Clinical Outcomes According to the Extent of Atherosclerotic Disease in Female Patients Undergoing Transcatheter Aortic Valve Replacement: An Analysis From the WIN-TAVI Registry.

Background: Limited data exist on the impact of polyvascular disease (PolyVD) on clinical outcomes in female patients undergoing transcatheter aortic valve replacement (TAVR). We therefore sought to investigate clinical outcomes in women with versus without PolyVD undergoing TAVR.

Methods: Female participants from the multicentre Women's International Transcatheter Aortic Valve Implantation (WIN-TAVI) registry were categorized based on the presence or absence of PolyVD.

High-frequency epidural electrical stimulation reduces spasticity and facilitates walking recovery in patients with spinal cord injury.

Spinal cord injury (SCI) causes severe motor and sensory deficits, and there are currently no approved treatments for recovery. Nearly 70% of patients with SCI experience pathological muscle cocontraction and spasticity, accompanied by clinical signs such as patellar hyperreflexia and ankle clonus. The integration of epidural electrical stimulation (EES) of the spinal cord with rehabilitation has substantial potential to improve recovery of motor functions; however, abnormal muscle cocontraction and spasticity may limit the benefit of these interventions and hinder the effectiveness of EES in promoting functional movements.

Investigating the Potential of Extracellular Vesicles as Delivery Systems for Chemotherapeutics.

Background/objectives: Standard chemotherapy is generally considered the best approach to treat many solid cancers, even accounting for severe side effects. Therefore, the development of a drug delivery system for chemotherapeutic administration could significantly improve standard chemotherapy by maintaining the cytotoxic effects of the drugs while decreasing the inherent side effects of the treatment. The aim of our study is the optimization of a loading strategy that conjugates the use of extracellular vesicles (EVs) as drug delivery carriers, by preserving their integrity, with the loading efficiency and activity maintenance of chemotherapeutics.

Exploring machine learning tools in a retrospective case-study of patients with metastatic non-small cell lung cancer treated with first-line immunotherapy: A feasibility single-centre experience.

Background: Artificial intelligence (AI) models are emerging as promising tools to identify predictive features among data coming from health records. Their application in clinical routine is still challenging, due to technical limits and to explainability issues in this specific setting. Response to standard first-line immunotherapy (ICI) in metastatic Non-Small-Cell Lung Cancer (NSCLC) is an interesting population for machine learning (ML), since up to 30% of patients do not benefit.

Radiation therapy volumes after primary systemic therapy in breast cancer patients: an international EUBREAST survey.

Purpose: After primary systemic therapy (PST), agreement on the extent of locoregional therapy is lacking in breast cancer patients who convert from a node-positive to a node-negative status. The aim of this survey was to investigate radiation therapy approaches after PST according to different axillary surgical strategies and disease responses.

Materials And Methods: The European Breast Cancer Research Association of Surgical Trialists developed a web-based survey containing 39 questions on locoregional management based on clinical scenarios in initially node positive breast cancer patients undergoing PST.

Characterization of Machine Learning-Based Surrogate Models of Neural Activation Under Electrical Stimulation.

Electrical stimulation of peripheral nerves via implanted electrodes has been shown to be a promising approach to restore sensation, movement, and autonomic functions across a wide range of illnesses and injuries. While in principle computational models of neuromodulation can allow the exploration of large parameter spaces and the automatic optimization of stimulation devices and strategies, their high time complexity hinders their use on a large scale. We recently proposed the use of machine learning-based surrogate models to estimate the activation of nerve fibers under electrical stimulation, producing a considerable speed-up with respect to biophysically accurate models of fiber excitation while retaining good predictivity.

SurfR: Riding the wave of RNA-seq data with a comprehensive bioconductor package to identify surface protein-coding genes.

Motivation: Proteins at the cell surface connect signaling networks and largely determine a cell's capacity to communicate and interact with its environment. In particular, variations in transcriptomic profiles are often observed between healthy and diseased cells, leading to distinct sets of cell-surface proteins. For these reasons, cell-surface proteins may act as biomarkers for the detection of cells of interest in tissues or body fluids, are often the target of pharmaceutical agents, and hold significant promise in the clinical practice for diagnosis, prognosis, treatment development, and evaluation of therapy response.

Concordance and test-retest consistency of sleep biomarker-based neurodegenerative disorder profiling.

Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD).

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists.

Background And Aims: We sought to ascertain how prior exposure to TNF antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 RCTs in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs. placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists.

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era.

Background: Activated Phosphoinositide 3-Kinase (PI3K) δ Syndrome (APDS), an inborn error of immunity due to upregulation of the PI3K pathway, leads to recurrent infections and immune dysregulation (lymphoproliferation and autoimmunity).

Methods: Clinical and genetic data of 28 APDS patients from 25 unrelated families were collected from fifteen Italian centers.

Results: Patients were genetically confirmed with APDS-1 (n = 20) or APDS-2 (n = 8), with pathogenic mutations in the PIK3CD or PIK3R1 genes.

Effect of systemic steroids administration in the clinical outcome of total hip arthroplasty: a systematic review and meta-analysis of prospective randomized controlled trials.

