Search Results (366)

Transthyretin amyloidosis (ATTR) is a disease caused by the deposition of transthyretin-derived fibrils in the body. Despite extensive research conducted over the years, there are currently only four drugs available in clinical use to treat this condition, two of which are repurposed drugs used off-label. However, these treatments present several limitations; therefore, there is an urgent need for new therapeutic options. In this context, dietary supplements containing natural compounds capable of stabilizing the transthyretin (TTR) protein could represent a promising approach to contrast the disease progression, potentially supporting the therapeutic effects of the aforementioned drugs. In light of this, the present review highlights and analyzes the natural compounds that have most recently been reported in the literature as TTR stabilizers. In particular, the studies elucidating the potential of these compounds in the treatment of ATTR, along with the available crystallographic data explaining their binding mode to TTR, are reported. Overall, although the use of natural compounds as supplements shows promise in managing ATTR, further research is still needed to explore its feasibility and confirm its effectiveness. Hopefully, this work will help shed light on these issues and serve as a useful starting point for the development of new strategies to treat this disease. Full article

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors, with a five-year overall survival rate below 10%. While the introduction of multi-agent chemotherapy regimens has improved outcomes marginally, most patients with advanced disease continue to have limited therapeutic options. Molecular profiling has uncovered actionable genomic alterations in select subgroups of PDAC, yet the clinical impact of targeted therapies remains modest. This review aims to provide a clinically oriented synthesis of emerging molecular targets in PDAC, their therapeutic relevance, and practical considerations for biomarker testing, including current FDA and EMA indications. Methods: A narrative review was conducted using data from PubMed, Embase, Scopus, and international guidelines (NCCN, ESMO, ASCO). The selection focused on evidence published between 2020 and 2025, highlighting molecularly defined PDAC subsets and the current status of targeted therapies. Results: Actionable genomic alterations in PDAC include KRAS G12C mutations, BRCA1/2 and PALB2-associated homologous recombination deficiency, MSI-H/dMMR status, and rare gene fusions involving NTRK, RET, and NRG1. While only a minority of patients are eligible for targeted treatments, early-phase trials and real-world data have shown promising results in these subgroups. Testing molecular profiling is increasingly standard in advanced PDAC. Conclusions: Despite the rarity of targetable mutations, systematic molecular profiling is critical in advanced PDAC to guide off-label therapy or clinical trial enrollment. A practical framework for identifying and acting on molecular targets is essential to bridge the gap between precision oncology and clinical management. Full article

Drug repurposing or drug repositioning is the process of identifying new therapeutic uses for approved or investigational drugs beyond the original treatment indication. The discovery of new drugs for cancer therapy needs this cost-effective and time-saving alternative strategy to traditional drug development for a rapid clinical translation in Phase II/III studies, especially for unmet medical needs and rare diseases. Neuroendocrine tumors (NETs) are a heterogeneous group of rare neoplasms arising from cells of the neuroendocrine system that, though often indolent, can be aggressive and metastatic. In this context, drug repurposing has emerged as a promising strategy to improve treatment options due to the limited number of effective treatments and the heterogeneity of the disease. Indeed, a large number of non-oncology drugs have the potential to address more than one target that could be therapeutic for cancer patients. Although many repurposed drugs are used off-label, efficacy for the new use must be demonstrated in clinical trials. Within regulatory frameworks, both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have procedures to reduce the need for extensive new studies and to expedite the review of drugs for serious conditions when preliminary evidence indicates substantial clinical improvement over available therapy. In spite of several advantages, including reduced development time, lower costs, known safety profiles, and faster regulatory approval, difficulty in obtaining new patents for old drugs with limited protection for intellectual property may reduce commercial returns and disincentivize investments. This review aims to provide comprehensive information on some marketed drugs currently under investigation to be repurposed or used in clinical practice for NETs and to discuss the major clinical challenges. Although drug repurposing is a useful strategy for early access to medicines, the monitoring of the clinical benefit of oncologic drugs during the post-marketing authorization is crucial to support the safety and effectiveness of treatments. Full article

