Search Results (84)

Cancer remains a highly complex and heterogeneous disease, causing major morbidity and mortality worldwide despite advances in diagnosis and treatment. The hallmarks of cancer enlighten the biological mechanisms supporting tumourigenesis and malignant evolution, while helping to identify potential therapeutic targets. Medical cannabis has mostly been used in oncology for supportive care, but increasing preclinical evidence suggests interference with cancer-related signalling pathways. This narrative review summarizes the current evidence on cannabinoids, in particular the phytocannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), framing their prospective anticancer effects in the hallmarks of cancer. Preclinical studies imply that CBD exerts antiproliferative effects by modulating oncogenic signalling pathways, including EGFR, PI3K/AKT, RAS/RAF/ERK, mTOR and Wnt/β-catenin, while also influencing tumour suppressor pathways involving p53, p21 and p27, causing cell cycle arrest. CBD has additionally been shown to promote programmed cell death via mitochondrial dysfunction and autophagy, altering cancer metabolism as well. Furthermore, CBD has shown anti-invasive and antiangiogenic properties and also appears to modulate immune responses and interactions with the tumour microenvironment, including emerging links with the microbiome. Overall, cannabinoids exhibit biologically plausible antitumour activity across multiple cancer hallmarks and may present promising candidates for combination therapeutic strategies. Nonetheless, the current evidence remains predominantly preclinical, and robust translational studies and clinical trials are needed to clarify their pharmacokinetic and pharmacodynamic profiles, determine their clinical efficacy and safety while assessing their potential integration into multimodal cancer treatment. Full article

Scoliosis is a complex three-dimensional spinal deformity that requires early detection, accurate radiological assessment, individualized treatment planning, and long-term monitoring. In recent years, artificial intelligence (AI) has emerged as a promising tool across multiple stages of scoliosis management, including screening, automated imaging analysis, deformity classification, prediction of progression, surgical planning, postoperative outcome assessment, and patient education. This narrative review summarizes current and emerging applications of AI in scoliosis, with particular emphasis on studies published after 2023. Deep learning algorithms, including convolutional neural networks, U-Net-based architectures, transformer models, and generative approaches, have demonstrated high accuracy in automated Cobb angle measurement, vertebral segmentation, coronal and sagittal parameter assessment, and radiation-free screening using surface topography or smartphone-based photographs. Machine learning models have also shown potential in predicting curve progression, treatment response, risk of postoperative complications, and patient-reported outcomes by integrating radiological, clinical, biomechanical, and, increasingly, multimodal data. In parallel, large language models and generative AI tools are being investigated for patient education, communication support, readability improvement, and research hypothesis generation. Despite these advances, important limitations remain, including limited external validation, dataset heterogeneity, potential algorithmic bias, insufficient interpretability, and incomplete integration into clinical workflows. Moreover, while AI systems show strong performance in automated measurement and screening tasks, their role in complex therapeutic decision-making, such as Lenke classification, fusion-level selection, and autonomous surgical planning, remains experimental. Overall, AI has the potential to improve the precision, efficiency, and personalization of scoliosis care; however, prospective multicentre studies, transparent reporting, explainable model design, and regulatory validation are essential before widespread clinical implementation. Full article

Hematologic malignancies, including acute myeloid leukemia, myelodysplastic syndromes, lymphoma, and multiple myeloma, are characterized by profound biological heterogeneity and highly dynamic treatment trajectories that conventional, static prognostic systems incompletely capture. Cellular therapies, such as chimeric antigen receptor T-cell therapy and hematopoietic stem cell transplantation, offer potentially curative options for relapsed or refractory disease, yet outcomes remain highly variable, and management decisions regarding conditioning intensity, lymphodepletion, immunosuppression, and toxicity surveillance continue to be largely protocol-driven rather than individually adapted. Artificial intelligence (AI) and machine learning (ML) have demonstrated substantial promise in diagnostic support, prognostic stratification, and multimodal data integration across hematologic malignancies, but existing models remain predominantly static and related to pre-treatment in orientation, limiting their utility for real-time clinical guidance. This review summarizes current AI applications in hematologic oncology; critically compares the strengths, limitations, and clinical applicability of major AI model classes, including traditional machine learning, deep learning, multimodal integrative frameworks, reinforcement learning, digital twins, and emerging foundation models and large language models; and proposes an adaptive, multimodal paradigm. We examine key enabling technologies and address the clinical, regulatory, ethical, and implementation challenges that must be resolved before these systems can be deployed at the bedside. We argue that the central challenge facing the field is no longer whether AI can predict outcomes, but whether it can actively guide real-time therapeutic decisions, and that achieving this transition will require interdisciplinary collaboration, prospective validation, and governance frameworks capable of ensuring interpretability, equity, and clinical trustworthiness. Full article

