Effectiveness and tolerability of rimegepant in the acute treatment of migraine: a real-world, prospective, multicentric study (GAINER study).

Background: Rimegepant, a novel oral calcitonin gene-related peptide receptor antagonist, has been recently approved for the acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, no data is available regarding real-life effectiveness and tolerability. GAINER, a prospective, multicentric study, aimed to evaluate rimegepant effectiveness and tolerability in the real-world setting.

Microglial suppression by myeloperoxidase inhibitor does not delay neurodegeneration in a mouse model of progressive multiple sclerosis.

Drugs able to efficiently counteract the progression of multiple sclerosis (MS) are still an unmet need. Numerous preclinical evidence indicates that reactive oxygen-generating enzyme myeloperoxidase (MPO), expressed by neutrophils and microglia, might play a key role in neurodegenerative disorders. Then, the MPO inhibition has been evaluated in clinical trials in Parkinson's and multiple system atrophy patients, and a clinical trial for the treatment of amyotrophic lateral sclerosis is underway.

An evolving machine-learning-based algorithm to early predict response to anti-CGRP monoclonal antibodies in patients with migraine.

Background: The present study aimed to determine whether machine-learning (ML)-based models can predict 3-, 6, and 12-month responses to the monoclonal antibodies (mAbs) against the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRPmAbs) in patients with migraine using early predictors (up to one month) and to create an evolving prediction tool.

Methods: In this prospective cohort study data from patients with migraine who had received anti-CGRP mAbs for 12 months were collected. Demographic and monthly clinical variables were collected, including monthly headache days (MHDs), days with acute medication use, number of analgesics and Headache Impact Test-6.

Mental Pain Questionnaire: Clinimetric Properties of a Potential Global Person-Centred Outcome Measure.

Introduction: The Mental Pain Questionnaire (MPQ) was developed using a clinimetric approach to bring together the key features of mental pain into a single, brief, transdiagnostic scale. The present study aims at extending the validation of the MPQ to people from three different clinical settings.

Methods: A multicentre, cross-sectional study on adults diagnosed with migraine (n = 256), systemic sclerosis (n = 219), or mental disorders (n = 138) was conducted.

Fever management in children and insights into fever of unknown origin: a survey among Italian pediatricians.

Background: Fever is a common symptom in children, but despite existing guidelines, pediatricians may not fully apply recommendations. Fever of Unknown Origin (FUO) is generally referred to as an unexplained prolonged fever. However, a standardized FUO definition and management is missing.

Outcomes, unmet needs, and challenges in the management of patients who withdraw from anti-CGRP monoclonal antibodies: A prospective cohort study.

Background: The anti-calcitonin gene-related peptide (CGRP), or its receptor (CGRP/R) monoclonal antibodies (mAbs), offer targeted, effective, and tolerated drugs for migraine. However, about 25% of patients fail to achieve a clinically meaningful response, usually leading to discontinuation. These patients often have a lengthy migraine history and multiple prior preventive treatment failures, resulting in limited therapeutic options.

Association of anti-calcitonin gene-related peptide with other monoclonal antibodies for different diseases: A multicenter, prospective, cohort study.

Background And Purpose: Although there is extensive evidence about the safety of monoclonal antibodies against calcitonin gene-related peptide (anti-CGRP mAbs) in combination with traditional drugs, scarce data are available on the safety of their combination with other mAbs. This study aimed to evaluate the 6-month effectiveness and tolerability of anti-CGRP mAbs in combination with other mAbs for different diseases.

Methods: Patients included in the Italian Headache Registry and treated concomitantly with an anti-CGRP mAb and another mAb were included.

Impact of duration of chronic migraine on long-term effectiveness of monoclonal antibodies targeting the calcitonin gene-related peptide pathway-A real-world study.

Objective: We assessed whether the effectiveness of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway changes according to the duration of chronic migraine (CM) over 12 months.

Background: In most patients, CM is a progressive disease starting with episodic migraine. Longer CM duration might be associated with more difficult treatment, probably because the mechanisms underlying chronicization are strengthened.

The Burden of Thin Melanomas in Tuscany, Italy, 1985-2017: Age- and Sex-Specific Temporal Trends in Incidence and Mortality.

A steady increase in the incidence and mortality burden correlated to thin melanomas (≤1 mm) has been reported in recent years in some international studies, but there is currently a paucity of data from the Mediterranean area. We aimed to describe the epidemiological characteristics of thin melanoma in Tuscany, Central Italy. A total of 6002 first cutaneous invasive melanomas occurring from 1985 to 2017 were selected for analysis; data were retrieved from the local population-based cancer registry.

Long-Term Treatment Over 52 Weeks with Monthly Fremanezumab in Drug-Resistant Migraine: A Prospective Multicenter Cohort Study.

Background: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up.

Objective: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine.

Methods: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures.

Glaucoma: neuroprotection with NAD-based therapeutic interventions.

