[Appropriateness of requests for urgent outpatient cardiological services and impact on waiting lists: the experience of the Azienda Socio-Sanitaria Territoriale of the Province of Lodi].

Background: The Cardiology Complex Structure of the Azienda Socio Sanitaria Territoriale (ASST) of Lodi, Italy, assists patients with clinical conditions ranging from emergency to chronicity. The model of Homogeneous Waiting Groups should guide the appropriateness of prescriptions categorized as U (urgent), B (brief), D (deferrable), and P (programmable). This study aims to describe and analyze the characteristics of prescription and delivery of clinical and instrumental cardiology outpatient services with U and B priority during the November 2023-January 2024 quarter, paying particular attention to the clinical appropriateness of prescribing.

Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.

Objectives: To study the molecular pathogenesis of PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome, a debilitating hereditary autoinflammatory disease caused by dominant mutation in .

Methods: Gene knock-out and knock-in mice were generated to develop an animal model. THP1 and retrovirally transduced U937 human myeloid leukaemia cell lines, peripheral blood mononuclear cells, small interfering RNA (siRNA) knock-down, site-directed mutagenesis, cytokine immunoassays, coimmunoprecipitation and immunoblotting were used to study inflammasome activation.

Structural basis of microtubule depolymerization by the kinesin-like activity of HIV-1 Rev.

HIV-1 Rev is an essential regulatory protein that transports unspliced and partially spliced viral mRNAs from the nucleus to the cytoplasm for the expression of viral structural proteins. During its nucleocytoplasmic shuttling, Rev interacts with several host proteins to use the cellular machinery for the advantage of the virus. Here, we report the 3.

AAV-mediated delivery of secreted acid α-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice.

Gene therapy is under advanced clinical development for several lysosomal storage disorders. Pompe disease, a debilitating neuromuscular illness affecting infants, children, and adults with different severity, is caused by a deficiency of lysosomal glycogen-degrading enzyme acid α-glucosidase (GAA). Here, we demonstrated that adeno-associated virus-mediated (AAV-mediated) systemic gene transfer reversed glycogen storage in all key therapeutic targets - skeletal and cardiac muscles, the diaphragm, and the central nervous system - in both young and severely affected old Gaa-knockout mice.

Infigratinib, a selective FGFR1-3 tyrosine kinase inhibitor, alters dentoalveolar development at high doses.

Background: Fibroblast growth factor receptor-3 (FGFR3) gain-of-function mutations are linked to achondroplasia. Infigratinib, a FGFR1-3 tyrosine kinase inhibitor, improves skeletal growth in an achondroplasia mouse model. FGFs and their receptors have critical roles in developing teeth, yet effects of infigratinib on tooth development have not been assessed.

Variant and Response to Ruxolitinib in an Autoinflammatory Syndrome.

Background: Disabling pansclerotic morphea (DPM) is a rare systemic inflammatory disorder, characterized by poor wound healing, fibrosis, cytopenias, hypogammaglobulinemia, and squamous-cell carcinoma. The cause is unknown, and mortality is high.

Methods: We evaluated four patients from three unrelated families with an autosomal dominant pattern of inheritance of DPM.

Influenza Defective Interfering Virus Promotes Multiciliated Cell Differentiation and Reduces the Inflammatory Response in Mice.

Influenza defective interfering (DI) viruses have long been considered promising antiviral candidates because of their ability to interfere with replication-competent viruses and induce antiviral immunity. However, the mechanisms underlying DI-mediated antiviral immunity have not been extensively explored. Here, we demonstrated the interferon (IFN)-independent protection conferred by the influenza DI virus against homologous virus infection in mice deficient in type I and III IFN signaling.

Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling.

Organismal homeostasis and regeneration are predicated on committed stem cells that can reside for long periods in a mitotically dormant but reversible cell-cycle arrest state defined as quiescence. Premature escape from quiescence is detrimental, as it results in stem cell depletion, with consequent defective tissue homeostasis and regeneration. Here, we report that Polycomb Ezh1 confers quiescence to murine muscle stem cells (MuSCs) through a non-canonical function.

Intratumor childhood vaccine-specific CD4 T-cell recall coordinates antitumor CD8 T cells and eosinophils.

