Drugs in Context最新文献

Background: Oxidative modifications of low-density lipoproteins (LDL) have been reported in patients with β-thalassaemia/haemoglobin E (HbE) and are related to cardiovascular complications. Deferiprone (L1) is an iron chelator that decreases iron overload and, consequently, reduces oxidative stress. This study assesses the protective effect of L1 on the oxidative status of LDL in patients with β-thalassaemia/HbE.

Methods: Twenty-nine patients with β-thalassaemia/HbE treated with L1 were recruited. The study included a 4-week washout period followed by 4 and 12 weeks of L1 treatment. Non-transferrin-bound iron (NTBI) levels and oxidative stress markers, including thiobarbituric acid reactive substances and α-tocopherol, were monitored at each visit. The rate and content of lipid radical formation following Cu²⁺-induced LDL oxidation in vitro were detected by NBD-Pen, a specific fluorescence probe.

Results: L1 was shown to prevent the depletion of α-tocopherol, decrease thiobarbituric acid reactive substances and preserve the levels of lipid components in LDL. A negative correlation between serum NTBI and LDL α-tocopherol indicated that the circulating non-redox-active NTBI can lead to the depletion of α-tocopherol. LDL from the washout period showed the highest oxidative susceptibility when evaluated by NBD-Pen.

Conclusion: Iron chelation therapy with L1 improves the oxidative status of LDL in patients with β-thalassaemia/HbE.

Advances in the understanding of the pathophysiology of psoriasis have led to the development of biologic therapies that target key components of the immune system involved in the inflammatory cascade of psoriasis, revolutionizing the management of moderate-to-severe cases. Alongside biologics, small molecules have emerged as promising treatment options. However, despite significant progress, several challenges remain. Additionally, long-term safety data for many newer agents are still lacking, necessitating ongoing surveillance and real-world evidence collection. This narrative review, performed by analysing the existing medical literature using PubMed, Ovid, Scopus, Embase and Cochrane Library databases up to 30 June 2025, explores new systemic therapies for psoriasis, including both approved and emerging biologics and small molecules, highlighting future directions in treatment. Despite advancements in psoriasis treatment, unmet needs persist, including specific clinical phenotypes such as pustular psoriasis, paradoxical reactions, patient comorbidities, treatment resistance or inefficacy, and high costs, underscoring the need for novel and emerging therapies. In the future, advances in pharmacogenetics and artificial intelligence could revolutionize psoriasis management. Artificial intelligence-driven models integrating clinical data, laboratory findings and biomarkers could enhance precision medicine by optimizing treatment selection and establishing standardized therapeutic algorithms, ensuring that patients receive the right drug at the right time.

N-acetylcysteine (NAC) is widely used for its mucolytic, antioxidant, anti-inflammatory and synergistic antibacterial properties in the treatment of respiratory diseases. NAC and other mucolytics and mucoactive medications are frequently employed in the adult population and in paediatric settings to improve mucus clearance in conditions such as cystic fibrosis, bronchiolitis, pneumonia, and both chronic and acute bronchitis, with varying degrees of success. This narrative review evaluates the efficacy and safety of NAC in paediatric acute and chronic respiratory diseases, synthesizing data from clinical trials, observational studies and real-world evidence, with a particular focus on optimizing dosing based on patient-specific characteristics. Numerous studies indicate that oral NAC doses of 20 mg/kg/day for acute conditions and 200 mg three times daily for chronic conditions are generally effective and well tolerated in children. However, most participants in these studies were older than 9 years, resulting in a lack of literature-based evidence for the optimal dosing in younger children over 2 years of age. Given the significant weight variations within this age group, weight-based dosing is recommended to ensure appropriate drug exposure and optimize treatment benefits. Weight-based dosing adjustments and patient monitoring may help optimize treatment outcomes and reinforce the overall positive safety and tolerability profile in paediatric settings. NAC is a valuable therapeutic agent for paediatric respiratory diseases, particularly in older children. In younger patients, weight-adjusted dosing and careful monitoring for potential adverse effects may help maximize efficacy and maintain its favourable tolerability profile.