Background and Clinical Significance: Iatrogenic atrophy following intralesional corticosteroid injections represents a rare but potentially disfiguring complication, particularly when administered in the facial region for the treatment of inflammatory acne. Unlike conventional post-acne atrophic scarring, corticosteroid-induced tissue loss involves both dermal and subcutaneous compartments, resulting in a clinically distinct presentation that poses significant therapeutic challenges, with no established consensus on optimal management. Case Presentation: We report the case of a 26-year-old Caucasian female (Fitzpatrick phototype III) presenting with severe iatrogenic facial atrophy of the left cheek, resulting from multiple intralesional corticosteroid injections performed by a previous physician for papulo-pustular acne. The condition had been clinically stable for approximately two years at first evaluation. The patient underwent a stepwise multimodal protocol delivered over approximately 18 months (November 2023 to April 2025), combining non-ablative fractional laser remodelling (LightScan—Eufoton), Autologous Regenerative Therapy (ART, Seffiller technique, Seffiline srl), hyperdiluted calcium hydroxylapatite (CaHA—Radiesse, Merz Aesthetics) biostimulation, and additional non-ablative fractional photothermolysis sessions, supported by a topical cosmeceutical protocol. Documented follow-up extended to December 2024, 13 months after the initiation of treatment at our centre. Clinician-assessed severity of the post-acne atrophic scarring component improved from Goodman & Baron Grade 3 to Grade 2. Global aesthetic improvement of the treated area was rated as +2 (“much improved”) on the GAIS, with a patient satisfaction score of 5/5. No validated grading instrument was applied to the subcutaneous volume deficit itself, for which no such instrument is currently available. Conclusions: This case documents the clinical management and favourable outcome of a patient with severe iatrogenic steroid-induced facial atrophy treated with a personalised multimodal protocol. While the observed improvement is encouraging, the single-case design does not permit conclusions regarding the efficacy, reproducibility, or generalisability of this approach. Future controlled studies are needed to determine the therapeutic value of this multimodal strategy for this rare condition. Full article

Breast cancer is a highly heterogeneous disease characterized by distinct molecular subtypes, dynamic tumor–microenvironment interactions, and variable therapeutic responses. Despite the availability of multiple preclinical platforms, a major challenge remains the lack of a coherent multiscale framework capable of integrating biological complexity across experimental systems. This limitation reduces the predictive power of individual models and highlights the need for complementary strategies that reproduce disease progression across multiple biological scales. In this context, advanced imaging technologies have emerged as essential tools for linking preclinical platforms and enhancing their translational relevance. This review examines how multimodal imaging supports the integration of in vitro, ex vivo, and in vivo breast cancer models. We discuss how optical imaging, high-frequency ultrasound, magnetic resonance imaging, positron emission tomography/computed tomography, and intravital microscopy provide complementary molecular, functional, anatomical, and cellular information for the longitudinal assessment of tumor growth, metastatic dissemination, microenvironment remodeling, and therapeutic response. Particular attention is given to emerging translational workflows that combine patient-derived models with advanced imaging to investigate drug sensitivity, treatment resistance, and tumor progression within a precision oncology perspective. We also highlight the role of multimodal imaging in biomarker validation across platforms and in the development of clinically relevant preclinical pipelines. Overall, advanced imaging represents a critical translational bridge across breast cancer model systems, improving the predictive value of preclinical studies and supporting imaging-guided precision oncology from bench to bedside. Full article

