An Evidence-Based Multidisciplinary Approach Focused at Creating Algorithms for Targeted Therapy of BSIs, cUTIs, and cIAIs Caused by in Critically Ill Adult Patients.

Prompt implementation of appropriate targeted antibiotic therapy represents a valuable approach in improving clinical and ecological outcome in critically septic patients. This multidisciplinary opinion article focused at developing evidence-based algorithms for targeted antibiotic therapy of bloodstream (BSIs), complicated urinary tract (cUTIs), and complicated intrabdominal infections (cIAIs) caused by . The aim was to provide a guidance for intensive care physicians either in appropriately placing novel antibiotics or in considering strategies for sparing the broadest-spectrum antibiotics.

Predictors of Patient-Reported Incontinence at Adjuvant/Salvage Radiotherapy after Prostatectomy: Impact of Time between Surgery and Radiotherapy.

Background: Baseline urinary incontinence (UI) strongly modulates UI recovery after adjuvant/salvage radiotherapy (ART/SRT), inducing clinicians to postpone it "as much as possible", maximizing UI recovery but possibly reducing efficacy. This series aims to analyze the trend of UI recovery and its predictors at radiotherapy start.

Methods: A population of 408 patients treated with ART/SRT enrolled in a cohort study (ClinicalTrials.

State of the Art in Artificial Intelligence and Radiomics in Hepatocellular Carcinoma.

The most common liver malignancy is hepatocellular carcinoma (HCC), which is also associated with high mortality. Often HCC develops in a chronic liver disease setting, and early diagnosis as well as accurate screening of high-risk patients is crucial for appropriate and effective management of these patients. While imaging characteristics of HCC are well-defined in the diagnostic phase, challenging cases still occur, and current prognostic and predictive models are limited in their accuracy.

Antimicrobial Dose Reduction in Continuous Renal Replacement Therapy: Myth or Real Need? A Practical Approach for Guiding Dose Optimization of Novel Antibiotics.

Acute kidney injury represents a common complication in critically ill patients affected by septic shock and in many cases continuous renal replacement therapy (CRRT) may be required. In this scenario, antimicrobial dose optimization is highly challenging as the extracorporeal circuit may cause several pharmacokinetic alterations, which add up to volume of distribution and clearance variations resulting from sepsis. Variations in CRRT settings (i.

European List of Essential Medicines for Medical Education: a protocol for a modified Delphi study.

Introduction: Junior doctors are responsible for a substantial number of prescribing errors, and final-year medical students lack sufficient prescribing knowledge and skills just before they graduate. Various national and international projects have been initiated to reform the teaching of clinical pharmacology and therapeutics (CP&T) during undergraduate medical training. However, there is as yet no list of commonly prescribed and available medicines that European doctors should be able to independently prescribe safely and effectively without direct supervision.

Positive bronchoalveolar lavage pepsin assay associated with viral and fungal respiratory infections in children with chronic cough.

Objective: To assess the association between commonly obtained endoscopic and serologic data and bronchoalveolar lavage pepsin assay (BAL) results in children with chronic cough.

Study Design: We performed a retrospective chart review of 72 children with a BAL pepsin obtained through our Aerodigestive Center over an 18-month period. BAL outcomes include evidence of viral, bacterial, or fungal infection, presence of lipid-laden macrophages, and cytology (eosinophils, neutrophils, and lymphocytes).

Machine Learning and Syncope Management in the ED: The Future Is Coming.

In recent years, machine learning (ML) has been promisingly applied in many fields of clinical medicine, both for diagnosis and prognosis prediction. Aims of this narrative review were to summarize the basic concepts of ML applied to clinical medicine and explore its main applications in the emergency department (ED) setting, with a particular focus on syncope management. Through an extensive literature search in PubMed and Embase, we found increasing evidence suggesting that the use of ML algorithms can improve ED triage, diagnosis, and risk stratification of many diseases.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.

Feature tracking myocardial strain analysis in patients with bileaflet mitral valve prolapse: relationship with LGE and arrhythmias.

Objectives: Anatomical substrate and mechanical trigger co-act in arrhythmia's onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA).

Clinically Significant Drug Interactions Between Psychotropic Agents and Repurposed COVID-19 Therapies.

As many patients with underlying psychiatric disorders may be infected with COVID-19, and COVID-19-affected subjects may frequently experience a new onset of psychiatric manifestations, concomitant use of psychotropic medications and COVID-19 therapies is expected to be highly likely and raises concerns of clinically relevant drug interactions. In this setting, four major mechanisms responsible for drug interactions involving psychotropic agents and COVID-19 therapies may be identified: (1) pharmacokinetic drug-drug interactions mainly acting on cytochrome P450; (2) pharmacodynamic drug-drug interactions resulting in additive or synergistic toxicity; (3) drug-disease interactions according to stage and severity of the disease; and (4) pharmacogenetic issues associated with polymorphisms of cytochrome P450 isoenzymes. In this review, we summarise the available literature on relevant drug interactions between psychotropic agents and COVID-19 therapies, providing practical clinical recommendations and potential management strategies according to severity of illness and clinical scenario.

Bone fracture as a novel immune-related adverse event with immune checkpoint inhibitors: Case series and large-scale pharmacovigilance analysis.

Although immune checkpoint inhibitors (ICIs) are associated with different immune-related adverse events (irAEs), the potential effect on the skeleton is poorly defined albeit biologically plausible and assessable through pharmacovigilance. We described a case series of patients experiencing skeletal fractures while on ICIs at the National Cancer Institute of Milan. To better characterize the clinical features of skeletal irAEs reported with ICIs, we queried the FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis by means of reporting odds ratios (RORs), deemed significant by a lower limit of the 95% confidence interval (LL95% CI) > 1.