Background: Off-label nebulization of tranexamic acid (TXA) solution is common practice for the treatment of hemoptysis. However, data regarding nebulization protocols, resulting aerodynamic parameters of the generated aerosol, and corresponding biopharmaceutical parameters are missing. The aim of this in vitro study was to investigate the aerosol characteristics of nebulized sterile, aqueous TXA solution. Methods: TXA solution 100 mg/mL was nebulized for 2 min by a multi-dose vibrating mesh nebulizer using 15 L/min and 30 L/min air flow rates. The generated aerosol was analyzed by a Next Generation Cascade Impactor. For each air flow rate, the mean Fine Particle Dose (FPD), Fine Particle Fraction (FPF), the Mass Median Aerodynamic Diameter (MMAD), and Geometric Standard Deviation (GSD) were quantified. Results: Nebulization at 15 L/min air flow rate resulted in a MMAD of 6.68 ± 0.23 µm and GSD of 2.02 ± 0.16. The FPD < 5 µm was 16.56 ± 0.45 mg, the FPF < 5 µm 28.91 ± 3.40%. Nebulization at 30 L/min air flow rate revealed a MMAD of 5.18 ± 0.12 µm and GSD of 2.14 ± 0.10. The FPD < 5 µm was 16.30 ± 1.38 mg, the FPF < 5 µm 35.43 ± 0.59%. Conclusions: Nebulization of TXA 100 mg/mL solution by a specified vibrating mesh nebulizer generated an aerosol particle distribution and deposition pattern suitable for the treatment of hemoptysis with bronchial origin. Full article

Background: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

This review explores the potential of magistral formulas (MFs) as a viable option to meet the needs of neonates, given the lack of adequate therapies for this vulnerable group. The scientific literature on medicines available for neonates is limited. The physiological differences between neonates and adults make it difficult to formulate these medicines. In addition, there are a variety of difficulties in conducting research on neonates: few clinical trials are performed, and there is frequent use of unauthorized medicines. Pharmacokinetics in neonates was investigated in comparison to adults, and different aspects of the absorption, distribution, metabolism, and excretion were observed. One of the main problems is the different pharmacokinetics between the two populations. It is necessary to promote and allow research related to pediatric drug design, approve a specific authorization for use in age-appropriate dosage forms, and improve the quality and availability of information on drugs. This study focused on the MFs typically used for pediatrics, specifically for neonates, analyzing the pharmaceutical forms currently available and the presence of indications and dosage recommendations of the European Medicines Agency. Medications were classified according to therapeutic group, as antihypertensives, corticosteroids, and antiepileptics. The use of off-label medicines remains high in neonatal intensive care units and in primary healthcare, besides in the preparation of MFs by pharmacists. The shortage of medicines specifically designed and approved for neonates is a serious problem for society. Neonates continue to be treated, on numerous occasions, with off-label medicines. Studies and research should be expanded in this vulnerable population group. Full article

Background: Female Sexual Dysfunction (FSD) encompasses a range of conditions that can profoundly impact quality of life and intimate relationships. The primary classifications of FSD include female sexual interest and arousal disorder (FSIAD), genitopelvic pain and penetration disorder (GPPPD), female orgasmic disorder (FOD), and substance or medication-induced sexual dysfunction (SM-ISD). Despite its prevalence, FSD is often underdiagnosed and undertreated. Objectives: This scoping review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the existing literature on both U.S. Food and Drug Administration (FDA)-approved and off-label pharmacotherapies for FSD by study type, outcomes, and limitations. Eligibility Criteria: Eligible studies comprised randomized controlled trials (RCTs), systematic reviews, and cohort studies involving adult women (≥18 years) with any subtype of FSD. These studies assessed pharmacologic interventions against a comparator and reported at least one treatment efficacy outcome. Studies outside this scope were excluded. Sources of Evidence: A 25-year literature search was conducted using PubMed/MEDLINE, the Cochrane Library, reference lists of relevant articles, academic handbooks, and targeted journals. Charting Methods: Three independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Findings were organized into summary tables and categorized by pharmaceutical agent, pertinent study information, outcomes, and limitations. Results: A total of 44 human-based pharmacologic studies met inclusion criteria. FDA-approved agents were the most thoroughly studied pharmacotherapies. Hormonal, topical, and adjunctive agents demonstrated less robust evidence. Heterogeneity in outcome measures and inadequate long-term data were common limitations. Conclusions: Pharmacologic treatment for FSD shows promise but requires further research. Individualized, multifaceted care is essential for optimizing FSD outcomes. Full article

Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age, often requiring complex pharmacological management. The heterogeneity of the syndrome and the use of on- and off-label therapeutic agents—ranging from insulin sensitizers and ovulation inducers to oral contraceptives and herbal supplements—pose significant challenges, including adverse effects, drug interactions, and poor adherence. This narrative review explores the role of pharmacists in identifying and mitigating drug-related problems (DRPs) associated with PCOS therapy. Through thematic synthesis of the current literature, the study highlights common DRPs such as suboptimal drug selection, inappropriate dosing, prolonged therapy duration, and treatment-related safety concerns. It underscores the value of pharmacists’ interventions in enhancing medication adherence, optimizing therapeutic regimens, providing patient education, and monitoring adverse events. A structured, patient-level pharmaceutical care model is proposed, emphasizing personalized assessment, interdisciplinary collaboration, and continuous follow-up. The integration of clinical pharmacists into PCOS care teams has the potential to improve treatment effectiveness, patient satisfaction, and long-term health outcomes. Pharmacists’ contributions are especially critical given the widespread use of off-label therapies and supplements with variable evidence of benefit. Tailored pharmaceutical care can thus bridge the existing gaps in PCOS management and enhance the quality of life for the affected individuals. Full article