Background: Antitumor mechanisms of CD4 T cells remain crudely defined, and means to effectively harness CD4 T-cell help for cancer immunotherapy are lacking. Pre-existing memory CD4 T cells hold potential to be leveraged for this purpose. Moreover, the role of pre-existing immunity in virotherapy, particularly recombinant poliovirus immunotherapy where childhood polio vaccine specific immunity is ubiquitous, remains unclear.

Parieto-Occipital Injury on Diffusion MRI Correlates with Poor Neurologic Outcome following Cardiac Arrest.

Background And Purpose: MR imaging of the brain provides unbiased neuroanatomic evaluation of brain injury and is useful for neurologic prognostication following cardiac arrest. Regional analysis of diffusion imaging may provide additional prognostic value and help reveal the neuroanatomic underpinnings of coma recovery. The purpose of this study was to evaluate global, regional, and voxelwise differences in diffusion-weighted MR imaging signal in patients in a coma after cardiac arrest.

Professional quality of life and psychopathological symptoms among first-line healthcare workers facing COVID-19 pandemic: an exploratory study in an Italian southern hospital.

Background: The COVID-19 pandemic has significantly affected the mental health of healthcare workers, who have taken on the major problems triggered by the emergency. The mental consequences concern high levels of insomnia, anxiety, depression and burnout, which inevitably affect their professional quality of life too.

Objective: The aim of this study was to analyze the relationship between psychopathological symptoms (tested with the Depression Anxiety Stress Scale, DASS-21) and professional quality of life (measured with the Professional Quality of Life Scale, ProQol) in a hospital of southern Italy.

Targeting the IL4 receptor with MDNA55 in patients with recurrent glioblastoma: Results of a phase IIb trial.

Background: MDNA55 is an interleukin 4 receptor (IL4R)-targeting toxin in development for recurrent GBM, a universally fatal disease. IL4R is overexpressed in GBM as well as cells of the tumor microenvironment. High expression of IL4R is associated with poor clinical outcomes.

The First Italian Telemedicine Program for Non-Critical COVID-19 Patients: Experience from Lodi (Italy).

Italy was the first Western country to face a massive SARS-CoV-2 outbreak. The limited information initially available on the natural course of the disease required caution in the discharge of patients accessing health facilities. This resulted in overcrowded health facilities and emergency services.

Occurrence of Natural and Synthetic Micro-Fibers in the Mediterranean Sea: A Review.

Among microplastics (MPs), fibers are one of the most abundant shapes encountered in the aquatic environment. Growing attention is being focused on this typology of particles since they are considered an important form of marine contamination. Information about microfibers distribution in the Mediterranean Sea is still limited and the increasing evidence of the high amount of fibers in the aquatic environment should lead to a different classification from MPs which, by definition, are composed only of synthetic materials and not natural.

Modified RANO, Immunotherapy RANO, and Standard RANO Response to Convection-Enhanced Delivery of IL4R-Targeted Immunotoxin MDNA55 in Recurrent Glioblastoma.

Purpose: The current study compared the standard response assessment in neuro-oncology (RANO), immunotherapy RANO (iRANO), and modified RANO (mRANO) criteria as well as quantified the association between progression-free (PFS) and overall survival (OS) in an immunotherapy trial in recurrent glioblastoma (rGBM).

Patients And Methods: A total of 47 patients with rGBM were enrolled in a prospective phase II convection-enhanced delivery of an IL4R-targeted immunotoxin (MDNA55-05, NCT02858895). Bidirectional tumor measurements were created by local sites and centrally by an independent radiologic faculty, then standard RANO, iRANO, and mRANO criteria were applied.

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy.

Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10-20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients.

Fostamatinib Inhibits Neutrophils Extracellular Traps Induced by COVID-19 Patient Plasma: A Potential Therapeutic.

Neutrophil extracellular traps (NETs) contribute to immunothrombosis and have been associated with mortality in coronavirus disease 2019 (COVID-19). We stimulated donor neutrophils with plasma from patients with COVID-19 and demonstrated that R406 can abrogate the release of NETs. These data provide evidence for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19 immunopathogenesis.

Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus.

Objectives: Low-density granulocytes (LDGs) are a distinct subset of proinflammatory and vasculopathic neutrophils expanded in systemic lupus erythematosus (SLE). Neutrophil trafficking and immune function are intimately linked to cellular biophysical properties. This study used proteomic, biomechanical and functional analyses to further define neutrophil heterogeneity in the context of SLE.