The Fenice project to evaluate and improve the quality of healthcare in high-dependency care units: results after the first year.

High-Dependency care Units (HDUs) have been introduced worldwide as intermediate wards between Intensive Care Units (ICUs) and general wards. Performing a comparative assessment of the quality of care in HDU is challenging because there are no uniform standards and heterogeneity among centers is wide. The Fenice network promoted a prospective cohort study to assess the quality of care provided by HDUs in Italy.

Molecular Typing and Resistance Profile of Isolates during the COVID-19 Pandemic: Findings from the "EPIRADIOCLINF" Project.

Due to the COVID-19 pandemic, there has been a shift in focus towards controlling the spread of SARS-CoV-2, which has resulted in the neglect of traditional programs aimed at preventing healthcare-associated infections and combating antimicrobial resistance. The present work aims to characterize the colonization or infection with of COVID-19 patients and to identify any clonality between different isolates. Specifically, data and resistance profiles of isolates were prospectively collected from patients recruited by the EPIRADIOCLINF project.

Assessing Humoral Immuno-Inflammatory Pathways Associated with Respiratory Failure in COVID-19 Patients.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to a bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease's worsening. In our sample, median age was 74 years (72-75) and 54% were men.

Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors.

Background: GSK3368715, a first-in-class, reversible inhibitor of type I protein methyltransferases (PRMTs) demonstrated anticancer activity in preclinical studies. This Phase 1 study (NCT03666988) evaluated safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK3368715 in adults with advanced-stage solid tumors.

Methods: In part 1, escalating doses of oral once-daily GSK3368715 (50, 100, and 200 mg) were evaluated.

Neutrophil-to-Lymphocyte Ratio (NLR) Is a Promising Predictor of Mortality and Admission to Intensive Care Unit of COVID-19 Patients.

The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker predicting the prognosis of several diseases. We aimed to assess its role as a predictor of mortality or admission to the intensive care unit in COVID-19 patients. We retrospectively evaluated a cohort of 411 patients with COVID-19 infection.

Reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) as a user-friendly system to detect SARS-CoV-2 infection: a multicentric study.

Although reverse transcriptase quantitative PCR remains the gold standard to perform viral detection, reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) is already used to perform diagnosis of various infections. This work reports the results of a multicentric study performed in Sicily to evaluate the diagnostic power of an RT-LAMP kit for the diagnosis of SARS-CoV-2 infection on a total of 551 samples collected in January and February 2021, revealing sensitivity, specificity, accuracy, positive and negative predictive values ≥95%. Our results suggest the potential employment of this kit as a screening test to be used where fast and reliable results are demanded without the need for expensive instruments and highly-skilled personnel.

Identification of hnRNP-A1 as a pharmacodynamic biomarker of type I PRMT inhibition in blood and tumor tissues.

Arginine methylation has been recognized as a post-translational modification with pleiotropic effects that span from regulation of transcription to metabolic processes that contribute to aberrant cell proliferation and tumorigenesis. This has brought significant attention to the development of therapeutic strategies aimed at blocking the activity of protein arginine methyltransferases (PRMTs), which catalyze the formation of various methylated arginine products on a wide variety of cellular substrates. GSK3368715 is a small molecule inhibitor of type I PRMTs currently in clinical development.

An Italian registry of chest pain patients in the emergency department: clinical predictors of acute coronary syndrome.

Background: The aim of this study was to describe the population of patients arriving in several Italian Emergency Departments (EDs) complaining of chest pain suggestive of acute coronary syndrome (ACS) in order to evaluate the incidence of ACS in this cohort and the association between ACS and different clinical parameters and risk factors.

Methods: This is an observational prospective study, conducted from the 1st January to the 31st December 2014 in 11 EDs in Italy. Patients presenting to ED with chest pain, suggestive of ACS, were consecutively enrolled.

SOFA Score prognostic performance among patients admitted to High-Dependency Units.

Background: The aim of this study was to assess prognostic stratification in patients admitted in two Italian Emergency-Department High-Dependency Units (ED-HDU).

Methods: From June 2014, to July 2016, we recorded all patients admitted in the ED-HDU of the Careggi University Hospital and the Vittorio Emanuele University Hospital in a standardized database. Charlson Index and SOFA Score were calculated to evaluate comorbidity burden and severity of organ dysfunction.

Outcomes of non-invasive ventilation in 'very old' patients with acute respiratory failure: a retrospective study.

Background: Non-invasive ventilation (NIV) is increasingly used to support very old (aged ≥85 years) patients with acute respiratory failure (ARF). This retrospective observational study evaluated the impact of NIV on the prognosis of very old patients who have been admitted to the intermediate care unit (IMC) of the Emergency Department of the University Hospital Policlinico-Vittorio Emanuele of Catania for ARF.

Methods: All patients admitted to the IMC between January and December 2015 who received NIV as the treatment for respiratory failure were included in this study.

Non-invasive positive pressure ventilation in pneumonia outside Intensive Care Unit: An Italian multicenter observational study.

Background And Objective: Non-Invasive Ventilation (NIV) represents a standard of care to treat some acute respiratory failure (ARF). Data on its use in pneumonia are lacking, especially in a setting outside the Intensive Care Unit (ICU). The aims of this study were to evaluate the use of NIV in ARF due to pneumonia outside the ICU, and to identify risk factors for in-hospital mortality.

Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.

Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Aβ) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Aβ levels was detected.

Effectiveness of Short-Term Dynamic Group Psychotherapy in Primary Care for Patients with Depressive Symptoms.

Unlabelled: An open prospective controlled study was designed to compare the efficacy of short-term dynamic group psychotherapy with the standard treatment in patients with depressive symptoms attended in the primary care setting. A total of 115 patients with depressive symptoms were assigned to receive psychotherapy (75 min) over 9 months (37 to 39 sessions) (n = 70) or the standard care (n = 45). Outcome measures were the differences between baseline and post-treatment in the 17-item Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HAM-A) and the Short-Form Health Survey (SF-12) questionnaire in the two study groups.

Discovery of a Novel, Orally Efficacious Liver X Receptor (LXR) β Agonist.

This article describes the application of Contour to the design and discovery of a novel, potent, orally efficacious liver X receptor β (LXRβ) agonist (17). Contour technology is a structure-based drug design platform that generates molecules using a context perceptive growth algorithm guided by a contact sensitive scoring function. The growth engine uses binding site perception and programmable growth capability to create drug-like molecules by assembling fragments that naturally complement hydrophilic and hydrophobic features of the protein binding site.

Identification of spirooxindole and dibenzoxazepine motifs as potent mineralocorticoid receptor antagonists.

Mineralocorticoid receptor (MR) antagonists continue to be a prevalent area of research in the pharmaceutical industry. Herein we report the discovery of various spirooxindole and dibenzoxazepine constructs as potent MR antagonists. SAR analysis of our spirooxindole hit led to highly potent compounds containing polar solubilizing groups, which interact with the helix-11 region of the MR ligand binding domain (LBD).

The medicinal chemistry of liver X receptor (LXR) modulators.

LXRs have been of interest as targets for the treatment of atherosclerosis for over a decade. In recent years, LXR modulators have also garnered interest for potential use in the treatment of inflammation, Alzheimer's disease (AD), dermatological conditions, hepatic steatosis, and oncology. To date, no LXR modulator has successfully progressed beyond phase I clinical trials.

Extra-cerebral severe infections associated with haemorrhagic hereditary telangiectasia (Rendu-Osler-Weber Disease): five cases and a review of the literature.

Hereditary haemorrhagic telangiectasia (HHT) is one of the most common autosomal dominant disorders and is characterized by genetically determined abnormalities of vascular structure. People affected by HHT are predisposed to severe infections such as cerebral abscesses, typical of patients with pulmonary arteriovenous malformations, and extra-cerebral infections such as bacteraemia, septic arthritis, osteomyelitis, hepatic abscesses, skin infections and infective endocarditis. We present a retrospective series of severe bacterial extra-cerebral infections in five patients affected by HHT, admitted to our Institute from January 2007 to June 2013.

Thirty and ninety days mortality predictive value of admission and in-hospital procalcitonin and mid-regional pro-adrenomedullin testing in patients with dyspnea. Results from the VERyfing DYspnea trial.

Introduction: Mid-regional pro-atrial natriuretic peptide (MR-proANP), procalcitonin (PCT), and mid-regional pro-adrenomedullin (MR-proADM) demonstrated usefulness for management of emergency department patients with dyspnea.

Methods: To evaluate in patients with dyspnea, the prognostic value for 30 and 90 days mortality and readmission of PCT, MR-proADM, and MR-proANP, a multicenter prospective study was performed evaluating biomarkers at admission, 24 and 72 hours after admission. Based on final diagnosis, patients were divided into acute heart failure (AHF), primary lung diseases, or both (AHF + NO AHF).

Molecular characterization of hepatitis A outbreak in the province of Rome, Lazio region, Italy, January-July 2013.

Reduced circulation of hepatitis A virus lead to an increase of susceptible individuals, and outbreaks occurred recently. In Northern Italy an outbreak is ongoing, attributed to a monophyletic genotype IA strain, with mixed frozen berries as probable source. From 01/01/2013 to 07/15/2013, 30 cases were diagnosed at National Institute for Infectious Diseases, Rome, Italy, representing about twice the number of cases in whole 2012.

Eye exercises enhance accuracy and letter recognition, but not reaction time, in a modified rapid serial visual presentation task.

Eye exercises have been prescribed to resolve a multitude of eye-related problems. However, studies on the efficacy of eye exercises are lacking, mainly due to the absence of simple assessment tools in the clinic. Because similar regions of the brain are responsible for eye movements and visual attention, we used a modified rapid serial visual presentation (RSVP) to assess any measurable effect of short-term eye exercise in improvements within these domains.

Additive value of blood neutrophil gelatinase-associated lipocalin to clinical judgement in acute kidney injury diagnosis and mortality prediction in patients hospitalized from the emergency department.

Introduction: Acute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients.

Methods: This is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED.

Regulation of sphingomyelin phosphodiesterase acid-like 3A gene (SMPDL3A) by liver X receptors.

Liver X receptor (LXR) α and LXRβ function as physiological sensors of cholesterol metabolites (oxysterols), regulating key genes involved in cholesterol and lipid metabolism. LXRs have been extensively studied in both human and rodent cell systems, revealing their potential therapeutic value in the contexts of atherosclerosis and inflammatory diseases. The LXR genome landscape has been investigated in murine macrophages but not in human THP-1 cells, which represent one of the frequently used monocyte/macrophage cell systems to study immune responses.