Do patients with fibromyalgia syndrome receive updated management strategies? A web-based survey among Italian physiotherapists.

Introduction: Fibromyalgia syndrome (FMS) causes significant pain, disability, and costs among patients. It is paramount that healthcare professionals have an updated knowledge of its characteristics and Clinical Practice Guidelines (CPGs).

Objectives: To determine the knowledge, adherence to CPGs, and confidence of Italian physiotherapists in managing patients with FMS, explore barriers to the implementation of CPG' recommendations, compare groups' adherence to CPGs, and determine which variables explained most of the participants' knowledge.

Epigenetic changes in patients with post-acute COVID-19 symptoms (PACS) and long-COVID: A systematic review.

Background: Up to 30% of people infected with SARS-CoV-2 report disabling symptoms 2 years after the infection. Over 100 persistent symptoms have been associated with Post-Acute COVID-19 Symptoms (PACS) and/or long-COVID, showing a significant clinical heterogeneity. To develop effective, patient-targeted treatment, a better understanding of underlying mechanisms is needed.

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.

Plain language summary: 5-year results from the CROWN study of lorlatinib vs crizotinib in non-small-cell lung cancer.

What Is This Study About?: This is a summary of the results of an ongoing study called CROWN. In the CROWN study, researchers looked at the effects of two medicines called lorlatinib (Lorbrena) and crizotinib (Xalkori) for people with advanced non-small cell lung cancer (NSCLC) who had not been treated yet. Everyone in the study had changes in a called anaplastic lymphoma kinase, or , in their cancer cells.

Comparative Efficacy and Safety of Lorlatinib Versus Alectinib and Lorlatinib Versus Brigatinib for ALK-Positive Advanced/Metastatic NSCLC: Matching-Adjusted Indirect Comparisons.

Introduction: The comparative efficacy and safety of lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), versus second-generation ALK TKIs as a first-line treatment for ALK+ advanced/metastatic nonsmall cell lung cancer (NSCLC) remains uncertain as there are no head-to-head clinical trials.

Methods: Matching-adjusted indirect comparisons (MAICs) were conducted using phase III trial data demonstrating superior efficacy over crizotinib, a first-generation ALK TKI. MAICs were conducted to compare lorlatinib (CROWN) versus alectinib (ALEX and ALESIA) and brigatinib (ALTA-1L) with matching based on prespecified effect modifiers.

Epigenetic Landscapes of Pain: DNA Methylation Dynamics in Chronic Pain.

Chronic pain is a prevalent condition with a multifaceted pathogenesis, where epigenetic modifications, particularly DNA methylation, might play an important role. This review delves into the intricate mechanisms by which DNA methylation and demethylation regulate genes associated with nociception and pain perception in nociceptive pathways. We explore the dynamic nature of these epigenetic processes, mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) enzymes, which modulate the expression of pro- and anti-nociceptive genes.

Radiotolerant endophytic bacteria and analysis of the effects of Cesium on the metabolome of Pantoea sp.

Some bacteria have developed mechanisms to withstand the stress caused by ionizing radiation. The ability of these radioresistant microorganisms to survive high levels of radiation is primarily attributed to their DNA repair mechanisms and the production of protective metabolites. To determine the effect of irradiation on bacterial growth, we propose to compare the metabolites produced by the irradiated isolates to those of the control (non-irradiated isolates) using mass spectrometry, molecular networking, and chemometric analysis.

Lorlatinib Versus Crizotinib in Patients With Advanced -Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study.

Purpose: Lorlatinib improved progression-free survival (PFS) and intracranial activity versus crizotinib in patients with previously untreated, advanced, -positive non-small cell lung cancer (NSCLC) in the phase III CROWN study. Here, we report long-term outcomes from CROWN after 5 years of follow-up.

Methods: Two hundred ninety-six patients with -positive NSCLC were randomly assigned 1:1 to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147).

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).

Italian versions of the Neurophysiology of Pain Questionnaire (NPQ): psychometric properties and an investigation on the understanding of pain neurophysiology in physical therapists.

Objectives: The Neurophysiology of Pain Questionnaire (NPQ) is widely used to assess pain knowledge among clinicians and patients with pain, but an Italian version is not available. This study aimed to translate and cross-culturally adapt the NPQ into Italian, to test its psychometric properties, to assess the knowledge of Italian physical therapists (PTs) on pain, and to evaluate which characteristics are associated with pain knowledge.

Methods: The NPQ was translated into Italian, integrated with some additional questions (IT-NPQ-New), and sent by email via the Italian Association of Physiotherapy newsletter.

Towards a Real-Life Understanding of the Altered Functional Behaviour of the Default Mode and Salience Network in Chronic Pain: Are People with Chronic Pain Overthinking the Meaning of Their Pain?