Extract: A Non-Invasive Strategy to Obtain Adjunct Attenuated Cultures.

This study aims at proposing the use of commonly known as Spirulina, extract as a non-invasive method to attenuate the growth rate of non-starter adjunct cultures, thus preventing the over-acidification that may occur during cheese manufacturing. A preliminary screening using four different concentrations (0.20%, 0.

MRI index lesion radiomics and machine learning for detection of extraprostatic extension of disease: a multicenter study.

Objectives: To build a machine learning (ML) model to detect extraprostatic extension (EPE) of prostate cancer (PCa), based on radiomics features extracted from prostate MRI index lesions.

Methods: Consecutive MRI exams of patients undergoing radical prostatectomy for PCa were retrospectively collected from three institutions. Axial T2-weighted and apparent diffusion coefficient map images were annotated to obtain index lesion volumes of interest for radiomics feature extraction.

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study.

Objective: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM).

Methods: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers.

Combined inhibition of Aurora-A and ATR kinase results in regression of -amplified neuroblastoma.

Amplification of is the driving oncogene in a subset of high-risk neuroblastoma. The MYCN protein and the Aurora-A kinase form a complex during S phase that stabilizes MYCN. Here we show that MYCN activates Aurora-A on chromatin, which phosphorylates histone H3 at serine 10 in S phase, promotes the deposition of histone H3.

Quantitative assessment of HCC wash-out on CT is a predictor of early complete response to TACE.

Objectives: To investigate the predictive value of four-phase contrast-enhanced CT (CECT) for early complete response (CR) to drug-eluting-bead transarterial chemoembolization (DEB-TACE), with a particular focus on the quantitatively assessed wash-in and wash-out.

Methods: A retrospective analysis of preprocedural CECTs was performed for 129 HCC nodules consecutively subjected to DEB-TACE as first-line therapy. Lesion size, location, and margins were recorded.

A Natural Language Processing-Based Virtual Patient Simulator and Intelligent Tutoring System for the Clinical Diagnostic Process: Simulator Development and Case Study.

Background: Shortage of human resources, increasing educational costs, and the need to keep social distances in response to the COVID-19 worldwide outbreak have prompted the necessity of clinical training methods designed for distance learning. Virtual patient simulators (VPSs) may partially meet these needs. Natural language processing (NLP) and intelligent tutoring systems (ITSs) may further enhance the educational impact of these simulators.

Quality of care indicators in the MAnageMent of BlOOdstream infections caused by Enterobacteriaceae (MAMBOO-E study): state of the art and research agenda.

Objectives: The impact on outcome of five interventions was reviewed in order to investigate the state of the art for management of Enterobacteriaceae bloodstream infection (E-BSI).

Methods: We searched for randomised controlled trials (RCTs) and observational studies published from January 2008 to March 2019 in PubMed, EMBASE and Cochrane Library. Populations consisted of patients with E-BSI.

Treatment of Chronic Venous Ulcers With Heterologous Fibrin Sealant: A Phase I/II Clinical Trial.

Background: Heterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from buffalo blood and a thrombin-like enzyme purified from snake venom. This study evaluated the safety and immunogenicity of HFS, estimated the best dose, and assessed its preliminary efficacy in the treatment of chronic venous ulcers (CVU).

Methods: A phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVUs.

Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors.

Introduction: Several novel beta-lactams (BLs) and/or beta lactams/beta-lactamase inhibitors (BL/BLIs) have been recently developed for the management of multidrug-resistant bacterial infections. Data concerning dose optimization in critically ill patients with altered renal function are scanty.

Areas Covered: This article provides a critical reappraisal of pharmacokinetic and clinical issues emerged with novel BLs and/or BL/BLIs in renal critically ill patients.

Emergency room comprehensive assessment of demographic, radiological, laboratory and clinical data of patients with COVID-19: determination of its prognostic value for in-hospital mortality.

Mortality risk in COVID-19 patients is determined by several factors. The aim of our study was to adopt an integrated approach based on clinical, laboratory and chest x-ray (CXR) findings collected at the patient's admission to Emergency Room (ER) to identify prognostic factors. Retrospective study on 346 consecutive patients admitted to the ER of two North-Western Italy hospitals between March 9 and April 10, 2020 with clinical suspicion of COVID-19 confirmed by reverse transcriptase-polymerase reaction chain test (RT-PCR), CXR performed within 24 h (analyzed with two different scores) and recorded prognosis.

Drug Repurposing in the COVID-19 Era: Insights from Case Studies Showing Pharmaceutical Peculiarities.

COVID-19 may lead to severe respiratory distress syndrome and high risk of death in some patients. So far (January 2021), only the antiviral remdesivir has been approved, although no significant benefits in terms of mortality and clinical improvement were recently reported. In a setting where effective and safe treatments for COVID-19 are urgently needed, drug repurposing may take advantage of the fact that the safety profile of an agent is already well known and allows rapid investigation of the efficacy of potential treatments, at lower costs and with reduced risk of failure.

Acute patient-reported intestinal toxicity in whole pelvis IMRT for prostate cancer: Bowel dose-volume effect quantification in a multicentric cohort study.

Background And Purpose: To assess bowel dose-volume relationships for acute patient-reported intestinal symptoms of patients treated with whole-pelvis intensity-modulated radiotherapy (WPRT) for prostate cancer.

Materials And Methods: Complete data of 415 patients enrolled in a multi institute, prospective trial (#NCT02803086) treated with radical (31%), adjuvant (33%) and salvage (36%) intent at a median dose to pelvic nodes/lymph-nodal area of 53 Gy were available. The most severe changes between baseline and radiotherapy mid-point/end toxicity assessed by Inflammatory Bowel Disease Questionnaire (only Bowel Domain) were considered (ΔIBDQ).