No abstract

Background: In multiple sclerosis (MS), up to 57% of white matter lesions are chronically active. These slowly expanding lesions (SELs) contribute to disability progression. Objective: The aim of this study is to compare fingolimod and natalizumab effects on progressive linearly enlarging lesions (i.e. SELs), a putative biomarker of smouldering inflammation. Methods: Relapsing-remitting MS patients starting fingolimod ( n = 24) or natalizumab ( n = 28) underwent 3T brain magnetic resonance imaging (MRI) at baseline, months 6, 12 and 24. SELs were identified among baseline-visible lesions showing ⩾ 12.5% of annual increase, calculated by linearly fitting the Jacobian of the nonlinear deformation field between timepoints obtained combining T1- and T2-weighted scans. SEL burden, magnetization transfer ratio (MTR) and T1 signal intensity were compared using linear models. Results: The prevalences of fingolimod (75%) and natalizumab patients (46%) with ⩾ 1 SEL were not significantly different (adjusted- p = 0.08). Fingolimod group had higher SEL number and volume (adjusted- p ⩽ 0.047, not false discovery rate (FDR) survived). In both groups, SELs versus non-SELs showed lower MTR and T1 signal intensity (adjusted- p ⩽ 0.01, FDR-survived). Longitudinally, non-SEL MTR increased in both treatment groups (adjusted- p ⩽ 0.005, FDR-survived). T1 signal intensity decreased in SELs with both treatments (adjusted- p ⩽ 0.049, FDR-survived in fingolimod group) and increased in natalizumab non-SELs (adjusted- p = 0.03, FDR-survived). Conclusion: The effects of natalizumab and fingolimod on SEL occurrence seem modest, with natalizumab being slightly more effective. Both treatments may promote reparative mechanisms in stable or chronic inactive lesions.

BackgroundRates of colonization and infection with multidrug-resistant (MDR) bacteria are increasing worldwide, in both acute care hospitals and long-term care facilities (LTCFs). Italy has one of the highest prevalence of MDR bacteria in European countries, especially with regard to methicillin-resistant Staphylococcus aureus (MRSA) and extended-spectrum β-lactamase (ESBL) or carbapenemase producing Enterobacteriaceae (CPE).MethodReview of studies on colonization by MDR bacteria from Italian LTCFs, risk factors for colonization and molecular characteristics of surveillance and clinical isolates, compared with other European countries.ResultsHigh variability of MDR colonization has been reported within and especially between European countries. Only a few surveillance studies have been performed in Italian LTCFs; these show MRSA colonization prevalence of 7.8–38.7 % for residents and 5.2–7.0 % for staff members, ESBL prevalence of 49.0–64.0 % for residents and 5.2–14.5 % for staff and prevalence of CPE of 1.0–6.3 % for residents and 0.0–1.5 % for staff. In Italian LTCFs, as well as in other European countries, the most prevalent ESBLs from surveillance or clinical Escherichia coli isolates were found to be CTX-M-type enzymes, particularly CTX-M-15, expressed by the pandemic ST131 clonal group; this lineage also expresses carbapenemase genes of the bla VIM and bla KPC types. Various risk factors for colonization of residents by MDR bacteria were identified.ConclusionsThe limited data from Italian LTCFs confirms these settings as important reservoirs for MDR organisms, allowing important considerations regarding the infection risk by these organisms. Nevertheless, more extended and countrywide screening studies for MDR colonization in Italian LTCFs are required. To promote further studies of various microbiological aspects related to LTCFs, the Association of Italian Clinical Microbiologists (Associazione Microbiologi Clinici Italiani; AMCLI) in 2016 has set up a new Working Group for the Study of Infections in LTCFs (Gruppo di Lavoro per lo Studio delle Infezioni nelle Residenze Sanitarie Assistite e Strutture Territoriali assimilabili; GLISTer), consisting of Clinical Microbiologists represented by the authors of this review article.

BackgroundRationale and aims of the study were to compare colonization frequencies with MDR bacteria isolated from LTCF residents in three different Northern Italian regions, to investigate risk factors for colonization and the genotypic characteristics of isolates. The screening included Enterobacteriaceae expressing extended-spectrum β-lactamases (ESβLs) and high-level AmpC cephalosporinases, carbapenemase-producing Enterobacteriaceae, Pseudomonas aeruginosa or Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).MethodsUrine samples and rectal, inguinal, oropharyngeal and nasal swabs were plated on selective agar; resistance genes were sought by PCR and sequencing. Demographic and clinical data were collected.ResultsAmong the LTCF residents, 75.0% (78/104), 69.4% (84/121) and 66.1% (76/115) were colonized with at least one of the target organisms in LTCFs located in Milan, Piacenza and Bolzano, respectively. ESβL producers (60.5, 66.1 and 53.0%) were highly predominant, mainly belonging to Escherichia coli expressing CTX-M group-1 enzymes. Carbapenemase-producing enterobacteria were found in 7.6, 0.0 and 1.6% of residents; carbapemenase-producing P. aeruginosa and A. baumannii were also detected. Colonization by MRSA (24.0, 5.7 and 14.8%) and VRE (20.2, 0.8 and 0.8%) was highly variable. Several risk factors for colonization by ESβL-producing Enterobacteriaceae and MRSA were found and compared among LTCFs in the three Provinces. Colonization differences among the enrolled LTCFs can be partially explained by variation in risk factors, resident populations and staff/resident ratios, applied hygiene measures and especially the local antibiotic resistance epidemiology.ConclusionsThe widespread diffusion of MDR bacteria in LTCFs within three Italian Provinces confirms that LTCFs are an important reservoir of MDR organisms in Italy and suggests that future efforts should focus on MDR screening, improved implementation of infection control strategies and antibiotic stewardship programs targeting the complex aspects of LTCFs.Electronic supplementary materialThe online version of this article (10.1186/s13756-018-0326-0) contains supplementary material, which is available to authorized users.