The pineal gland is a neuroendocrine gland located in the epithalamus. Primary pineal tumours are uncommon and metastatic cancer spreading to the pineal gland is even more unusual. Brain metastases from adenocarcinoma of upper gastrointestinal tract occur in less than 1.5% of patients, yet no clear data about the incidence of metastases in the pineal region are available. This study presents the case of a 73-year-old man who presented to the emergency room with neurological symptoms. MRI revealed a pathological lesion in the pineal gland with histological findings of metastasis from adenocarcinoma of gastrointestinal origin. An oesophagogastroduodenoscopy was performed and a distal lesion was found, which was biopsied and histologically defined as oesophageal adenocarcinoma. A literature search identified six articles regarding pineal metastases from oesophageal carcinoma. Our clinical case was compared to the literature cases examining, in particular, nine parameters of analysis: age, sex, histological diagnosis, timing of metastatic pineal onset, overall metastatic sites, clinical presentation, imaging features, size and specific treatment for the pineal lesion. Despite the small sample and 'niche' topic in the medical literature, some important conclusions can be drawn: pineal metastases are rare, their origin is difficult to define, they require multidisciplinary management, and they can produce neurological symptoms; consequently, they must be treated through a well-timed locoregional approach (surgical or radiotherapy). Finally, further scientific research is needed to better understand the pathological mechanisms of malignant cellular homing at the pineal level.

Background: Virtually all patients with extensive-stage small cell lung cancer (SCLC) develop resistance to first-line platinum-based chemoimmunotherapy and experience relapse. Second-line therapy is therefore an integral part of the treatment paradigm.

Methods: Evidence was reviewed for key second-line regimens recommended in major guidelines for treatment of patients with platinum-sensitive relapse (chemotherapy-free interval ≥90 days), focusing on recent prospective clinical trials and post hoc analyses. Case studies of second-line lurbinectedin are presented as examples of the current management approach to platinum-sensitive relapsed SCLC.

Results: Subject to the limitations of cross-trial comparisons, the evidence review allowed us to draw broad conclusions about the place in therapy of approved options for platinum-sensitive relapse. Platinum rechallenge is more effective and better tolerated than topotecan and is a reasonable second-line choice in suitable patients. Topotecan provides modest clinical benefit and has the potential to cause dose-limiting haematological toxicities. Cyclophosphamide-doxorubicin-vincristine combination therapy offers no clear advantages over topotecan. Efficacy outcomes with second-line lurbinectedin are similar or better than those reported with platinum rechallenge, and lurbinectedin has a more favourable safety profile and simpler administration schedule. Second-line lurbinectedin preserves platinum rechallenge for later use and may resensitize tumour cells to platinum with potential survival advantages. Lurbinectedin safety is not affected by advanced age (≥65 years). Case studies highlight objective and durable responses to second-line lurbinectedin, along with good tolerability and quality of life.

Conclusions: Available evidence supports second-line lurbinectedin as a useful alternative to platinum rechallenge, topotecan and cyclophosphamide-doxorubicin-vincristine in patients with platinum-sensitive relapsed SCLC.

Background: Palmoplantar pustulosis (PPP) is a chronic, relapsing skin condition characterized by sterile, pruritic pustules on erythematous, thickened skin of the palms and soles. It often causes painful fissures, leading to functional impairment and reduced quality of life. Due to its limited response to conventional therapies and biologic therapies, PPP remains a therapeutic challenge. Recent findings implicate both T helper 17 (T_H17)-mediated and T_H2-mediated inflammation, prompting interest in broader immunomodulatory treatments such as Janus kinase (JAK) inhibitors.

Methods: This narrative review evaluates current evidence on the efficacy and safety of JAK inhibitors in the treatment of PPP. Published studies involving tofacitinib, upadacitinib and baricitinib were identified and reviewed.

Results: Clinical improvements with JAK inhibitors have been reported, particularly in cases refractory to conventional systemic therapy. Findings include reductions in the Palmoplantar Pustulosis Area and Severity Index (PPPASI) and improvements in patient-reported quality of life, with a low incidence of adverse effects. An ongoing trial investigating deucravacitinib reflects growing interest in this drug class.

Conclusion: JAK inhibitors show promise as a novel therapeutic option for PPP, given their ability to modulate multiple inflammatory pathways. Although current evidence is limited to case series and reports, results are encouraging and warrant confirmation through well-designed clinical trials.

