Drugs in Context最新文献

Osteoarthritis (OA) is increasingly understood as a complex, inflammatory disease rather than a purely mechanical disorder. Apremilast, a selective phosphodiesterase 4 inhibitor approved for psoriatic arthritis, is amongst several new treatment alternatives that target one of the most important inflammatory pathways involved in OA. Apremilast decreases pro-inflammatory cytokines, such as TNF, IL-1 and IL-6, which are central to cartilage degradation and synovial inflammation. This review explores the mechanistic rationale and available evidence supporting the repurposing of apremilast in OA. We highlight its potential to reduce pain and slow structural progression. Although the data are currently scarce, there remains a strong rationale for its repurposing for the treatment of OA based on its safety profile, oral route of administration and positive treatment adherence. Nevertheless, clinical investigation remains limited. Further research is needed to clarify its therapeutic potential and identify patient populations most likely to benefit.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with a relapsing and remitting course often necessitating the use of advanced therapy to maintain disease control. Sphingosine-1-phosphate receptor modulators (S1PRMs) represent a new class of oral small molecules approved for the management of moderate-to-severe UC. Evidence from pivotal trials shows promising results for the induction and maintenance of remission in UC. This comprehensive review of S1PRMs explores their mechanism of action, key clinical trial data, real-world insights, and an overview of their safety, including considerations for special populations and comparative effectiveness. S1PRMs offer distinct advantages, including oral administration and a lack of immunogenicity, positioning them as valuable additions to the UC treatment landscape. However, future research will be required to understand their position in the evolving UC treatment paradigms.

Background: Invasive disease-free survival in adjuvant treatment of HR⁺/HER2^- early-stage breast cancer is improved by the use of CDK4/6 inhibitors. However, to date, minimal data are available on their safety and effectiveness in older patients (≥70 years old).

Methods: A retrospective, multi-centre cohort study was conducted in two oncology centres in Pavia, Italy. Patients had to have received at least 3 months of therapy with adjuvant abemaciclib (a CDK4/6 inhibitor). Data on demographics, toxicity, dose reductions and clinical outcomes were analysed. Analyses were descriptive, with continuous variables reported as median (IQR) and categorical variables as counts and percentages.

Results: Fifty-four patient records were reviewed (median age 55; six patients ≥70 years (older-age subgroup). Adverse events of any grade were reported in 53/54 patients (98.1%), most commonly haematological and gastrointestinal. Dose reductions occurred more frequently and earlier in the older-age subgroup (66.7% versus 45.8%; median 4.2 versus 8.3 months). Toxicities were generally of low-moderate grade and manageable.

Conclusion: During adjuvant abemaciclib, low-moderate-grade toxicities were common, particularly haematological and gastrointestinal events. Older patients showed a numerically higher rate of dose reductions, suggesting a potential need for personalized dosing and early monitoring in this subgroup. These findings should be considered hypothesis-generating and warrant confirmation in larger prospective studies.

Rupatadine is a modern, long-acting, non-sedating antihistamine that targets the H₁ receptor and exhibits additional strong antagonist activity toward platelet-activating factor (PAF) receptors as well as exerting other anti-inflammatory effects. All these properties have positioned rupatadine as a remarkable treatment option for adults and children with various allergic and skin disorders, including allergic rhinitis and urticaria of different causes. This case series shows the real-world effectiveness and safety of off-label rupatadine use in paediatric patients with clinically relevant complex allergy-related and dermatology-related conditions, whose underlying pathogenetic mechanisms were successfully addressed by the pharmacological profile of rupatadine.

Although mild upper respiratory tract infections (MURTIs) are typically self-limiting and benign, they can substantially impair a patient's quality of life. The wide range of pathogens causing MURTIs often necessitates a symptomatic treatment approach rather than a pathogen-specific treatment. The present article introduces a patient-centred classification system that distinguishes between self-care-oriented, pharmacist-oriented and physician-oriented patients. Building on this framework, we propose a 360° holistic care model that considers contextual factors and addresses the whole person, under the premise that the effectiveness, safety and suitability of the treatment are tailored to the individual's symptoms and circumstances. To support practical implementation, a stepwise guide for MURTI management is presented, encompassing all steps from initial patient assessment to pharmacological and non-pharmacological treatment approaches, lifestyle advice, patient education, and follow-up care. This structured approach not only facilitates symptom resolution but also promotes long-term health by empowering patients with the knowledge, tools and support they need to maintain their well-being. By shifting the focus from isolated symptom management to comprehensive care, our 360° holistic care model may enhance the overall treatment experience and outcome for patients affected by MURTIs.

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.