Avelumab + axitinib vs sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase 3 JAVELIN Renal 101 trial.

Background: In the phase 3 JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).

Patients And Methods: Patients with untreated aRCC (any prognostic risk score) were enrolled.

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The aim of the work was to create a survey related to health questions to be distributed to associations active for trans* people's rights. 165 answers were obtained: among these, 45.6% are from trans* people and 31.

Resurgence of scabies in Italy: The new life of an old disease.

Scabies, an old parasitic disease with a worldwide presence, has witnessed a recent resurgence in many parts of the world even in the light of the COVID-19 pandemic. We conducted a study on this resurgence in the Italian province of Messina, Sicily, evaluating the general features of affected people to better understand the possible modes of transmission. Specifically, we considered all the scabies notifications made in the period 2003-2022.

Detecting Multi-Scale Defects in Material Extrusion Additive Manufacturing of Fiber-Reinforced Thermoplastic Composites: A Review of Challenges and Advanced Non-Destructive Testing Techniques.

Additive manufacturing (AM) defects present significant challenges in fiber-reinforced thermoplastic composites (FRTPCs), directly impacting both their structural and non-structural performance. In structures produced through material extrusion-based AM, specifically fused filament fabrication (FFF), the layer-by-layer deposition can introduce defects such as porosity (up to 10-15% in some cases), delamination, voids, fiber misalignment, and incomplete fusion between layers. These defects compromise mechanical properties, leading to reduction of up to 30% in tensile strength and, in some cases, up to 20% in fatigue life, severely diminishing the composite's overall performance and structural integrity.

First-line encorafenib plus binimetinib and pembrolizumab for advanced BRAF V600-mutant melanoma: Safety lead-in results from the randomized phase III STARBOARD study.

Background: BRAF inhibitors plus MEK inhibitors (BRAFi/MEKi) and immune checkpoint inhibitors (CPIs) are approved for BRAF V600-mutant advanced melanoma. Combinations of BRAFi/MEKi with CPIs may further improve outcomes and could offer additional treatment strategies.

Methods: STARBOARD (NCT04657991) is a phase III study with an initial safety lead-in (SLI) phase conducted to determine the recommended phase III dose (RP3D) for encorafenib in combination with binimetinib and pembrolizumab.

Sterile inflammation induced by respirable micro and nano polystyrene particles in the pathogenesis of pulmonary diseases.

Sterile inflammation is involved in the lung pathogenesis induced by respirable particles, including micro- and nanoplastics. Their increasing amounts in the ambient and in indoor air pose a risk to human health. In two human cell lines (A549 and THP-1) we assessed the proinflammatory behavior of polystyrene nanoplastics (nPS) and microplastics (mPS) (Ø 0.

Smart Industrial Internet of Things Framework for Composites Manufacturing.

Composite materials are increasingly important in making high-performance products. However, contemporary composites manufacturing processes still encounter significant challenges that range from inherent material stochasticity to manufacturing process variabilities. This paper proposes a novel smart Industrial Internet of Things framework, which is also referred to as an Artificial Intelligence of Things (AIoT) framework for composites manufacturing.

Molecular Dialogue During Host Manipulation by the Vascular Wilt Fungus .

Vascular wilt fungi are a group of hemibiotrophic phytopathogens that infect diverse crop plants. These pathogens have adapted to thrive in the nutrient-deprived niche of the plant xylem. Identification and functional characterization of effectors and their role in the establishment of compatibility across multiple hosts, suppression of plant defense, host reprogramming, and interaction with surrounding microbes have been studied mainly in model vascular wilt pathogens and .

A novel in vitro model for investigating oligodendroglial maturation and myelin deposition under demyelinating and remyelinating conditions: Impact of microglial depletion and repopulation.

Experimental models of multiple sclerosis (MS) have significantly contributed to our understanding of pathophysiology and the development of therapeutic interventions. Various in vivo animal models have successfully replicated key features of MS and associated pathophysiological processes, shedding light on the sequence of events leading to disease initiation, progression, and resolution. Nevertheless, these models often entail substantial costs and prolonged treatment periods.

Vaccinomics and adversomics: key elements for a personalized vaccinology.

Vaccines are one of the most important and effective tools in the prevention of infectious diseases and research about all the aspects of vaccinology are essential to increase the number of available vaccines more and more safe and effective. Despite the unquestionable value of vaccinations, vaccine hesitancy has spread worldwide compromising the success of vaccinations. Currently, the main purpose of vaccination campaigns is the immunization of whole populations with the same vaccine formulations and schedules for all individuals.

