Late Hepatocellular Carcinoma Occurrence in Patients Achieving Sustained Virological Response After Direct-Acting Antiviral Therapy: A Matter of Follow-Up or Something Else?

: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. : In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018.

The pharmacological management of asthma in adults: 2023 update.

Introduction: The pharmacotherapy of asthma is a dynamic process that changes as our knowledge of the underlying pathophysiology and treatment of this disease continues to evolve. This implies the need for continuous revision of the recommendations of asthma guidelines and strategies.

Areas Covered: This review summarizes the latest key practical information on the pharmacological management of asthma in adults.

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro.

Background: Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.

Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update.

Introduction: Strong scientific evidence and large experience support the use of β-agonists for the symptomatic alleviation of COPD. Therefore, there is considerable effort in discovering highly potent and selective β-agonists.

Areas Covered: Recent research on novel β-agonists for the treatment of COPD.

Is it preferable to administer a bronchodilator once- or twice-daily when treating COPD?

Nocturnal and early morning symptoms are common and uncomfortable in many patients with COPD, and are likely to affect their long-term outcomes. However, it is still debated whether it is better to give long-acting bronchodilators once- or twice-daily to symptomatic COPD patients. The functional link between circadian rhythms of autonomic tone and airway calibre explains why the timing of administration of bronchodilators in chronic airway diseases can induce different effects when taken at different biological (circadian) times.

Strategies for overcoming the biological barriers associated with the administration of inhaled monoclonal antibodies for lung diseases.

Introduction: Monoclonal antibodies (mAbs) should be administered by inhalation rather than parenterally to improve their efficiency in lung diseases. However, the pulmonary administration of mAbs in terms of aerosol technology and the formulation for inhalation is difficult.

Areas Covered: The feasible or suitable strategies for overcoming the barriers associated with administering mAbs are described.

Pharmacokinetic considerations surrounding triple therapy for uncontrolled asthma.

Introduction: Solid pharmacological rationale and clinical evidence support the use of a combination of an inhaled corticosteroid (ICS), a long-acting β-agonist, and a long-acting muscarinic antagonist in severe asthma, which clinically results in increased lung function, improved symptoms, and decreased exacerbation rates.

Areas Covered: We examined the pharmacokinetic issues associated with triple therapy for uncontrolled asthma. We considered the pharmacokinetic characteristics of the three drug classes, the role of inhalers in influencing their pharmacokinetic behavior, and the impact of severe asthma on the pharmacokinetics of inhaled drugs.

The long-term exercise after traumatic brain injury: Reharmonizing brain by sound body.

Traumatic brain injuries (TBI) refer to multiple acquired dysfunctions arising from damage to the brain caused by an external force, including rapid acceleration/deceleration and concussion. Among them, mild TBI (mTBI) accounts for most cases (up to 90%) of injuries. It is responsible for a variety of symptoms, including anxiety, depression, and cognitive impairments that remain difficult to be treated.

Early pathological changes of peri-coronal tissue in the distal area of erupted or partially impacted lower third molars.

Aim: This study was performed to histologically evaluate peri-coronal tissues of partially impacted and erupted third molars that did not exhibit pathologic peri-coronal radiolucency.

Materials And Methods: Healthy patients with erupted or partially erupted (with part or all of the dental crown present in the oral cavity) mandibular third molars (classified as IA and IIA according to the Pell and Gregory classification) and vertically positioned (according to the Winter classification or erupted third molars) associated with peri coronal radiolucency of equal to or less than 2.5 mm.

Comparative study of the anaesthetic efficacy of 4% articaine versus 2% mepivacaine in mandibular third molar germectomy using different anaesthetic techniques: a split-mouth clinical trial.

Background: Currently, one of the most discouraging aspects for many patients undergoing dental procedures is the administration of local anaesthesia. Therefore, there is a constant search for new techniques to avoid the invasive and painful nature of the injection. This study aimed to compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine 2% (both with epinephrine 1:100.

Clinical characteristics, treatment patterns and adherence in patients with asthma on multiple inhaler triple therapy: a review of findings.

Introduction: The value of treating asthma with the triple regimen of inhaled corticosteroid (ICS), long-acting β-agonist (LABA), and long-acting muscarinic antagonist (LAMA) delivered using multiple inhalers (MITT), or a single inhaler (SITT) is supported by a growing body of evidence, although research is still limited regarding the use of MITT.

Areas Covered: Clinical characteristics, treatment patterns, disease burden, and persistence/adherence associated with MITT use in asthma. The MEDLINE database was searched to identify references from inception until October 2022.

Current and emerging treatment modalities for bacterial rhinosinusitis in adults: a comprehensive review.

Introduction: Rhinosinusitis (RS) is defined as acute when it lasts up to 4 weeks and chronic when it lasts at least 12 weeks. Most acute forms begin with a viral upper respiratory infection that spreads into the paranasal sinuses and is followed by bacterial infection. It is uncertain how bacteria affect chronic rhinosinusitis (CRS).

