Ivermectin, a broad-spectrum anti-parasitic agent, demonstrates potential therapeutic benefits in treating non-parasitic ailments, particularly in neurological, respiratory, inflammatory, dermal, cardiovascular, and neoplastic disorders. For instance, ivermectin targets both DNA and RNA viruses, inhibits angiogenesis, and has anti-cancer properties, which result from inhibiting RNA helicase, inducing mitochondrial dysfunction, apoptosis, necrosis, and autophagy, as well as promoting oxidative stress. While the precise neurological impacts of ivermectin are not fully understood, it also has anticonvulsant properties in rats. Recent discoveries have revealed the neuroprotective effects of ivermectin in cerebral ischemia/reperfusion and Alzheimer's disease. Although there is limited research on the influence of ivermectin on the cardiovascular system, some studies have reported cardioprotective effects of ivermectin. However, a recent study suggested that ivermectin pre-treatment may have detrimental effects on myocardial ischemia. Consequently, numerous questions regarding the therapeutic/adverse effects of ivermectin remain unanswered and necessitate further investigation. We review the effects of ivermectin in non-parasitic diseases with an emphasis on current research in this field.

Intestinal ultrasound (IUS) is an increasingly utilized, non-invasive imaging modality in the management of inflammatory bowel disease (IBD). While its application in monitoring medical therapy is well recognized, its potential to support surgical decision-making remains underappreciated. This narrative review examines the role of IUS across the perioperative continuum in Crohn's disease (CD) and ulcerative colitis (UC), with a focus on practical surgical relevance. In CD, IUS might contribute to the differentiation between inflammatory and fibrotic strictures, assessment of penetrating disease, and identification of real-time functional signs such as prestenotic dilation and swirling luminal contents. These findings guide early surgical referral and avoid unnecessary delays. Postoperatively, IUS allows for dynamic surveillance, with bowel wall thickness and Doppler flow serving as early markers of recurrence in CD. Assessments at 3, 6, and 12 months can guide therapeutic escalation or confirm remission without requiring invasive endoscopy. In acute severe UC, IUS can predict steroid non-response within 48 h and help define disease extent which might directly influences surgical strategy. Adjunct techniques such as contrast-enhanced ultrasound (CEUS), small intestinal contrast ultrasound (SICUS), and shear wave elastography (SWE) enhance diagnostic accuracy in specific settings. Moreover, muscle ultrasound provides a practical bedside tool to evaluate nutritional status and support preoperative risk stratification. IUS offers surgeons a repeatable, accessible, and real-time diagnostic approach that bridges medical and surgical care. As evidence grows and standardization improves, IUS is poised to become a cornerstone in multidisciplinary IBD surgery, supporting precision, shared decision-making, and better outcomes.

Despite progress with biologics and small molecules, a substantial proportion of patients with inflammatory bowel disease (IBD) continue to face unmet needs, including non-response, disease recurrence, and impaired quality of life. These limitations highlight the need for novel therapeutic strategies that go beyond current pharmacological approaches, including biologics and small molecules. This review explores emerging therapies aimed at restoring immune balance, repairing intestinal function and improving long-term outcomes in IBD. Cellular and genetic therapies offer promising avenues to restore immune tolerance and promote mucosal healing in IBD. Likewise, microbiome-based interventions aim to rebalance gut inflammation and host-microbe interactions. Additional strategies focus on targeted immunomodulation through therapeutic peptides, RNA-based agents, and vaccines directed against intestinal antigens. Complementary and alternative medicine, including dietary approaches, nutraceuticals and psychological therapies is also gaining attention within integrative care models. While these approaches are conceptually compelling, most remain in the early stages of clinical or preclinical development. Their therapeutic potential has yet to be fully validated and further research is essential to establish their efficacy, safety, and long-term impact. Taken together, these emerging strategies represent a shift beyond conventional therapies, moving toward modifying disease trajectory and improving patient-centered outcomes. However, their successful integration into IBD clinical practice will require robust evidence, standardized protocols, and a multidisciplinary framework grounded in real-world applicability.