POLARIS: A phase 2 trial of encorafenib plus binimetinib evaluating high-dose and standard-dose regimens in patients with V600-mutant melanoma with brain metastasis.

Background: POLARIS (phase 2 [ph2]; NCT03911869) evaluated encorafenib (BRAF inhibitor) in combination with binimetinib (MEK1/2 inhibitor) in BRAF/MEK inhibitor-naïve patients with V600-mutant melanoma with asymptomatic brain metastases.

Methods: The safety lead-in (SLI) assessed tolerability for high-dose encorafenib 300 mg twice daily (BID) plus binimetinib 45 mg BID. If the high dose was tolerable in ph2, patients would be randomized to receive high or standard dose (encorafenib 450 mg once daily [QD] plus binimetinib 45 mg BID).

COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600E/K-mutant melanoma.

Background: Treatment with encorafenib plus binimetinib and encorafenib monotherapy is associated with improved progression-free survival (PFS) and overall survival (OS) compared with vemurafenib in patients with BRAF V600E/K-mutant metastatic melanoma. We report results from the 7-year analysis of COLUMBUS part 1 (NCT01909453) at 99.7 months (median duration between randomization and data cutoff).

Integrative Analyses of Tumor and Peripheral Biomarkers in the Treatment of Advanced Renal Cell Carcinoma.

Unlabelled: The phase III JAVELIN Renal 101 trial demonstrated prolonged progression-free survival (PFS) in patients (N = 886) with advanced renal cell carcinoma treated with first-line avelumab + axitinib (A+Ax) versus sunitinib. We report novel findings from integrated analyses of longitudinal blood samples and baseline tumor tissue. PFS was associated with elevated lymphocyte levels in the sunitinib arm and an abundance of innate immune subsets in the A+Ax arm.

Impact of the COVID-19 pandemic on the infectious disease epidemiology.

Introduction: COVID-19 pandemic has exerted a huge impact on different aspects of public health. Mandatory notifications are a fundamental tool to have a general picture of infection disease spread in a population. The aim of this study was to evaluate the impact the COVID-19 pandemic had on infectious disease epidemiology.

Exploratory analyses of treatment subgroup interaction by PD-L1 status and according to PD-L1 expression in the JAVELIN Bladder 100 trial.

Purpose: Post hoc analysis of the JAVELIN Bladder 100 trial of avelumab maintenance in locally advanced/metastatic urothelial carcinoma (la/mUC) to determine the interaction by programmed death ligand 1 (PD-L1) status for overall survival (OS), and additional analyses of survival per a different PD-L1 expression cutoff of ≥ 1% in tumor cells or immune cells (TC/IC).

Methods: JAVELIN Bladder 100 data were used for the analysis of the interaction by PD-L1 status (per cutoff used in the trial) for OS and, additionally, OS and progression-free survival (PFS) analyses per a different ≥ 1% TC/IC PD-L1 expression cutoff (Ventana SP263 assay).

Results: No significant interaction between treatment and PD-L1 status was observed for OS.

Neuroimmune activation and increased brain aging in chronic pain patients after the COVID-19 pandemic onset.

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRI-estimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history.

Efficacy of adding selective electrical muscle stimulation to usual physical therapy for Bell's palsy: immediate and six-month outcomes.

Bell's palsy is the most common cause of facial paralysis, affecting one in every 60 people in their lifetime. Transcutaneously applied selective electrical muscle stimulation could potentially accelerate recovery from Bell's palsy but this intervention remains controversial. Studies have shown benefit, but concerns for lack of efficacy and potential for worsening synkinesis remain.

Efficacy of avelumab plus axitinib versus sunitinib by numbers of IMDC risk factors and target tumor sites at baseline in advanced renal cell carcinoma: long-term follow-up results from JAVELIN Renal 101.

Background: In the phase III JAVELIN Renal 101 trial, first-line avelumab + axitinib improved progression-free survival (PFS) and objective response rate versus sunitinib in patients with advanced renal cell carcinoma across all International Metastatic RCC Database Consortium (IMDC) risk groups (favorable, intermediate, and poor); analyses of overall survival (OS) remain immature. Here, we report post hoc analyses of efficacy from the third interim analysis (data cut-off, April 2020) by the numbers of IMDC risk factors and target tumor sites at baseline.

Methods: Efficacy endpoints assessed were PFS, objective response, and best overall response per investigator assessment (RECIST v1.