Cell-Wall Glycolipid Mutations and Their Effects on Virulence of E. faecalis in a Rat Model of Infective Endocarditis

Enterococci are among the major pathogens implicated in cardiac infections and biofilm formation. E. faecalis has been shown to play an important role in infectious endocarditis. Several distinct mechanisms for biofilm formation have been identified in E. faecalis. Our group has previously characterized two distinct bacterial glucosyltransferases playing key roles in the production of the major cell wall glycolipids and leading to reduced biofilm production. To assess if this mechanism is involved in the pathogenesis of enterococcal endocarditis we compared the wild-type strain of E. faecalis 12030 with two mutants in gene EF2891 and EF2890 respectively in a rat model of infective endocarditis. The results showed less endocarditic lesions and reduced colony counts per vegetation in the two mutants. indicating that the modification of bacterial surface lipids results in significantly reduced virulence in infective endocarditis. These results underscore the important role of biofilm formation in the pathogenicity of enterococcal endocarditis and may indicate an interesting target for novel therapeutic strategies

Leukocytoclastic vasculitis as a complication of recombinant granulocyte colony-stimulating factor therapy in a heart transplant patient.

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a myeloid growth factor that is widely used in haematology to recover neutropenia secondary to myelosuppressive chemotherapy. Leukocytoclastic vasculitis is an acknowledged side effect of the above therapy. Its pathogenesis involves many mechanisms that collectively induce an increase in neutrophil function and a subsequent release of cytokines. Here, we report a case of leukocytoclastic vasculitis proven by skin biopsy, following the use of rG-CSF in a heart transplant patient with leukopenia secondary to immunosuppressive therapy

Cell-wall glycolipid mutations and their effects on virulence of E. faecalis in a rat model of infective endocarditis.

Enterococci are among the major pathogens implicated in cardiac infections and biofilm formation. E. faecalis has been shown to play an important role in infectious endocarditis. Several distinct mechanisms for biofilm formation have been identified in E. faecalis. Our group has previously characterized two distinct bacterial glucosyltransferases playing key roles in the production of the major cell wall glycolipids and leading to reduced biofilm production. To assess if this mechanism is involved in the pathogenesis of enterococcal endocarditis we compared the wild-type strain of E. faecalis 12030 with two mutants in gene EF2891 and EF2890 respectively in a rat model of infective endocarditis. The results showed less endocarditic lesions and reduced colony counts per vegetation in the two mutants. indicating that the modification of bacterial surface lipids results in significantly reduced virulence in infective endocarditis. These results underscore the important role of biofilm formation in the pathogenicity of enterococcal endocarditis and may indicate an interesting target for novel therapeutic strategies

Grover's Disease after Heart Transplantation: A Case Report

Grover's disease is a transient acantholytic dermatosis of unknown cause, manifesting clinically as a papular skin eruption that is usually located on the anterior chest and abdomen. Histologically characterized by an acantholytic pattern, it has been associated with numerous disorders, including hematologic malignancies, chronic renal failure, and HIV infection, as well as with chemotherapy and bone marrow and/or kidney transplant. Evaluation of followup and treatment is often complicated by spontaneous remission and the occasionally fluctuant course of the disease. Here we report the case of a patient with sudden onset of Grover's disease after heart transplantation. To the best of our knowledge, this is the first observation of Grover's disease as diagnosed after heart transplantation

Compassionate use of ruxolitinib in patients with SARS‐Cov‐2 infection not on mechanical ventilation: Short‐term effects on inflammation and ventilation