The efficacy of acupuncture as a nonpharmacological therapy for autism spectrum disorder (ASD) has been increasingly studied. To evaluate the current research methodologies and outcome measures in randomised controlled trials (RCTs) of acupuncture for ASD, we systematically searched eight major databases for relevant Chinese and English language literature published between 1 January 2015 and 31 December 2024. A total of 31 relevant studies were included in the literature review. Studies on acupuncture interventions for ASD were categorised into two- or three-arm designs, primarily employing indirect controls. Interventions predominantly utilised head acupoints for 12 weeks, and the acupuncture techniques were mainly tonifying and reducing techniques with moderate stimulation. Outcome indicators (n = 37) were categorised into six domains, selected a total of 111 times: symptoms and signs (59.46 %), physical and chemical test indicators (20.72 %), quality of life (8.11 %), safety events (7.21 %), functional status (2.70 %), and Chinese medical symptoms/syndrome (2.70 %). The Childhood Autism Rating Scale had the highest reporting rate among the indicators (23.24 %). Measurements were predominantly performed before treatment, post-treatment, and at the 12-week follow-up visit. Current evidence from RCTs on acupuncture for ASD is limited, restricting the clinical implementation of acupuncture protocols. Future high-quality studies should focus on standardising clinical trial designs, minimising bias, establishing consensus-driven outcome measurement selection, and developing a core outcome set for acupuncture in patients with ASD. These steps are essential for enhancing the methodological rigor and clinical relevance of acupuncture research in ASD.

Doxorubicin (DOX) remains a cornerstone in the treatment of various malignancies, but its clinical use is limited by cardiotoxicity, a leading cause of heart failure in cancer survivors. While oxidative stress and direct myocardial injury have long been implicated in DOX-induced cardiotoxicity (DIC), emerging evidence highlights the central role of immune dysregulation in disease progression. In particular, neutrophils, macrophages, and T cells orchestrate inflammatory responses that contribute to cardiomyocyte injury, adverse remodeling, and fibrosis. Recent findings also point to novel mediators that may serve as biomarkers or therapeutic targets. This review synthesizes current evidence on immune mechanisms underlying DIC and discusses how improved understanding of these pathways may inform immunomodulatory strategies to reduce cardiac injury without compromising anticancer efficacy.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by alternating periods of disease flare and remission, necessitating precise monitoring to guide therapeutic decisions. Traditionally, endoscopy has served as the cornerstone of disease assessment. However, its invasiveness, cost and limited accessibility have underscored the need for alternative approaches. Intestinal ultrasound (IUS) has emerged as a valuable, non-invasive tool capable of providing real-time information about intestinal inflammation at the bedside. This review explores the evolving role of IUS in UC monitoring and management, highlighting its utility in diagnosing disease activity, guiding therapeutic decisions, and supporting treat-to-target strategies. Despite current challenges such as operator dependency and variability in technique, growing evidence supports the incorporation of IUS into routine clinical practice, with ultrasound parameters being integrated into validated and predictive scoring systems to enhance disease monitoring and guide treatment decisions. By offering a safe, reproducible, and patient-friendly modality, IUS represents a significant advancement in the proactive management of UC, promising improved outcomes and greater quality of care.

Intestinal ultrasound (IUS) is increasingly recognized as a valuable tool in the monitoring of Crohn's disease (CD), offering a non-invasive, real-time assessment of transmural inflammation. Unlike conventional endpoints based on clinical scores, biomarkers, or mucosal evaluation, IUS allows direct visualization of bowel wall changes, enabling earlier detection of treatment response and more accurate prognostic assessment. IUS has demonstrated good diagnostic performance for the detection of strictures, penetrating complications, and postoperative recurrence. The development of advanced modalities such as contrast-enhanced ultrasound (CEUS) and elastography has further expanded its potential, particularly in differentiating inflammatory from fibrotic lesions-an emerging clinical need in the context of anti-fibrotic therapies. Evidence suggests that IUS findings can influence therapeutic decisions in routine practice, supporting treatment escalation, de-escalation, or switching in a timely and objective manner. Special applications, including transperineal ultrasound and use during pregnancy, reinforce the versatility and safety of IUS in challenging clinical scenarios. While technical limitations persist in certain patient subgroups, IUS remains a repeatable, accessible, and well-tolerated imaging modality that complements other diagnostic tools. As artificial intelligence enhances image interpretation and quantitative analysis, IUS is poised to become a cornerstone of precision medicine in CD. Its capacity to guide timely, individualized decisions makes it an essential component of modern disease monitoring and treatment optimization strategies.