Pharmacotherapy of LAMA/LABA inhaled therapy combinations for chronic obstructive pulmonary disease: a clinical overview.

Introduction: Long-acting muscarinic receptor antagonist (LAMA)/β-agonist (LABA) combinations represent a significant improvement in the treatment of chronic obstructive pulmonary disease (COPD) due to their remarkable ability to improve lung function, dyspnea, quality of life, and exercise capacity compared to mono-components.

Areas Covered: This article aims to report the latest information on the clinical impact of dual bronchodilation in COPD.

Expert Opinion: The available data supports the use of inhaled LAMA/LABA FDCs in treating COPD patients, particularly those with severe or very severe disease.

Protective Effect of Resveratrol against Hypoxia-Induced Neural Oxidative Stress.

Oxidative stress plays an important role in brain aging and in neurodegenerative diseases. New therapeutic agents are necessary to cross the blood-brain barrier and target disease pathogenesis without causing disagreeable side effects. Resveratrol (RSV) may act as a neuroprotective compound, but little is known about its potential in improving the cognitive and metabolic aspects that are associated with neurodegenerative diseases.

PEA-OXA ameliorates allodynia, neuropsychiatric and adipose tissue remodeling induced by social isolation.

Chronic social isolation generates a persistent state of stress associated with obesity along with some neuro-endocrine disorders and central behavioral sequelae (eg anxiety, depression, aggression, and allodynia). In this study, we evaluated the effect of social isolation on body weight, depressive- and anxious-aggressive-like behavior, as well as on phenotypic changes of adipocytes from visceral adipose tissue of control (group-housed) or socially isolated (single-housed) male mice. The effect of treatment with pentadecyl-2-oxazoline (PEA-OXA), a natural alpha2 antagonist and histamine H3 protean partial agonist, on these alterations was also evaluated.

HCC and Molecular Targeting Therapies: Back to the Future.

Hepatocellular carcinoma (HCC) is one of the leading causes of death from cancer in the world. Recently, the effectiveness of new antiviral therapies and the HBV vaccine have reduced HCC's incidence, while non-alcoholic steato-hepatitis is an emerging risk factor. This review focuses on antiangiogenic molecules and immune checkpoint inhibitors approved for HCC treatment and possible future approaches.

New perspectives on the role of muscarinic antagonists in asthma therapy.

Introduction: There is increasing evidence that tiotropium, a long-acting muscarinic agent (LAMA), is useful in the presence of severe-uncontrolled asthma despite the optimization of therapy with inhaled corticosteroids (ICSs) and long-acting β agonists (LABAs) as recommended by the current guidelines. Furthermore, in recent years there have been several  preclinical and clinical studies on the pharmacological and therapeutic impact of other LAMAs in asthma.

Areas Covered: We have conducted an extensive search on muscarinic antagonists in asthma therapy throughout several sources and discuss what has emerged in the last 3 years (January 2017-March 2020).

Emerging muscarinic receptor antagonists for the treatment of asthma.

Introduction: The increased acetylcholine signaling in asthma pathophysiology offers the rationale for the use of LAMAs in the treatment of asthmatic patients. Tiotropium is still the only LAMA approved for use in asthma but there is a real interest in developing novel LAMAs for the treatment of asthma, or at least to extend this indication to other LAMAs already on the market.

Areas Covered: We examined and discussed trials and research that have studied or are evaluating the role of LAMAs already on the market in asthma and possible novel muscarinic acetylcholine receptor antagonists.

A review of the pharmacokinetics of M muscarinic receptor antagonists used for the treatment of asthma.

: There is solid evidence that in patients with poorly controlled severe asthma despite the use of ICS and LABA, the addition of LAMAs, such as tiotropium, significantly increases the time to the first severe exacerbation and provides a modest but sustained bronchodilation. However, only a very limited number of pharmacokinetic studies with these agents have been performed in asthmatic patients.: The pharmacokinetic profile of inhaled tiotropium, umeclidinium and glycopyrronium in healthy volunteers and that of inhaled tiotropium and umeclidinium in asthmatic patients have been reviewed.

Pharmacokinetics and pharmacodynamics of inhaled corticosteroids for asthma treatment.

The differences in the pharmacokinetic (PK) characteristics of inhaled corticosteroids (ICSs) critically influence the profile of each of them, but also the significant differences in glucocorticoid receptor selectivity, potency, and physicochemical properties are critical in defining the pharmacodynamic (PD) profile of an ICS. The PK and PD properties of ICSs used in asthma and the importance of their interrelationship have been reviewed. The differences among the ICSs in PK and PD must be considered when an ICS should be prescribed to an asthmatic patient because a better understanding of the PK/PD interrelationship of ICSs could be important to better fit with the between-patient variability and within-patient repeatability in the response to ICSs that often complicate the therapeutic approach to the asthmatic patient.