Introduction: Perioperative steroids administration in total joint arthroplasty gained popularity for pain relief, reduction of postoperative nausea and vomiting (PONV) and enhanced recovery. The purpose of this study is to systematically review and meta-analyze comparative results of prospective randomized trials focused on the effect of systemic steroid administration at different dosages in THA for hip osteoarthritis. The hypothesis is that perioperative systemic steroid administration has a positive impact on postoperative outcomes.

Update on Autoimmune Pancreatitis and IgG4-Related Disease.

Autoimmune pancreatitis is an increasingly recognized inflammatory type of subacute pancreatitis; two subtypes of autoimmune pancreatitis have been identified so far: the "lymphoplasmacytic" type 1 variant and the "neutrophilic" type 2 variant. Type 1 autoimmune pancreatitis represents the most common manifestation of IgG4-related disease, a fibro-inflammatory disorder characterized by elevated IgG4 levels in the serum and affected tissues. Type 2 autoimmune pancreatitis is a pancreas-specific disorder that frequently occurs in the context of inflammatory bowel diseases.

Rethinking chromatin accessibility: from compaction to dynamic interactions.

The genome is traditionally divided into condensed heterochromatin and open euchromatin. However, recent findings challenge this binary classification and the notion that chromatin condensation solely governs the accessibility of transcription factors (TFs) and, consequently, gene expression. Instead, chromatin accessibility is emerging as a factor-specific property that is influenced by multiple determinants.

Serious games in child and adolescent health education campaigns: a systematic review.

Background: The use of playful tools to promote children's and adolescents' health in schools is growing. Educational games are proven tools for promoting virtuous behaviours. This systematic review explores the significance of serious games in promoting health education among young audiences, particularly about hand, oral and respiratory hygiene, immunisation, antimicrobial resistance (AMR) and sexually transmitted infections.

The Italian National Vaccine Prevention Plans, 1999/2020-2023/2025: challenges and obstacles to vaccine coverage goals. Commentary.

Five consecutive national vaccination plans (from 1999 to 2025) were revised, outlining their objectives, challenges, and results. Vaccination coverage for children consistently approached target levels, though regional differences emerged. In contrast, coverage for adolescents, the elderly, and vulnerable groups, consistently fell short of targets.

When an underestimated zoonosis and antimicrobial resistance collide: Corynebacterium ulcerans.

In the European region, diphtheria is now rarely suspected in patients presenting with upper respiratory tract symptoms. is the underestimated zoonosis that is replacing infections in industrialized countries, but extensive human and animal prevalence studies are lacking. The range of hosts that can act as reservoirs for is very broad, companion pets currently being the main source of human infection.

Identification of an early subset of cerebellar nuclei neurons in mice.

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium.

Clinical, histological and safety outcomes with long-term maintenance therapies for eosinophilic esophagitis: A systematic review and meta-analysis.

Background And Aim: Our aim was to evaluate outcomes of maintenance treatments for EoE among observational studies (OSs) and randomized controlled trials (RCTs).

Materials And Methods: Studies reporting histological success of maintenance therapy ≥ 48 weeks were included. Primary outcome was histological success rate (defined as <15/<6 eos/HPF).

Effectiveness of Ustekinumab for patients with moderate to severe Ulcerative Colitis: A Multi-Center Real-World Canadian Study.

Background: We aimed to evaluate the real-world effectiveness and safety of ustekinumab for the treatment of both bio-naïve and bio-exposed ulcerative colitis (UC) patients in a real-world setting.

Methods: Retrospective, Canadian multicenter cohort study. Primary outcomes were clinical remission and endoscopic remission.

Health literacy: a new challenge for laboratory medicine.

Poor health literacy and inappropriate test prescribing hamper the value of laboratory medicine. The disintermediation between test producers and interpreters may happen both in Point of Care Tests, where doctor mediation is provided, but laboratory expert supervision is not, and in Direct to Consumer Testing, where no medical mediation is provided at all. In these cases, the respect for patient's autonomy must not preclude the principles of non-maleficence (as an individual concern) and justice (as a societal concern), as wrong test interpretation can generate confusion, anxiety, inappropriate social behavior, useless medical examinations and considerable cost increase.

Diazoxide toxicity in congenital hyperinsulinism: A case report.

Background: Diazoxide is the sole approved drug for congenital hyperinsulinism; however, diuretic administration and vigilant monitoring are crucial to prevent and promptly identify potentially life-threatening adverse effects. This report aims to highlight a seldom-considered rare side effect of diazoxide. We believe that this brief report is of general interest to readership and increase the physicians' awareness of the guideline importance.

Altered calcium responses and antioxidant properties in Friedreich's ataxia-like cerebellar astrocytes.

Friedreich's ataxia (FRDA) is a neurodegenerative disorder characterized by severe neurological signs, affecting the peripheral and central nervous system, caused by reduced frataxin protein (FXN) levels. While several studies highlight cellular dysfunctions in neurons, there is limited information on the effects of FXN depletion in astrocytes and on the potential non-cell autonomous mechanisms affecting neurons in FRDA. In this study, we generated a model of FRDA cerebellar astrocytes to unveil phenotypic alterations that might contribute to cerebellar atrophy.

Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA.

JCO SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.