1,721,047 research outputs found
Dual β-lactams for the treatment of Mycobacterium abscessus: a review of the evidence and a call to act against an antibiotic nightmare
Mycobacterium abscessus complex is a group of rapidly growing non-Tuberculous mycobacteria (NTM), increasingly emerging as opportunistic pathogens. Current treatment options for these microorganisms are limited and associated with a high rate of treatment failure, toxicity and recurrence. In search of new therapeutic strategies, interest has grown in dual β-lactam (DBL) therapy, as research recently discovered that M. abscessus cell wall synthesis is mainly regulated by two types of enzymes (d,d-Transpeptidases and l,d-Transpeptidases) differently susceptible to inhibition by distinct β-lactams. In vitro studies testing several DBL combinations have shown synergy in extracellular broth cultures as well as in the intracellular setting: cefoxitin/imipenem, ceftaroline/imipenem, ceftazidime/ceftaroline and ceftazidime/imipenem. The addition of specific β-lactamase inhibitors (BLIs) targeting M. abscessus β-lactamase did not significantly enhance the activity of DBL combinations. However, in vivo data are lacking. We reviewed the literature on DBL/DBL-BLI-based therapies for M. abscessus infections to raise greater attention on this promising yet overlooked treatment option and to guide future preclinical and clinical studies
Lowering SARS-CoV-2 viral load might affect transmission but not disease severity in secondary cases
Further considerations on the use of cerebrospinal fluid C-X-C motif chemokine ligand 13 in the diagnosis of neurosyphilis among people with HIV
The role of bacteria and viruses in Behçet syndrome: Should we move towards new paradigms?
The etiological complexity of Behçet syndrome (BS), an immune-mediated rare form of vasculitis characterized by multi-organ involvement, is still elusive due to an incomplete understanding of the synergy between genetic susceptibility, environmental triggers, and an abnormal immune response. Long-standing theories regarding the origins of BS include the involvement of infectious organisms supporting an aberrant immunological response through different mechanisms, including molecular mimicry. Additionally, it has been demonstrated that the BS phenotypes are linked to oral and gut microbiome dysbiosis, which is a dynamic reservoir of millions of microbes containing proteins and metabolites that can mimic the autoantigens. Infections, including viral pathogens, could potentially trigger the inflammation and symptoms of BS. In this review, we aim to describe the available evidence on the cross-talk between BS and infections in order to discuss potential clinical implications and possible therapeutic targets
Risk of Reactivation of Latent Tuberculosis in Psoriasis Patients on Biologic Therapies: A Retrospective Cohort from a Tertiary Care Centre in Northern Italy
Psoriatic patients with latent tuberculosis infection and properly treated active tuberculosis need careful management when prescribing modern biological drugs. Although data and guidelines regarding tumour necrosis factor-α inhibitors advise caution and initiation of prophylactic therapy in patients with latent tuberculosis infection, the same indications do not seem to find equal force for interleukin (IL)-23 and IL-17 inhibitors. In order to evaluate the risk of reactivation in patients with latent tuberculosis infection or properly treated active tuberculosis, an observational retrospective study was conducted on the population referred to our centre at Dermatologic Clinic of University of Turin, Italy. In the last 10 years at the clinic 19 psoriatic patients were found to be at risk of tuberculosis reactivation: 10 patients were QuantiFERON- TB-positive at baseline, 2 became positive during treatment, 6 reported prior tuberculous infection, and 1 was QuantiFERON-TB-negative at baseline and developed disseminated tuberculosis during treatment with anti-tumour necrosis factor-α. Overall, 10.5% of this group of patients developed active tuberculosis; however, stratifying by biologic therapy, zero cases were observed among patients treated with anti-IL-17, -23, or -12/23 over a relatively long follow-up (48.1 months) A review of the available literature following our experience confirms the increased risk of tuberculosis reactivation with tumour necrosis factor-α inhibitors. Concerning anti-IL-23 and IL-17 drugs, available data showed high safety in patients at risk of tuberculosis reactivation. Screening of patients who should be taking IL-17 and IL-23 inhibitors is recommended for public health purposes. In case of a positive result with these therapies, consulting with an infectious diseases specialist is suggested in order to weigh up the risks and benefits of prophylactic treatment
A review of the potential mechanisms of neuronal toxicity associated with antiretroviral drugs
Highly active antiretroviral treatment has led to unprecedented efficacy and tolerability in people living with HIV. This effect was also observed in the central nervous system with the nowadays uncommon observation of dementias; yet in more recent works milder forms are still reported in 20-30% of optimally treated individuals. The idea of a subclinical neuronal toxicity induced by antiretrovirals has been proposed and was somehow supported by the late-emerging effects associated with efavirenz use. In this manuscript we are reviewing all the potential mechanisms by which antiretroviral drugs have been associated with in vitro, ex vivo, or in vivo toxicity to cells pertaining to the central nervous system (neurons, astrocytes, oligodendrocytes, and endothelial cells). These include direct or indirect effects and pathological pathways such as amyloid deposition, damage to small cerebral vessels, and impairment in neurotransmission. The aim of this review is therefore to provide a detailed description of the available literature in order to guide further clinical research for improving patients' neurocognition and quality of life
Real-life Evidence of Lower Lung Virulence in COVID-19 Inpatients Infected with SARS-CoV-2 Omicron Variant Compared to Wild-Type and Delta SARS-CoV-2 Pneumonia
In vitro and animal models described lower replication capacity and virulence of SARS-CoV-2 Omicron lineage in lower respiratory airways compared to wild type and other variants of concern (oVOCs). Among adult subjects admitted to our hospital (Turin, Italy) due to wild type, oVOCs, and Omicron SARS-CoV-2-related pneumonia (n = 100 for each lineage), the cases of Omicron pneumonia showed lower degree of lung parenchyma involvement (aβ -1.471, p = 0.037), less tendency to parenchyma consolidation (aOR 0.500, p = 0.011), and better respiratory functions (assessed by ambient air arterial blood gas analysis). After adjusting for demographic, previous immunity, and comorbidities, Omicron pneumonia still associated with lower risk of respiratory failure (for severe respiratory failure, Wild-type versus Omicron aOR 15.6, p = 0.005 and oVOCs versus Omicron aOR 31.7, p < 0.001). These observations are in line with preliminary findings from in vitro and animal models and could explain why Omicron infection has been associated with lower mortality and hospitalization in human
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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