JC virus (JCV) is an unique virus, but eight different JCV genotypes and various subtypes have been individuated, with a geographic distribution that has been described in general but still needs to be detailed. To define JCV genotype epidemiology in Italy, the authors collected urine from 211 healthy individuals living in Northern, Central, and Southern Continental Italy, and in the two main Italian islands. As screening, JCV DNA was searched using a polymerase chain reaction (PCR) designed to amplify the highly conserved large T (LT) antigen-coding region. Then, to define JCV genotype and trascriptional control region (TCR) organization, fragments of major capsid protein (VP1) and TCR region were amplified and subjected to nucleotide sequencing. The mean frequency of JCV viruria was of 46%, without differences among the four geographically divided groups and between females and males. JCV types 1 and 4 were the most frequently detected, whereas JCV type 2 was rare, and type 3 was found only in one subject. The low frequency of JCV type 2 contrasts with the reported high frequency of this subtype in progressive multifocal leukoencephalopathy (PML), and supports its specific role in PML. The data indicate that JCV genotype epidemiology in Italy is quite different from that of other European countries; moreover, differences between the various Italian regions have been observed. An unexpected high frequency of a new variant of JCV type 4 with a stable point mutation (C --> G) at nucleotide 1851 was found. Furthermore, all the urinary strains had a TCR showing an archetypal organization.

Ceftolozane/tazobactam exhibited potent in vitro activity against P. aeruginosa causing invasive infections in Italy. Carbapenemase production was the most common mechanism of resistance to ceftolozane/tazobactam.

In order to investigate the possible involvement of viruses in Multiple Sclerosis (MS), the study evaluated the presence of viral genomic sequences in cerebrospinal fluid (CSF), as markers of viral replication within the central nervous system (CNS). A total of 85 CSF samples were collected from 38 MS patients, 28 patients with other neurological diseases and 19 subjects without neurological diseases. Using nested-PCR, the investigation focused on the presence of human herpes virus DNA, including herpes simplex virus 1 (HSV-1) and 2 (HSV-2), the Epstein-Barr virus (EBV), varicella zoster virus (VZV), human cytomegalovirus (HCMV), human herpes virus 6 (HHV-6) and JC virus (JCV). All the CSF samples from the individuals without neurological diseases were negative for viral DNA. Genomic sequences of HSV-1, HCMV, EBV, HHV6, and JCV were found in patients with MS and other neurological diseases without significant differences between the two groups. VZV DNA was detected more frequently (P < 0.05) in the MS group (31.6%), particularly among the relapsing-remitting MS patients (43.5%), compared with patients with other neurological diseases (10.7%). In addition, the results indicated that JCV and HHV-6 were replicating actively in the CNS of a small, but significant number of patients with MS and other neurological diseases. Most importantly, the study revealed a high frequency of VZV DNA in the CSF of patients with MS, suggesting a possible role of this virus in the pathogenesis of MS.

Little is known regarding coronavirus disease 2019 (COVID-19) clinical spectrum in non-Asian populations. We herein describe the impact of COVID-19 on liver function in 100 COVID-19 consecutive patients (median age 70 years, range 25–97; 79 males) who were admitted to our internal medicine unit in March 2020. We retrospectively assessed liver function tests, taking into account demographic characteristics and clinical outcome. A patient was considered as having liver injury when alanine aminotransferase (ALT) was > 50 mU/ml, gamma-glutamyl transpeptidase (GGT) > 50 mU/ml, or total bilirubin > 1.1 mg/dl. Spearman correlation coefficient for laboratory data and bivariable analysis for mortality and/or need for intensive care were assessed. A minority of patients (18.6%) were obese, and most patients were non- or moderate-drinkers (88.5%). Liver function tests were altered in 62.4% of patients, and improved during follow-up. None of the seven patients with known chronic liver disease had liver decompensation. Only one patient developed acute liver failure. In patients with altered liver function tests, PaO2/FiO2 < 200 was associated with greater mortality and need for intensive care (HR 2.34, 95% CI 1.07–5.11, p = 0.033). To conclude, a high prevalence of altered liver function tests was noticed in Italian patients with COVID-19, and this was associated with worse outcomes when developing severe acute respiratory distress syndrome.