Alcohol is a prevalent psychoactive substance and a risk factor for developing injuries and non-communicable diseases, representing a significant health and economic burden. Alcohol involves numerous molecular pathways. Its metabolism is regulated by alcohol dehydrogenases and aldehyde dehydrogenases; it also stimulates cholinergic interneurons, increasing the sensitivity of 5-HT3 receptors, while chronic alcohol consumption alters the mesolimbic dopaminergic system involved in reward processing. The treatment of alcohol use disorder (AUD) is essential to manage complex patients, following an evidence-based approach. The aim of this narrative review is to provide a clear and practical summary to support and assist healthcare professionals in the Italian context. Approved pharmacological treatments for AUD include oral naltrexone and acamprosate, sodium oxybate, disulfiram, and nalmefene. Off-label therapies include baclofen, topiramate, gabapentin, pregabalin, ondansetron, and cytisine. A more informed clinical and practical approach that understands the altered neuronal signaling pathways is essential for offering effective, efficient, appropriate, and safe therapeutic algorithms for complex patients with alcohol use disorder. A comprehensive framework should include integrated treatments with a personalized approach. Full article

Antimicrobial resistance (AMR) is a growing global concern, influenced by antibiotic use in both human and veterinary medicine, especially in companion animals. In low- and middle-income countries, regulatory oversight on veterinary prescriptions is often limited, creating gaps that can accelerate AMR. This study aimed to characterize the use of antibiotics approved for human use that are prescribed by veterinarians for companion animals in Brazil, a country representative of broader regulatory challenges. We conducted a retrospective analysis of five years (2017–2021) of national sales data recorded by the National System for the Management of Controlled Products (SNGPC), maintained by the Brazilian Health Regulatory Agency (ANVISA). A total of 789,893 veterinary antibiotic prescriptions were analyzed over the five-year period, providing a comprehensive overview of prescribing patterns. The dataset included all oral and injectable antibiotics purchased in human pharmacies with veterinary prescriptions. Data wrangling and cleaning procedures were applied to extract information on volume, antibiotic classes, seasonal variation, and regional distribution. The results revealed a predominance of penicillins, first- and second-generation cephalosporins, and a marked increase in macrolide use, especially azithromycin. Notable regional disparities were observed, with the southeastern region leading in prescription volume. The findings, particularly the disproportionate use of azithromycin and the marked regional disparities, highlight the need for targeted monitoring policies and a stricter regulation of off-label antibiotic use in veterinary medicine. They also offer insights applicable to other countries facing similar AMR threats due to limited surveillance and regulatory frameworks. Full article

Vitiligo, an autoimmune disorder causing depigmented skin patches, includes two types, segmental (SV) and non-segmental (NSV). Previously, NSV was off-label treated using Calcineurine inhibitors (Tacrolimus and Pimecrolimus). In 2022, the FDA approved Ruxolitinib cream, targeting the JAK/STAT pathway for NSV treatment based on promising results. This research conducts a retrospective descriptive safety assessment of Tacrolimus, Pimecrolimus, and Ruxolitinib safety in vitiligo treatment, utilizing the FDA Adverse Event Reporting System (FAERS) database spanning the period from 2013 to 2023 and including patients aged 2 years and above, encompassing both brand and generic names. A total of 844 adverse event reports involving 388 patients were extracted and categorized into dermatological and systemic groups for analysis. Tacrolimus resulted in 12 hospitalizations, two life-threatening events, and four disabilities. Pimecrolimus exhibited urticaria and pigmentation disorders, with tooth fracture as the primary systemic event. Pericarditis was the predominant systemic side effect of Ruxolitinib, followed by anemia, headache, and urosepsis. Local dermatological side effects reported were generally mild, not warranting treatment cessation. In conclusion, vitiligo significantly impacts patients’ psychological well-being, necessitating continuous post-marketing safety monitoring for topical medications. Full article

