidemiological analysis of 302 patients

Objectives: Patients who arrive at the emergency department (ED) with COVID-19, who test negative at the first real-time polymerase chain reaction (RT-PCR), represent a clinical challenge. This study aimed to evaluate if the clinical manifestation at presentation, the laboratory and imaging results, and the prognosis of COVID-19 differ in patients who tested negative at the first RT-PCR compared with those who tested positive and also to evaluate if comorbid conditions patient-related or the period of arrival are associated with negative testing. Study design: We retrospectively collected clinical data of patients who accessed the ED from March 1 to May 15, 2020. Methods: We compared clinical variables, comorbid conditions, and clinical outcomes in the two groups by univariate analysis and logistic regression. Results: Patients who tested negative at the first RT-PCR showed a higher prevalence of cardiopathy, immunosuppression, and diabetes, as well as a higher leukocyte and lower lymphocyte counts compared with patients who tested positive. A bilateral interstitial syndrome and a typical pattern at computed tomography scan were prevalent in the test-negative group. Test-negative patients were more likely to be admitted to the hospital but less likely to need admission in a high level of care ward. The false-negative rate increased from March to May. Conclusion: False-negative RT-PCR COVID-19 patients present a similar spectrum of symptoms compared with positive cohort, but more comorbidities. Imaging helps to identify them. True positives had a higher risk of serious complications

Thermodynamic properties of atrial fibrillation cryoablation: A model-based approach to improve knowledge on energy delivery

The objective of this study is to describe a suitable model of atrial fibrillation cryoablation thermodynamic properties. Three different thermal loads were applied to a cylindrical copper element simulating the cryoprobe, thermally coupled with a Peltier stack producing the freezing effect, and in contact with a bovine liver sample. Thermal events occurring inside the samples were measured using mirror image technique. Heat subtracted flux during ice formation and minimum temperature measured at probe–tissue interface were, respectively, 1.33Wcm−2 and −27.8°C for Sample#0, 1.88Wcm−2 and −35.6°C for Sample#1 and 1.82Wcm−2 and 1.44Wcm−2 before and after the ice trigger, respectively, and −29.3°C for Sample#2. Ice trigger temperature was around −8.5°C for Sample#0 and Sample#2, and −10.4°C for Sample#1. In all the investigated samples, ice front penetration was proportional to the square root of time and its velocity depended on the heat flux subtracted. The fraction of the useful energy spent for ice formation was less than 60% for Sample#0, and about 80% for Sample#1 and for Sample#2, before the reduction of the removed heat flux. Freezing time exceeding a cut-off, according to the heat subtracted flux, does not improve the procedure effectiveness and is detrimental to the surrounding tissues

OECD/NEA/CSNI/WGAMA PERSEO benchmark: main outcomes and conclusions

In the framework of the OECD/NEA/CSNI/WGAMA, an activity on the "Status report on thermal-hydraulic passive systems design and safety assessment" has been conducted. Within this activity, a benchmark exercise, based on the experimental data developed in the full scale PERSEO (in-Pool Energy Removal System for Emergency Operation) component separate effect test facility, built at SIET (Piacenza, Italy), has been proposed and carried out. An "OPEN" benchmark exercise, hosted by ENEA, has been conducted. Twelve results from eleven Organizations were submitted. PERSEO is a full-scale separate effect test facility designed to study a new passive decay heat removal system operating in natural circulation. Test 7 is a full pressure test (7 MPa) and investigates the system stability and the system operation. The accuracy of the calculated results has been evaluated both qualitatively and quantitatively. The latter has been conducted adopting the Fast Fourier Transform Based Method. The present paper summarizes the main features of the PERSEO facility and Test 7 and discusses the main results and outcome of the benchmark exercise

OECD/NEA/CSNI/WGAMA PERSEO benchmark:Main outcomes and conclusions

In the framework of the OECD/NEA/CSNI/WGAMA, an activity on the "Status report on thermal-hydraulic passive systems design and safety assessment" has been conducted. Within this activity, a benchmark exercise, based on the experimental data developed in the full scale PERSEO (in-Pool Energy Removal System for Emergency Operation) component separate effect test facility, built at SIET (Piacenza, Italy), has been proposed and carried out. An "OPEN" benchmark exercise, hosted by ENEA, has been conducted. Twelve results from eleven Organizations were submitted. PERSEO is a full-scale separate effect test facility designed to study a new passive decay heat removal system operating in natural circulation. Test 7 is a full pressure test (7 MPa) and investigates the system stability and the system operation. The accuracy of the calculated results has been evaluated both qualitatively and quantitatively. The latter has been conducted adopting the Fast Fourier Transform Based Method. The present paper summarizes the main features of the PERSEO facility and Test 7 and discusses the main results and outcome of the benchmark exercise

OECD/NEA/CSNI/WGAMA PERSEO benchmark. Main outcomes and conclusions

In the framework of the OECD/NEA/CSNI/WGAMA, an activity on the “Status report on thermal–hydraulic passive systems design and safety assessment” has been conducted. Within this activity, a benchmark exercise, based on the experimental data developed in the full scale PERSEO (in-Pool Energy Removal System for Emergency Operation) component separate effect test facility, built at SIET (Piacenza, Italy), has been proposed and carried out. An “OPEN” benchmark exercise, hosted by ENEA, has been conducted. Twelve results from eleven Organizations were submitted. PERSEO is a full-scale separate effect test facility designed to study a new passive decay heat removal system operating in natural circulation. Test 7 is a full pressure test (7 MPa) and investigates the system stability and the system operation. The accuracy of the calculated results has been evaluated both qualitatively and quantitatively. The latter has been conducted adopting the Fast Fourier Transform Based Method. The present paper summarizes the main features of the PERSEO facility and Test 7 and discusses the main results and outcome of the benchmark exercise

Design, Synthesis of Novel, Potent, Selective, Orally Bioavailable Adenosine A_2A Receptor Antagonists and Their Biological Evaluation

Our initial structure–activity relationship studies on 7-methoxy-4-morpholino-benzothiazole derivatives featured by aryloxy-2-methylpropanamide moieties at the 2-position led to identification of compound <b>25</b> as a potent and selective A_2A adenosine receptor (A_2AAdoR) antagonist with reasonable ADME and pharmacokinetic properties. However, poor intrinsic solubility and low to moderate oral bioavailability made this series unsuitable for further development. Further optimization using structure-based drug design approach resulted in discovery of potent and selective adenosine A_2A receptor antagonists bearing substituted 1-methylcyclohexyl-carboxamide groups at position 2 of the benzothiazole scaffold and endowed with better solubility and oral bioavailability. Compounds <b>41</b> and <b>49</b> demonstrated a number of positive attributes with respect to in vitro ADME properties. Both compounds displayed good pharmacokinetic properties with 63% and 61% oral bioavailability, respectively, in rat. Further, compound <b>49</b> displayed oral efficacy in 6-OHDA lesioned rat model of Parkinson diseases