Head and neck squamous cell carcinoma (HNSCC) remains a significant global health burden with limited survival improvement in locally advanced disease despite multimodal therapy. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have demonstrated substantial clinical benefit in recurrent or metastatic HNSCC, establishing PD-1 blockade as a standard of care. Similar approaches in locally advanced disease, including concurrent administration with chemoradiotherapy or use in the adjuvant setting, have not demonstrated improvement in survival outcomes across multiple randomized trials. Perioperative strategies incorporating neoadjuvant and adjuvant checkpoint inhibition have shown improved event-free and disease-free survival in resectable disease. Meta-analyses of concurrent and adjuvant approaches confirm limited benefit in unselected populations, with modest improvements restricted to biologically defined subgroups. Trial outcomes across disease settings demonstrate a consistent pattern in which therapeutic efficacy varies despite the use of similar agents. Rather than simply summarizing these clinical findings, this review integrates evidence across recurrent/metatstatic, unresected locally advanced and perioperative disease settings into a biologically focused framework to help explain the varying efficacies of immune checkpoint inhibition in HNSCC. Current evidence indicates that the effectiveness of immunotherapy in HNSCC is determined by the biologic context of treatment, including tumor antigen availability, host immune competence, and timing of immune activation. Administration of checkpoint blockade in the presence of intact tumor antigen and preserved immune function is associated with improved outcomes, whereas treatment delivered during or after cytotoxic therapy is limited by lymphopenia and reduced antigen exposure. By synthesizing randomized clinical evidence through this biologic framework, the review provides a conceptual perspective that may help explain previous trial outcomes and inform future biomarker-driven patient selection and treatment sequencing. Optimization of immunotherapy in HNSCC will depend on the integration of immune activation with disease context rather than an escalation of therapeutic intensity. Full article

Extramedullary disease (EMD)—the proliferation of clonal plasma cells in soft tissues without direct bone connection—represents one of the most challenging manifestations of multiple myeloma, associated with aggressive biology, treatment resistance, and poor outcomes. EMD is driven by distinct pathophysiologic mechanisms including downregulation of adhesion molecules, acquisition of high-risk cytogenetic abnormalities (del(17p), gain(1q)), activation of the RAS–MAPK pathway, epigenetic dysregulation such as EZH2 upregulation, and remodeling of the immune microenvironment toward an immunosuppressive, T-cell-depleted phenotype. Conventional therapies, including anti-CD38-based regimens, yield limited efficacy in EMD, with pooled overall response rates of approximately 20% in triple-class-exposed relapsed/refractory disease. T-cell-redirecting therapies have emerged as the most promising treatment strategy. Both chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies have demonstrated clinically meaningful activity in soft tissue EMD, with CAR T-cell therapy providing the deepest and most durable responses, and dual-targeting bispecific combinations showing particularly encouraging efficacy. Central nervous system (CNS) myeloma, the most devastating form of EMD, has historically carried a dismal prognosis. Emerging retrospective data suggest that both CAR T-cell therapy and bispecific antibodies can achieve meaningful CNS responses with acceptable safety profiles, as part of multimodal approaches incorporating CNS-directed therapies. Despite these advances, EMD remains associated with inferior outcomes even in the immunotherapy era, underscoring the need for strategies targeting the immunosuppressive microenvironment, novel therapeutic approaches, and prospective EMD-focused clinical trials. This review provides a comprehensive overview of the biology, classification, and evolving treatment landscape of both non-CNS and CNS EMD in the era of T-cell-redirecting immunotherapy. Full article