Clinical evidence shows that intraocular hypertension is not the primary pathogenetic event of glaucoma, whereas early neurodegeneration of retinal ganglion cells (RGCs) represents a key therapeutic target. Unfortunately, failure of clinical trials with neuroprotective agents, in particular those testing the anti-excitotoxic drug memantine, generated widespread skepticism regarding the possibility of counteracting neurodegeneration during glaucoma. New avenues for neuroprotective approaches to counteract glaucoma evolution have been opened by the identification of a programmed axonal degeneration (PAD) program triggered by increased nicotinamide mononucleotide (NMN)/NAD concentration ratio.

Paracetamol and ibuprofen combination for the management of acute mild-to-moderate pain in children: expert consensus using the Nominal Group Technique (NGT).

Background: Acute pain is a common symptom in children of all ages, and is associated with a variety of conditions. Despite the availability of guidelines, pain often remains underestimated and undertreated. Paracetamol and ibuprofen are the most commonly used drugs for analgesia in Pediatrics.

Validation of the Italian version of the Cluster Headache Impact Questionnaire (CHIQ).

Background: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ.

Methods: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe).

Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: A retrospective cohort study.

Background: A pharmacological class effect was initially proposed for monoclonal antibodies against the calcitonin gene related peptide pathway. However, preliminary evidence shows that switching patients who were non-responding to one monoclonal antibody to another could provide some benefit. Herein, we assess treatment response to an anti-calcitonin gene related peptide/receptor monoclonal antibody in patients who have failed to respond to anti-calcitonin gene related peptide/ligand monoclonal antibodies calcitonin gene related peptide/ligand monoclonal antibodies and vice versa.

Early derangement of axonal mitochondria occurs in a mouse model of progressive but not relapsing-remitting multiple sclerosis.

Introduction: Derangement of axonal mitochondrial bioenergetics occurs during progressive multiple sclerosis (PMS). However, whether this is a delayed epiphenomenon or an early causative event of disease progression waits to be understood. Answering this question might further our knowledge of mechanisms underlying neurobiology of PMS and related therapy.

Dexamethasone Promotes a Stem-Like Phenotype in Human Melanoma Cells Tryptophan 2,3 Dioxygenase.

In addition to its well-established immunosuppressive actions, tryptophan 2,3-dioxygenase (TDO) appears to elicit direct effects on tumor cell function. Although TDO has been associated with cancer stemness, its involvement in melanoma stem cell biology remains largely unknown. Since we showed that by upregulating TDO, dexamethasone (dex) promotes proliferation and migration of SK-Mel-28 human melanoma cells, we sought to investigate dex effects on melanoma spherogenesis and stemness, and whether these events are mediated by TDO.

Effectiveness of anti-CGRP monoclonal antibodies on central symptoms of migraine.

Background: Clinical trials and observational studies with anti-calcitonin gene-related peptide antibodies poorly investigated their impact on migraine prodromal and accompanying symptoms. This information might help deciphering the biologics' pharmacodynamic and provide hints on migraine pathogenesis. Herein, we report the effects of erenumab, fremanezumab and galcanezumab on attack prodromal and accompanying symptoms and on neurological and psychiatric traits.

Effects of cluster headache preventatives on mouse hypothalamic transcriptional homeostasis.

Objective: To investigate how cluster headache preventatives verapamil, lithium and prednisone affect expression of hypothalamic genes involved in chronobiology.

Methods: C57Bl/6 mice were exposed to daily, oral treatment with verapamil, lithium, prednisone or amitriptyline (as negative control), and transcripts of multiple genes quantified in the anterior, lateral and posterior hypothalamus.

Results: Verapamil, lithium or prednisone did not affect expression of clock genes of the anterior hypothalamus (, , and ).

Long-Term Effectiveness of Three Anti-CGRP Monoclonal Antibodies in Resistant Chronic Migraine Patients Based on the MIDAS score.

Background: Criteria, including clinical features and effective outcomes, for access and persistence of novel but costly treatments may vary between countries, thus affecting the health of patients. Monoclonal antibodies against the calcitonin gene-related peptide pathway (anti-CGRP mAbs) for migraine treatment are currently prescribed following strict criteria.

Objective: The aim was to assess the effectiveness and safety of three anti-CGRP mAbs (erenumab, galcanezumab, and fremanezumab) in consecutive resistant chronic migraine patients presenting at our Headache Center and the impact of criteria set by the Italian Medicines Agency to start and continue (achieving a ≥ 50% reduction in Migraine Disability Assessment [MIDAS] score) with treatment under the reimbursement program.

Predictors of sustained response and effects of the discontinuation of anti-calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine.

Background And Purpose: Guidelines for migraine prophylaxis suggest stopping medication after 6-12 months to reevaluate treatment appropriateness. The Italian Medicines Agency set a mandatory regulation to stop anti-calcitonin gene related protein (CGRP) pathway monoclonal antibody (anti-CGRP mAb) treatments for 3 months after 12 months of treatment. Herein, the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients are assessed, evaluating predictive factors of sustained response.