Myasthenia gravis (MG) mostly affects women of childbearing age. Since the disease course may be affected during pregnancy and postpartum, monitoring and appropriate treatment of MG in pregnant women are crucial. Current treatment options for pregnant women with refractory MG are limited by possible teratogenicity and inadequate lactation data. This case report describes a successful pregnancy in a patient who received eculizumab for refractory generalized MG that was difficult to manage during the pre-pregnancy period. We also report the experience of preterm labour and neonatal MG and the 1-year follow-up of the neonate. Considering the risk-benefit balance, eculizumab can be recommended during pregnancy and postpartum, especially in women with refractory generalized MG.

Background: Reducing the microbial load in the upper respiratory tract can reduce the risk of transmission and spread of respiratory tract infections.

Methods: The in vitro antimicrobial activity of a new oral spray combining 0.15% benzydamine hydrochloride and 0.5% cetylpyridinium chloride (Tantum Verde DUO^®, Angelini Pharma S.p.A., spray duo) was investigated.

Results: Spray duo showed bacterial, yeasticidal and virucidal activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Enterococcus hirae (1 minute contact), Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes (30 second contact), Candida albicans (5 minute contact), modified vaccinia Ankara (3 minute contact), influenza A virus subtype H1N1, herpes simplex virus 1, and SARS-CoV-2 (1 minute contact).

Conclusions: Spray duo showed antimicrobial activity under in vitro conditions. Further investigations are warranted to evaluate the antimicrobial activity in clinical practice.

We report the case of an 18-year-old woman with early-onset severe allergic asthma and no other type 2 biomarkers except the presence of IgE, complicated by persistent airflow limitation, air trapping and forced oscillation technique-defined small airway dysfunction, who achieved significant clinical improvement with first-line tezepelumab (TZP) therapy. Initial treatments, including high-dose extrafine-inhaler triple therapy with a beclomethasone-formoterol-glycopyrronium combination, failed to improve asthma control and lung function. Given the discordance between allergic phenotype and treatable traits, such as persistent airflow limitation and small airway dysfunction, TZP, a thymic stromal lymphopoietin inhibitor with broad anti-inflammatory effects, was initiated instead of omalizumab. After 6 months of treatment, the patient showed marked clinical and functional improvement: Asthma Control Test score increased from 12 to 22, forced expiratory volume in 1 second rose from 67% to 95%, residual volume normalized, and forced oscillation technique parameters improved substantially. This case illustrates how the identification of specific treatable traits can guide personalized biologic therapy, even when conventional phenotype-driven algorithms suggest otherwise. In patients with early-onset allergic asthma and atypical functional profiles, TZP may offer a superior therapeutic option by targeting upstream airway inflammation and reversing small airway dysfunction. Our findings support a precision medicine approach in severe asthma, emphasizing multidimensional assessment and biomarker-guided biologic selection.

Background: Hip osteoarthritis (OA) is a leading cause of disability in older adults, yet long-term, non-surgical treatment options remain limited. Viscosupplementation with intra-articular hyaluronic acid has shown promise, but evidence for its sustained efficacy in hip OA is scarce. This study evaluates the 10-year efficacy and safety of repeated ultrasound (US)-guided injections of HyalOne^®/Hyalubrix^® 60 in patients with symptomatic hip OA.

Methods: A retrospective, observational, open-label study was conducted on 681 patients with symptomatic hip OA treated with HyalOne^® between 2010 and 2013, with follow-up through 2023. Patients received one US-guided intra-articular injection every 6 months, with additional injections as needed. Pain and functional outcomes were assessed using the Visual Analogue Scale and the Lequesne Index. Non-steroidal anti-inflammatory drug (NSAID) consumption and adverse events were also monitored.

Results: Overall, 481 patients completed the 10-year follow-up. Pain reduction was observed across all age and body mass index groups, with the highest improvement in patients under 40 years old (-54.3%). Functional status improved significantly, with the greatest reduction in Lequesne Index scores observed in patients over 80 years old (-32.5%). NSAID use decreased by 84% in younger patients and by 62-71% in older patients or those with obesity. No major systemic adverse events were reported, and transient local reactions occurred in 4% of patients.

Conclusions: This study provides the first real-world evidence of the sustained efficacy and safety of a 10-year US-guided HyalOne^® injection regimen in managing hip OA, highlighting significant improvements in pain, function and NSAID reduction across diverse patient populations.