Abstract Ruxolitinib is an anti‐inflammatory drug that inhibits the Janus kinase‐signal transducer (JAK‐STAT) pathway on the surface of immune cells. The potential targeting of this pathway using JAK inhibitors is a promising approach in patients affected by coronavirus disease 2019 (COVID‐19). Ruxolitinib was provided as a compassionate use in patients consecutively admitted to our institution for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection. Inclusion criteria were oxygen saturation less than or equal to 92%, signs of interstitial pneumonia, and no need of mechanical ventilation. Patients received 5 mg b.i.d. of ruxolitinib for 15 days, data were collected at baseline and on days 4, 7, and 15 during treatment. Two main targets were identified, C‐reactive protein (CRP) and PaO2/FiO2 ratio. In the 31 patients who received ruxolitinib, symptoms improved (dyspnea scale) on day 7 in 25 of 31 patients (80.6%); CRP decreased progressively from baseline (79.1 ± 73.4 mg/dl) to day 15 (18.6 ± 33.2, p = 0.022). In parallel with CRP, PO2/FiO2 ratio increased progressively during the 3 steps from 183 ± 95 to 361 ± 144 mmHg (p < 0.001). In those patients with a reduction of polymerase chain reaction less than or equal to 80%, delta increase of the PO2/FiO2 ratio was significantly more pronounced (129 ± 118 vs. 45 ± 35 mmHg, p = 0.02). No adverse side effects were recorded during treatment. In patients hospitalized for COVID‐19, compassionate‐use of ruxolitinib determined a significant reduction of biomarkers of inflammation, which was associated with a more effective ventilation and reduced need for oxygen support. Data on ruxolitinib reinforces the hypothesis that targeting the hyperinflammation state, may be of prognostic benefit in patients with SARS‐CoV‐2 infection. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Some evidence suggest that patients affected by coronavirus disease 2019 (COVID‐19) present an exuberant inflammatory response represented by a massive production of type I interferons and different pro‐inflammatory cytokines. Nonetheless, as for the present, there are no proven therapeutic agents for COVID‐19, in particular anti‐inflammatory and antiviral, with a significant and reproducible positive clinical response. WHAT QUESTION DID THIS STUDY ADDRESS? Targeted therapeutic management of pro‐inflammatory pathways appears to be a promising strategy against COVID‐19, and ruxolitinib, due to its established broad and fast anti‐inflammatory effect, appears to be a promising candidate worthy of focused investigations in this field. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Ruxolitinib rapidly reduces the systemic inflammation, which accompanies the disease, thereby improving respiratory function and the need of oxygen support. This effect may contribute to avoid progression of the disease and the use of invasive ventilation. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Data on ruxolitinib contributes the reinforcement of the hypothesis that it is crucial to counteract the early hyperinflammation state, particularly of the lungs, induced by COVID‐19 infection

Macroscopic grading and absolute weight of vegetation of endocarditic lesions of 12030wt and 12030ΔbgsB, showing significantly higher grades (p<0.05) and weights in the wild type (p<0.05).

<p>Macroscopic grading and absolute weight of vegetation of endocarditic lesions of 12030wt and 12030ΔbgsB, showing significantly higher grades (p<0.05) and weights in the wild type (p<0.05).</p

Macroscopic grading system.

<p>Macroscopic grading system.</p

Genetic organization of the bgs-locus and biosynthetic pathway of glycolipid synthesis.

<p>Genetic organization of the bgs-locus and biosynthetic pathway of glycolipid synthesis.</p

Rapid HIA to support decision making in the Public Administration in Italy THE Vispa PROJECT

Since a decade HIA background and practice is growing up in Italy. The Ministry of Health endorsed the promotion and development of HIA practice funding the VISPA project to adapt HIA processes and tools in Public Administration (PA) activities and to prepare recommendations in view of national guideline. Methods/approaches. The feasibility of a rapid HIA protocol for plans and projects embedded in the PA decision-making process was tested involving 34 trained operators in six different Italian Regions. Twenty-eight casestudies regarding waste, city planning, energy, industrial districts and farms, were selected by a screening-scoping exercise. The developed toolkit supported the involved Public Officials during the phases of assessment, appraisal and reporting of results. Results. The proposed rapid HIA was always feasible with few exceptions. Positive outputs were achieved in terms of capacity building, identification of relevant subject, integration with other assessment tools. A final step-by-step procedure was validated and actors, tools and timing were identified. An audio-video guide was released to facilitate the use and transferability of the products. Conclusions. The experimental approach adopted highlighted a positive feedback. The burdensome of the application was recognised and critical issues appeared the citizen participation and the inter-departments cooperation