0000000000466436
AUTHOR
Cristina Mussini
MMP-7 promoter polymorphisms do not influence CD4+ recovery and changes in plasma viral load during antiretroviral therapy for HIV-1 infection.
Summary Matrix metalloproteinase-7 (MMP-7) generates soluble Fas Ligand (FasL), which is involved in the apoptotic loss of CD4+ T cells during HIV infection. We evaluated whether two polymorphisms in MMP-7 promoter could influence CD4+ recover in response to antiretroviral therapy, and found that these polymorphisms are ineffective.
Ceftazidime-avibactam use for klebsiella pneumoniae carbapenemase-producing k. pneumoniae infections: A retrospective observational multicenter study
Abstract Background A growing body of observational evidence supports the value of ceftazidime-avibactam (CAZ-AVI) in managing infections caused by carbapenem-resistant Enterobacteriaceae. Methods We retrospectively analyzed observational data on use and outcomes of CAZ-AVI therapy for infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae (KPC-Kp) strains. Multivariate regression analysis was used to identify variables independently associated with 30-day mortality. Results were adjusted for propensity score for receipt of CAZ-AVI combination regimens versus CAZ-AVI monotherapy. Results The cohort comprised 577 adults with bloodstream infections (n = 391) or nonba…
Stable changes in CD4+ T lymphocyte miRNA expression after exposure to HIV-1
Abstract MicroRNAs (miRNAs) inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. We evaluated the expression of 377 miRNAs in CD4+ T cells from HIV-1 élite long-term nonprogressors (éLTNPs), naive patients, and multiply exposed uninfected (MEU) patients, and we observed that the éLTNP patients clustered with naive patients, whereas all MEU subjects grouped together. The discriminatory power of miRNAs showed that 21 miRNAs significantly differentiated éLTNP from MEU patients and 23 miRNAs distinguished naive from MEU patients, whereas only 1 miRNA (miR-155) discriminated éLTNP from naive patients. We proposed that miRNA expression ma…
Impact of Pre-Analytical Time on the Recovery of Pathogens from Blood Cultures: Results from a Large Retrospective Survey.
Background Prompt identification of bloodstream pathogens is essential for optimal management of patients. Significant changes in analytical methods have improved the turnaround time for laboratory diagnosis. Less attention has been paid to the time elapsing from blood collection to incubation and to its potential effect on recovery of pathogens. We evaluated the performance of blood cultures collected under typical hospital conditions in relation to the length of their pre-analytical time. Methods We carried out a large retrospective study including 50,955 blood cultures collected, over a 30-month period, from 7,035 adult septic patients. Cultures were accepted by the laboratory only durin…
Changes in CD4+ cells’ miRNA expression following exposure to HIV-1
Background: Micro RNAs (miRNAs) inhibit HIV-1 expression by either modulating host innate immunity or by directly interfering with viral mRNAs. Here, we investigated the miRNA profile that discriminates different classes of HIV-1-infected patients from multiple-exposed uninfected individuals. Methods: The expression levels of 377 miRNAs were selectively analysed in CD4+ cells isolated from whole blood of HIV-1 elite LTNP (eLTNP), naive, and multiply exposed uninfected individuals (MEUs). MiRNA extraction was performed by the mir Vana™ miRNA Isolation Kit (Ambion), and their expression was subsequently examined by real-time PCR-based arrays. The expression of miRNAs was also determined in pr…
Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicentre Italian CORIST Study
Abstract Introduction A hypercoagulable condition was described in patients with coronavirus disease 2019 (COVID-19) and proposed as a possible pathogenic mechanism contributing to disease progression and lethality. Aim We evaluated if in-hospital administration of heparin improved survival in a large cohort of Italian COVID-19 patients. Methods In a retrospective observational study, 2,574 unselected patients hospitalized in 30 clinical centers in Italy from February 19, 2020 to June 5, 2020 with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection were analyzed. The primary endpoint in a time-to event analysis was in-hospital death, comparing patients who receive…
Additional file 1: of Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: an observational cohort study
Table S1. Baseline third drugs in patients who switched to triple, dual, or monotherapy. (DOCX 12 kb)
Compassionate use of meropenem/vaborbactam for infections caused by KPC-producing Klebsiella pneumoniae: a multicentre study
Abstract Objectives To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam. Methods A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included. Results The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respira…
Estimating minimum adult HIV prevalence: A cross-sectional study to assess the characteristics of people living with HIV in Italy
In 2012, we conducted a retrospective cross-sectional study to assess the number of people living with HIV linked to care and, among these, the number of people on antiretroviral therapy. The health authority in each of the 20 Italian Regions provided the list of Public Infectious Diseases Clinics providing antiretroviral therapy and monitoring people with HIV infection. We asked every Public Infectious Diseases Clinic to report the number of HIV-positive people diagnosed and linked to care and the number of those on antiretroviral therapy during 2012. In 2012, 94,146 people diagnosed with HIV and linked to care were reported. The majority were males (70.1%), Italians (84.4%), and aged betw…
Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study.
Abstract Background Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19. Objective We set-up a multicenter Italian collaboration to investigate the relationship between HCQ therapy and COVID-19 in-hospital mortality. Methods In a retrospective observational study, 3,451 unselected patients hospitalized in 33 clinical centers in Italy, from February 19, 2020 to May 23, 2020, with laboratory-confirmed SARS-CoV-2 infection, were analyzed. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received HCQ with patients who did not. We used multivariable Cox proportional-hazards regression models with inverse probability for treatme…
Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults
Objective: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. Design: Observational European cohort collaboration study. Methods: Eligible patients were antiretroviral-naive with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load ( 50 copies/ml) after initial s…
RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies
Abstract Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, compar…
Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study.
Background and aims There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a…
Lopinavir/ritonavir and darunavir/cobicistat in hospitalized covid-19 patients: Findings from the multicenter italian corist study
Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients.Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients.Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of…
Switching to dual/monotherapy determines an increase in CD8+ in HIV-infected individuals: An observational cohort study
Background The CD4/CD8 ratio has been associated with the risk of AIDS and non-AIDS events. We describe trends in immunological parameters in people who underwent a switch to monotherapy or dual therapy, compared to a control group remaining on triple antiretroviral therapy (ART). Methods We included patients in Icona who started a three-drug combination ART regimen from an ART-naïve status and achieved a viral load ≤ 50 copies/mL; they were subsequently switched to another triple or to a mono or double regimen. Standard linear regression at fixed points in time (12-24 months after the switch) and linear mixed model analysis with random intercepts and slopes were used to compare CD4 and CD8…
Clinical Experience with Ceftazidime-Avibactam for the Treatment of Infections due to Multidrug-Resistant Gram-Negative Bacteria Other than Carbapenem-Resistant Enterobacterales
Background: Experience in real clinical practice with ceftazidime-avibactam for the treatment of serious infections due to gram&minus
Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February–May 2020). Patients’ characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distan…
Therapeutic strategies for severe COVID-19: a position paper from the Italian Society of Infectious and Tropical Diseases (SIMIT)
Abstract Scope Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting. Methods The panel conducted a detailed review of the literature and eventual press rele…