Background: Stroke remains a significant cause of persistent long-term disability globally. Post-stroke neuroplasticity is critical for neurological functional recovery and reducing disability. Nevertheless, the existing scoping reviews rarely systematically integrate its intrinsic mechanisms, predictive biomarkers, and actionable intervention strategies. This scoping review aims to map the current research landscape, synthesize the core research findings, and identify existing research gaps in this field. Methods: This scoping review was conducted following the PRISMA-ScR guidelines. Eligible studies published between 31 January 2021, and 31 January 2026, were retrieved from three major mainstream electronic databases: PubMed, Scopus, and Web of Science. All retrieved evidence was synthesized via narrative approach, focusing on core research findings concerning post-stroke neuroplasticity mechanisms, biomarkers, and therapeutic interventions. Results: The existing research on neuroplastic mechanisms following ischemic stroke is predominantly derived from in vitro and animal studies, which have collectively demonstrated multiple core adaptive alterations, including enhanced synaptic plasticity, dendritic and axonal structural remodeling, restored interhemispheric connectivity, endogenous neurogenesis, and functional reorganization of neural networks. In contrast, mechanistic investigations in human stroke patients primarily highlight compensatory activation within peri-infarct tissues and functionally remote brain regions. The relevant clinical biomarkers are mainly imaging and electrophysiological indicators. Research on therapeutic interventions has mainly focused on rehabilitation treatments such as non-pharmacological magnetic stimulation. Conclusions: This scoping review synthesized the current body of evidence on post-ischemic stroke neuroplasticity and identified critical research gaps, particularly regarding multimodal biomarkers and their translational relevance. The present findings confirm that neuroplastic alterations after ischemic stroke are regulated by multiple pathways, among which those involved in synaptic structure, dendrites, and neural network connections exert pivotal effects. Nevertheless, most existing investigations remain confined to in vitro experiments and animal models. The identification of neuroplasticity biomarkers has opened up new avenues for the development of targeted stroke therapies and offers promising prospects for rehabilitative treatment of stroke patients. Full article

Graphene oxide (GO), a functionalized derivative of graphene, has emerged as one of the most promising nanomaterials for biomedical applications owing to its unique physicochemical properties, including a large specific surface area, abundant oxygen-containing functional groups, excellent dispersibility, and versatile surface chemistry. This review provides a comprehensive overview of the progress made between 2005 and 2025 in the development and application of GO-based nanomaterials across diverse biomedical fields, including drug and gene delivery, cancer therapy, tissue engineering, antimicrobial treatment, bioimaging, and biosensing. Recent studies demonstrate that GO serves as an effective platform for the delivery of therapeutic agents, enabling targeted delivery, controlled release, and enhanced cellular uptake. Functionalized GO systems have also shown considerable potential in gene delivery and cancer treatment, particularly in combined therapeutic approaches involving chemotherapy and photothermal therapy. Furthermore, GO-based composites have been widely explored in tissue engineering due to their ability to support cell growth, proliferation, and tissue regeneration. In antimicrobial applications, GO exhibits promising activity against a broad range of microorganisms through multiple mechanisms, while its optical and magnetic properties have facilitated advancements in multimodal bioimaging and biosensing technologies. Despite these significant advances, challenges remain regarding the clinical translation of GO-based nanomaterials. Variations in synthesis methods, physicochemical properties, and surface modifications contribute to differences in biological responses, including biocompatibility and toxicity. The long-term safety, environmental impact, and lack of standardized evaluation protocols continue to be major concerns. Overall, graphene oxide represents a versatile and multifunctional nanomaterial with substantial potential for next-generation biomedical applications; however, further studies are required to establish standardized fabrication methods, comprehensive safety assessments, and clinically relevant performance evaluations. Full article