The area postrema (AP) is a circumventricular organ (CVO) at the base of the fourth ventricle. It has a crucial role in regulating nausea and vomiting due to its unique blood–brain barrier (BBB)-permeability and extensive neural connectivity. Here, we present two cases of area postrema syndrome (APS), a rare condition of intractable nausea and vomiting resulting from direct AP injury. Our cases each occurred in the context of infratentorial neoplasms or their treatment. Using these cases as a framework, we review the literature on central emetic pathways and propose a treatment algorithm for managing refractory nausea and vomiting of central origin. We also highlight other targets beyond conventional serotonergic, dopaminergic, or histaminergic blockade and their roles in central hyperemesis. Our literature review suggests that APS is due to the disruption of the baseline inhibitory tone of outgoing AP signals. When other options fail, our algorithm culminates in the off-label use of combined serotonergic and neurokinin-1 blockade, which is otherwise used to manage chemotherapy-induced nausea and vomiting (CINV). We believe multimodal CNS receptor blockade is efficacious in APS because it addresses the underlying central neural dysregulation, rather than solely targeting peripheral emetic triggers. Full article

Background: Lateral lumbar or thoracic interbody fusion (LLIF) is increasingly considered for anterior column reconstruction and restoring segmental lordosis in degenerative, infectious, or deformity conditions. Reports about using LLIF with expandable interbody spacers for spine trauma are scarce. Methods: In this retrospective, single-center observational cohort study, we reviewed all patients treated by an expandable LLIF interbody spacer (ELSA^® Expandable Integrated LLIF Spacer, Globus Medical Inc) for trauma indication at our spine center between September 2018 and January 2024. The primary outcome measures were fusion rate at 12 months, change in segmental sagittal Cobb angle, and clinical outcome according to the MacNab criteria. Secondary outcomes included adverse events and complications. Results: We identified n = 21 patients with a mean age of 48.3 (standard deviation (SD) 15.7), 47.6% were female. LLIF was mostly performed at T11/12 (n = 4; 19.1%) and T12/L1 (n = 10; 47.5%). Indications were AO Spine type A2 (n = 4, 19.1%), A3 (n = 14; 66.7%) or A4 fractures (n = 3; 14.3%) with ligamentous (B2-type) in eight (38.1%) and hyperextension (B3-type) injury in one patient (4.8%). Surgery included the release of the anterior longitudinal ligament in four cases (19.1%). Intraoperative AEs were noted in n = 1 (4.8%), postoperative AEs in n = 3 (14.3%) at discharge, n = 4 (19.1%) at three, and n = 2 (9.5%) at twelve months. Segmental sagittal Cobb angle changed from 1.3° (preoperative) to 13.3° at twelve months (p < 0.001). Functional outcome was excellent/good in n = 15 (71.4%; four missing) at 12 months. The fusion rate at the LLIF level was 100% at the 12-month follow-up. Conclusions: LLIF with expandable interbody spacers for spine trauma (off-label use) is safe, promotes solid fusion (100% fusion rate at 12 months), and enables correction of sagittal segmental Cobb angle (mean improvement of 12°), with good or excellent clinical outcomes in most patients (71.4%). Full article

A 10-year-old male neutered British Shorthair cat with diabetes mellitus presented with an acute onset of unilateral swelling, erythema, alopecia and coalescing ulcerations of the face and periocular skin. Initial clinical differential diagnoses were trauma, infections (including feline respiratory viruses), arthropod bites, and eosinophilic dermatoses such as eosinophilic granuloma complex, mosquito-bite hypersensitivity and cutaneous adverse drug reaction. Histopathology revealed fulminant furunculosis with abundant eosinophils and vasculitis. Initial topical glucocorticoid treatment partially improved the clinical signs but severely raised serum glucose levels. As a result, systemic glucocorticoids and ciclosporin were not considered optimal treatments, and the off-label and short-term use of oclacitinib was chosen with the owner’s informed consent. This treatment induced fast remission of clinical signs with no recurrence for 17 months. Secondary fusion of the eyelids caused by cicatrization was surgically reconstructed to restore full function. Full article

Lichen planus (LP) is a chronic inflammatory disorder affecting approximately 1% of the population. It presents with a wide range of clinical manifestations, mainly involving the skin, mucosal surfaces, and skin appendages, and is often characterized by a relapsing course and variable response to treatment. Although several therapeutic strategies are available, many are off-label and show limited efficacy in resistant forms. Increasing evidence points to the central role of the JAK/STAT signaling pathway in the immunopathogenesis of LP, with cytokines such as interferon-gamma and interleukin-21 playing key roles in sustaining chronic inflammation. Based on this rationale, Janus kinase (JAK) inhibitors have recently been proposed as potential therapeutic agents in LP. This review explores the biological basis for their use and systematically summarizes the existing clinical evidence on the use of JAK inhibitors in cutaneous, mucosal, appendageal, and nail variants of LP. The preliminary data suggests favorable outcomes in many patients with difficult-to-treat disease, with an acceptable safety profile. Further prospective trials are needed to establish their definitive role in the management of LP. Full article