CRISPR-Cas9 gene editing technology has gained attention as a new, reliable and manageable tool for the treatment of previously incurable monogenic diseases. Besides exciting results in this setting, ethical, safety and crucial technical issues have not been fully clarified. More importantly, the role of this potent editing tool in the context of a genetically complex and heterogeneous hematologic malignancy such as acute myeloid leukemia (AML) has not yet been defined to date. In this review we aim to summarize and exploring the ultimate CRISPR-cas9 based strategies for diagnosis, risk stratification and treatment in the context of AML.

Neuroinflammation plays a central role in the pathogenesis of numerous neurological and neurodegenerative diseases, driven by complex interactions among glial activation, cytokine release, blood-brain barrier (BBB) dysfunction, and autonomic dysregulation. While pharmacological therapies targeting inflammatory mediators show promise, their efficacy is often limited by poor BBB permeability and systemic side effects. Electroacupuncture (EA), a neuromodulatory technique that combines acupuncture with electrical stimulation, has emerged as a promising adjunctive intervention for modulating neuroimmune dynamics. EA activates defined somatosensory afferents and transmits signals to key autonomic and limbic nuclei, including the brainstem and hypothalamus, which regulate immune responses. At the molecular level, EA suppresses pro-inflammatory pathways such as TLR4/NF- κB and NLRP3 inflammasome activation while promoting anti-inflammatory signaling via the JAK2/STAT3 and PI3K/Akt pathways. It also influences microglial polarization toward the reparative M2 phenotype and modulates BBB permeability and gut-brain axis interactions. Notably, EA has demonstrated synergistic potential when combined with pharmacologic agents such as l-DOPA, selegiline, donepezil, and minocycline, enhancing neuroprotective efficacy and reducing inflammatory and oxidative burdens. This highlights EA's potential integration into clinical strategies for treating neurodegenerative disorders. Understanding the neural circuits and immunological cascades engaged by EA may inform its future integration with pharmacotherapy in personalized neuroimmune interventions.

Depression, a leading global health burden, involves neuroimmune dysregulation and neuroinflammation. As a promising non-pharmacological approach, acupuncture has been supported by numerous studies as an effective intervention for alleviating depression. The antidepressant mechanisms of acupuncture involve a multitarget modulation of neuroimmune crosstalk, such as restoring hypothalamic-pituitary-adrenal (HPA) axis homeostasis, inhibiting microglial and astrocytic activation, regulating autophagy, inhibiting key inflammatory signaling pathways, activating anti-inflammatory pathways via the vagus nerve, and rebalancing gut-brain axis communication by modifying microbiota. Integrating acupuncture with advanced neuromodulation techniques may enhance its effectiveness in treating depression. It needs further study to validate acupuncture as an effective therapeutic strategy in the field of neuroimmunology for depression. This review summarizes evidence elucidating how acupuncture regulates neuroimmune crosstalk in depression. It not only provides a scientific basis for its application but also advances the understanding of the pathophysiology of depression by highlighting the interplay between neuroimmune interaction and inflammatory pathways.

Mucosal healing has long been the primary therapeutic goal in inflammatory bowel disease (IBD). Although ileocolonoscopy remains the reference standard to explore this target, the invasiveness and limited acceptability of endoscopic procedures have accelerated a move toward noninvasive, cross-sectional assessments that capture transmural disease. In this context, transmural healing has been proposed as an ambitious target that can be evaluated with several tools, including intestinal ultrasound (IUS). IUS has emerged as a radiation-free, bedside tool that enables real-time monitoring of transmural inflammation in both Crohn's disease) and ulcerative colitis (UC). However, achieving full transmural healing is uncommon with available therapies and currently carries modest prognostic value in UC. To improve clinical decision-making, several standardized IUS activity indices have been developed to provide a more nuanced readout of disease activity and therapeutic response. In this review, we summarize the current evidence on transmural inflammation in IBD and propose to differentiate 'ultrasound remission,' as defined by composite IUS scores, from the traditional definition of complete transmural healing.

Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Assessment Reports and FDA review packages for ODs targeting neuromuscular indications. Each document was screened for mention of RWD sources and by the regulatory weight assigned to the resulting RWE. We identified 14 OD approvals by the EMA and 13 by the FDA, with greater use of RWE by the FDA. Indications comprised spinal muscular atrophy (3/3 EMA/FDA), amyotrophic lateral sclerosis (1/3), amyloid neuropathies (2/2), Friedreich ataxia (1/1), Lambert-Eaton syndrome (1/1), myasthenia gravis (2/2), myotonic disorders (1/0), and Duchenne muscular dystrophy (2/1). Among 18 evaluable dossiers, clinical outcome assessments (COA) were reported as follows: patient-reported outcomes - 39.1%, clinician-reported outcomes - 34.7%, observer-reported outcomes - 13.1 %, and performance outcomes - 13.1%. Only tofersen incorporated all COA types. The use of RWE for the evaluation of ODs is increasing for both the FDA and the EMA, more so for the former than for the latter. Harmonized methodological standards and transparent reporting frameworks are urgently needed to generate quality evidence that benefits stakeholders.

Nanotechnology-enhanced transdermal drug delivery systems (NETS) show great potential in treating infectious diseases by improving drug penetration, stability, and bioavailability. Unlike traditional methods, NETS overcome skin barrier limitations through the use of lipid-based, polymeric nanoparticles, and dendrimers, enabling efficient drug transport and controlled release. This results in enhanced therapeutic efficacy and reduced systemic side effects for bacterial, viral, and fungal infections. However, challenges related to toxicity, stability, and regulatory hurdles remain. This paper examines the mechanisms, advantages, and limitations of NETS, while highlighting promising future research opportunities and clinical applications in combating infectious diseases.

Ionic liquids have emerged as promising vehicles for drug delivery, with choline and geranic acid (CAGE) demonstrating exceptional potential in topical formulation for skin tissue regeneration and antimicrobial properties. CAGE exhibits unique physicochemical properties such as viscosity, high ionic conductivity, and enhanced solubility that contribute to efficacy in enhanced drug permeation with controlled drug release. CAGE possesses the inherent antimicrobial properties, making it an ideal candidate for the management of dermal complications. The review discusses the recent advancements in CAGE-oriented formulations, emphasizing their role in wound healing, followed by formulation strategies and key process parameters.

Clinical trial design in inflammatory bowel disease (IBD) is evolving to address challenges in drug development and approvals. For clinical development, notable innovations include Bayesian designs, adaptive designs, integrated-phase trials and master protocols (such as umbrella, basket, and platform trials). The inclusion of biomarker-driven strategies and precision medicine (PM) trials bring aim to enable patient stratification based on prognostic or predictive markers, leveraging molecular signatures to customize therapy. However, recent studies highlight both the promise and complexity of this approach. Patient-reported outcomes (PROs) have gained prominence as key endpoints, aligning trials with patient-centric measures and regulatory guidance that emphasize symptoms and quality-of-life metrics. Digital health tools and artificial intelligence (AI) are being integrated to streamline trial conduct, from remote monitoring and telemedicine visits to AI-assisted recruitment and data analysis. Pragmatic trials and the integration of real-world evidence (RWE) aim to complement traditional efficacy trials by evaluating treatments in routine care settings. Together, these innovations mark a new era in IBD clinical trial design, aiming to expedite therapeutic development and enhance the relevance of trials to patient care.

The number of diagnoses and drug prescriptions for dementia patients is poorly available. Delay in the diagnosis of Alzheimer's disease (AD), for which missed diagnoses amount to over half cases, and undertreatment of chronic and neuropathic pain mirroring excessive use of harmful antipsychotics and antidepressants is reported. Our study aimed at diagnosing AD through the most advanced artificial intelligence (AI) methodologies even in patients who escaped clinical observation. To this end, pharmacoepidemiology data collected as part of the first retrospective community study in a wide sample of 298,000 individuals, 84,235 aged over 60 years, were used to set up an AI algorithm for the rescue of missed diagnoses of AD. The core of the algorithm consisted in the management of time series represented by pharmacological therapies through a distance matrix and in the use of autoencoders. Patients without a diagnosis of AD based on pharmacotherapy were 114.920, while diagnosed patients were 1.150, mainly aged between 75 and 84 years, pointing at late start of treatment. Increased use of antidepressants, neuroleptics, and mood stabilizers is found in patients treated with acetylcholinesterase inhibitors (AChEIs) and memantine, while nonsteroidal anti-inflammatory drugs, paracetamol-codeine and opioids are mostly prescribed to patients not receiving AChEIs and memantine. The classification model demonstrated good global accuracy at the end of training, equal to 79.12%. Further studies and longitudinal monitoring of patients are needed to improve disease detection and management. The deep learning-based pharmacoutilization algorithm generated in the present study will aid the diagnosis of AD and the understanding of neuropsychiatric symptoms treatment.