Bispecific antibodies (bsAbs) have emerged as a novel therapeutic class in oncogene-driven non-small-cell lung cancer (NSCLC), designed to simultaneously target multiple signaling pathways and overcome resistance mechanisms associated with tyrosine kinase inhibitors (TKIs). Unlike small-molecule TKIs, bsAbs enable dual receptor blockade and immune effector engagement, offering a mechanistically distinct advantage in the context of tumor heterogeneity and bypass signaling. This review summarizes the structural and biological principles underlying bsAb design, with a focus on clinically approved agents such as amivantamab (EGFR/MET) and zenocutuzumab (HER2/HER3) and a growing pipeline of investigational agents. We evaluate key clinical evidence from Phase I-III trials including CHRYSALIS, PAPILLON, MARIPOSA, MARIPOSA-2 and eNRGy, and compare the efficacy, toxicity, and CNS penetration profile of bsAbs relative to TKIs and antibody–drug conjugates (ADCs). While bsAbs demonstrate meaningful clinical activity, particularly in TKI-resistant disease and molecularly defined subsets such as EGFR exon 20 insertions and NRG1 fusions, their limitations, including intravenous administration, increased immune-mediated and thromboembolic toxicity, currently preclude replacement of TKIs in most settings. Collectively, available evidence supports a complementary role for bsAbs within evolving multimodal treatment paradigms, particularly in combination strategies. Future directions include biomarker-driven patient selection, improved drug engineering and integration into adaptive therapeutic sequencing frameworks. Full article

Despite advances in multimodal treatment, head and neck squamous cell carcinoma (HNSCC) remains a major clinical problem owing to its high recurrence rate and frequent development of treatment resistance. Abnormal histone modifications, particularly lysine methylation regulated by methyltransferases (KMTs) and demethylases (KDMs), have emerged as key drivers of HNSCC initiation, progression, and cellular plasticity. This review aims to comprehensively evaluate the role of selected KMTs and KDMs in HNSCC biology, with a focus on their contribution to resistance to immunotherapy, radiotherapy, and cytotoxic chemotherapy. We summarize and critically analyze preclinical and clinical studies investigating histone methylation dynamics in HNSCC, with particular emphasis on enzymes such as KMT2C/D, EZH2, NSD1/NSD2, SMYD3, G9a/EHMT2, LSD1, KDM2A/B, KDM3, KDM4, KDM5, KDM6, KDM7, and KDM8. Attention is given particularly to pharmacological approaches targeting these proteins: we discuss small-molecule inhibitors of EZH2, LSD1, KDM4/5/6, and other KMT/KDMs that are currently in preclinical development or in early clinical trials, and we highlight completed and ongoing studies testing EZH1/2 inhibitors and epigenetic combinations in patients with recurrent and metastatic HNSCC. The deregulation of specific KMTs and KDMs reshapes histone methylation at key residues, thereby controlling cell cycle progression, epithelial–mesenchymal transition (EMT), stem cell phenotypes, DNA damage responses, and multiple interactions with the immune system in HNSCC. Targeting disrupted histone methylation pathways may partially reverse the epigenetic reprogramming of HNSCC cells and represents a promising strategy to improve treatment efficacy in patients with advanced disease. We also summarize the preclinical evidence and the currently limited clinical data on targeting histone methylation dynamics in HNSCC and discuss their therapeutic implications. Full article

Background/Objectives: Glioblastoma multiforme (GBM) treatment is limited by tumor hypoxia and poor specificity of therapeutic agents. To address these challenges, we developed brain-targeted liposomes co-encapsulating 5-aminolevulinic acid (5-ALA) and catalase (CAT), termed brain-targeted 5-ALA-CAT liposomes (BACL), which were surface-modified with the Angiopep-2 ligand to enhance blood–brain barrier penetration and achieve multimodal therapy combining targeted delivery and oxygen generation. Methods: BACL was prepared and characterized. Tumor targeting was verified by flow cytometry and in vivo imaging. In vitro antitumor activity was evaluated by wound-healing assay, colony formation assay, live/dead staining, MTT assay, and Western blotting. In vivo efficacy, apoptosis, and safety were assessed in a subcutaneous xenograft model. Transcriptome sequencing and qRT-PCR were employed to identify molecular mechanisms and novel targets. Results: BACL exhibited favorable physicochemical properties (size: 122.4 nm, PDI: 0.189, zeta potential: −12.3 mV) and spherical morphology as observed by TEM, with encapsulation efficiencies of 51.2% for 5-ALA and 43.8% for CAT. Compared with unmodified 5-ALA, BACL increased the cellular uptake efficiency by 1.6-fold in glioma cells while maintaining catalytic stability for sustained oxygen generation. In vitro experiments demonstrated that BACL significantly inhibited glioma cell migration, colony formation, and cell viability, and induced apoptosis. In a subcutaneous xenograft tumor model, BACL-mediated photodynamic therapy (PDT) achieved a tumor growth inhibition rate of 52%, with apoptosis induction via regulation of Bcl-2, Bax, and p53 expression, and no obvious toxicity to major organs was observed. Transcriptomic analysis combined with qRT-PCR validation revealed that BACL activates multiple antitumor signaling pathways, including targeted inhibition of IL-10 and CXCL13 to disrupt cytokine–receptor interactions, as well as coordinated regulation of S100A3 and IGSF-9 expression to suppress glioma progression. Conclusions: These multimodal actions enhanced PDT efficacy while remodeling the tumor microenvironment. Our findings position BACL as a promising therapeutic platform integrating targeted delivery, hypoxia alleviation, and immunomodulation for GBM therapy. Full article