Chronic pain is a source of substantial physical and psychological suffering, yet a clear understanding of the pathogenesis of chronic pain is lacking. Repeated studies have reported an altered behaviour of the salience network (SN) and default mode network (DMN) in people with chronic pain, and a majority of these studies report an altered behaviour of the dorsal ventromedial prefrontal cortex (vmPFC) within the anterior DMN. In this topical review, we therefore focus specifically on the role of the dorsal vmPFC in chronic pain to provide an updated perspective on the cortical mechanisms of chronic pain.

Personalized Multimodal Lifestyle Intervention as the Best-Evidenced Treatment for Chronic Pain: State-of-the-Art Clinical Perspective.

Chronic pain is the most prevalent disease worldwide, leading to substantial disability and socioeconomic burden. Therefore, it can be regarded as a public health disease and major challenge to scientists, clinicians and affected individuals. Behavioral lifestyle factors, such as, physical (in)activity, stress, poor sleep and an unhealthy diet are increasingly recognized as perpetuating factors for chronic pain.

The Role of the Brain-Derived Neurotrophic Factor in Chronic Pain: Links to Central Sensitization and Neuroinflammation.

Chronic pain is sustained, in part, through the intricate process of central sensitization (CS), marked by maladaptive neuroplasticity and neuronal hyperexcitability within central pain pathways. Accumulating evidence suggests that CS is also driven by neuroinflammation in the peripheral and central nervous system. In any chronic disease, the search for perpetuating factors is crucial in identifying therapeutic targets and developing primary preventive strategies.

Antitumor and antibacterial activity of metabolites of endophytic Colletotrichum siamense isolated from coffee (Coffea arabica L. cv IAPAR-59).

Endophytic fungi produce a range of known metabolites and several others, not yet explored, which present important biological activities from the pharmaceutical and industrial perspective. Several studies have reported the diversity of endophytes in Coffea arabica plants, although few have been described in organic cultures. In the current paper, we describe the chemical profile of specialized metabolites in the ethyl acetate phase in a strain of the endophytic fungus Colletotrichum siamense associated with coffee (Coffea arabica L.

Synthesis, characterization, and reusability of novel nanobiocomposite of endophytic fungus Aspergillus flavus and magnetic nanoparticles (FeO) with dye bioremediation potential.

The incorrect disposal of textile dyes, such as Reactive Black 5 (RB5), causes several problems for living beings and the quality of the environment. Nanobiocomposites (NBC) produced from endophytic fungi (potentially remediation dyes-agents) and magnetic nanoparticles have high biotechnological potential due to their superparamagnetic behavior, which would allow their recovery through the magnetic field after the bioremediation process. This work aimed to obtain a new nanobiocomposite from the interaction of magnetite nanoparticles (FeO) with the endophyte Aspergillus flavus (Af-CL-7) to evaluate its bioremediation capacity and to reduce the toxicity of RB5 and its reuse.

Efficacy of Lorlatinib in Treatment-Naive Patients With ALK-Positive Advanced NSCLC in Relation to EML4::ALK Variant Type and ALK With or Without TP53 Mutations.

Introduction: Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, improved outcomes compared with crizotinib in patients with previously untreated ALK-positive advanced NSCLC in the phase 3 CROWN study. Here, we investigated response correlates using plasma circulating tumor DNA (ctDNA) and tumor tissue profiling.

Methods: ALK fusions and ALK with or without TP53 mutations were assessed by next-generation sequencing.

Plain language summary of the updated results from the CROWN study comparing lorlatinib with crizotinib in people with advanced non-small-cell lung cancer.

What Is This Summary About?: This summary shows the updated results of an ongoing research study called CROWN that was published in in December 2022. In the CROWN study, researchers looked at the effects of two study medicines called lorlatinib and crizotinib. The study included people with advanced non-small-cell lung cancer (NSCLC) that had not been treated previously.

Early Circulating Tumor DNA Dynamics and Efficacy of Lorlatinib in Patients With Treatment-Naive, Advanced, ALK-Positive NSCLC.

Introduction: Circulating tumor DNA (ctDNA) has been used as a biomarker for prognostication and response to treatment. Here, we evaluate ctDNA as a potential biomarker for response to lorlatinib, a third-generation ALK tyrosine kinase inhibitor in patients with treatment-naive, advanced, ALK-positive NSCLC in the ongoing phase 3 CROWN study (NCT03052608).

Methods: Molecular responses were calculated using mean variant allele frequency (VAF), longitudinal mean change in VAF (dVAF), and ratio to baseline.

Asian Subgroup Analysis of the Randomized Phase 3 CROWN Study of First-Line Lorlatinib Versus Crizotinib in Advanced -Positive NSCLC.

Introduction: Lorlatinib is a potent, third-generation inhibitor of ALK. In the planned interim analysis of the ongoing, phase 3, randomized, global CROWN trial (NCT03052608), lorlatinib resulted in significantly longer progression-free survival than crizotinib in patients with previously untreated, advanced, -positive NSCLC. Here, we present a subgroup analysis of Asian patients in the CROWN study.