Background and Clinical Significanc: Neuropathic corneal pain is a debilitating condition characterized by ocular pain disproportionate to clinical signs, often resulting from peripheral and central sensitization of the corneal somatosensory pathway. Emerging evidence suggests that chronic involuntary muscle contraction in blepharospasm may lead to irritation of trigeminal afferents and corneal neurogenic inflammation, potentially predisposing patients to neuropathic corneal pain. Given its debilitating nature, early recognition can prevent the progression of neuropathic sequelae. This study examines the potential role of blepharospasm as a predisposing factor contributing to neuropathic corneal pain. Case Presentation: This retrospective case series describes three cases (median age: 50 years) of neuropathic corneal pain in association with blepharospasm and their clinical course following multimodal treatment over a median follow-up period of one year. Ocular surface was evaluated using slit-lamp biomicroscopy, while corneal nerve structure and morphology were assessed with in vivo confocal microscopy. All the three subjects presented with minimal ocular surface staining but disproportionate ocular pain characterized by burning sensation and photophobia. Proparacaine challenge testing was performed to determine the subtype of neuropathic corneal pain. Pain symptoms and quality of life were evaluated using the Ocular Pain Assessment Survey and Ocular Surface Disease Index questionnaires. In vivo confocal microscopy demonstrated characteristic corneal nerve abnormalities including reduced corneal nerve density, increased nerve tortuosity, and the presence of microneuromas. Treatment included oral Pregabalin or Gabapentin, topical lubricants, Cyclosporine 0.05% (1 case), and 20% autologous serum eye drops (1 case). Two of the three cases received four to five injections of botulinum toxin for blepharospasm, whereas one had undergone a single injection prior to review. All patients also received weekly periorbital quantum molecular resonance electrotherapy for two months. Improvements were observed across multiple domains of the Ocular Pain Assessment Survey and Ocular Surface Disease Index evaluation, including ocular pain, photophobia, non-ocular pain, and quality-of-life measures following multimodal treatment. The co-existence of blepharospasm and neuropathic corneal pain observed in our cases supports a possible association between chronic periocular muscle hyperactivity and corneal nociceptor sensitization. Proposed mechanisms include chronic trigeminal nerve irritation, neurogenic inflammation, and sensitization mediated by pro-inflammatory neuropeptides. Multimodal treatment targeting both motor hyperactivity and neuropathic pain pathways appeared to provide symptomatic relief, including the use of quantum molecular resonance electrotherapy, which might modulate pain pathways, block nociceptor neurotransmission, and accelerate corneal nerve regeneration. Given the complexity of the neural pathways responsible for ocular discomfort, further studies are required to elucidate the relationship between neuropathic corneal pain and blepharospasm in larger cohorts, as well as refine existing therapeutic approaches, including evaluating the therapeutic role of electrotherapy. Conclusions: Blepharospasm may represent a potential predisposing factor of neuropathic corneal pain. Early recognition and concurrent treatment of blepharospasm and neuropathic corneal pain can effectively relieve symptoms and improve quality of life. Adopting a multimodal treatment approach is therefore recommended. Full article

Background: Rosacea is a chronic inflammatory dermatosis characterized by vascular dysregulation, immune dysfunction, neurovascular alterations, and microbial involvement. Recent advances in understanding its pathophysiology have led to the development of targeted therapeutic strategies addressing multiple disease mechanisms. This systematic review aimed to evaluate contemporary evidence regarding emerging and established treatment approaches for rosacea. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, and Web of Science were searched for studies published between 2016 and 2025. Original human studies evaluating therapeutic interventions for rosacea were included. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Methodological quality was assessed using Joanna Briggs Institute (JBI) critical appraisal tools appropriate for each study design. Results: Fifteen studies involving 537 patients with rosacea and 77 controls (614 participants in total) met the eligibility criteria. Evaluated interventions included vascular-targeted therapies, topical anti-inflammatory agents, systemic and immunomodulatory treatments, and microbiome-oriented approaches. Oxymetazoline, pulsed-dye laser, platelet-rich plasma, ivermectin, azelaic acid, dapsone, sulfur preparations, and metronidazole demonstrated clinical benefits in reducing erythema, inflammatory lesions, or overall disease severity. Emerging therapies, including tofacitinib and oral ivermectin, showed promising results in refractory disease. Microbiome-related interventions, particularly Demodex-targeted therapies and Helicobacter pylori eradication, were also associated with clinical improvement. Risk-of-bias assessment identified two studies with low risk of bias, twelve with moderate risk of bias, and one study with high risk of bias. Conclusions: Current evidence supports a multimodal and mechanism-based approach to rosacea management, integrating vascular, inflammatory, immunological, and microbiological targets. However, the available evidence remains limited by small sample sizes, heterogeneous methodologies, short follow-up periods, and a predominance of non-randomized study designs. Large, well-designed randomized controlled trials are needed to establish optimal evidence-based treatment strategies and define the long-term efficacy and safety of emerging therapies. Full article

Walking is not merely locomotion but a window into the nervous system, integrating cortical, subcortical, cerebellar, spinal, and peripheral networks into a unified motor behavior. Across neurological diseases—including Parkinson’s disease, atypical parkinsonism, cerebellar ataxias, stroke, multiple sclerosis, neuropathies, neuromuscular disorders, and functional gait syndromes—gait disturbances are among the most disabling clinical features, contributing to falls, loss of independence, institutionalization, and premature mortality. Traditional bedside observation remains indispensable, but it lacks the sensitivity and reproducibility needed to capture subtle, episodic, or prodromal abnormalities. Over the past decade, advances in wearable sensors, marker-based and markerless motion capture, pressure-sensitive walkways, force plates, artificial intelligence, and machine learning have positioned digital mobility outcomes as promising, ecologically valid biomarkers of neurological function. These measures can support differential diagnosis, provide prognostic information on falls and survival, and serve as sensitive endpoints in therapeutic trials. They may also detect early abnormalities, such as increased stride-to-stride variability or prolonged double-support time, before overt clinical deterioration becomes evident. Clinical applications are increasingly evident across disorders, including distinguishing Parkinson’s disease from atypical parkinsonism, quantifying treatment response in normal-pressure hydrocephalus, tracking progression in ataxia and multiple sclerosis, predicting functional decline in motor neuron disease, and guiding rehabilitation after stroke. Integration with neuroimaging, electrophysiology, and molecular biomarkers is beginning to reveal the circuits underlying variability, instability, and freezing, positioning gait as a systems-level marker of neural integrity. Nevertheless, methodological heterogeneity, limited disease-specific validation, insufficient longitudinal data, and lack of consensus on clinically meaningful parameters continue to constrain translation. Cognitive, affective, and environmental influences also remain insufficiently represented in digital frameworks, while equity, accessibility, algorithmic bias, and privacy require careful ethical governance. Reconceptualizing gait as a “sixth vital sign” reframes mobility as a multidimensional biomarker of neural and systemic health. With harmonized protocols, robust validation, multimodal integration, and appropriate ethical frameworks, gait analysis could become a cornerstone of precision neurology. Full article